Sample records for hind limb function
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Kharlamova, Anastasia V.; Trut, Lyudmila N.; Carrier, David R.; Chase, Kevin; Lark, Karl G.
2008-01-01
Synopsis Genetic variation in functionally integrated skeletal traits can be maintained over 10 million years despite bottlenecks and stringent selection. Here, we describe an analysis of the genetic architecture of the canid axial skeleton using populations of the Portuguese Water Dog Canis familiaris) and silver fox (Vulpes vulpes). Twenty-one skeletal metrics taken from radiographs of the forelimbs and hind limbs of the fox and dog were used to construct separate anatomical principal component (PC) matrices of the two species. In both species, 15 of the 21 PCs exhibited significant heritability, ranging from 25% to 70%. The second PC, in both species, represents a trade-off in which limb-bone width is inversely correlated with limb-bone length. PC2 accounts for approximately 15% of the observed skeletal variation, ~30% of the variation in shape. Many of the other significant PCs affect very small amounts of variation (e.g., 0.2–2%) along trade-off axes that partition function between the forelimbs and hind limbs. These PCs represent shape axes in which an increase in size of an element of the forelimb is associated with a decrease in size of an element of the hind limb and vice versa. In most cases, these trade-offs are heritable in both species and genetic loci have been identified in the Portuguese Water Dog for many of these. These PCs, present in both the dog and the fox, include ones that affect lengths of the forelimb versus the hind limb, length of the forefoot versus that of the hind foot, muscle moment (i.e., lever) arms of the forelimb versus hind limb, and cortical thickness of the bones of the forelimb versus hind limb. These inverse relationships suggest that genetic regulation of the axial skeleton results, in part, from the action of genes that influence suites of functionally integrated traits. Their presence in both dogs and foxes suggests that the genes controlling the regulation of these PCs of the forelimb versus hind limb may be found in other tetrapod taxa. PMID:18458753
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Scaling and functional morphology in strigiform hind limbs
Madan, Meena A.; Rayfield, Emily J.; Bright, Jen A.
2017-01-01
Strigiformes are an order of raptorial birds consisting exclusively of owls: the Tytonidae (barn owls) and the Strigidae (true owls), united by a suite of adaptations aiding a keen predatory lifestyle, including robust hind limb elements modified for grip strength. To assess variation in hind limb morphology, we analysed how the dimensions of the major hind limb elements in subfossil and modern species scaled with body mass. Comparing hind limb element length, midshaft width, and robusticity index (RI: ratio of midshaft width to maximum length) to body mass revealed that femoral and tibiotarsal width scale with isometry, whilst length scales with negative allometry, and close to elastic similarity in the tibiotarsus. In contrast, tarsometatarsus width shows strong positive allometry with body mass, whilst length shows strong negative allometry. Furthermore, the tarsometatarsi RI scales allometrically to mass0.028, whilst a weak relationship exists in femora (mass0.004) and tibiotarsi (mass0.004). Our results suggest that tarsometatarsi play a more substantial functional role than tibiotarsi and femora. Given the scaling relationship between tarsometatarsal width and robusticity to body mass, it may be possible to infer the body mass of prehistoric owls by analysing tarsometatarsi, an element that is frequently preserved in the fossil record of owls. PMID:28327549
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Ranking of physiotherapeutic evaluation methods as outcome measures of stifle functionality in dogs.
Hyytiäinen, Heli K; Mölsä, Sari H; Junnila, Jouni T; Laitinen-Vapaavuori, Outi M; Hielm-Björkman, Anna K
2013-04-08
Various physiotherapeutic evaluation methods are used to assess the functionality of dogs with stifle problems. Neither validity nor sensitivity of these methods has been investigated. This study aimed to determine the most valid and sensitive physiotherapeutic evaluation methods for assessing functional capacity in hind limbs of dogs with stifle problems and to serve as a basis for developing an indexed test for these dogs. A group of 43 dogs with unilateral surgically treated cranial cruciate ligament deficiency and osteoarthritic findings was used to test different physiotherapeutic evaluation methods. Twenty-one healthy dogs served as the control group and were used to determine normal variation in static weight bearing and range of motion.The protocol consisted of 14 different evaluation methods: visual evaluation of lameness, visual evaluation of diagonal movement, visual evaluation of functional active range of motion and difference in thrust of hind limbs via functional tests (sit-to-move and lie-to-move), movement in stairs, evaluation of hind limb muscle atrophy, manual evaluation of hind limb static weight bearing, quantitative measurement of static weight bearing of hind limbs with bathroom scales, and passive range of motion of hind limb stifle (flexion and extension) and tarsal (flexion and extension) joints using a universal goniometer. The results were compared with those from an orthopaedic examination, force plate analysis, radiographic evaluation, and a conclusive assessment. Congruity of the methods was assessed with a combination of three statistical approaches (Fisher's exact test and two differently calculated proportions of agreeing observations), and the components were ranked from best to worst. Sensitivities of all of the physiotherapeutic evaluation methods against each standard were calculated. Evaluation of asymmetry in a sitting and lying position, assessment of muscle atrophy, manual and measured static weight bearing, and measurement of stifle passive range of motion were the most valid and sensitive physiotherapeutic evaluation methods. Ranking of the various physiotherapeutic evaluation methods was accomplished. Several of these methods can be considered valid and sensitive when examining the functionality of dogs with stifle problems.
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Ranking of physiotherapeutic evaluation methods as outcome measures of stifle functionality in dogs
2013-01-01
Background Various physiotherapeutic evaluation methods are used to assess the functionality of dogs with stifle problems. Neither validity nor sensitivity of these methods has been investigated. This study aimed to determine the most valid and sensitive physiotherapeutic evaluation methods for assessing functional capacity in hind limbs of dogs with stifle problems and to serve as a basis for developing an indexed test for these dogs. A group of 43 dogs with unilateral surgically treated cranial cruciate ligament deficiency and osteoarthritic findings was used to test different physiotherapeutic evaluation methods. Twenty-one healthy dogs served as the control group and were used to determine normal variation in static weight bearing and range of motion. The protocol consisted of 14 different evaluation methods: visual evaluation of lameness, visual evaluation of diagonal movement, visual evaluation of functional active range of motion and difference in thrust of hind limbs via functional tests (sit-to-move and lie-to-move), movement in stairs, evaluation of hind limb muscle atrophy, manual evaluation of hind limb static weight bearing, quantitative measurement of static weight bearing of hind limbs with bathroom scales, and passive range of motion of hind limb stifle (flexion and extension) and tarsal (flexion and extension) joints using a universal goniometer. The results were compared with those from an orthopaedic examination, force plate analysis, radiographic evaluation, and a conclusive assessment. Congruity of the methods was assessed with a combination of three statistical approaches (Fisher’s exact test and two differently calculated proportions of agreeing observations), and the components were ranked from best to worst. Sensitivities of all of the physiotherapeutic evaluation methods against each standard were calculated. Results Evaluation of asymmetry in a sitting and lying position, assessment of muscle atrophy, manual and measured static weight bearing, and measurement of stifle passive range of motion were the most valid and sensitive physiotherapeutic evaluation methods. Conclusions Ranking of the various physiotherapeutic evaluation methods was accomplished. Several of these methods can be considered valid and sensitive when examining the functionality of dogs with stifle problems. PMID:23566355
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Maliye, Sylvia; Marshall, John F
2016-10-15
OBJECTIVE To characterize and describe the compensatory load redistribution that results from unilateral hind limb lameness in horses. DESIGN Retrospective case series. ANIMALS 37 client-owned horses. PROCEDURES Medical records were reviewed to identify horses with unilateral hind limb lameness that responded positively (by objective assessment) to diagnostic local anesthesia during lameness evaluation and that were evaluated before and after diagnostic local anesthesia with an inertial sensor-based lameness diagnosis system. Horses were grouped as having hind limb lameness only, hind limb and ipsilateral forelimb lameness, or hind limb and contralateral forelimb lameness. Measures of head and pelvic movement asymmetry before (baseline) and after diagnostic local anesthesia were compared. The effect of group on baseline pelvic movement asymmetry variables was analyzed statistically. RESULTS Maximum pelvic height significantly decreased from the baseline value after diagnostic local anesthesia in each of the 3 lameness groups and in all horses combined. Minimum pelvic height significantly decreased after the procedure in all groups except the hind limb and contralateral forelimb lameness group. Head movement asymmetry was significantly decreased after diagnostic local anesthesia for horses with hind limb and ipsilateral forelimb lameness and for all horses combined, but not for those with hind limb lameness only or those with hind limb and contralateral forelimb lameness. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that hind limb lameness can cause compensatory load redistribution evidenced as ipsilateral forelimb lameness. In this population of horses, contralateral forelimb lameness was not compensatory and likely reflected true lameness. Further studies are needed to investigate the source of the contralateral forelimb lameness in such horses.
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Crook, T C; Cruickshank, S E; McGowan, C M; Stubbs, N; Wakeling, J M; Wilson, A M; Payne, R C
2008-02-01
The Quarter Horse (bred for acceleration) and the Arab (bred for endurance) are situated at either end of the equine athletic spectrum. Studies into the form and function of the leg muscles in human sprint and endurance runners have demonstrated that differences exist in their muscle architecture. It is not known whether similar differences exist in the horse. Six Quarter Horse and six Arab fresh hind limb cadavers were dissected to gain information on the muscle mass and architecture of the following muscles: gluteus medius; biceps femoris; semitendinosus; vastus lateralis; gastrocnemius; tibialis cranialis and extensor digitorum longus. Specifically, muscle mass, fascicle length and pennation angle were quantified and physiological cross-sectional area (PCSA) and maximum isometric force were estimated. The hind limb muscles of the Quarter Horse were of a significantly greater mass, but had similar fascicle lengths and pennation angles when compared with those of the Arab; this resulted in the Quarter Horse hind limb muscles having greater PCSAs and hence greater isometric force potential. This study suggests that Quarter Horses as a breed inherently possess large strong hind limb muscles, with the potential to accelerate their body mass more rapidly than those of the Arab.
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Possible role of thromboxane A2 in remote hind limb preconditioning-induced cardioprotection.
Sharma, Roohani; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh
2016-01-01
Remote hind limb preconditioning (RIPC) is a protective strategy in which short episodes of ischemia and reperfusion in a remote organ (hind limb) protects the target organ (heart) against sustained ischemic reperfusion injury. The present study was designed to investigate the possible role of thromboxane A2 in RIPC-induced cardioprotection in rats. Remote hind limb preconditioning was performed by four episodes of 5 min of inflation and 5 min of deflation of pressure cuff. Occlusion of the hind limb with blood pressure cuff is most feasible, non-invasive, clinically relevant, and safe method for inducing RIPC. Isolated rat hearts were perfused on Langendorff apparatus and were subjected to global ischemia for 30 min followed by 120-min reperfusion. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were measured in coronary effluent to assess the degree of myocardial injury. The extent of myocardial infarct size along with the functional parameters including left ventricular developed pressure (LVDP), dp/dtmax, and dp/dtmin were also measured. Ozagrel (thromboxane synthase inhibitor) and seratrodast (thromboxane A2 receptor antagonist) were employed as pharmacological modulators of thromboxane A2. Remote hind limb preconditioning significantly attenuated ischemia/reperfusion-induced myocardial injury and produced cardioprotective effects. However, administration of ozagrel and seratrodast completely abolished the cardioprotective effects of RIPC suggesting the key role of thromboxane A2 in RIPC-induced cardioprotection. It may be concluded that brief episodes of preconditioning ischemia and reperfusion activates the thromboxane synthase enzyme that produces thromboxane A2, which may elicit cardioprotection either involving humoral or neurogenic pathway.
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Kelmer, Gal; Keegan, Kevin G; Kramer, Joanne; Wilson, David A; Pai, Frank P; Singh, Prableen
2005-04-01
To characterize compensatory movements of the head and pelvis that resemble lameness in horses. 17 adult horses. Kinematic evaluations were performed while horses trotted on a treadmill before and after shoe-induced lameness. Lameness was quantified and the affected limb determined by algorithms that measured asymmetry in vertical movement of the head and pelvis. Induced primary lameness and compensatory movements resembling lameness were assessed by the Friedman test. Association between induced lameness and compensatory movements was examined by regression analysis. Compensatory movements resembling lameness in the ipsilateral forelimb were seen with induced lameness of a hind limb. There was less downward and less upward head movement during and after the stance phase of the ipsilateral forelimb. Doubling the severity of lameness in the hind limb increased severity of the compensatory movements in the ipsilateral forelimb by 50%. Compensatory movements resembling lameness of the hind limb were seen after induced lameness in a forelimb. There was less upward movement of the pelvis after the stance phase of the contralateral hind limb and, to a lesser extent, less downward movement of the pelvis during the stance phase of the ipsilateral hind limb. Doubling the severity of lameness in the forelimb increased compensatory movements of the contralateral hind limb by 5%. Induced lameness in a hind limb causes prominent compensatory movements resembling lameness in the ipsilateral forelimb. Induced lameness in a forelimb causes slight compensatory movements resembling lameness in the ipsilateral and contralateral hind limbs.
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Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh
2016-08-01
Remote ischemic preconditioning is a well reported therapeutic strategy that induces cardioprotective effects but the underlying intracellular mechanisms have not been widely explored. The current study was designed to investigate the involvement of TRP and especially TRPV channels in remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 alternate cycles of inflation and deflation of 5 min each) was delivered using a blood pressure cuff tied on the hind limb of the anesthetized rat. Using Langendorff's system, the heart was perfused and subjected to 30-min ischemia and 120-min reperfusion. The myocardial injury was assessed by measuring infarct size, lactate dehydrogenase (LDH), creatine kinase (CK), LVDP, +dp/dtmax, -dp/dtmin, heart rate, and coronary flow rate. Gadolinium, TRP blocker, and ruthenium red, TRPV channel blocker, were employed as pharmacological tools. Remote hind limb preconditioning significantly reduced the infarct size, LDH release, CK release and improved coronary flow rate, hemodynamic parameters including LVDP, +dp/dtmax, -dp/dtmin, and heart rate. However, gadolinium (7.5 and 15 mg kg(-1)) and ruthenium red (4 and 8 mg kg(-1)) significantly attenuated the cardioprotective effects suggesting the involvement of TRP especially TRPV channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus possibly activates TRPV channels on the heart or sensory nerve fibers innervating the heart to induce cardioprotective effects. Alternatively, remote hind limb preconditioning stimulus may also activate the mechanosensitive TRP and especially TRPV channels on the sensory nerve fibers innervating the skeletal muscles to trigger cardioprotective neurogenic signaling cascade. The cardioprotective effects of remote hind limb preconditioning may be mediated via activation of mechanosensitive TRP and especially TRPV channels.
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Kawano, Sandy M; Blob, Richard W
2013-08-01
The invasion of land was a pivotal event in vertebrate evolution that was associated with major appendicular modifications. Although fossils indicate that the evolution of fundamentally limb-like appendages likely occurred in aquatic environments, the functional consequences of using early digited limbs, rather than fins, for terrestrial propulsion have had little empirical investigation. Paleontological and experimental analyses both have led to the proposal of an early origin of "hind limb-driven" locomotion among tetrapods or their ancestors. However, the retention of a pectoral appendage that had already developed terrestrial adaptations has been proposed for some taxa, and few data are available from extant functional models that can provide a foundation for evaluating the relative contributions of pectoral and pelvic appendages to terrestrial support among early stem tetrapods. To examine these aspects of vertebrate locomotor evolution during the invasion of land, we measured three-dimensional ground reaction forces (GRFs) produced by isolated pectoral fins of mudskipper fishes (Periophthalmus barbarus) during terrestrial crutching, and compared these to isolated walking footfalls by the forelimbs and hind limbs of tiger salamanders (Ambystoma tigrinum), a species with subequally-sized limbs that facilitate comparisons to early tetrapods. Pectoral appendages of salamanders and mudskippers exhibited numerous differences in GRFs. Compared with salamander forelimbs, isolated fins of mudskippers bear lower vertical magnitudes of GRFs (as a proportion of body weight), and had GRFs that were oriented more medially. Comparing the salamanders' forelimbs and hind limbs, although the peak net GRF occurs later in stance for the forelimb, both limbs experience nearly identical mediolateral and vertical components of GRF, suggesting comparable contributions to support. Thus, forelimbs could also have played a significant locomotor role among basal tetrapods that had limbs of sub-equal size. However, the salamander hind limb and mudskipper pectoral fin had a greater acceleratory role than did the salamander forelimb. Together, data from these extant taxa help to clarify how structural change may have influenced locomotor function through the evolutionary invasion of land by vertebrates.
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Krompecher, T; Fryc, O
1978-01-01
The use of new methods and an appropriate apparatus has allowed us to make successive measurements of rigor mortis and a study of its evolution in the rat. By a comparative examination on the front and hind limbs, we have determined the following: (1) The muscular mass of the hind limbs is 2.89 times greater than that of the front limbs. (2) In the initial phase rigor mortis is more pronounced in the front limbs. (3) The front and hind limbs reach maximum rigor mortis at the same time and this state is maintained for 2 hours. (4) Resolution of rigor mortis is accelerated in the front limbs during the initial phase, but both front and hind limbs reach complete resolution at the same time.
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Meteyer, C.U.; Loeffler, I.K.; Fallon, J.F.; Converse, K.A.; Green, E.; Helgen, J.C.; Kersten, S.; Levey, R.; Eaton-Poole, L.; Burkhart, J.G.
2000-01-01
Background Reports of malformed frogs have increased throughout the North American continent in recent years. Most of the observed malformations have involved the hind limbs. The goal of this study was to accurately characterize the hind limb malformations in wild frogs as an important step toward understanding the possible etiologies. Methods During 1997 and 1998, 182 recently metamorphosed northern leopard frogs (Rana pipiens) were collected from Minnesota, Vermont, and Maine. Malformed hind limbs were present in 157 (86%) of these frogs, which underwent necropsy and radiographic evaluation at the National Wildlife Health Center. These malformations are described in detail and classified into four major categories: (1) no limb (amelia); (2) multiple limbs or limb elements (polymelia, polydactyly, polyphalangy); (3) reduced limb segments or elements (phocomelia, ectromelia, ectrodactyly, and brachydactyly; and (4) distally complete but malformed limb (bone rotations, bridging, skin webbing, and micromelia). Results Amelia and reduced segments and/or elements were the most common finding. Frogs with bilateral hind limb malformations were not common, and in only eight of these 22 frogs were the malformations symmetrical. Malformations of a given type tended to occur in frogs collected from the same site, but the types of malformations varied widely among all three states, and between study sites within Minnesota. Conclusions Clustering of malformation type suggests that developmental events may produce a variety of phenotypes depending on the timing, sequence, and severity of the environmental insult. Hind limb malformations in free-living frogs transcend current mechanistic explanations of tetrapod limb development.
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West, Christopher R; Crawford, Mark A; Poormasjedi-Meibod, Malihe-Sadat; Currie, Katharine D; Fallavollita, Andre; Yuen, Violet; McNeill, John H; Krassioukov, Andrei V
2014-04-15
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.
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GH/IGF-I Transgene Expression on Muscle Homeostasis
NASA Technical Reports Server (NTRS)
Schwartz, Robert J.
1999-01-01
We propose to test the hypothesis that the growth hormone/ insulin like growth factor-I axis through autocrine/paracrine mechanisms may provide long term muscle homeostasis under conditions of prolonged weightlessness. As a key alternative to hormone replacement therapy, ectopic production of hGH, growth hormone releasing hormone (GHRH), and IGF-I will be studied for its potential on muscle mass impact in transgenic mice under simulated microgravity. Expression of either hGH or IGF-I would provide a chronic source of a growth-promoting protein whose biosynthesis or secretion is shut down in space. Muscle expression of the IGF-I transgene has demonstrated about a 20% increase in hind limb muscle mass over control nontransgenic litter mates. These recent experiments, also establish the utility of hind-limb suspension in mice as a workable model to study atrophy in weight bearing muscles. Thus, transgenic mice will be used in hind-limb suspension models to determine the role of GH/IGF-I on maintenance of muscle mass and whether concentric exercises might act in synergy with hormone treatment. As a means to engineer and ensure long-term protein production that would be workable in humans, gene therapy technology will be used by to monitor muscle mass preservation during hind-limb suspension, after direct intramuscular injection of a genetically engineered muscle-specific vector expressing GHRH. Effects of this gene-based therapy will be assessed in both fast twitch (medial gastrocnemius) and slow twitch muscle (soleus). End-points include muscle size, ultrastructure, fiber type, and contractile function, in normal animals, hind limb suspension, and reambutation.
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Lipoate ameliorates ischemia-reperfusion in animal models.
Freisleben, H J
2000-01-01
Ischemia and reperfusion were studied in isolated working rat hearts and in exarticulated rat hind limbs. Free radicals are known to be generated in ischemia/reperfusion and to propagate complications. To reduce reperfusion injury, conditions were ameliorated including the treatment with antioxidants, lipoate or dihydrolipoate. In isolated working rat hearts, cardiac and mitochondrial parameters are impaired during hypoxia and partially recover in reperfusion. Dihydrolipoate, if added into the perfusion buffer at 0.3 microM concentration, keeps the pH higher (7.15) during hypoxia, as compared to controls (6.98). This compound accelerates and stabilizes the recovery of the aortic flow. With dihydrolipoate, ATP synthesis is increased, ATPase activity (ATP hydrolysis) reduced, intracellular creatine kinase activity maintained and thus phosphocreatine contents are higher than in controls. For exarticulated rat hind limbs, the dihydrolipoate group contained 8.3 microM in the modified reperfusate. Recovery of the contractile function was 49% vs. 34% in controls and muscle flexibility was maintained whereas it decreased by 15% in the controls. Release of creatine kinase from cells was significantly lower with dihydrolipoate. Lipoate/dihydrolipoate effectively reduced reperfusion injury in isolated working rat hearts and in exarticulated rat hind limbs after extended ischemia. Finally, the compound was successfully applied in an in vivo pig hind limb model.
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Effects of immobilization on rat hind limb muscles under non-weight-bearing conditions
NASA Technical Reports Server (NTRS)
Jaspers, Stephen R.; Fagan, Julie M.; Satarug, Soisungwan; Cook, Paul H.; Tischler, Marc E.
1988-01-01
The effect of stretched and unstretched immobilization of a hind limb on the concentration and the metabolism of proteins in the hind-limb muscles of rats was investigated. The animals were divided into three groups: (1) weight-bearing controls, (2) tail-cast-suspended, and (3) suspended, with one hind limb immobilized with the ankle in dorsiflexion (30-40 deg angle) and the other freely moving. It was found that unloading the hind limbs for 6 days by tail cast suspension caused soleus to atrophy and reduced growth of the gastrocnemius and plantaris muscles; unloading resulted in a higher degradation rate and lower synthesis rate in both in vitro and in vivo. Chronic stretch of the unloaded soleus not only prevented its atrophy but led to significant hypertrophy, relative to weight-bearing controls, with increases in both the sarcoplasmic and myofibrillar protein fractions. Immobilizing one ankle in dorsiflexion prevented the inhibition of growth in the plantaris and gastrocnemius muscles due to unloading.
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Length asymmetry of the bovine digits.
Muggli, E; Sauter-Louis, C; Braun, U; Nuss, K
2011-06-01
The lengths of the digital bones of the fore- and hind-limbs obtained post mortem from 40 cattle of different ages were measured using digital radiographs. The lengths of the individual digital bones and the overall length of the digit were determined using computer software. The lateral metacarpal/metatarsal condyle, and lateral P1 and P2 were significantly longer than their medial counterparts, whereas P3 of the medial digit was longer than its lateral partner. Measured from the cannon bone epiphysis to the tip of the pedal bone, the mean increased length of the lateral digit was 0.8 mm in the fore- and 1.5 mm in the hind-limb. When the lengths of the digital bones were summed, the mean length of the lateral digit was 1.8 mm longer in the fore-limb and 2.1 mm longer in the hind-limb. Based on these findings, it can be concluded that the lengths of the paired digits differ in cattle. The majority of cattle have longer lateral digits in the fore- and hind-limbs. This asymmetry might explain why the lateral hind-limb claws are predisposed to sole ulcers on hard surfaces. In the hind-limbs, the impact is transferred from the pelvis directly to the longer lateral digit. In the fore-limb claws, the tenomuscular attachment to the trunk may be involved in a more even weight distribution and in a shift of weight to the medial claw. Copyright © 2010 Elsevier Ltd. All rights reserved.
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Effect of lungeing on head and pelvic movement asymmetry in horses with induced lameness.
Rhodin, M; Pfau, T; Roepstorff, L; Egenvall, A
2013-12-01
Lungeing is an important part of lameness examinations, since the circular path enforced during lungeing is thought to accentuate low grade lameness. However, during lungeing the movement of sound horses becomes naturally asymmetric, which may mimic lameness. Also, compensatory movements in the opposite half of the body may mimic lameness. The aim of this study was to objectively study the presence of circle-dependent and compensatory movement asymmetries in horses with induced lameness. Ten horses were trotted in a straight line and lunged in both directions on a hard surface. Lameness was induced (reversible hoof pressure) in each limb, one at a time, in random order. Vertical head and pelvic movements were measured with body-mounted, uni-axial accelerometers. Differences between maximum and minimum height observed during/after left and right stance phases for the head (HDmax, HDmin) and pelvis (PDmax, PDmin) were measured. Mixed models were constructed to study the effect of lungeing direction and induction, and to quantify secondary compensatory asymmetry mechanisms in the forelimbs and hind limbs. Head and pelvic movement symmetries were affected by lungeing. Minimum pelvic height difference (PDmin) changed markedly, increasing significantly during lungeing, giving the impression of inner hind limb lameness. Primary hind limb lameness induced compensatory head movement, which mimicked an ipsilateral forelimb lameness of almost equal magnitude to the primary hind limb lameness. This could contribute to difficulty in correctly detecting hind limb lameness. Induced forelimb lameness caused both a compensatory contralateral (change in PDmax) and an ipsilateral (change in PDmin) hind limb asymmetry, potentially mimicking hind limb lameness, but of smaller magnitude. Both circle-dependent and compensatory movement mechanisms must be taken into account when evaluating lameness. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Cooper, Tyler T; Sherman, Stephen E; Kuljanin, Miljan; Bell, Gillian I; Lajoie, Gilles A; Hess, David A
2018-05-01
Blood-derived progenitor cell transplantation holds potential for the treatment of severe vascular diseases. Human umbilical cord blood (UCB)-derived hematopoietic progenitor cells purified using high aldehyde dehydrogenase (ALDH hi ) activity demonstrate pro-angiogenic functions following intramuscular (i.m.) transplantation into immunodeficient mice with hind-limb ischemia. Unfortunately, UCB ALDH hi cells are rare and prolonged ex vivo expansion leads to loss of high ALDH-activity and diminished vascular regenerative function. ALDH-activity generates retinoic acid, a potent driver of hematopoietic differentiation, creating a paradoxical challenge to expand UCB ALDH hi cells while limiting differentiation and retaining pro-angiogenic functions. We investigated whether inhibition of ALDH-activity during ex vivo expansion of UCB ALDH hi cells would prevent differentiation and expand progeny that retained pro-angiogenic functions after transplantation into non-obese diabetic/severe combined immunodeficient mice with femoral artery ligation-induced unilateral hind-limb ischemia. Human UCB ALDH hi cells were cultured under serum-free conditions for 9 days, with or without the reversible ALDH-inhibitor, diethylaminobenzaldehyde (DEAB). Although total cell numbers were increased >70-fold, the frequency of cells that retained ALDH hi /CD34+ phenotype was significantly diminished under basal conditions. In contrast, DEAB-inhibition increased total ALDH hi /CD34+ cell number by ≥10-fold, reduced differentiation marker (CD38) expression, and enhanced the retention of multipotent colony-forming cells in vitro. Proteomic analysis revealed that DEAB-treated cells upregulated anti-apoptotic protein expression and diminished production of proteins implicated with megakaryocyte differentiation. The i.m. transplantation of DEAB-treated cells into mice with hind-limb ischemia stimulated endothelial cell proliferation and augmented recovery of hind-limb perfusion. DEAB-inhibition of ALDH-activity delayed hematopoietic differentiation and expanded multipotent myeloid cells that accelerated vascular regeneration following i.m. transplantation in vivo. Stem Cells 2018;36:723-736. © AlphaMed Press 2018.
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Influence of training on the biokinematics in trotting Andalusian horses.
Cano, M R; Miró, F; Diz, A M; Agüera, E; Galisteo, A M
2000-11-01
The aim of this study was to determine the influence of a 10-month training programme on the linear, temporal and angular characteristics of the fore and hind limbs at the trot in the Andalusian horse, using standard computer-aided videography. Sixteen male Andalusian horses were observed before and after training. Six strides were randomly selected for analysis in each horse and linear, temporal and angular parameters were calculated for fore and hind limbs. The training programme used here produced significant changes in kinematic parameters, such as shortening of stride length, and increase in swing duration and a decrease in hind limb stance percentage. No significant differences were recorded in the angular values for the forelimb joints. In trained horses, the more proximal joints of the hind limb, especially the hip and stifle, had a greater flexion while the fetlock showed a smaller extension angle. At the beginning of the swing phase, hip and stifle joints presented angles that were significantly more flexed. When the hind limbs came into contact with the ground, all the joints presented greater flexion after training.
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West, Christopher R; Crawford, Mark A; Poormasjedi-Meibod, Malihe-Sadat; Currie, Katharine D; Fallavollita, Andre; Yuen, Violet; McNeill, John H; Krassioukov, Andrei V
2014-01-01
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. PMID:24535438
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Gómez Álvarez, C B; Gustås, P; Bergh, A; Rhodin, M
2017-11-01
Compensatory limb loading has been studied in lame dogs; however, little is known about how these compensations relate to motion of the head and pelvis, assessment of which is an important component of lameness examinations. The aim of this study was to describe the patterns of vertical head and pelvic motion symmetry at the trot in dogs with induced supporting limb lameness in the forelimbs or hind limbs. Ten sound dogs were trotted on a treadmill before and after temporary induction of moderate lameness (grade 2/5) in each limb. Reflective markers were located on the head, pelvis and right forelimb, and kinematic data were captured with a motion capture system. Upper body symmetry parameters were calculated, including differences in the highest (HDmax) and in the lowest (HDmin) positions of the head, and in the highest (PDmax) and in the lowest (PDmin) positions of the mid-pelvis, with a value of zero indicating symmetry. The head was lowered more during the sound limb stance phase and lowered less during the lame limb stance phase in supporting forelimb lameness (HDmin: 4.6mm in dogs when sound, -18.3mm when left limb lameness was induced and 20.5mm when right limb lameness was induced). The mid-pelvis was lowered more during the sound limb stance phase and lowered and lifted less during the lame limb stance phase in supporting hind limb lameness (PDmin: 1mm in dogs when sound, -10.1mm in left limb lameness and 8.4mm in right limb lameness). The hip of the lame side, measured at the level of the greater trochanter, had an increased downwards displacement during the lame limb swing phase (-21mm in left hind limb lameness, P=0.005; 23.4mm in right hind limb lameness, P=0.007). Asymmetry in the lowering of the head or mid-pelvis is a more sensitive indicator of supporting forelimb and hind limb lameness, respectively, than asymmetry in the raising of the head. Increased displacement of the hip ('hip drop' of the lame side during its swing phase) is a good indicator of hind limb lameness in dogs. Copyright © 2017. Published by Elsevier Ltd.
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Wang, Fangyong; Yuan, Yuan; Li, Jianjun
2015-12-01
To investigate the effects of the first neuron connection for the reconstruction of lower extremity function of complete spinal cord injury rats. Forty adult female Sprague Dawley rats of 300-350 g in weight were selected to prepare the models of L₁ transverse spinal cord injury. After 2 weeks of establishing model, the rats were randomly divided into control group (n = 20) and experimental group (n = 20). In the experimental group, the right hind limb function was reconstructed directly by the first neuron; in the control group, the other treatments were the same to the experimental group except that the distal tibial nerve and the proximal femoral nerve were not sutured. The recovery of motor function of lower extremity was observed by the Basso-Beattie-Bresnahan (BBB) scoring system on bilateral hind limbs at 7, 30, 50, and 70 days after operation. The changes of the spinal cord were observed by HE staining, neurofilament 200 immunohistochemistry staining, and the technique of horseradish peroxidase (HRP) tracing. After establishing models, 6 rats died. The right hind limb had no obvious recovery of the motor function, with the BBB score of 0 in 2 groups; the left hind limb motor function was recovered in different degrees, and there was no significant difference in BBB score between 2 groups (P > 0.05). In the experimental group, HE staining showed that the spinal cord was reconstructed with the sciatic nerve, which was embedded in the spinal cord, and the sciatic nerve membrane was clearly identified, and there was no obvious atrophy in the connecting part of the spinal cord. In the experimental group, the expression of nerve fiber was stained with immunohistochemistry, and the axons of the spinal cord were positively by stained and the peripheral nerve was connected with the spinal cord. HRP labelled synapses were detected by HRP retrograde tracing in the experimental group, while there was no HRP labelled synapse in the control group. Direct reconstruction of the first neurons is sufficient in the regeneration of corresponding neural circuit by the growth of residual axon; but the motor function recovery of the target muscles innervated by peripheral nerve is not observed.
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Effects of simulated weightlessness and sympathectomy on maximum VO2 of male rats
NASA Technical Reports Server (NTRS)
Woodman, C. R.; Stump, C. S.; Beaulieu, S. M.; Rahman, Z.; Sebastian, L. A.
1989-01-01
The effects of simulated weightlessness (hind-limb suspension) and chemical sympathectomy (by repeated injections with guanethidine sulfate) on the maximum oxygen consumption (VO2 max) of female rats were investigated in rats assigned for 14 days to one of three groups: a head-down hind-limb suspension, a horizontal suspension with hind limbs weight bearing, or the caged control. The VO2 max values were assessed by having rats run on a treadmill enclosed in an airtight chamber. The hind-limb-suspended sympathectomized rats were found to exhibit shorter run times and lower mechanical efficiencies, compared to their presuspension values or the values from saline-injected suspended controls. On the other hand, the suspended sympathectomized rats did not demonstrate a decrease in the VO2 max values that was observed in saline-injected controls.
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Makungu, M; du Plessis, W M; Groenewald, H B; Barrows, M; Koeppel, K N
2015-12-01
The red panda (Ailurus fulgens) is a quadrupedal arboreal animal primarily distributed in the Himalayas and southern China. It is a species commonly kept in zoological collections. This study was carried out to describe the morphology of the pelvis and hind limb of the red panda evidenced by gross osteology, radiography and computed tomography as a reference for clinical use and identification of skeletons. Radiography of the pelvis and right hind limb was performed in nine and seven animals, respectively. Radiographic findings were correlated with bone specimens from three adult animals. Computed tomography of the torso and hind limb was performed in one animal. The pelvic bone had a wide ventromedial surface of the ilium. The trochlea of the femur was wide and shallow. The patella was similar to that seen in feline species. The medial fabella was not seen radiographically in any animal. The cochlea grooves of the tibia were shallow with a poorly defined intermediate ridge. The trochlea of the talus was shallow and presented with an almost flattened medial ridge. The tarsal sesamoid bone was always present. The lateral process of the base of the fifth metatarsal (MT) bone was directed laterally. The MT bones were widely spaced. The morphology of the pelvis and hind limb of the red panda indicated flexibility of the pelvis and hind limb joints as an adaptation to an arboreal quadrupedal lifestyle. © 2014 Blackwell Verlag GmbH.
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Li, Li; Liu, Hong-Ju; Yang, Ming-Hao; Li, Jing-Long; Wang, Lu; Chen, Xiao-Ping; Fan, Ming
2012-03-01
To explore the relationship between contractile characteristics and fiber type conversion in hind-limb unloading mice soleus. After 28-day hind-limb unloading and muscle atrophy, we used the method of isolated muscle perfusion with different stimulated protocols to determine the changes in contractile characteristics including the isometric twitch force and tetanus force and fatigue index of slow twitch muscle in mice. The muscle myofibrillar composition and fiber type conversion were detected by immunofluorescence staining and real-time PCR. The isometric twitch force and the tetanus force and fatigue index were decreased progressively in 28-day unloaded mice soleus, with the increase in fast twitch fiber subtype and the decrease in slow twitch fiber subtype. The alteration of contractile characteristics is relevant to the slow-to-fast fiber conversion in mice soleus after 28-day hind-limb unloading.
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Chan, Yau-Chi; Ng, Joyce H. L.; Au, Ka-Wing; Wong, Lai-Yung; Siu, Chung-Wah; Tse, Hung-Fat
2013-01-01
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 tissue ischemia. PMID:23472116
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Kopp, Hans-Georg; Hooper, Andrea T.; Broekman, M. Johan; Avecilla, Scott T.; Petit, Isabelle; Luo, Min; Milde, Till; Ramos, Carlos A.; Zhang, Fan; Kopp, Tabitha; Bornstein, Paul; Jin, David K.; Marcus, Aaron J.; Rafii, Shahin
2006-01-01
Thrombopoietic cells may differentially promote or inhibit tissue vascularization by releasing both pro- and antiangiogenic factors. However, the molecular determinants controlling the angiogenic phenotype of thrombopoietic cells remain unknown. Here, we show that expression and release of thrombospondins (TSPs) by megakaryocytes and platelets function as a major antiangiogenic switch. TSPs inhibited thrombopoiesis, diminished bone marrow microvascular reconstruction following myelosuppression, and limited the extent of revascularization in a model of hind limb ischemia. We demonstrate that thrombopoietic recovery following myelosuppression was significantly enhanced in mice deficient in both TSP1 and TSP2 (TSP-DKO mice) in comparison with WT mice. Megakaryocyte and platelet levels in TSP-DKO mice were rapidly restored, thereby accelerating revascularization of myelosuppressed bone marrow and ischemic hind limbs. In addition, thrombopoietic cells derived from TSP-DKO mice were more effective in supporting neoangiogenesis in Matrigel plugs. The proangiogenic activity of TSP-DKO thrombopoietic cells was mediated through activation of MMP-9 and enhanced release of stromal cell–derived factor 1. Thus, TSP-deficient thrombopoietic cells function as proangiogenic agents, accelerating hemangiogenesis within the marrow and revascularization of ischemic hind limbs. As such, interference with the release of cellular stores of TSPs may be clinically effective in augmenting neoangiogenesis. PMID:17143334
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Males that drop a sexually selected weapon grow larger testes.
Joseph, Paul N; Emberts, Zachary; Sasson, Daniel A; Miller, Christine W
2018-01-01
Costly sexually selected weapons are predicted to trade off with postcopulatory traits, such as testes. Although weapons can be important for achieving access to females, individuals of some species can permanently drop (i.e. autotomize) their weapons, without regeneration, to escape danger. We capitalized on this natural behavior to experimentally address whether the loss of a sexually selected weapon leads to increased testes investment in the leaf-footed cactus bug, Narnia femorata Stål (Hemiptera: Coreidae). In a second experiment, we measured offspring production for males that lost a weapon during development. As predicted, males that dropped a hind limb during development grew significantly larger testes than the control treatments. Hind-limb autotomy did not result in the enlargement of other nearby traits. Our results are the first to experimentally demonstrate that males compensate for natural weapon loss by investing more in testes. In a second experiment we found that females paired with males that lost a hind limb had 40% lower egg hatching success than females paired with intact males, perhaps because of lower mating receptivity to males with a lost limb. Importantly, in those cases where viable offspring were produced, males missing a hind limb produced 42% more offspring than males with intact limbs. These results suggest that the loss of a hind-limb weapon can, in some cases, lead to greater fertilization success. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.
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Park, In-Su; Chung, Phil-Sang; Ahn, Jin Chul
2014-11-01
The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on transplanted human adipose-derived mesenchymal stem cells (hASCs) spheroid in a hind limb ischemia animal model. LLLT, hASCs spheroid and hASCs spheroid transplantation with LLLT (spheroid + LLLT) were applied to the ischemic hind limbs in athymic mice. The survival, differentiation and secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), and hepatocyte growth factor (HGF) of the spheroid ASCs were evaluated by immunohistochemistry and western blots. Spheroid + LLLT group had enhanced the tissue regeneration, including angiogenesis, compared with the ASC group. The spheroid ASCs contributed to tissue regeneration via differentiation and secretion of growth factors. In the spheroid + LLLT group, the survival of spheroid hASCs increased with a concomitant decrease in apoptosis of spheroid hASCs in the ischemic hind limb. The secretion of growth factors was stimulated in the spheroid + LLLT group compared with the ASCs and spheroid group. These data suggested that LLLT is an effective biostimulator of spheroid hASCs in tissue regeneration that enhanced the survival of ASCs and stimulated the secretion of growth factors in the ischemic hind limb. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Singh, Baljeet; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh
2016-05-01
The cardioprotective effects of remote hind limb preconditioning (RIPC) are well established, but its mechanisms still remain to be explored. Therefore, the present study was aimed to explore the possible involvement of 5-lipoxygenase-derived leukotrienes in RIPC. The hind limb was tied by a pressure cuff and was subjected to four episodes of inflation and deflation (5min each) to induce remote hind-limb preconditioning. Thereafter, the hearts were isolated and were subjected to global ischemia (30min) followed by reperfusion (120min) on the Langendorff apparatus. The extent of myocardial injury was assessed by measuring lactate dehydrogenase (LDH) and creatine kinase (CK) levels in the coronary effluent; the infarct size using TTC staining, and the hemodynamic parameters including LVDP, dp/dtmax and dp/dtmin. RIPC significantly decreased ischemia and reperfusion-induced increase in LDH, CK release, infarct size and improved LVDP, dp/dtmax and dp/dtmin. Administration of montelukast, leukotriene receptor antagonist (10 and 20mg/kg) and zileuton, 5-lipoxygenase inhibitor, (2.5 and 5mg/kg) abolished RIPC-induced cardioprotection. It may be concluded that hind limb ischemia stimulates 5-lipoxygenase to release leukotrienes which may elicit cardioprotection by humoral or neurogenic pathway. Copyright © 2016 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Luan, Huiqin; Sun, Lian-wen; Fan, Yu-bo
2012-07-01
Humans in Space suffer from microgravity-induced attenuated bone strength that needs to be addressed by on-orbit exercise countermeasures. However, exercise prescriptions so far did not adequately counteract the bone loss of astronauts in spaceflight because even active muscle contractions were converted to passive mode during voluntary bouts. We tested our hypothesis in unloaded rat hind limb following twenty-one days of tail-suspension (TS) combined with exercise using a hind limb stepper device designed by our group. Female Sprague Dawley rats (250g b.wt.) were divided into four groups (n=5, each): TS-only (hind limb unloading), TS plus passive mode exercise (TSP) induced by mechanically-forced passive hind limb lifting, TS plus active mode exercise (TSA) entrained by plantar electrostimulation, and control (CON) group. Standard measures of bone (e.g., mineral density, trabecular microstructure, biomechanics and ash weight) were monitored. Results provided that the attenuated properties of unloaded hind limb bone in TS-rats were more effectively supported by active mode than by passive mode motions. We here propose a modified exercise regimen combined with spontaneous muscle contractions thereby considering the biodynamic demands of both muscle and bone during resistive-load exercise in microgravity. Keywords: rat, BMD, DXA, passive exercise, active exercise, bone loss, tail suspension, spaceflight analogue, exercise countermeasure.
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Development of five digits is controlled by a bipartite long-range cis-regulator.
Lettice, Laura A; Williamson, Iain; Devenney, Paul S; Kilanowski, Fiona; Dorin, Julia; Hill, Robert E
2014-04-01
Conservation within intergenic DNA often highlights regulatory elements that control gene expression from a long range. How conservation within a single element relates to regulatory information and how internal composition relates to function is unknown. Here, we examine the structural features of the highly conserved ZRS (also called MFCS1) cis-regulator responsible for the spatiotemporal control of Shh in the limb bud. By systematically dissecting the ZRS, both in transgenic assays and within in the endogenous locus, we show that the ZRS is, in effect, composed of two distinct domains of activity: one domain directs spatiotemporal activity but functions predominantly from a short range, whereas a second domain is required to promote long-range activity. We show further that these two domains encode activities that are highly integrated and that the second domain is crucial in promoting the chromosomal conformational changes correlated with gene activity. During limb bud development, these activities encoded by the ZRS are interpreted differently by the fore limbs and the hind limbs; in the absence of the second domain there is no Shh activity in the fore limb, and in the hind limb low levels of Shh lead to a variant digit pattern ranging from two to four digits. Hence, in the embryo, the second domain stabilises the developmental programme providing a buffer for SHH morphogen activity and this ensures that five digits form in both sets of limbs.
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NASA Technical Reports Server (NTRS)
Thierry-Palmer, M.; Cephas, S.; Sayavongsa, P.; Clark, T.; Arnaud, S. B.
2004-01-01
Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have demonstrated that female S rats are more vulnerable than female R rats to decreases in plasma 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations during hind limb unloading (a space flight model). We report here on the response of the vitamin D endocrine system of S and R rats to hind limb unloading during high salt intake. Dahl female rats (9.7-week-old) were tail-suspended (hind limb unloaded) for 28 days, while fed a diet containing twice the salt in standard rat chow (2 % sodium chloride). Control rats were fed the same diet, but were not hind limb unloaded. Vitamin D metabolites were analyzed by HPLC and radioimmunoassay kits from Diasorin.
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Fasciotomy worsens the amount of myonecrosis in a porcine model of crotaline envenomation.
Tanen, David A; Danish, David C; Grice, Guerard A; Riffenburgh, Robert H; Clark, Richard F
2004-08-01
We evaluate the efficacy of fasciotomy or crotaline snake antivenom in reducing myonecrosis. We used a randomized, blinded, controlled acute animal preparation. Twenty anesthetized swine were injected intramuscularly in the anterior tibiales muscle of both hind limbs with 6 mg/kg of Crotalus atrox venom (total of 12 mg/kg of venom per animal). Immediately after venom injection, the right hind limb underwent fasciotomy. Muscle biopsies were obtained from the fasciotomized hind limb at 0, 4, and 8 hours and from the other hind limb at the conclusion of the study (8 hours). In addition, animals received either 8 vials of reconstituted Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) or an equal volume of normal saline solution intravenously 1 hour after venom injection. A pathologist blinded to the study determined the percentage of myonecrotic cells in each biopsy. Statistical analysis was performed using repeated measures analysis of variance for compartment pressure. Rank-order methods were used for comparison of myonecrosis between groups. Biopsies from hind limbs undergoing fasciotomy revealed a progressive increase in the amount of myonecrosis over time (myonecrosis median at 0, 4, or 8 hours [or death]: 0%, 14%, or 14.5%, respectively; P<.001). Comparison of the amount of myonecrosis of biopsies at death or 8 hours revealed that limbs that underwent fasciotomy had significantly more myonecrosis than those that did not (myonecrosis median: 14.5% versus 2.5%, P=.048). No difference was detected in the amount of myonecrosis when FabAV was compared with normal saline solution on final biopsies from either fasciotomy or nonfasciotomy hind limb (myonecrosis median: 10.0% versus 10.0%, P=.64). Fasciotomy significantly worsens the amount of myonecrosis in a porcine model of intramuscular crotaline venom injection. No change in the amount of myonecrosis was detected with the use of FabAV treatment at the dosages used in this animal model.
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Bateman, Philip W; Fleming, Patricia A
2005-01-01
Both male and female field crickets (Gryllus bimaculatus) autotomize front (tympanal) limbs more slowly than hind limbs. Arguably, this pattern could reflect possible differences in the mechanism of limb autotomy. However, we demonstrate that, for females, limb autotomy is also dependent on their mating status: virgin females autotomize front legs significantly more slowly than mated females. This response suggests a central control for leg autotomy in these animals, and less readiness to autotomize a front leg, possibly because the tympanum is crucial for mate location. PMID:17148319
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Development of five digits is controlled by a bipartite long-range cis-regulator
Lettice, Laura A.; Williamson, Iain; Devenney, Paul S.; Kilanowski, Fiona; Dorin, Julia; Hill, Robert E.
2014-01-01
Conservation within intergenic DNA often highlights regulatory elements that control gene expression from a long range. How conservation within a single element relates to regulatory information and how internal composition relates to function is unknown. Here, we examine the structural features of the highly conserved ZRS (also called MFCS1) cis-regulator responsible for the spatiotemporal control of Shh in the limb bud. By systematically dissecting the ZRS, both in transgenic assays and within in the endogenous locus, we show that the ZRS is, in effect, composed of two distinct domains of activity: one domain directs spatiotemporal activity but functions predominantly from a short range, whereas a second domain is required to promote long-range activity. We show further that these two domains encode activities that are highly integrated and that the second domain is crucial in promoting the chromosomal conformational changes correlated with gene activity. During limb bud development, these activities encoded by the ZRS are interpreted differently by the fore limbs and the hind limbs; in the absence of the second domain there is no Shh activity in the fore limb, and in the hind limb low levels of Shh lead to a variant digit pattern ranging from two to four digits. Hence, in the embryo, the second domain stabilises the developmental programme providing a buffer for SHH morphogen activity and this ensures that five digits form in both sets of limbs. PMID:24715461
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Kelly, Scott A.; Bell, Timothy A.; Selitsky, Sara R.; Buus, Ryan J.; Hua, Kunjie; Weinstock, George M.; Garland, Theodore; Pardo-Manuel de Villena, Fernando; Pomp, Daniel
2013-01-01
Replicated artificial selection for high levels of voluntary wheel running in an outbred strain of mice favored an autosomal recessive allele whose primary phenotypic effect is a 50% reduction in hind-limb muscle mass. Within the High Runner (HR) lines of mice, the numerous pleiotropic effects (e.g., larger hearts, reduced total body mass and fat mass, longer hind-limb bones) of this hypothesized adaptive allele include functional characteristics that facilitate high levels of voluntary wheel running (e.g., doubling of mass-specific muscle aerobic capacity, increased fatigue resistance of isolated muscles, longer hind-limb bones). Previously, we created a backcross population suitable for mapping the responsible locus. We phenotypically characterized the population and mapped the Minimsc locus to a 2.6-Mb interval on MMU11, a region containing ∼100 known or predicted genes. Here, we present a novel strategy to identify the genetic variant causing the mini-muscle phenotype. Using high-density genotyping and whole-genome sequencing of key backcross individuals and HR mice with and without the mini-muscle mutation, from both recent and historical generations of the HR lines, we show that a SNP representing a C-to-T transition located in a 709-bp intron between exons 11 and 12 of the Myosin heavy polypeptide 4 (Myh4) skeletal muscle gene (position 67,244,850 on MMU11; assembly, December 2011, GRCm38/mm10; ENSMUSG00000057003) is responsible for the mini-muscle phenotype, Myh4Minimsc. Using next-generation sequencing, our approach can be extended to identify causative mutations arising in mouse inbred lines and thus offers a great avenue to overcome one of the most challenging steps in quantitative genetics. PMID:24056412
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Kelly, Scott A; Bell, Timothy A; Selitsky, Sara R; Buus, Ryan J; Hua, Kunjie; Weinstock, George M; Garland, Theodore; Pardo-Manuel de Villena, Fernando; Pomp, Daniel
2013-12-01
Replicated artificial selection for high levels of voluntary wheel running in an outbred strain of mice favored an autosomal recessive allele whose primary phenotypic effect is a 50% reduction in hind-limb muscle mass. Within the High Runner (HR) lines of mice, the numerous pleiotropic effects (e.g., larger hearts, reduced total body mass and fat mass, longer hind-limb bones) of this hypothesized adaptive allele include functional characteristics that facilitate high levels of voluntary wheel running (e.g., doubling of mass-specific muscle aerobic capacity, increased fatigue resistance of isolated muscles, longer hind-limb bones). Previously, we created a backcross population suitable for mapping the responsible locus. We phenotypically characterized the population and mapped the Minimsc locus to a 2.6-Mb interval on MMU11, a region containing ∼100 known or predicted genes. Here, we present a novel strategy to identify the genetic variant causing the mini-muscle phenotype. Using high-density genotyping and whole-genome sequencing of key backcross individuals and HR mice with and without the mini-muscle mutation, from both recent and historical generations of the HR lines, we show that a SNP representing a C-to-T transition located in a 709-bp intron between exons 11 and 12 of the Myosin heavy polypeptide 4 (Myh4) skeletal muscle gene (position 67,244,850 on MMU11; assembly, December 2011, GRCm38/mm10; ENSMUSG00000057003) is responsible for the mini-muscle phenotype, Myh4(Minimsc). Using next-generation sequencing, our approach can be extended to identify causative mutations arising in mouse inbred lines and thus offers a great avenue to overcome one of the most challenging steps in quantitative genetics.
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NASA Astrophysics Data System (ADS)
Park, Ji Hyung; Seo, Dong-Hyun; Cho, Seungkwan; Kim, Seo-Hyun; Eom, Sinae; Kim, Han Sung
2015-09-01
Musculoskeletal disorders during and after spaceflight are considered as a serious health issue. In space, weight-bearing exercise recognized as the main countermeasure to bone loss, since many anti-resorptive medications have not yet been approved for spaceflight or have been unsuccessful in their limited application. We need to investigate a complementary or alternative way to prevent bone loss and muscle atrophy resulting from microgravity condition. Partial vibration was chosen because it is one of the most feasible ways to adopt safely and effectively. Moreover, although the influence of hind-limb suspension has been studied in both male and female rodents, only rarely are both genders evaluated in the same study. Thus, to further extend our knowledge, the present study performed comparative analysis between genders. A total of 36 12-week-old male and female Sprague-Dawley rats were used and were randomly assigned to control (CON), hind-limb suspension without vibration stimulus (HS), and hind-limb suspension with vibration stimulus (HV) groups. Hind-limb suspension has led to increasing the rate of bone loss and muscle atrophy regardless of gender. The rates of bone loss in male group obviously increased than that of female group. All structural parameters were showed significant difference between HS and HV ( p < 0.05) in male group whereas there are no significant differences in female group. In female, the muscle volume with treatment of partial vibration stimulus significantly increased which compared with that of hind-limb suspension ( p < 0.05) whereas there are no significant differences in male group. Thus partial vibration could prevent bone loss of tibia in males and muscle atrophy in females induced by hind-limb suspension. In other words, partial vibration has positive effects on damaged musculoskeletal tissues that differ based on gender.
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Crawford, Robert S.; Albadawi, Hassan; Robaldo, Alessandro; Peck, Michael A.; Abularrage, Christopher J.; Yoo, Hyung-Jin; LaMuraglia, Glenn M.; Watkins, Michael T.
2013-01-01
Introduction Studies were designed to determine whether the ApoE−/− phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE−/− phenotype is an experimental model for atherosclerosis in humans. Methods Aged female ApoE −/− and C57BL6 mice underwent femoral artery ligation, then divided into sedentary and demand ischemia (exercise) groups on day 14. Baseline and post exercise limb perfusion and hind limb function were assessed. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, plasma and skeletal muscle from ischemic limbs were harvested from sedentary and exercised mice. Muscle was assayed for angiogenic and pro-inflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Results Hind limb ischemia was similar in ApoE −/− and C57 mice prior to the onset of exercise. Under sedentary conditions, plasma VEGF, IL-6, but not KC or MIP-2 were higher in ApoE (P<0.0001). Following exercise, plasma levels of VEGF, KC and MIP-2, but not IL-6 were lower in ApoE (P<0.004). The cytokines KC and MIP-2 in muscle was greater in exercised ApoE−/− mice as compared to C57BL6 mice (p=0.01). Increased PAR activity, and mature muscle regeneration was associated with demand ischemia in the C57BL6 mice as compared to the ApoE −/− mice (p=0.01). Conclusion Demand limb ischemia in the ApoE−/− phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration. PMID:23528286
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Home-care treatment of swimmer syndrome in a miniature schnauzer dog.
Kim, Sun-A; Na, Ki-Jeong; Cho, Jong-Ki; Shin, Nam-Shik
2013-09-01
A 50-day-old, female miniature schnauzer dog was presented for astasia, dorsoventral flattening of the thorax, hypoplasia of hind-limb muscles, stiffness of hind-limb joints, paddling leg motion, and panting. The dog was diagnosed with swimmers syndrome. The dog recovered completely following 40 days of home-care treatment that involved environmental and nutritional management along with intensive physiotherapy.
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Martin, Miriam S; Kline, Helen C; Wagner, Dana R; Alexander, Lacey R; Edwards-Callaway, Lily N; Grandin, Temple
2018-05-03
The objective of this study was to assess the effects of captive bolt length and breed type on post-stun leg activity in cattle. A total of 2850 Holstein (HOL) and non-Holstein British/Continental bred (NHOL) steers and heifers were observed post-stunning at a large commercial slaughter facility. A pneumatically powered penetrating captive bolt stunner was used with three different bolt lengths: CON, 15.24 cm; MED, 16.51 cm; and LON, 17.78 cm. Hind limb kicking, forelimb activity, take away belt stops, carcass swing and number of knife sticks during exsanguination were recorded for each animal from video recording. Hind limb and forelimb kicks observed ranged from 0 to 25 and 0 to 8, respectively. Analysis of post-stun hind limb and forelimb activity indicated that increasing pneumatically powered penetrating captive bolt length does not decrease post-stun leg activity. There was a higher percentage of cattle experiencing take away belt stops and carcass swing in HOL as compared with NHOL. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Goh, Colleen; Blanchard, Mary L; Crompton, Robin H; Gunther, Michael M; Macaulay, Sophie; Bates, Karl T
2017-10-01
Three-dimensional musculoskeletal models have become increasingly common for investigating muscle moment arms in studies of vertebrate locomotion. In this study we present the first musculoskeletal model of a western lowland gorilla hind limb. Moment arms of individual muscles around the hip, knee and ankle were compared with previously published data derived from the experimental tendon travel method. Considerable differences were found which we attribute to the different methodologies in this specific case. In this instance, we argue that our 3D model provides more accurate and reliable moment arm data than previously published data on the gorilla because our model incorporates more detailed consideration of the 3D geometry of muscles and the geometric constraints that exist on their lines-of-action about limb joints. Our new data have led us to revaluate the previous conclusion that muscle moment arms in the gorilla hind limb are optimised for locomotion with crouched or flexed limb postures. Furthermore, we found that bipedalism and terrestrial quadrupedalism coincided more regularly with higher moment arms and torque around the hip, knee and ankle than did vertical climbing. This indicates that the ability of a gorilla to walk bipedally is not restricted by musculoskeletal adaptations for quadrupedalism and vertical climbing, at least in terms of moment arms and torque about hind limb joints. © 2017 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.
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Johnson, P.T.J.; Lunde, K.B.; Thurman, E.M.; Ritchie, E.G.; Wray, S.N.; Sutherland, D.R.; Kapfer, J.M.; Frest, T.J.; Bowerman, J.; Blaustein, A.R.
2002-01-01
Parasites and pathogens can influence the survivorship, behavior, and very structure of their host species. For example, experimental studies have shown that trematode parasites can cause high frequencies of severe limb malformations in amphibians. In a broad-scale field survey covering parts of California, Oregon, Washington, Idaho, and Montana, we examined relationships between the frequency and types of morphological abnormalities in amphibians and the abundance of trematode parasite infection, pH, concentrations of 61 pesticides, and levels of orthophosphate and total nitrate. We recorded severe malformations at frequencies ranging from 1% to 90% in nine amphibian species from 53 aquatic systems. Infection of larvae by the trematode Ribeiroia ondatrae was associated with, and functionally related to, higher frequencies of amphibian limb malformations than found in uninfected populations (≤5%). Parasites were concentrated around the basal tissue of hind limbs in infected anurans, and malformations associated with infection included skin webbings, supernumerary limbs and digits, and missing or malformed hind limbs. In the absence of Ribeiroia, amphibian populations exhibited low (0-5%) frequencies of abnormalities involving missing digits or distal portions of a hind limb. Species were affected differentially by the parasite, and Ambystoma macrodactylum, Hyla regilla, Rand aurora, R. luteiventris, and Taricha torosa typically exhibited the highest frequencies of abnormalities. None of the water-quality variables measured was associated with malformed amphibians, but aquatic snail hosts (Planorbella spp.) were significant predictors of the presence and abundance of Ribeiroia infection. Morphological comparisons of adult specimens of Ribeiroia collected from different sites and raised in experimental definitive hosts suggested that all samples represented the same species - R. ondatrae. These field results, coupled with experimental research on the effects of Ribeiroia on amphibians, demonstrate that Ribeiroia infection is an important and widespread cause of amphibian limb malformations in the western United States. The relevance of trematode infection to declines of amphibian populations and the influence of habitat modification on the pathology and life cycle of Ribeiroia are emphasized as areas requiring further research.
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Wang, Xiao; Zhang, Yong-Le; Zhang, Ya-Dong; Xue, Feng
2017-01-01
This study aims to explore the role of the SDF-1/CXCR4 axis in mediating BMSCs and SCI recovery. BMSCs were collected and SCI rat models were established. Wistar rats were assigned into the blank control, sham, SCI, SCI + BMSCs, SCI + BMSCs + SDF-1, SCI + BMSCs + AMD3100 (an inhibitor of SDF-1/CXCR4 axis) and SCI + BMSCs + SDF-1 + AMD3100 groups. Hind limb motor function was measured 7, 14, 21 and 28 days after operation. qRT-PCR, western blotting and ELISA was performed to determine the expressions of SDF-1, CXCR4, NGF, BDNF, GFAP and GAP-43, TNF-α, IL-1β, L-6 and IFN-γ. Hind limb motor function scores 7 days after the operation were reduced in the SCI rats of the blank control and sham groups. Hind limb function was found to be better in the SCI + BMSCs and SCI + BMSCs + SDF-1 groups than in the SCI, SCI + BMSCs + AMD3100 and SCI + BMSCs + SDF-1 + AMD3100 groups 14, 21 and 28 days after operation. Furthermore, the SCI group had lower SDF-1, CXCR4, NGF, BDNF and GAP-43 expressions but higher GFAP, TNF-α, IL-1β, IL-6 and IFN-γ than the blank control and sham groups 28 days after operation. While, the SCI + BMSCs, SCI + BMSCs + SDF-1 and SCI + BMSCs + SDF-1 + AMD3100 groups displayed opposite trends to the SCI and SCI + BMSCs + AMD3100 groups. In conclusion, SDF-1/CXCR4 axis promotes recovery after SCI by mediating BMSCs. PMID:28099928
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Prenatal Development of Interlimb Motor Learning in the Rat Fetus
Robinson, Scott R.; Kleven, Gale A.; Brumley, Michele R.
2010-01-01
The role of sensory feedback in the early ontogeny of motor coordination remains a topic of speculation and debate. On E20 of gestation (the 20th day after conception, 2 days before birth), rat fetuses can alter interlimb coordination after a period of training with an interlimb yoke, which constrains limb movement and promotes synchronized, conjugate movement of the yoked limbs. The aim of this study was to determine how the ability to express this form of motor learning may change during prenatal development. Fetal rats were prepared for in vivo study at 4 ages (E18–21) and tested in a 65-min training-and-testing session examining hind limb motor learning. A significant increase in conjugate hind limb activity was expressed by E19, but not E18 fetuses, with further increases in conjugate hind limb activity on E20 and E21. These findings suggest substantial development of the ability of fetal rats to modify patterns of interlimb coordination in response to kinesthetic feedback during motor training before birth. PMID:20198121
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Home-care treatment of swimmer syndrome in a miniature schnauzer dog
Kim, Sun-A; Na, Ki-Jeong; Cho, Jong-Ki; Shin, Nam-Shik
2013-01-01
A 50-day-old, female miniature schnauzer dog was presented for astasia, dorsoventral flattening of the thorax, hypoplasia of hind-limb muscles, stiffness of hind-limb joints, paddling leg motion, and panting. The dog was diagnosed with swimmers syndrome. The dog recovered completely following 40 days of home-care treatment that involved environmental and nutritional management along with intensive physiotherapy. PMID:24155492
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Transcriptomic insights into the genetic basis of mammalian limb diversity.
Maier, Jennifer A; Rivas-Astroza, Marcelo; Deng, Jenny; Dowling, Anna; Oboikovitz, Paige; Cao, Xiaoyi; Behringer, Richard R; Cretekos, Chris J; Rasweiler, John J; Zhong, Sheng; Sears, Karen E
2017-03-23
From bat wings to whale flippers, limb diversification has been crucial to the evolutionary success of mammals. We performed the first transcriptome-wide study of limb development in multiple species to explore the hypothesis that mammalian limb diversification has proceeded through the differential expression of conserved shared genes, rather than by major changes to limb patterning. Specifically, we investigated the manner in which the expression of shared genes has evolved within and among mammalian species. We assembled and compared transcriptomes of bat, mouse, opossum, and pig fore- and hind limbs at the ridge, bud, and paddle stages of development. Results suggest that gene expression patterns exhibit larger variation among species during later than earlier stages of limb development, while within species results are more mixed. Consistent with the former, results also suggest that genes expressed at later developmental stages tend to have a younger evolutionary age than genes expressed at earlier stages. A suite of key limb-patterning genes was identified as being differentially expressed among the homologous limbs of all species. However, only a small subset of shared genes is differentially expressed in the fore- and hind limbs of all examined species. Similarly, a small subset of shared genes is differentially expressed within the fore- and hind limb of a single species and among the forelimbs of different species. Taken together, results of this study do not support the existence of a phylotypic period of limb development ending at chondrogenesis, but do support the hypothesis that the hierarchical nature of development translates into increasing variation among species as development progresses.
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Wang, Zhihong; Gu, Hongbin; Yang, Fan; Xie, Huajie; Sheng, Lei; Li, Mingfei
2017-11-01
Objective To investigate the effect of over-expressed endothelial Per-Arnt-Sim domain protein 1 (EPAS1) on peripheral arterial disease (PAD) in a rat model. Methods PAD rat model was established by external iliac artery ligation followed by lentivirus-mediated EPAS1 gene injection into rat right adductor magnus. The models were evaluated by quantitative analysis of gait disturbance. The changes of blood flow in the posterior extremity of the rats were detected using laser Doppler. The expressions of EPAS1, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) mRNAs were tested by real-time quantitative PCR. The expression of α-smooth muscle actin (αSMA) was detected by immunohistochemical staining. Results Compared with lenti-EGFP group, rat hind limb function and circulation got recovered obviously 7 days after lenti-EPAS1 injection. The mRNA expressions of EPAS1, HGF, bFGF, and VEGF were up-regulated in the lenti-EPAS1-treated sites.The expression of αSMA showed an obvious increase in the lenti-EPAS1-treated muscles. Conclusion Over-expressed lenti-EPAS1 can promote angiogenesis via the up-regulation of EPAS1-related angiogenic factors in the muscles of the affected hind limb and reduce gait disturbance.
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Nakajima, Keisuke; Tazawa, Ichiro; Yaoita, Yoshio
2018-02-01
Thyroid hormone (TH) binds TH receptor α (TRα) and β (TRβ) to induce amphibian metamorphosis. Whereas TH signaling has been well studied, functional differences between TRα and TRβ during this process have not been characterized. To understand how each TR contributes to metamorphosis, we generated TRα- and TRβ-knockout tadpoles of Xenopus tropicalis and examined developmental abnormalities, histology of the tail and intestine, and messenger RNA expression of genes encoding extracellular matrix-degrading enzymes. In TRβ-knockout tadpoles, tail regression was delayed significantly and a healthy notochord was observed even 5 days after the initiation of tail shortening (stage 62), whereas in the tails of wild-type and TRα-knockout tadpoles, the notochord disappeared after ∼1 day. The messenger RNA expression levels of genes encoding extracellular matrix-degrading enzymes (MMP2, MMP9TH, MMP13, MMP14, and FAPα) were obviously reduced in the tail tip of TRβ-knockout tadpoles, with the shortening tail. The reduction in olfactory nerve length and head narrowing by gill absorption were also affected. Hind limb growth and intestinal shortening were not compromised in TRβ-knockout tadpoles, whereas tail regression and olfactory nerve shortening appeared to proceed normally in TRα-knockout tadpoles, except for the precocious development of hind limbs. Our results demonstrated the distinct roles of TRα and TRβ in hind limb growth and tail regression, respectively. Copyright © 2018 Endocrine Society.
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Crawford, Robert S; Albadawi, Hassan; Robaldo, Alessandro; Peck, Michael A; Abularrage, Christopher J; Yoo, Hyung-Jin; Lamuraglia, Glenn M; Watkins, Michael T
2013-08-01
We designed studies to determine whether the ApoE-/- phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE-/- phenotype is an experimental model for atherosclerosis in humans. Aged female ApoE-/- and C57BL6 mice underwent femoral artery ligation, then were divided into sedentary and demand ischemia (exercise) groups on day 14. We assessed baseline and postexercise limb perfusion and hind limb function. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, we harvested plasma and skeletal muscle from ischemic limbs from sedentary and exercised mice. We assayed muscle for angiogenic and proinflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Hind limb ischemia was similar in ApoE-/- and C57 mice before the onset of exercise. Under sedentary conditions, plasma vascular endothelial cell growth factor and interleukin-6, but not keratinocyte chemoattractant factor (KC) or macrophage inflammatory protein-2 (MIP-2), were higher in ApoE (P < 0.0001). After exercise, plasma levels of vascular endothelial cell growth factor, KC, and MIP-2, but not IL-6, were lower in ApoE (P < 0.004). The cytokines KC and MIP-2 in muscle were greater in exercised ApoE-/- mice compared with C57BL6 mice (P = 0.01). Increased poly-ADP-ribose activity and mature muscle regeneration were associated with demand ischemia in the C57BL6 mice, compared with the ApoE-/- mice (P = 0.01). Demand limb ischemia in the ApoE-/- phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration. Copyright © 2013 Elsevier Inc. All rights reserved.
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O'Neill, Matthew C; Lee, Leng-Feng; Demes, Brigitte; Thompson, Nathan E; Larson, Susan G; Stern, Jack T; Umberger, Brian R
2015-09-01
The common chimpanzee (Pan troglodytes) is a facultative biped and our closest living relative. As such, the musculoskeletal anatomies of their pelvis and hind limbs have long provided a comparative context for studies of human and fossil hominin locomotion. Yet, how the chimpanzee pelvis and hind limb actually move during bipedal walking is still not well defined. Here, we describe the three-dimensional (3-D) kinematics of the pelvis, hip, knee and ankle during bipedal walking and compare those values to humans walking at the same dimensionless and dimensional velocities. The stride-to-stride and intraspecific variations in 3-D kinematics were calculated using the adjusted coefficient of multiple correlation. Our results indicate that humans walk with a more stable pelvis than chimpanzees, especially in tilt and rotation. Both species exhibit similar magnitudes of pelvis list, but with segment motion that is opposite in phasing. In the hind limb, chimpanzees walk with a more flexed and abducted limb posture, and substantially exceed humans in the magnitude of hip rotation during a stride. The average stride-to-stride variation in joint and segment motion was greater in chimpanzees than humans, while the intraspecific variation was similar on average. These results demonstrate substantial differences between human and chimpanzee bipedal walking, in both the sagittal and non-sagittal planes. These new 3-D kinematic data are fundamental to a comprehensive understanding of the mechanics, energetics and control of chimpanzee bipedalism. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Multi-functional foot use during running in the zebra-tailed lizard (Callisaurus draconoides).
Li, Chen; Hsieh, S Tonia; Goldman, Daniel I
2012-09-15
A diversity of animals that run on solid, level, flat, non-slip surfaces appear to bounce on their legs; elastic elements in the limbs can store and return energy during each step. The mechanics and energetics of running in natural terrain, particularly on surfaces that can yield and flow under stress, is less understood. The zebra-tailed lizard (Callisaurus draconoides), a small desert generalist with a large, elongate, tendinous hind foot, runs rapidly across a variety of natural substrates. We use high-speed video to obtain detailed three-dimensional running kinematics on solid and granular surfaces to reveal how leg, foot and substrate mechanics contribute to its high locomotor performance. Running at ~10 body lengths s(-1) (~1 m s(-1)), the center of mass oscillates like a spring-mass system on both substrates, with only 15% reduction in stride length on the granular surface. On the solid surface, a strut-spring model of the hind limb reveals that the hind foot saves ~40% of the mechanical work needed per step, significant for the lizard's small size. On the granular surface, a penetration force model and hypothesized subsurface foot rotation indicates that the hind foot paddles through fluidized granular medium, and that the energy lost per step during irreversible deformation of the substrate does not differ from the reduction in the mechanical energy of the center of mass. The upper hind leg muscles must perform three times as much mechanical work on the granular surface as on the solid surface to compensate for the greater energy lost within the foot and to the substrate.
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Hsieh, Ming-Jer; Liu, Hsien-Ta; Wang, Chao-Nin; Huang, Hsiu-Yun; Lin, Yuling; Ko, Yu-Shien; Wang, Jong-Shyan; Chang, Vincent Hung-Shu; Pang, Jong-Hwei S
2017-03-01
BPC 157, a pentadecapeptide with extensive healing effects, has recently been suggested to contribute to angiogenesis. However, the underlying mechanism is not yet clear. The present study aimed to explore the potential therapeutic effect and pro-angiogenic mechanism of BPC 157. As demonstrated by the chick chorioallantoic membrane (CAM) assay and endothelial tube formation assay, BPC 157 could increase the vessel density both in vivo and in vitro, respectively. BPC 157 could also accelerate the recovery of blood flow in the ischemic muscle of the rat hind limb as detected by laser Doppler scanning, indicating the promotion of angiogenesis. Histological analysis of the hind limb muscle confirmed the increased number of vessels and the enhanced vascular expression of vascular endothelial growth factor receptor 2 (VEGFR2) in rat with BPC 157 treatment. In vitro study using human vascular endothelial cells further confirmed the increased mRNA and protein expressions of VEGFR2 but not VEGF-A by BPC 157. In addition, BPC 157 could promote VEGFR2 internalization in vascular endothelial cells which was blocked in the presence of dynasore, an inhibitor of endocytosis. BPC 157 time dependently activated the VEGFR2-Akt-eNOS signaling pathway which could also be suppressed by dynasore. The increase of endothelial tube formation induced by BPC 157 was also inhibited by dynasore. This study demonstrates the pro-angiogenic effects of BPC 157 that is associated with the increased expression, internalization of VEGFR2, and the activation of VEGFR2-Akt-eNOS signaling pathway. BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation. BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation.
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Kummrow, Maya S; Tseng, Florina; Hesse, Leah; Court, Michael
2008-12-01
Buprenorphine, a mu opioid receptor agonist, is expected to be a suitable analgesic drug for use in reptiles. However, to date, dosage recommendations have been based on anecdotal observations. The aim of this study was to provide baseline pharmacokinetic data in red-eared sliders (Trachemys scripta elegans) targeting a plasma level of 1 ng/ml reported effective for analgesia in humans. Serial blood samples were taken after subcutaneous injection of buprenorphine, and plasma buprenorphine levels were measured by radioimmunoassay. Pharmacokinetic parameters of a lower dose (0.02 mg/kg) injected into the forelimb were compared with a higher dose (0.05 mg/kg) given in the same forelimb as well as a lower dose (0.02 mg/kg) given in the hind limb of the same animals with 2 wk between studies. After administration of 0.05 mg/kg in the front limb, 85% of animals maintained the minimum effective plasma level for 24 hr, while only 43% of animals maintained this level after 0.02 mg/kg. After hind limb injection at 0.02 mg/kg, maximum plasma concentrations and areas under the buprenorphine concentration-time curve were less than 20% and 70%, respectively, of values after forelimb injection, consistent with substantial first pass extraction by the liver. Furthermore, a secondary rise in the buprenorphine level was found after having only a hind limb injection, probably from enterohepatic recirculation of glucuronidated drug. In conclusion, buprenorphine dosages of at least 0.075 mg/kg s.i.d. should be appropriate for evaluation of analgesia efficacy, and front limb administration may be preferable to hind limb administration for optimal drug exposure.
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Culp, William T. N.; Glaiberman, Craig B.; Pollard, Rachel E.; Wisner, Erik R.
2015-01-01
Case Description An 11-year-old castrated male Tibetan Mastiff was evaluated because of a visibly enlarged blood vessel and progressively worsening swelling of the right hind limb. Clinical Findings On physical examination, the right hind limb was markedly larger than the left hind limb and the dog was minimally weight bearing on the affected limb. A bruit was auscultated over the affected region. Ultrasonography of the tarsal region of the right hind limb revealed an artery with turbulent flow that communicated with venous drainage. A CT scan confirmed the presence of an arteriovenous malformation (AVM). Treatment and Outcome Embolization of the AVM with a liquid embolic agent (ethylene-vinyl alcohol copolymer dissolved in dimethyl sulfoxide) was elected. An arteriogram was performed prior to treatment and delineated the vessels that were targeted for embolization. The embolic agent was infused into the AVM, and a postinjection arteriogram confirmed complete occlusion of the AVM nidus and normal arterial flow to the paw with subsequent normal venous drainage. The circumference of the abnormal paw was 51 cm before the procedure and 22.9 cm at 4 weeks after the procedure. Additionally, the gait of the dog dramatically improved. No complications associated with the procedure developed. Clinical Relevance Peripheral AVMs in dogs are uncommon, and described treatment options are limited and generally associated with serious morbidity. A liquid embolic agent, ethylene-vinyl alcohol copolymer dissolved in dimethyl sulfoxide, was successfully administered in this case, and no morbidity was observed secondary to the procedure. Clinical success was characterized by substantial improvement in limb swelling and marked improvement in the gait of the dog. PMID:24984133
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Suspected panosteitis in a camel.
Levine, David G; Smith, Jennifer J; Richardson, Dean W; Brown, Valerie; Beech, Jill; Habecker, Perry; Adam, Emma
2007-08-01
A 6-month-old male Bactrian camel was examined because of a 3-week history of lameness of the left hind limb. Lameness was initially detected in the left hind limb but resolved and was detected in the right hind limb during treatment. Lameness increased during periods of rapid growth. Radiography revealed multiple small opacities of the medullary cavity of several long bones throughout treatment. Core bone biopsies of lesions in the tibiae revealed lamellar bone with areas of loose connective tissue, osteoblasts in the medullary cavity, and periosteal new bone formation, all which were consistent with panosteitis. Palliative treatment was attempted with epidural and transdermal administration of analgesics. Flunixin meglumine was administered PO, which coincided with an abrupt increase in serum creatinine concentration. Performance of multiple diagnostic bone biopsies led to remission of clinical signs of pain. Panosteitis should be a differential diagnosis for shifting limb lameness in young camels. Bone biopsies can be useful for diagnosis of panosteitis and possible relief of pain associated with the disease. Bactrian camels may be susceptible to the renal toxicity of flunixin meglumine, especially when dehydrated.
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Tetanus toxoid-pulsed monocyte vaccination for augmentation of collateral vessel growth.
Herold, Joerg; Francke, Alexander; Weinert, Soenke; Schmeisser, Alexander; Hebel, Katrin; Schraven, Burkhart; Roehl, Friedich-Wilhelm; Strasser, Ruth H; Braun-Dullaeus, Ruediger C
2014-04-14
The pathogenesis of collateral growth (arteriogenesis) has been linked to both the innate and adaptive immune systems. While therapeutic approaches for the augmentation of arteriogenesis have focused on innate immunity, exploiting both innate and adaptive immune responses has not been examined. We hypothesized that tetanus toxoid (tt) immunization of mice followed by transplantation of monocytes (Mo) exposed ex vivo to tt augments arteriogenesis after ligation of the hind limb. Mo were generated from nonimmunized BALB/c mice, exposed ex vivo to tt for 24 hours and intravenously injected (ttMo, 2.5×10(6)) into the tail veins of tt-immunized syngeneic mice whose hind limbs had been ligated 24 hours prior to transplantation. Laser Doppler perfusion imaging was applied, and a perfusion index (PI) was calculated (ratio ligated/unligated). Twenty-one days after ligation, the arteriogenesis of untreated BALB/c mice was limited (PI=0.49±0.09). Hind limb function was impaired in 80% of animals. Injection of non-engineered Mo insignificantly increased the PI to 0.56±0.07. However, ttMo transplantation resulted in a strong increase of the PI to 0.82±0.08 (n=7; P<0.001), with no (0%) detectable functional impairment. ttMo injected into nonimmunized mice had no effect. The strong arteriogenic response of ttMo transplantation into immunized mice was prevented when mice had been depleted of T-helper cells by CD4-antibody pretreatment (PI=0.50±0.08; n=17; P<0.001), supporting the hypothesis that transplanted cells interact with recipient lymphocytes. Transplantation of ttMo into pre-immunized mice strongly promotes arteriogenesis. This therapeutic approach is feasible and highly attractive for the alleviation of morbidity associated with vascular occlusive disease.
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Tetanus Toxoid‐Pulsed Monocyte Vaccination for Augmentation of Collateral Vessel Growth
Herold, Joerg; Francke, Alexander; Weinert, Soenke; Schmeisser, Alexander; Hebel, Katrin; Schraven, Burkhart; Roehl, Friedich‐Wilhelm; Strasser, Ruth H.; Braun‐Dullaeus, Ruediger C.
2014-01-01
Background The pathogenesis of collateral growth (arteriogenesis) has been linked to both the innate and adaptive immune systems. While therapeutic approaches for the augmentation of arteriogenesis have focused on innate immunity, exploiting both innate and adaptive immune responses has not been examined. We hypothesized that tetanus toxoid (tt) immunization of mice followed by transplantation of monocytes (Mo) exposed ex vivo to tt augments arteriogenesis after ligation of the hind limb. Methods and Results Mo were generated from nonimmunized BALB/c mice, exposed ex vivo to tt for 24 hours and intravenously injected (ttMo, 2.5×106) into the tail veins of tt‐immunized syngeneic mice whose hind limbs had been ligated 24 hours prior to transplantation. Laser Doppler perfusion imaging was applied, and a perfusion index (PI) was calculated (ratio ligated/unligated). Twenty‐one days after ligation, the arteriogenesis of untreated BALB/c mice was limited (PI=0.49±0.09). Hind limb function was impaired in 80% of animals. Injection of non‐engineered Mo insignificantly increased the PI to 0.56±0.07. However, ttMo transplantation resulted in a strong increase of the PI to 0.82±0.08 (n=7; P<0.001), with no (0%) detectable functional impairment. ttMo injected into nonimmunized mice had no effect. The strong arteriogenic response of ttMo transplantation into immunized mice was prevented when mice had been depleted of T‐helper cells by CD4‐antibody pretreatment (PI=0.50±0.08; n=17; P<0.001), supporting the hypothesis that transplanted cells interact with recipient lymphocytes. Conclusions Transplantation of ttMo into pre‐immunized mice strongly promotes arteriogenesis. This therapeutic approach is feasible and highly attractive for the alleviation of morbidity associated with vascular occlusive disease. PMID:24732919
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Hendrikx, Geert; Vries, Mark H; Bauwens, Matthias; De Saint-Hubert, Marijke; Wagenaar, Allard; Guillaume, Joël; Boonen, Levinia; Post, Mark J; Mottaghy, Felix M
2016-12-01
We aimed to determine the accuracy of laser Doppler perfusion imaging (LDPI) in an animal model for hind limb ischemia. We used a murine (C57Bl/6 mice) ischemic hind limb model in which we compared LDPI with the clinically used (99m)Tc-sestamibi SPECT perfusion imaging (n = 7). In addition, we used the SPECT tracer (99m)Tc-pyrophosphate ((99m)Tc-PyP) to image muscular damage (n = 6). LDPI indicated a quick and prominent decrease in perfusion immediately after ligation, subsequently recovering to 21.9 and 25.2 % 14 days later in the (99m)Tc-sestamibi and (99m)Tc-PyP group, respectively. (99m)Tc-sestamibi SPECT scans also showed a quick decrease in perfusion. However, nearly full recovery was reached 7 days post ligation. Muscular damage, indicated by the uptake of (99m)Tc-PyP, was highest at day 3 and recovered to baseline levels at day 14 post ligation. Postmortem histology supported these findings, as a significantly increased collateral diameter was found 7 and 14 days after ligation and peak macrophage infiltration and TUNEL positivity was found on day 3 after ligation. Here, we indicate that LDPI strongly underestimates perfusion recovery in a hind limb model for profound ischemia.
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Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease.
Merkulova-Rainon, Tatyana; Mantsounga, Chris S; Broquères-You, Dong; Pinto, Cristina; Vilar, José; Cifuentes, Diana; Bonnin, Philippe; Kubis, Nathalie; Henrion, Daniel; Silvestre, Jean-Sébastien; Lévy, Bernard I
2018-03-07
The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0.001), collateral recruitment (- 24%, P < 0.001), capillary density (- 22%; P < 0.01) and arteriole density (- 28%; P < 0.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aβ in the hind limb; thus, circulating Aβ is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-β1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (P = 0.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (P < 0.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD.
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Caldwell, Marc; Passler, Thomas; Purohit, Ram C; Pascoe, David; Wolfe, Dwight F
2017-03-01
CASE DESCRIPTION An 8-year-old Brahman-cross bull was evaluated for left hind limb lameness of 2 months' duration. The lameness was first noticed during a rodeo bucking performance, immediately after the bull appeared to land inappropriately on the affected limb. CLINICAL FINDINGS Physical examination findings revealed left hind limb lameness, ataxia, and left-sided epaxial muscle atrophy. Palpation per rectum along the lumbar portion of the vertebral column revealed evidence of exostosis of the ventral aspect. High-definition infrared thermal imaging revealed a pattern of reduced skin temperature in the area of the left lumbar and gluteal regions suggestive of a disruption in the sympathetic control of peripheral blood flow. Nuclear scintigraphy revealed a focal area of increased radioisotope uptake on the left ventrolateral aspect of the L2-3 intervertebral joint. A presumptive diagnosis of ventrolateral vertebral spondylosis resulting in spinal nerve impingement was made. TREATMENT AND OUTCOME 200 mg of methylprednisolone was epidurally injected at the site of the lesion, and treatment with polysulfated glycosaminoglycans was initiated (500 mg, IM, every 4 days for 7 treatments, then monthly thereafter). The lameness and ataxia observed in the left hind limb resolved within 1 week after treatment began. Subsequently, the bull was discharged from the hospital and was used successfully for semen collection and live-cover breeding. CLINICAL RELEVANCE Use of thermography for the bull of this report provided additional insight into neurovascular physiologic function that classical imaging modalities are unable to provide and, when combined with nuclear scintigraphy, aided in identifying the most critical lesion in a complex clinical case.
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Singh, Amritpal; Randhawa, Puneet Kaur; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh
2017-04-01
The cardioprotective effects of remote hind limb preconditioning (RIPC) are well known, but mechanisms by which protection occurs still remain to be explored. Therefore, the present study was designed to investigate the role of TRPV and CGRP in adenosine and remote preconditioning-induced cardioprotection, using sumatriptan, a CGRP release inhibitor and ruthenium red, a TRPV inhibitor, in rats. For remote preconditioning, a pressure cuff was tied around the hind limb of the rat and was inflated with air up to 150 mmHg to produce ischemia in the hind limb and during reperfusion pressure was released. Four cycles of ischemia and reperfusion, each consisting of 5 min of inflation and 5 min of deflation of pressure cuff were used to produce remote limb preconditioning. An ex vivo Langendorff's isolated rat heart model was used to induce ischemia reperfusion injury by 30 min of global ischemia followed by 120 min of reperfusion. RIPC demonstrated a significant decrease in ischemia reperfusion-induced significant myocardial injury in terms of increase in LDH, CK, infarct size and decrease in LVDP, +dp/dt max and -dp/dt min . Moreover, pharmacological preconditioning with adenosine produced cardioprotective effects in a similar manner to RIPC. Pretreatment with sumatriptan, a CGRP release blocker, abolished RIPC and adenosine preconditioning-induced cardioprotective effects. Administration of ruthenium red, a TRPV inhibitor, also abolished adenosine preconditioning-induced cardioprotection. It may be proposed that the cardioprotective effects of adenosine and remote preconditioning are possibly mediated through activation of a TRPV channels and consequent, release of CGRP.
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van den Hengel, Lisa G; Hellingman, Alwine A; Nossent, Anne Yael; van Oeveren-Rietdijk, Annemarie M; de Vries, Margreet R; Spek, C Arnold; van Zonneveld, Anton Jan; Reitsma, Pieter H; Hamming, Jaap F; de Boer, Hetty C; Versteeg, Henri H; Quax, Paul H A
2013-01-01
In collateral development (i.e. arteriogenesis), mononuclear cells are important and exist as a heterogeneous population consisting of pro-inflammatory and anti-inflammatory/repair-associated cells. Protease-activated receptor (PAR)1 and PAR2 are G-protein-coupled receptors that are both expressed by mononuclear cells and are involved in pro-inflammatory reactions, while PAR2 also plays a role in repair-associated responses. Here, we investigated the physiological role of PAR1 and PAR2 in arteriogenesis in a murine hind limb ischemia model. PAR1-deficient (PAR1-/-), PAR2-deficient (PAR2-/-) and wild-type (WT) mice underwent femoral artery ligation. Laser Doppler measurements revealed reduced post-ischemic blood flow recovery in PAR2-/- hind limbs when compared to WT, while PAR1-/- mice were not affected. Upon ischemia, reduced numbers of smooth muscle actin (SMA)-positive collaterals and CD31-positive capillaries were found in PAR2-/- mice when compared to WT mice, whereas these parameters in PAR1-/- mice did not differ from WT mice. The pool of circulating repair-associated (Ly6C-low) monocytes and the number of repair-associated (CD206-positive) macrophages surrounding collaterals in the hind limbs were increased in WT and PAR1-/- mice, but unaffected in PAR2-/- mice. The number of repair-associated macrophages in PAR2-/- hind limbs correlated with CD11b- and CD115-expression on the circulating monocytes in these animals, suggesting that monocyte extravasation and M-CSF-dependent differentiation into repair-associated cells are hampered. PAR2, but not PAR1, is involved in arteriogenesis and promotes the repair-associated response in ischemic tissues. Therefore, PAR2 potentially forms a new pro-arteriogenic target in coronary artery disease (CAD) patients.
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Chao, Wu; Zhang, Yuhui; Chai, Lihong; Wang, Hongyuan
2018-06-10
Endochondral ossification, the process by which most of the bone is formed, is regulated by many specific groups of molecules and extracellular matrix components. Hind limb of Bufo gargarizans is a model to study endochondral ossification during metamorphosis. Chinese toad (Bufo gargarizans) were exposed to different fluoride concentrations (0, 1, 5, 10 and 20 mg L -1 ) from G3 to G42. The development of hind limb of B. gargarizans was observed using the double staining methodology. The transcriptome of hind limb of B. gargarizans was conducted using RNA-seq approach, and differentially expressed gene was also validated. In addition, the location of Sox9 and Ihh in the growth cartilage was determined using in situ hybridization. Our results showed that 5 mg L -1 stimulated bone mineralization, while 10 and 20 mg L -1 exposure could inhibit the tibio-fibula, tarsus and metacarpals ossification. Besides, 10 mg F/L treatment could down-regulate Ihh, Sox9, D2, D3, TRα, TRβ, Wnt10, FGF3 and BMP6 expression, while up-regulate ObRb and HHAT mRNA expression in the hind limb of B. gargarizans. Transcript level changes of Ihh, Sox9, D2, D3, TRα, TRβ, Wnt10, FGF3 and BMP6 were consistent with the results of RT-qPCR. In situ hybridization revealed that Ihh was expressed in prehypertrophic chondrocytes, while Sox9 was abundantly expressed in proliferous, prehypertrophic and hypertrophic chondrocytes. However, 10 mg F-/L did not cause any affect in the location of the Ihh and Sox9 mRNA. Therefore, high concentration of fluoride could affect the ossification-related genes mRNA expression and then inhibit the endochondral ossification. The present study thus will greatly contribute to our understanding of the effect of environmental contaminant on ossification in amphibian. Copyright © 2018 Elsevier B.V. All rights reserved.
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[Kinetics of heifers and cows walking on an instrumented treadmill].
Nuss, K; Waldern, N M; Weishaupt, M A; Wiestner, T
2015-01-01
Kinetic data of stride characteristics and ground reaction forces of cattle become increasingly important as automated lameness detection may be installed in dairy cow housing systems in the future. Therefore, sound heifers and cows were measured on an instrumented treadmill to collect such basic data. Nine heifers and 10 cows were trained to walk on an instrumented treadmill. Vertical ground reaction forces as well as step and stride timing and length variables were measured for all limbs simultaneously. On average, 16 stride cycles in cows and 24 strides in heifers were analysed in each case. The cows walked on the treadmill at an average speed of 1.2 ± 0.05 m/s (mean ± standard deviation), with a stride rate of 43.0 ± 1.9/min and a stride length of 1.68 ± 0.1 m. The heifers had average values of 1.3 ± 0.04 m/s, 53.7 ± 2.2/min and 1.49 ± 0.05 m, respectively. The stance duration relative to stride duration (the duty factor) was for the cows significantly longer in the forelimbs (67%) than in the hind limbs (64%). Force-time-curves of all limbs showed two peaks, one after landing (FP1) and another during push off (FP2). Vertical ground reaction force was highest for FP1 in the hind limbs, but for FP2 in the forelimbs. At all limbs, force minimum between the peaks occurred shortly before midstance. The vertical impulse carried by both forelimbs amounted to 53.7% of the total stride impulse in cows and to 55.0% in heifers. The location of the centre of body mass varied during the stride cycle but was always located more towards the front limbs. Cows and heifers showed a symmetrical walk with minimal intra-individual variations. Relative stride impulse of the front limbs was higher than that of the hind limbs. Peak vertical force in the hind limbs was highest at landing and in the forelimbs at push off. The present study offers kinetic data of sound cows and heifers which might be helpful as guidelines for automated systems for lameness detection in cattle.
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Evaluation of the response of rat skeletal muscle to a model of weightlessness
NASA Technical Reports Server (NTRS)
Templeton, G. H.; Padalino, M.; Glasberg, M.; Manton, J.; Silver, P.; Sutko, J.
1982-01-01
Suspension of rats in a head-down tilt position such that their hind limbs are non-load bearing has been proposed as a model for weightlessness. Changes observed in metabolism, bone formation (Morey et al., 1979), and muscle catabolism (Mussachia et al., 1980) support the validity of the model. To further document this model, the effects of suspension on the mechanical, biochemical and histochemical characteristics of two hind limb skeletal muscles, the gastrocnemius and the soleus, are investigated.
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Load redistribution in walking and trotting Beagles with induced forelimb lameness.
Abdelhadi, Jalal; Wefstaedt, Patrick; Galindo-Zamora, Vladimir; Anders, Alexandra; Nolte, Ingo; Schilling, Nadja
2013-01-01
To evaluate the load redistribution mechanisms in walking and trotting dogs with induced forelimb lameness. 7 healthy adult Beagles. Dogs walked and trotted on an instrumented treadmill to determine control values for peak and mean vertical force as well as vertical impulse for all 4 limbs. A small sphere was attached to the ventral pad of the right forelimb paw to induce a reversible lameness, and recordings were repeated for both gaits. Additionally, footfall patterns were assessed to test for changes in temporal gait variables. During walking and trotting, peak and mean vertical force as well as vertical impulse were decreased in the ipsilateral forelimb, increased in the contralateral hind limb, and remained unchanged in the ipsilateral hind limb after lameness was induced. All 3 variables were increased in the contralateral forelimb during trotting, whereas only mean vertical force and vertical impulse were increased during walking. Stance phase duration increased in the contralateral forelimb and hind limb during walking but not during trotting. Analysis of the results suggested that compensatory load redistribution mechanisms in dogs depend on the gait. All 4 limbs should be evaluated in basic research and clinical studies to determine the effects of lameness on the entire body. Further studies are necessary to elucidate specific mechanisms for unloading of the affected limb and to determine the long-term effects of load changes in animals with chronic lameness.
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Mechanisms of spinal motoneurons survival in rats under simulated hypogravity on earth
NASA Astrophysics Data System (ADS)
Islamov, R. R.; Mishagina, E. A.; Tyapkina, O. V.; Shajmardanova, G. F.; Eremeev, A. A.; Kozlovskaya, I. B.; Nikolskij, E. E.; Grigorjev, A. I.
2011-05-01
It was previously shown that different cell types in vivo and in vitro may die via apoptosis under weightlessness conditions in space as well as in simulated hypogravity on the Earth. We assessed survivability of spinal motoneurons of rats after 35-day antiorthostatic hind limb suspension. Following weight bearing, unloading the total protein content in lumbar spinal cord is dropped by 21%. The electrophysiological studies of m. gastrocnemius revealed an elevated motoneurons' reflex excitability and conduction disturbances in the sciatic nerve axons. The number of myelinated fibers in the ventral root of experimental animals was insignificantly increased by 35-day of antiorthostatic hind limb suspension, although the retrograde axonal transport was significantly decreased during the first week of simulated hypogravity. The results of the immunohistochemical assay with antibodies against proapoptotic protein caspase 9 and cytotoxicity marker neuron specific nitric oxide synthase (nNOS) and the TUNEL staining did not reveal any signs of apoptosis in motoneurons of suspended and control animals. To examine the possible adaptation mechanisms activated in motoneurons in response to simulated hypogravity we investigated immunoexpression of Hsp25 and Hsp70 in lumbar spinal cord of the rats after 35-day antiorthostatic hind limb suspension. Comparative analysis of the immunohistochemical reaction with anti-Hsp25 antibodies revealed differential staining of motoneurons in intact and experimental animals. The density of immunoprecipitate with anti-Hsp25 antibodies was substantially higher in motoneurons of the 35-day suspended than control rats and the more intensive precipitate in this reaction was observed in motoneuron neuritis. Quantitative analysis of Hsp25 expression demonstrated an increase in the Hsp25 level by 95% in experimental rats compared to the control. The immunoexpression of Hsp70 found no qualitative and quantitative differences in control and experimental lumbar spinal cords. Taken together our results show that (1) rat motoneurons survived after 35-day antiorthostatic hind limb suspension and the changes in neurons had a mostly functional character, and (2) the increased immunoexpression of Hsp25 can be considered as the anti-apoptotic factor.
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Lerner, Zachary F; Gadomski, Benjamin C; Ipson, Allison K; Haussler, Kevin K; Puttlitz, Christian M; Browning, Raymond C
2015-08-01
Sheep are a predominant animal model used to study a variety of orthopedic conditions. Understanding and controlling the in-vivo loading environment in the sheep hind limb is often necessary for investigations relating to bone and joint mechanics. The purpose of this study was to develop a musculoskeletal model of an adult sheep hind limb and investigate the effects of treadmill walking speed on muscle and joint contact forces. We constructed the skeletal geometry of the model from computed topography images. Dual-energy x-ray absorptiometry was utilized to establish the inertial properties of each model segment. Detailed dissection and tendon excursion experiments established the requisite muscle lines of actions. We used OpenSim and experimentally-collected marker trajectories and ground reaction forces to quantify muscle and joint contact forces during treadmill walking at 0.25 m• s(-1) and 0.75 m• s(-1) . Peak compressive and anterior-posterior tibiofemoral contact forces were 20% (0.38 BW, p = 0.008) and 37% (0.17 BW, p = 0.040) larger, respectively, at the moderate gait speed relative to the slower speed. Medial-lateral tibiofemoral contact forces were not significantly different. Adjusting treadmill speed appears to be a viable method to modulate compressive and anterior-posterior tibiofemoral contact forces in the sheep hind limb. The musculoskeletal model is freely-available at www.SimTK.org. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
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Lv, Bokang; Huan, Yanqiang; Liu, Bin; Li, Yutang; Jia, Lizhou; Qu, Chenhui; Wang, Dongsheng; Yu, Hai
2018-01-01
The aim of the present study was to observe the effect of zhenbao pill on the motor function of acute spinal cord injury (ASCI) rats and the molecular mechanisms involving miR-146a-5p and G-protein-coupled receptor 17 (GPR17). ASCI rat model was established by modified Allen method, and then the rats were divided into three groups. SH-SY5Y cells were cultured overnight in hypoxia condition and transfected with miR-146a-5p mimic or miR-146a-5p inhibitor. The hind limb motor function of the rats was evaluated by Basso, Beattie, Bresnahan (BBB) scoring system. Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of miR-146a-5p, GPR17, inducible nitric oxide synthase (iNOS), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α). Neuronal apoptosis was measured using flow cytometry assay. Luciferase reporter assay was performed to determine the regulation of miR-146a-5p on GPR17. Zhenbao pill could enhance hind limb motor function and attenuate the inflammatory response caused by ASCI. Moreover, zhenbao pill increased the level of miR-146a-5p and decreased GPR17 expression in vivo and in vitro. Bioinformatics software predicted that GPR17 3′-UTR had a binding site with miR-146a-5p. Luciferase reporter assay showed that miR-146a-5p had a negative regulatory effect on GPR17 expression. Knockdown of miR-146a-5p could reverse the effect of zhenbao pill on the up-regulation of GPR17 induced by hypoxia, reversed the inhibitory effect of zhenbao pill on the cell apoptosis induced by hypoxia and the recovery of zhenbao pill on hind limb motor function in ASCI rats. Zhenbao pill could inhibit neuronal apoptosis by regulating miR-146a-5p/GPR17 expression, and then promoting the recovery of spinal cord function. PMID:29187582
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Suspected disseminated histiocytic sarcoma in a 3-year-old Perro de Presa Canario dog
Denstedt, Emily
2014-01-01
A 3-year-old intact male Perro de Presa Canario dog was presented with acutely inflamed and edematous right hind limb, scrotum, prepuce, and an enlarged left carpus. Two weeks later the dog returned with weight loss, draining tracts in the right hind limb, dermal nodules, a palpable abdominal mass, and uveitis in the left eye. The dog succumbed to his illness 2 days later and a widely disseminated round cell tumor compatible with histiocytic sarcoma was diagnosed following postmortem examination. PMID:24489399
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McClung, Joseph M; McCord, Timothy J; Ryan, Terence E; Schmidt, Cameron A; Green, Tom D; Southerland, Kevin W; Reinardy, Jessica L; Mueller, Sarah B; Venkatraman, Talaignair N; Lascola, Christopher D; Keum, Sehoon; Marchuk, Douglas A; Spangenburg, Espen E; Dokun, Ayotunde; Annex, Brian H; Kontos, Christopher D
2017-07-18
Critical limb ischemia is a manifestation of peripheral artery disease that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered 2 overlapping quantitative trait loci in mice, Lsq-1 and Civq-1 , that affected limb muscle survival and stroke volume after femoral artery or middle cerebral artery ligation, respectively. Here, we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hind-limb ischemia. We treated mice with either adeno-associated viruses encoding a control (green fluorescent protein) or 2 BAG3 (Bcl-2-associated athanogene-3) variants, namely Met81 or Ile81, and subjected the mice to hind-limb ischemia. We found that the BAG3 Ile81Met variant in the C57BL/6 (BL6) mouse background segregates with protection from tissue necrosis in a shorter congenic fragment of Lsq-1 (C.B6- Lsq1-3 ). BALB/c mice treated with adeno-associated virus encoding the BL6 BAG3 variant (Ile81; n=25) displayed reduced limb-tissue necrosis and increased limb tissue perfusion compared with Met81- (n=25) or green fluorescent protein- (n=29) expressing animals. BAG3 Ile81 , but not BAG3 Met81 , improved ischemic muscle myopathy and muscle precursor cell differentiation and improved muscle regeneration in a separate, toxin-induced model of injury. Systemic injection of adeno-associated virus-BAG3 Ile81 (n=9), but not BAG3 Met81 (n=10) or green fluorescent protein (n=5), improved ischemic limb blood flow and limb muscle histology and restored muscle function (force production). Compared with BAG3 Met81 , BAG3 Ile81 displayed improved binding to the small heat shock protein (HspB8) in ischemic skeletal muscle cells and enhanced ischemic muscle autophagic flux. Taken together, our data demonstrate that genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis. These results highlight a pathway that preserves tissue survival and muscle function in the setting of ischemia. © 2017 American Heart Association, Inc.
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Biochemical adaptations of antigravity muscle fibers to disuse atrophy
NASA Technical Reports Server (NTRS)
Booth, F. W.
1978-01-01
Studies are presented in four parts of this report. The four parts include; (1) studies to gain information on the molecular basis of atrophy by antigravity muscle; (2) studies on the work capacity of antigravity muscles during atrophy and during recovery from atrophy; (3) studies on recovery of degenerated antigravity fibers after removal of hind-limb casts; and (4) studies on the atrophy and recovery of bone. The philosophy of these studies was to identify the time sequence of events in the soleus muscle of the rat following immobilization of the hind limbs, so that the length of the soleus muscle within the fixed limb is less than its resting length. In two separate studies, no decline in the weight of the soleus muscle could be detected during the first 72 hours of limb immobilization.
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Oosterlinck, M; Pille, F; Back, W; Dewulf, J; Gasthuys, F
2011-10-01
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.
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Calcium Balance in Mature Rats Exposed to a Space Flight Model
NASA Technical Reports Server (NTRS)
Wolinsky, Ira
1996-01-01
Negative calcium balances are seen in humans during spaceflight and bed rest, an analog of space flight. Due to the infrequency and costliness of space flight and the difficulties, cost, and restraints in using invasive procedures in bed rest studies, several ground based animal models of space flight have been employed. The most useful and well developed of these models is hind limb unloading in the rat. In this model the hind limbs are non-weight bearing (unloaded) but still mobile; there is a cephalad fluid shift similar to that seen in astronauts in flight; the animals are able to feed, groom and locomote using their front limbs; the procedure is reversible; and, importantly, the model has been validated by comparison to space flight. Several laboratories have studied calcium balance using rats in hind limb unweighting. Roer and Dillaman used young male rats to study calcium balance in this model for 25 days. They found no differences in dietary calcium intake, percent calcium absorption, urinary and fecal excretion, hence indicating no differences in calcium balance between control and unloaded rats. In another study, employing 120 day old females, rats' hind limbs were unloaded for 28 days. While negative calcium balances were observed during a 25 day recovery period no balance measurements were possible during unweighting since the researchers did not employ appropriate metabolic cages. In a recent study from this laboratory, using 200 g rats in the space flight model for two weeks, we found depressed intestinal calcium absorption and increased fecal calcium excretion (indicating less positive calcium balances) and lower circulating 1,25-dihydroxyvitamin D. The above studies indicate that there remains a dearth of information on calcium balance during the hind limb unloading rat space flight model, especially in mature rats, whose use is a better model for planned manned space flight than juvenile or growing animals. With the aid of a newly designed metabolic cage developed in our laboratory it is now possible to accurately measure urinary and fecal calcium excretions in this space flight model. The purpose of this study, then, was to extend and enlarge our previous findings viz: to measure calcium balances in mature rats exposed to a space flight model.
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Mangiamele, Lisa A; Fuxjager, Matthew J; Schuppe, Eric R; Taylor, Rebecca S; Hödl, Walter; Preininger, Doris
2016-05-17
Physical gestures are prominent features of many species' multimodal displays, yet how evolution incorporates body and leg movements into animal signaling repertoires is unclear. Androgenic hormones modulate the production of reproductive signals and sexual motor skills in many vertebrates; therefore, one possibility is that selection for physical signals drives the evolution of androgenic sensitivity in select neuromotor pathways. We examined this issue in the Bornean rock frog (Staurois parvus, family: Ranidae). Males court females and compete with rivals by performing both vocalizations and hind limb gestural signals, called "foot flags." Foot flagging is a derived display that emerged in the ranids after vocal signaling. Here, we show that administration of testosterone (T) increases foot flagging behavior under seminatural conditions. Moreover, using quantitative PCR, we also find that adult male S. parvus maintain a unique androgenic phenotype, in which androgen receptor (AR) in the hind limb musculature is expressed at levels ∼10× greater than in two other anuran species, which do not produce foot flags (Rana pipiens and Xenopus laevis). Finally, because males of all three of these species solicit mates with calls, we accordingly detect no differences in AR expression in the vocal apparatus (larynx) among taxa. The results show that foot flagging is an androgen-dependent gestural signal, and its emergence is associated with increased androgenic sensitivity within the hind limb musculature. Selection for this novel gestural signal may therefore drive the evolution of increased AR expression in key muscles that control signal production to support adaptive motor performance.
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2012-01-01
Background Modern high-velocity projectiles produce temporary cavities and can thus cause extensive tissue destruction along the bullet path. It is still unclear whether gelatin blocks, which are used as a well-accepted tissue simulant, allow the effects of projectiles to be adequately investigated and how these effects are influenced by caliber size. Method Barium titanate particles were distributed throughout a test chamber for an assessment of wound contamination. We fired .22-caliber Magnum bullets first into gelatin blocks and then into porcine hind limbs placed behind the chamber. Two other types of bullets (.222-caliber bullets and 6.5 × 57 mm cartridges) were then shot into porcine hind limbs. Permanent and temporary wound cavities as well as the spatial distribution of barium titanate particles in relation to the bullet path were evaluated radiologically. Results A comparison of the gelatin blocks and hind limbs showed significant differences (p < 0.05) in the mean results for all parameters. There were significant differences between the bullets of different calibers in the depth to which barium titanate particles penetrated the porcine hind limbs. Almost no particles, however, were found at a penetration depth of 10 cm or more. By contrast, gas cavities were detected along the entire bullet path. Conclusion Gelatin is only of limited value for evaluating the path of high-velocity projectiles and the contamination of wounds by exogenous particles. There is a direct relationship between the presence of gas cavities in the tissue along the bullet path and caliber size. These cavities, however, are only mildly contaminated by exogenous particles. PMID:22490236
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Lewis, Melissa J; Olby, Natasha J
2017-07-01
OBJECTIVE To develop a spasticity scale for dogs with chronic deficits following severe spinal cord injury (SCI) for use in clinical assessment and outcome measurement in clinical trials. ANIMALS 20 chronically paralyzed dogs with a persistent lack of hind limb pain perception caused by an acute SCI at least 3 months previously. PROCEDURES Spasticity was assessed in both hind limbs via tests of muscle tone, clonus, and flexor and extensor spasms adapted from human scales. Measurement of patellar clonus duration and flexor spasm duration and degree was feasible. These components were used to create a canine spasticity scale (CSS; overall score range, 0 to 18). Temporal variation for individual dogs and interrater reliability were evaluated. Gait was quantified with published gait scales, and CSS scores were compared with gait scores and clinical variables. Owners were questioned regarding spasticity observed at home. RESULTS 20 dogs were enrolled: 18 with no apparent hind limb pain perception and 2 with blunted responses; 5 were ambulatory. Testing was well tolerated, and scores were repeatable between raters. Median overall CSS score was 7 (range, 3 to 11), and flexor spasms were the most prominent finding. Overall CSS score was not associated with age, SCI duration, lesion location, or owner-reported spasticity. Overall CSS score and flexor spasm duration were associated with gait scores. CONCLUSIONS AND CLINICAL RELEVANCE The CSS could be used to quantify hind limb spasticity in dogs with chronic thoracolumbar SCI and might be a useful outcome measure. Flexor spasms may represent an integral part of stepping in dogs with severe SCI.
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Mangiamele, Lisa A.; Fuxjager, Matthew J.; Schuppe, Eric R.; Taylor, Rebecca S.; Hödl, Walter; Preininger, Doris
2016-01-01
Physical gestures are prominent features of many species’ multimodal displays, yet how evolution incorporates body and leg movements into animal signaling repertoires is unclear. Androgenic hormones modulate the production of reproductive signals and sexual motor skills in many vertebrates; therefore, one possibility is that selection for physical signals drives the evolution of androgenic sensitivity in select neuromotor pathways. We examined this issue in the Bornean rock frog (Staurois parvus, family: Ranidae). Males court females and compete with rivals by performing both vocalizations and hind limb gestural signals, called “foot flags.” Foot flagging is a derived display that emerged in the ranids after vocal signaling. Here, we show that administration of testosterone (T) increases foot flagging behavior under seminatural conditions. Moreover, using quantitative PCR, we also find that adult male S. parvus maintain a unique androgenic phenotype, in which androgen receptor (AR) in the hind limb musculature is expressed at levels ∼10× greater than in two other anuran species, which do not produce foot flags (Rana pipiens and Xenopus laevis). Finally, because males of all three of these species solicit mates with calls, we accordingly detect no differences in AR expression in the vocal apparatus (larynx) among taxa. The results show that foot flagging is an androgen-dependent gestural signal, and its emergence is associated with increased androgenic sensitivity within the hind limb musculature. Selection for this novel gestural signal may therefore drive the evolution of increased AR expression in key muscles that control signal production to support adaptive motor performance. PMID:27143723
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Lee, Kah Meng; Chand, Kirat K; Hammond, Luke A; Lavidis, Nickolas A; Noakes, Peter G
2017-03-14
Laminin-α4 is involved in the alignment of active zones to postjunctional folds at the neuromuscular junction (NMJ). Prior study has implicated laminin-α4 in NMJ maintenance, with altered NMJ morphology observed in adult laminin-α4 deficient mice ( lama 4 -/- ). The present study further investigated the role of laminin-α4 in NMJ maintenance by functional characterization of transmission properties, morphological investigation of synaptic proteins including synaptic laminin-α4, and neuromotor behavioral testing. Results showed maintained perturbed transmission properties at lama 4 -/- NMJs from adult (3 months) through to aged (18-22 months). Hind-limb grip force demonstrated similar trends as transmission properties, with maintained weaker grip force across age groups in lama 4 -/- . Interestingly, both transmission properties and hind-limb grip force in aged wild-types resembled those observed in adult lama 4 -/- . Most significantly, altered expression of laminin-α4 was noted at the wild-type NMJs prior to the observed decline in transmission properties, suggesting that altered laminin-α4 expression precedes the decline of neurotransmission in aging wild-types. These findings significantly support the role of laminin-α4 in maintenance of the NMJ during aging.
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[Fundamental biological model for trials of wound ballistics].
Krajsa, J; Hirt, M
2006-10-01
The aim of our experiment was the testing of effects of common ammunition on usable and slightly accessible biological tissue thereby to create fundamental simple biological model for trials of wounded ballistic. Like objective tissue was elected biological material - pork and beef hind-limbs, pork head, pork bodily cavity. It was discovered that objective tissue is able to react to singles types of shots in all spectrum results namely simple smooth penetration wound as well as splintery fracture in dependence on kind of using ammunition. Pork hind-limb was evaluated like the most suitable biological material for given object.
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Size-Related Changes in Foot Impact Mechanics in Hoofed Mammals
Warner, Sharon Elaine; Pickering, Phillip; Panagiotopoulou, Olga; Pfau, Thilo; Ren, Lei; Hutchinson, John Richard
2013-01-01
Foot-ground impact is mechanically challenging for all animals, but how do large animals mitigate increased mass during foot impact? We hypothesized that impact force amplitude scales according to isometry in animals of increasing size through allometric scaling of related impact parameters. To test this, we measured limb kinetics and kinematics in 11 species of hoofed mammals ranging from 18–3157 kg body mass. We found impact force amplitude to be maintained proportional to size in hoofed mammals, but that other features of foot impact exhibit differential scaling patterns depending on the limb; forelimb parameters typically exhibit higher intercepts with lower scaling exponents than hind limb parameters. Our explorations of the size-related consequences of foot impact advance understanding of how body size influences limb morphology and function, foot design and locomotor behaviour. PMID:23382967
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Cryopreservation and replantation of amputated rat hind limbs
2014-01-01
Background In spite of the relatively high success rate of limb replantation, many patients cannot undergo replantation surgery because the preservation time of an amputated limb is only about six hours. In addition, although allotransplantation of composite tissues is being performed more commonly with increasingly greater success rates, the shortage of donors limits the number of patients that can be treated. So the purpose of this study is to examine the feasibility of cryopreservation and replantation of limbs in a rat model. Methods Twelve five-month-old Sprague-Dawley rats were divided evenly into group A (above-knee amputation) and group B (Syme’s amputation). One hind limb was amputated from each rat. The limbs were irrigated with cryoprotectant, cooled in a controlled manner to -140°C, and placed in liquid nitrogen. Thawing and replantation were performed 14 days later. Results In group A, the limbs became swollen after restoration of blood flow resulting in blood vessel compression and all replantations failed. In group B, restoration of blood flow was noted in all limbs after replantation. In one case, the rat chewed the replanted limb and replantation failed. The other five rats were followed for three months with no abnormalities noted in the replanted limbs. Conclusions Limbs with a minimal amount of muscle tissue can be successfully cryopreserved and replanted. PMID:24886622
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Suppression of morphogenesis in embryonic mouse limbs exposed in vitro to excess gravity
NASA Technical Reports Server (NTRS)
Duke, Jackie C.
1983-01-01
The effect of excess gravity on in vitro mammalian limb chondrogenesis is studied. Limb buds from mice of various gestational stages were exposed to excess gravity (2.6G) using a culture centrifuge. Both forelimbs and hind limbs were cultured, and the development of various limb elements was scored after four to six days. The 2.6G force significantly depressed the development of limb elements when applied during the teratogen-sensitive period of chondrogenesis.
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Geckos significantly alter foot orientation to facilitate adhesion during downhill locomotion
Birn-Jeffery, Aleksandra V.; Higham, Timothy E.
2014-01-01
Geckos employ their adhesive system when moving up an incline, but the directionality of the system may limit function on downhill surfaces. Here, we use a generalist gecko to test whether limb modulation occurs on downhill slopes to allow geckos to take advantage of their adhesive system. We examined three-dimensional limb kinematics for geckos moving up and down a 45° slope. Remarkably, the hind limbs were rotated posteriorly on declines, resulting in digit III of the pes facing a more posterior direction (opposite to the direction of travel). No significant changes in limb orientation were found in any other condition. This pes rotation leads to a dramatic shift in foot function that facilitates the use of the adhesive system as a brake/stabilizer during downhill locomotion and, although this rotation is not unique to geckos, it is significant for the deployment of adhesion. Adhesion is not just advantageous for uphill locomotion but can be employed to help deal with the effects of gravity during downhill locomotion, highlighting the incredible multi-functionality of this key innovation. PMID:25319816
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Barstow, Amy; Pfau, Thilo; Bolt, David M; Smith, Roger K; Weller, Renate
2014-01-01
The ability to recognize lameness in the horse is an important skill for veterinary graduates; however, opportunities to develop this skill at the undergraduate level are limited. Computer-aided learning programs (CALs) have been successful in supplementing practical skills teaching. The aim of this study was to design and validate a CAL for the teaching of equine lameness recognition (CAL1). A control CAL was designed to simulate learning by experience (CAL2). Student volunteers were randomly assigned to either CAL and tested to establish their current ability to recognize lameness. Retesting occurred both immediately following exposure and 1 week later. At each test point, the number of correct responses for forelimb and hind limb cases was determined. Student confidence was assessed before and after CAL exposure, with previous opportunities to recognize lameness taken into account. Immediately following exposure, the number of correct responses was significantly higher for CAL1 than for CAL2, both overall and for forelimb cases but not for hind limb cases. After 1 week, the CAL1 group performed significantly better overall compared to the CAL2 group, with no significant difference between forelimb and hind limb cases. Student confidence and ability to recognize lameness were significantly improved following exposure to CAL1. When considered as one category, students in years 4 and 5 performed significantly better than year 3 students. Gender did not significantly affect performance. CAL1 could be used to supplement current lameness recognition opportunities. CAL1 is, however, limited in its ability to improve lameness recognition, especially in relation to hind limb lameness where it was unable to attain a significant difference from CAL2.
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Long, Chandler A.; Boloum, Valy; Albadawi, Hassan; Tsai, Shirling; Yoo, Hyung-Jin; Oklu, Rahmi; Goldman, Mitchell H.; Watkins, Michael T.
2013-01-01
Introduction Diabetes is known to increase poly-ADP-ribose-polymerase (PARP) activity and posttranslational poly-ADP-ribosylation of several regulatory proteins involved in inflammation and energy metabolism. These experiments test the hypothesis that PARP inhibition will modulate hind limb ischemia reperfusion (IR) in a mouse model of type-II diabetes; ameliorate the ribosylation and the activity/transnuclear localization of the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Methods db/db mice underwent 1.5hrs of hind limb ischemia followed by 1, 7, or 24hrs reperfusion. The treatment group received the PARP inhibitor PJ34 (PJ34) over a 24hrs period; the untreated group received Lactated ringer’s (LR) at the same time points. IR muscles were analyzed for indices of PARP activity, fiber injury, metabolic activity, inflammation, GAPDH activity /intracellular localization and poly-ADP-ribosylation of GAPDH. Results PARP activity was significantly lower in the PJ34 treated groups compared to the LR group at 7 and 24 hours reperfusion. There was significantly less muscle fiber injury in the PJ34 treated group compared to LR treated mice at 24 hrs reperfusion. PJ34 lowered levels of select proinflammatory molecules at 7hrs and 24hrs IR. There were significant increases in metabolic activity only at 24 hours IR in the PJ34 group, which temporally correlated with increase in GAPDH activity, decreased GAPDH poly ADP-ribosylation and nuclear translocation of GAPDH. Conclusions PJ34 reduced PARP activity, GAPDH ribosylation, GAPDH translocation, ameliorated muscle fiber injury, and increased metabolic activity following hind limb IR injury in a murine model of type-II diabetes. PARP inhibition might be a therapeutic strategy following IR in diabetic humans. PMID:23549425
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Davey, Rachel A; Clarke, Michele V; Russell, Patricia K; Rana, Kesha; Seto, Jane; Roeszler, Kelly N; How, Jackie M Y; Chia, Ling Yeong; North, Kathryn; Zajac, Jeffrey D
2017-10-01
Although it is well established that exogenous androgens have anabolic effects on skeletal muscle mass in humans and mice, data from muscle-specific androgen receptor (AR) knockout (ARKO) mice indicate that myocytic expression of the AR is dispensable for hind-limb muscle mass accrual in males. To identify possible indirect actions of androgens via the AR in neurons to regulate muscle, we generated neuron-ARKO mice in which the dominant DNA binding-dependent actions of the AR are deleted in neurons of the cortex, forebrain, hypothalamus, and olfactory bulb. Serum testosterone and luteinizing hormone levels were elevated twofold in neuron-ARKO males compared with wild-type littermates due to disruption of negative feedback to the hypothalamic-pituitary-gonadal axis. Despite this increase in serum testosterone levels, which was expected to increase muscle mass, the mass of the mixed-fiber gastrocnemius (Gast) and the fast-twitch fiber extensor digitorum longus hind-limb muscles was decreased by 10% in neuron-ARKOs at 12 weeks of age, whereas muscle strength and fatigue of the Gast were unaffected. The mass of the soleus muscle, however, which consists of a high proportion of slow-twitch fibers, was unaffected in neuron-ARKOs, demonstrating a stimulatory action of androgens via the AR in neurons to increase the mass of fast-twitch hind-limb muscles. Furthermore, neuron-ARKOs displayed reductions in voluntary and involuntary physical activity by up to 60%. These data provide evidence for a role of androgens via the AR in neurons to positively regulate fast-twitch hind-limb muscle mass and physical activity in male mice. Copyright © 2017 Endocrine Society.
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Normann, R A; Dowden, B R; Frankel, M A; Wilder, A M; Hiatt, S D; Ledbetter, N M; Warren, D A; Clark, G A
2012-04-01
The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.
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NASA Astrophysics Data System (ADS)
Normann, R. A.; Dowden, B. R.; Frankel, M. A.; Wilder, A. M.; Hiatt, S. D.; Ledbetter, N. M.; Warren, D. A.; Clark, G. A.
2012-04-01
The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.
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An attempt to detect lameness in galloping horses by use of body-mounted inertial sensors.
Lopes, Marco A F; Dearo, Antonio C O; Lee, Allen; Reed, Shannon K; Kramer, Joanne; Pai, P Frank; Yonezawa, Yoshiharu; Maki, Hiromitchi; Morgan, Terry L; Wilson, David A; Keegan, Kevin G
2016-10-01
OBJECTIVE To evaluate head, pelvic, and limb movement to detect lameness in galloping horses. ANIMALS 12 Thoroughbreds. PROCEDURES Movement data were collected with inertial sensors mounted on the head, pelvis, and limbs of horses trotting and galloping in a straight line before and after induction of forelimb and hind limb lameness by use of sole pressure. Successful induction of lameness was determined by measurement of asymmetric vertical head and pelvic movement during trotting. Differences in gallop strides before and after induction of lameness were evaluated with paired-sample statistical analysis and neural network training and testing. Variables included maximum, minimum, range, and time indices of vertical head and pelvic acceleration, head rotation in the sagittal plane, pelvic rotation in the frontal plane, limb contact intervals, stride durations, and limb lead preference. Difference between median standardized gallop strides for each limb lead before and after induction of lameness was calculated as the sum of squared differences at each time index and assessed with a 2-way ANOVA. RESULTS Head and pelvic acceleration and rotation, limb timing, stride duration measurements, and limb lead preference during galloping were not significantly different before and after induction of lameness in the forelimb or hind limb. Differences between limb leads before induction of lameness were similar to or greater than differences within limb leads before and after lameness induction. CONCLUSIONS AND CLINICAL RELEVANCE Galloping horses maintained asymmetry of head, pelvic, and limb motion between limb leads that was unrelated to lameness.
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Verdugo, Mirela R; Rahal, Sheila C; Agostinho, Felipe S; Govoni, Verônica M; Mamprim, Maria J; Monteiro, Frederico O B
2013-06-27
Several factors may influence kinetic data measurements, including body conformation and body mass. In addition, gender differences in gait pattern have been observed in healthy humans. Therefore, the aim of this study was to compare the kinetic and temporospatial parameters in clinically healthy male and female cats using a pressure-sensitive walkway. Eighteen crossbreed adult cats were divided into two groups: G1 had ten male cats (nine neutered) aged from 1 to 4 years and body mass 3.1-6.8 kg; G2 had eight spayed female cats, aged from 1 to 6 years and body mass 3.3-4.75 kg. The data from the first five valid trials were collected for each cat. A trial was considered valid if the cat maintained a velocity between 0.54-0.74 m/s and acceleration from -0.20 to 0.20 m/s2. The peak vertical force (PVF), vertical impulse (VI), gait cycle time, stance time, swing time, stride length, and percentage body weight distribution among the four limbs were determined. In addition, the lengths of each forelimb and each hind limb were measured using a tape with the animal standing. No significant differences were observed in each group in either the forelimbs or the hind limbs or between the left and right sides for any of the variables. For both groups, the PVF (%BW), the VI, and the percentage body weight distribution were higher at the forelimbs than the hind limbs. The stride length was larger for males; however, the other kinetic and temporospatial variables did not show any statistically significant differences between the groups. The lengths of the forelimbs and hind limbs were larger in the male cats. There was a significant moderate positive correlation between the stride length and the length of the limbs. In conclusion, the only difference observed between male and female cats was the stride length, and this was due to the greater body size of male cats. This difference did not affect other temporospatial or kinetics variables.
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Pelvic girdle mobility of cryptodire and pleurodire turtles during walking and swimming.
Mayerl, Christopher J; Brainerd, Elizabeth L; Blob, Richard W
2016-09-01
Movements of the pelvic girdle facilitate terrestrial locomotor performance in a wide range of vertebrates by increasing hind limb excursion and stride length. The extent to which pelvic movements contribute to limb excursion in turtles is unclear because the bony shell surrounding the body presents a major obstacle to their visualization. In the Cryptodira, which are one of the two major lineages of turtles, pelvic anatomy indicates the potential for rotation inside the shell. However, in the Pleurodira, the other major suborder, the pelvis shows a derived fusion to the shell, preventing pelvic motion. In addition, most turtles use their hind limbs for propulsion during swimming as well as walking, and the different locomotor demands between water and land could lead to differences in the contributions of pelvic rotation to limb excursion in each habitat. To test these possibilities, we used X-ray reconstruction of moving morphology (XROMM) to compare pelvic mobility and femoral motion during walking and swimming between representative species of cryptodire (Pseudemys concinna) and pleurodire (Emydura subglobosa) turtles. We found that the pelvis yawed substantially in cryptodires during walking and, to a lesser extent, during swimming. These movements contributed to greater femoral protraction during both walking and swimming in cryptodires when compared with pleurodires. Although factors related to the origin of pelvic-shell fusion in pleurodires are debated, its implications for their locomotor function may contribute to the restriction of this group to primarily aquatic habits. © 2016. Published by The Company of Biologists Ltd.
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Kaliontzopoulou, Antigoni; Carretero, M A; Llorente, G A
2010-06-01
Morphological variation in relation to habitat is known to occur in several lizard groups. Comparative studies have linked morphology and habitat use, showing that locomotion is the principal mediator of this evolutionary relationship. Here, we investigate intraspecific ecomorphological variation in Podarcis bocagei by examining three habitat types, representing a variety between saxicolous and ground-dwelling habits. Our results indicate variation in absolute and relative limb length, but patterns are only partially concordant to biomechanical predictions. Whereas the femur and hind foot are longer in ground-dwelling lizards, confirming previous observations, the tibia and hind limb are relatively shorter, contradicting expectations. Additionally, head shape varies substantially between habitats, in line with a hypothesis of mechanical restrictions related to microhabitat and refuge use. Finally, we detect male-specific variation between habitats in total body size and head size, providing evidence for interactions between natural and sexual selection. Although performance and behaviour studies are necessary to definitely confirm the functional and evolutionary significance of the observed patterns, our study indicates that ecomorphological adaptations can arise in a very short evolutionary time in this group of lizards.
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In Vivo Hypobaric Hypoxia Performed During the Remodeling Process Accelerates Bone Healing in Mice
Durand, Marjorie; Collombet, Jean-Marc; Frasca, Sophie; Begot, Laurent; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline
2014-01-01
We investigated the effects of respiratory hypobaric hypoxia on femoral bone-defect repair in mice because hypoxia is believed to influence both mesenchymal stromal cell (MSC) and hematopoietic stem cell mobilization, a process involved in the bone-healing mechanism. To mimic conditions of non-weight-bearing limb immobilization in patients suffering from bone trauma, our hypoxic mouse model was further subjected to hind-limb unloading. A hole was drilled in the right femur of adult male C57/BL6J mice. Four days after surgery, mice were subjected to hind-limb unloading for 1 week. Seven days after surgery, mice were either housed for 4 days in a hypobaric room (FiO2 at 10%) or kept under normoxic conditions. Unsuspended control mice were housed in either hypobaric or normoxic conditions. Animals were sacrificed on postsurgery day 11 to allow for collection of both contralateral and lesioned femurs, blood, and spleen. As assessed by microtomography, delayed hypoxia enhanced bone-healing efficiency by increasing the closing of the cortical defect and the newly synthesized bone volume in the cavity by +55% and +35%, respectively. Proteome analysis and histomorphometric data suggested that bone-repair improvement likely results from the acceleration of the natural bone-healing process rather than from extended mobilization of MSC-derived osteoprogenitors. Hind-limb unloading had hardly any effect beyond delayed hypoxia-enhanced bone-healing efficiency. PMID:24944208
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Reverse Saphenous Conduit Flap in 19 Dogs and 1 Cat.
Cavalcanti, Jacqueline V J; Barry, Sabrina L; Lanz, Otto I; Barnes, Katherine; Coutin, Julia V
2018-05-14
The purpose of this retrospective study was to report the outcomes of 19 dogs and 1 cat undergoing reverse saphenous conduit flap between 1999 and 2016. Reverse saphenous conduit flap was used to treat traumatic wounds and wounds resulting from tumor excision in the hind limb; the majority of cases had medial shearing injuries. All animals had complete flap survival. In five animals (20%), minor donor site dehiscence occurred, which did not require surgery. Other postoperative complications included signs of severe venous congestion in one dog. Reverse saphenous conduit flap is a useful technique to repair skin defects of the distal hind limb.
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Metastatic carcinoma presenting as hind-limb lameness: diagnosis by synovial fluid cytology.
Meinkoth, J H; Rochat, M C; Cowell, R L
1997-01-01
A dog presented for evaluation of left hind-limb lameness and pain associated with manipulation of the tail. Synovial metastasis of a carcinoma was diagnosed by joint fluid examination. A primary bronchiolar-alveolar carcinoma with widespread (including synovial and skeletal) metastases was diagnosed on postmortem examination. Metastasis to synovial surfaces is uncommon, but when it occurs, the metastasis-induced arthritis may be the initial presenting complaint for which medical attention is sought. Although rarely reported, cytological examination of synovial fluid may be diagnostic. This paper presents an interesting clinical case and reviews the literature concerning metastatic disease of the synovium.
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Xu, Yan-Jun; Elimban, Vijayan; Dhalla, Naranjan S
2017-08-01
In this study, we investigated the effects of CO 2 water-bath therapy on blood flow and angiogenesis in the ischemic hind limb, as well as some plasma angiogenic factors in peripheral ischemic model. The hind limb ischemia was induced by occluding the femoral artery for 2 weeks in rats and treated with or without CO 2 water-bath therapy at 37 °C for 4 weeks (20 min treatment every day for 5 days per week). The peak blood flow and minimal and mean blood flow in the ischemic skeletal muscle were markedly increased by the CO 2 water-bath therapy. This increase in blood flow was associated with development of angiogenesis in the muscle, as well as reduction in the ischemia-induced increase in plasma malondialdehyde levels. Although plasma vascular endothelial growth factor and nitric oxide levels were increased in animals with peripheral ischemia, the changes in these biomarkers were not affected by CO 2 water-bath therapy. These results suggest that augmentation of blood flow in the ischemic hind limb by CO 2 water-bath therapy may be due to the development of angiogenesis and reduction in oxidative stress.
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The molecular response of bone to growth hormone during skeletal unloading: regional differences
NASA Technical Reports Server (NTRS)
Bikle, D. D.; Harris, J.; Halloran, B. P.; Currier, P. A.; Tanner, S.; Morey-Holton, E.
1995-01-01
Hind limb elevation of the growing rat provides a good model for the skeletal changes that occur during space flight. In this model the bones of the forelimbs (normally loaded) are used as an internal control for the changes that occur in the unloaded bones of the hind limbs. Previous studies have shown that skeletal unloading of the hind limbs results in a transient reduction of bone formation in the tibia and femur, with no change in the humerus. This fall in bone formation is accompanied by a fall in serum osteocalcin (bone Gla protein, BGP) and bone BGP messenger RNA (mRNA) levels, but a rise in bone insulin-like growth factor-I (IGF-I) protein and mRNA levels and resistance to the skeletal growth-promoting actions of IGF-I. To determine whether skeletal unloading also induced resistance to GH, we evaluated the response of the femur and humerus of sham and hypophysectomized rats, control and hind limb elevated, to GH (two doses), measuring mRNA levels of IGF-I, BGP, rat bone alkaline phosphatase (RAP), and alpha 1(1)-procollagen (coll). Hypophysectomy (HPX) decreased the mRNA levels of IGF-I, BGP, and coll in the femur, but was either less effective or had the opposite effect in the humerus. GH at the higher dose (500 micrograms/day) restored these mRNA levels to or above the sham control values in the femur, but generally had little or no effect on the humerus. RAP mRNA levels were increased by HPX, especially in the femur. The lower dose of GH (50 micrograms/day) inhibited this rise in RAP, whereas the higher dose raised the mRNA levels and resulted in the appearance of additional transcripts not seen in controls. As for the other mRNAs, RAP mRNA in the humerus was less affected by HPX or GH than that in the femur. Hind limb elevation led to an increase in IGF-I, coll, and RAP mRNAs and a reduction in BGP mRNA in the femur and either had no effect or potentiated the response of these mRNAs to GH. We conclude that GH stimulates a number of markers of bone formation by raising their mRNA levels, and that skeletal unloading does not block this response, but the response varies substantially from bone to bone.
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Bermingham, E N; McNabb, W C; Sinclair, B R; Tavendale, M H; Roy, N C
2011-11-01
Intestinal parasitic infection increases the demand for AA because of increased protein synthesis in the intestine and increased luminal losses of AA, and these increased demands may be supported by increased mobilization of AA from the skeletal muscles. Two experiments were conducted to determine the effects of parasitic infection on valine kinetics within the gastrointestinal tract and hind limbs of lambs fed fresh forages. On d 1, lambs were given 6,000 stage-3 Trichostrongylus colubriformis larvae per day for 6 d (n = 6) or kept as parasite-free controls (n = 6) and fed fresh lucerne (Medicago sativa; Exp. 1) or fresh sulla (Hedysarum coronarium; Exp. 2). On d 48, valine kinetics within the mesenteric- (MDV) and portal-drained viscera (PDV) and hind limbs were obtained by carrying out concurrent infusions of para-amminohippuric acid into the mesenteric vein and indocyanin green into the abdominal aorta (for blood flow), and [3,4-(3)H]valine into the jugular vein and [1-(13)C]valine into the abomasum for 8 h (for kinetics). During the infusions, blood was collected from the mesenteric and portal veins and from the mesenteric artery and vena cava, and plasma was harvested. After the 8-h infusion, lambs were euthanized, ileal digesta were collected, and tissues were sampled from the intestine and muscle (biceps femoris). Tissues, digesta, and plasma were analyzed for valine concentration, specific radioactivity, and isotopic enrichment. In both experiments, intestinal worm burdens on d 48 were greater in parasitized lambs (P = 0.0001 and 0.003). In Exp. 1, parasitic infection increased (P = 0.03) the total valine irreversible loss rate (ILR) in the MDV and PDV. In Exp. 2, luminal ILR of valine in the MDV was reduced (P = 0.01); however, ILR of valine in the PDV was unaffected. Despite these changes within the MDV and PDV, parasitic infection did not affect the ILR of valine within the hind limbs, and valine transport rates were largely unchanged. We suggest that the increased mobilization of AA from the hind limbs that might have occurred in the early phase of inflammation was no longer required when the parasitic infection was established. The MDV and PDV data may indicate that the non-MDV parts of the PDV play an important role in this adaptation, which warrants further study.
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Ruff, Christopher B; Burgess, M Loring; Bromage, Timothy G; Mudakikwa, Antoine; McFarlin, Shannon C
2013-12-01
Behavioral studies indicate that adult mountain gorillas (Gorilla beringei) are the most terrestrial of all nonhuman hominoids, but that infant mountain gorillas are much more arboreal. Here we examine ontogenetic changes in diaphyseal strength and length of the femur, tibia, humerus, radius, and ulna in 30 Virunga mountain gorillas, including 18 immature specimens and 12 adults. Comparisons are also made with 14 adult western lowland gorillas (Gorilla gorilla gorilla), which are known to be more arboreal than adult mountain gorillas. Infant mountain gorillas have significantly stronger forelimbs relative to hind limbs than older juveniles and adults, but are nonsignificantly different from western lowland gorilla adults. The change in inter-limb strength proportions is abrupt at about two years of age, corresponding to the documented transition to committed terrestrial quadrupedalism in mountain gorillas. The one exception is the ulna, which shows a gradual increase in strength relative to the radius and other long bones during development, possibly corresponding to the gradual adoption of stereotypical fully pronated knuckle-walking in older juvenile gorillas. Inter-limb bone length proportions show a contrasting developmental pattern, with hind limb/forelimb length declining rapidly from birth to five months of age, and then showing no consistent change through adulthood. The very early change in length proportions, prior to significant independent locomotion, may be related to the need for relatively long forelimbs for climbing in a large-bodied hominoid. Virunga mountain gorilla older juveniles and adults have equal or longer forelimb relative to hind limb bones than western lowland adults. These findings indicate that both ontogenetically and among closely related species of Gorilla, long bone strength proportions better reflect actual locomotor behavior than bone length proportions. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Heritabilities of Directional Asymmetry in the Fore- and Hindlimbs of Rabbit Fetuses
Breno, Matteo; Bots, Jessica; Van Dongen, Stefan
2013-01-01
Directional asymmetry (DA), where at the population level symmetry differs from zero, has been reported in a wide range of traits and taxa, even for traits in which symmetry is expected to be the target of selection such as limbs or wings. In invertebrates, DA has been suggested to be non-adaptive. In vertebrates, there has been a wealth of research linking morphological asymmetry to behavioural lateralisation. On the other hand, the prenatal expression of DA and evidences for quantitative genetic variation for asymmetry may suggest it is not solely induced by differences in mechanic loading between sides. We estimate quantitative genetic variation of fetal limb asymmetry in a large dataset of rabbits. Our results showed a low but highly significant level of DA that is partially under genetic control for all traits, with forelimbs displaying higher levels of asymmetry. Genetic correlations were positive within limbs, but negative across bones of fore and hind limbs. Environmental correlations were positive for all, but smaller across fore and hind limbs. We discuss our results in light of the existence and maintenance of DA in locomotory traits. PMID:24130770
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Walker, Suellen M; Fitzgerald, Maria; Hathway, Gareth J
2015-06-01
Neonatal pain and injury can alter long-term sensory thresholds. Descending rostroventral medulla (RVM) pathways can inhibit or facilitate spinal nociceptive processing in adulthood. As these pathways undergo significant postnatal maturation, the authors evaluated long-term effects of neonatal surgical injury on RVM descending modulation. Plantar hind paw or forepaw incisions were performed in anesthetized postnatal day (P)3 Sprague-Dawley rats. Controls received anesthesia only. Hind limb mechanical and thermal withdrawal thresholds were measured to 6 weeks of age (adult). Additional groups received pre- and post-incision sciatic nerve levobupivacaine or saline. Hind paw nociceptive reflex sensitivity was quantified in anesthetized adult rats using biceps femoris electromyography, and the effect of RVM electrical stimulation (5-200 μA) measured as percentage change from baseline. In adult rats with previous neonatal incision (n = 9), all intensities of RVM stimulation decreased hind limb reflex sensitivity, in contrast to the typical bimodal pattern of facilitation and inhibition with increasing RVM stimulus intensity in controls (n = 5) (uninjured vs. neonatally incised, P < 0.001). Neonatal incision of the contralateral hind paw or forepaw also resulted in RVM inhibition of hind paw nociceptive reflexes at all stimulation intensities. Behavioral mechanical threshold (mean ± SEM, 28.1 ± 8 vs. 21.3 ± 1.2 g, P < 0.001) and thermal latency (7.1 ± 0.4 vs. 5.3 ± 0.3 s, P < 0.05) were increased in both hind paws after unilateral neonatal incision. Neonatal perioperative sciatic nerve blockade prevented injury-induced alterations in RVM descending control. Neonatal surgical injury alters the postnatal development of RVM descending control, resulting in a predominance of descending inhibition and generalized reduction in baseline reflex sensitivity. Prevention by local anesthetic blockade highlights the importance of neonatal perioperative analgesia.
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NASA Astrophysics Data System (ADS)
Bruns, Tim M.; Wagenaar, Joost B.; Bauman, Matthew J.; Gaunt, Robert A.; Weber, Douglas J.
2013-04-01
Objective. Functional electrical stimulation (FES) approaches often utilize an open-loop controller to drive state transitions. The addition of sensory feedback may allow for closed-loop control that can respond effectively to perturbations and muscle fatigue. Approach. We evaluated the use of natural sensory nerve signals obtained with penetrating microelectrode arrays in lumbar dorsal root ganglia (DRG) as real-time feedback for closed-loop control of FES-generated hind limb stepping in anesthetized cats. Main results. Leg position feedback was obtained in near real-time at 50 ms intervals by decoding the firing rates of more than 120 DRG neurons recorded simultaneously. Over 5 m of effective linear distance was traversed during closed-loop stepping trials in each of two cats. The controller compensated effectively for perturbations in the stepping path when DRG sensory feedback was provided. The presence of stimulation artifacts and the quality of DRG unit sorting did not significantly affect the accuracy of leg position feedback obtained from the linear decoding model as long as at least 20 DRG units were included in the model. Significance. This work demonstrates the feasibility and utility of closed-loop FES control based on natural neural sensors. Further work is needed to improve the controller and electrode technologies and to evaluate long-term viability.
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Bruns, Tim M; Wagenaar, Joost B; Bauman, Matthew J; Gaunt, Robert A; Weber, Douglas J
2013-01-01
Objective Functional electrical stimulation (FES) approaches often utilize an open-loop controller to drive state transitions. The addition of sensory feedback may allow for closed-loop control that can respond effectively to perturbations and muscle fatigue. Approach We evaluated the use of natural sensory nerve signals obtained with penetrating microelectrode arrays in lumbar dorsal root ganglia (DRG) as real-time feedback for closed-loop control of FES-generated hind limb stepping in anesthetized cats. Main results Leg position feedback was obtained in near real-time at 50 ms intervals by decoding the firing rates of more than 120 DRG neurons recorded simultaneously. Over 5 m of effective linear distance was traversed during closed-loop stepping trials in each of two cats. The controller compensated effectively for perturbations in the stepping path when DRG sensory feedback was provided. The presence of stimulation artifacts and the quality of DRG unit sorting did not significantly affect the accuracy of leg position feedback obtained from the linear decoding model as long as at least 20 DRG units were included in the model. Significance This work demonstrates the feasibility and utility of closed-loop FES control based on natural neural sensors. Further work is needed to improve the controller and electrode technologies and to evaluate long-term viability. PMID:23503062
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Alexander, David E.; Gong, Enpu; Martin, Larry D.; Burnham, David A.; Falk, Amanda R.
2010-01-01
Fossils of the remarkable dromaeosaurid Microraptor gui and relatives clearly show well-developed flight feathers on the hind limbs as well as the front limbs. No modern vertebrate has hind limbs functioning as independent, fully developed wings; so, lacking a living example, little agreement exists on the functional morphology or likely flight configuration of the hindwing. Using a detailed reconstruction based on the actual skeleton of one individual, cast in the round, we developed light-weight, three-dimensional physical models and performed glide tests with anatomically reasonable hindwing configurations. Models were tested with hindwings abducted and extended laterally, as well as with a previously described biplane configuration. Although the hip joint requires the hindwing to have at least 20° of negative dihedral (anhedral), all configurations were quite stable gliders. Glide angles ranged from 3° to 21° with a mean estimated equilibrium angle of 13.7°, giving a lift to drag ratio of 4.1:1 and a lift coefficient of 0.64. The abducted hindwing model’s equilibrium glide speed corresponds to a glide speed in the living animal of 10.6 m·s−1. Although the biplane model glided almost as well as the other models, it was structurally deficient and required an unlikely weight distribution (very heavy head) for stable gliding. Our model with laterally abducted hindwings represents a biologically and aerodynamically reasonable configuration for this four-winged gliding animal. M. gui’s feathered hindwings, although effective for gliding, would have seriously hampered terrestrial locomotion. PMID:20133792
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Suspension restraint - Induced hypokinesia and antiorthostasis as a simulation of weightlessness
NASA Technical Reports Server (NTRS)
Musacchia, X. J.; Steffen, J. M.; Deavers, D. R.
1982-01-01
Muscle, renal, fluid and electrolyte responses were measured in suspended rats; the hind limbs are non-load bearing and the front limbs can be used for feeding and grooming. Hind limb hypokinesia reverses after removal from the suspension harness. This suspension system is adjustable for a head-down tilt to produce antiorthostatic responses which are also reversible. Responses to hypokinesia or antiorthostatic hypokinesia for up to 14 days were measured, e.g., muscle atrophy: soleus greater than gastrocnemius equals plantaris greater than extensor digitorum longus, kaliuresis, and increased excretion of urea, NH3, and 3 methylhistidine. Muscle protein loss, a response to a reduction in RNA, is also reversible. A head-down tilt for 7-14 days results in diuresis and natriuresis. These changes are reversed within 24 hours after removal from the restraint harness. Physiological effects of suspension restraint can be used to simulate and predict responses to microgravity exposure.
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NASA Technical Reports Server (NTRS)
Goldspink, G.; Goldspink, D.; Loughna, P.
1984-01-01
The morphological and biochemical changes which occur in the hind limb muscles of the rat in response to hypokinesia and hypodynamia were investigated. Hind limb cast fixation and suspension techniques were employed to study the musclar atrophy after five days of hypokinesia and hypodynamia induced by suspension, appreciable muscular atrophy was apparent, particularly in the anti-gravity muscles. The effect of passive stretching and electrical stimulation on muscle atrophy was studied. Changes in muscle protein mass were assessed with spectrophotometric and radioactive techniques. Passive stretch is shown to counteract muscle disuse atrophy. The change in the numbers of specific muscle fibers in atrophied muscles is discussed.
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Effect of demedullation on freezing injury in hind limbs of rats
NASA Astrophysics Data System (ADS)
Dhingra, Shashi; Bhatia, B.; Chhina, G. S.; Singh, Baldev
1987-09-01
Freezing incidence and tissue loss on exposure of hind limbs of female Wistar rats to freezing mixture was reduced by demedullation 6 days prior to cold exposure (p<0.01 and p<0.001 respectively); demedullation 1 h after freezing injury had no effect on tissue loss. Noradrenaline (1 mg/kg i.p.) 5 min before exposure increased the freezing incidence in intact (p<0.05) as well as in demedullated rats (p<0.01), with no effect on tissue loss. Adrenaline (500 mg/kg i.p.) had no effect on either. A sustained fall in plasma adrenaline after demedullation leading to reduced reactivity of the blood vessels to some vasoactive agents is postulated.
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2005-01-01
Abstract The study objectives were to provide a province-wide description of stall dimensions and the aspects of cattle welfare linked to stall design in the tie-stall industry. Data on stall design; stall dimensions; and the prevalence of lameness, injury, and hind limb and udder cleanliness in lactating dairy cattle were collected from a sample of 317 tie-stall farms across Ontario. The majority of the study farms (90%) had stalls with dimensions (length, width, tie-chain length, and tie rail height) that were less than the current recommendations. This may explain, in part, the prevalence of lameness measured as the prevalence of back arch (3.2%) and severe hind claw rotation (23%), hock lesions (44%), neck lesions (3.8%), broken tails (3%), dirty hind limbs (23%), and dirty udders (4.6%). Veterinarians and producers may use this information to compare farms with the industry averages and target areas in need of improvement. PMID:16454382
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Tékus, Valéria; Hajna, Zsófia; Borbély, Éva; Markovics, Adrienn; Bagoly, Teréz; Szolcsányi, János; Thompson, Victoria; Kemény, Ágnes; Helyes, Zsuzsanna; Goebel, Andreas
2014-02-01
The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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McGowan, C P; Skinner, J; Biewener, A A
2008-01-01
The aim of this study was to examine hind limb scaling of the musculoskeletal system in the Macropodoidea, the superfamily containing wallabies and kangaroos, to re-examine the effect of size on the locomotor mechanics and physiology of marsupial hopping. Morphometric musculoskeletal analyses were conducted of 15 species and skeletal specimens of 21 species spanning a size range from 0.8 to 80 kg that included representatives of 12 of the 16 extant genera of macropodoids. We found that unlike other groups, macropodoids are able to match force demands associated with increasing body size primarily through a combination of positive allometry in muscle area and muscle moment arms. Isometric scaling of primary hind limb bones suggests, however, that larger species experience relatively greater bone stresses. Muscle to tendon area ratios of the ankle extensors scale with strong positive allometry, indicating that peak tendon stresses also increase with increasing body size but to a lesser degree than previously reported. Consistent with previous morphological and experimental studies, large macropodoids are therefore better suited for elastic strain energy recovery but operate at lower safety factors, which likely poses an upper limit to body size. Scaling patterns for extant macropodoids suggest that extinct giant kangaroos (∼250 kg) were likely limited in locomotor capacity. PMID:18086129
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Hanaka, Megumi; Iba, Kousuke; Dohke, Takayuki; Kanaya, Kumiko; Okazaki, Shunichiro; Yamashita, Toshihiko
2018-05-01
Our recent studies demonstrated that regional bone loss in the unloaded hind limbs of tail-suspended mice triggered pain-like behaviors due to the acidic environment in the bone induced by osteoclast activation. The aims of the present study were to examine whether TRPV1, ASIC and P2X (known as nociceptors) are expressed in bone, and whether the antagonists to those receptors affect the expression of osteoblast and osteoclast regulators, and prevent the triggering of not only pain-like behaviors but also high bone turnover conditions in tail-suspension model mice. The hind limb-unloaded mice were subjected to tail suspension with the hind limbs elevated for 14days. The effects of the TRPV1, ASIC3, P2X2/3 antagonists on pain-like behaviors as assessed by the von Frey test, paw flick test and spontaneous pain scale; the expressions of TRPV1, ASICs, and P2X2 in the bone; and the effects of those antagonists on osteoblast and osteoclast regulators were examined. In addition, we evaluated the preventive effect of continuous treatment with a TRPV1 antagonist on the trigger for pain-like behavior and bone loss in tail-suspended mice. Pain-like behaviors were significantly improved by the treatment with TRPV1, ASIC, P2X antagonists; TRPV1, ASICs and P2X were expressed in the bone tissues; and the antagonists to these receptors down-regulated the expression of osteoblast and osteoclast regulators in tail-suspended mice. In addition, continuous treatment with a TRPV1 antagonist during tail-suspension prevented the induction of pain-like behaviors and regional bone loss in the unloaded hind limbs. We, therefore, believe that those receptor antagonists have a potential role in preventing the triggering of skeletal pain with associated regional bone metabolic disorder. Copyright © 2018 Elsevier Inc. All rights reserved.
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Karahan, M A; Yalcin, S; Aydogan, H; Büyükfirat, E; Kücük, A; Kocarslan, S; Yüce, H H; Taskın, A; Aksoy, N
2016-06-01
Curcumin and dexmedetomidine have been shown to have protective effects in ischemia-reperfusion injury on various organs. However, their protective effects on kidney tissue against ischemia-reperfusion injury remain unclear. We aimed to determine whether curcumin or dexmedetomidine prevents renal tissue from injury that was induced by hind limb ischemia-reperfusion in rats. Fifty rats were divided into five groups: sham, control, curcumin (CUR) group (200 mg/kg curcumin, n = 10), dexmedetomidine (DEX) group (25 μg/kg dexmedetomidine, n = 10), and curcumin-dexmedetomidine (CUR-DEX) group (200 mg/kg curcumin and 25 μg/kg dexmedetomidine). Curcumin and dexmedetomidine were administered intraperitoneally immediately after the end of 4 h ischemia, just 5 min before reperfusion. The extremity re-perfused for 2 h and then blood samples were taken and total antioxidant capacity (TAC), total oxidative status (TOS) levels, and oxidative stress index (OSI) were measured, and renal tissue samples were histopathologically examined. The TAC activity levels in blood samples were significantly lower in the control than the other groups (p < 0.01 for all comparisons). The TOS activity levels in blood samples were significantly higher in Control group and than the other groups (p < 0.01 for all comparison). The OSI were found to be significantly increased in the control group compared to others groups (p < 0.001 for all comparisons). Histopathological examination revealed less severe lesions in the sham, CUR, DEX, and CUR-DEX groups, compared with the control group (p < 0.01). Rat hind limb ischemia-reperfusion causes histopathological changes in the kidneys. Curcumin and dexmedetomidine administered intraperitoneally was effective in reducing oxidative stress and renal histopathologic injury in an acute hind limb I/R rat model.
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NASA Astrophysics Data System (ADS)
Li, J.; Rutkove, S. B.
2013-04-01
Electrical impedance myography (EIM) is a bioelectrical impedance technique focused on the assessment of neuromuscular diseases using tetrapolar surface arrays. Recently, we have shown that reproducible and sensitive EIM measurements can be made on the gastrocnemius muscle of the mouse hind limb and that these are sensitive to disease alterations. A dedicated array would help speed data acquisition and provide additional sensitivity to disease-induced alterations. A flexible electrode array was developed with electrode sizes of 1mm × 1mm by Parlex, Inc. Tetrapolar electrode sets were arranged both parallel to (longitudinal) and orthogonally to (transverse) the major muscle fiber direction of the gastrocnemius muscle. Measurements were made with a dedicated EIM system. A total of 11 healthy animals and 7 animals with spinal muscular atrophy (a form of motor neuron disease) were evaluated after the fur was completely removed with a depilatory agent from the hind limb. Standard electrophysiologic testing (compound motor action potential amplitude and motor unit number estimation) was also performed. The flexible electrode array demonstrated high repeatability in both the longitudinal and transverse directions in the healthy and diseased animals (with intraclass correlation coefficients of 0.94 and 0.89, respectively, for phase angle measured transversely). In addition, differences between healthy and diseased animals were identifiable. For example, the 50 kHz transverse phase angle was higher in the healthy as compared to the SMA animals (16.8° ± 0.5 vs. 14.3° ± 0.7, respectively) at 21 weeks of age (p = 0.01). Differences in anisotropy were also identifiable. Correlations to several standard neurophysiologic parameters also appeared promising. This novel flexible tetrapolar electrode array can be used on the mouse hind limb and provides multidirectional data that can be used to assess muscle health. This technique has the potential of finding widespread use in the evaluation of drug therapies in neuromuscular animal disease models.
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Dose Range-Finding Developmental Toxicity (Segment II) Study of WR242511 in Rabbits
1994-07-26
NA = Not applicable R = Right NK = Neck PT = Protruded tongue CP = Cleft palate N = No visible L = Left HL = Hind limb SB = Spina bifida CL = Cleft ... lip abnormalities M = Male FL = Fore limb SUBQ = Subcutaneous HT = Hematoma A = Alive F = Female DI = Digit P = Petechial EX = Exophthalmos D
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5-AZA-2'-DEOXYCYTIDINE INDUCED CYTOTOXICITY AND LONG BONE REDUCTION DEFECTS IN THE MURINE LIMB
The antineoplastic drug 5-aza-2'-deoxycytidine (dAZA) is a DNA hypomethylating agent that can be used to induce hind limb phocomelia in the offspring of CD-1 Swiss Webster mice. Previously, our laboratory investigated the possibility that dAZA induced alterations in gene express...
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2014-02-01
Sebesta JA, Blackbourne LH, Herbert GS, Kauvar DS, Baer DG, Walters TJ, Mullenix PS, Holcomb JB, 31 st Combat Support Hospital Research Group...K, Dixon P, Cowart J, Spencer J, Rasmussen TE. Hemorrhagic shock worsens neuromuscular recovery in a porcine model of hind limb vascular injury and
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Mumby, C; Bouts, T; Sambrook, L; Danika, S; Rees, E; Parry, A; Rendle, M; Masters, N; Weller, R
2013-10-05
Foot problems are extremely common in elephants and radiography is the only imaging method available but the radiographic anatomy has not been described in detail. The aims of this study were to develop a radiographic protocol for elephant feet using digital radiography, and to describe the normal radiographic anatomy of the Asian elephant front and hind foot. A total of fifteen cadaver foot specimens from captive Asian elephants were radiographed using a range of projections and exposures to determine the best radiographic technique. This was subsequently tested in live elephants in a free-contact setting. The normal radiographic anatomy of the Asian elephant front and hind foot was described with the use of three-dimensional models based on CT reconstructions. The projection angles that were found to be most useful were 65-70° for the front limb and 55-60° in the hind limb. The beam was centred 10-15 cm proximal to the cuticle in the front and 10-15 cm dorsal to the plantar edge of the sole in the hind foot depending on the size of the foot. The protocol developed can be used for larger-scale diagnostic investigations of captive elephant foot disorders, while the normal radiographic anatomy described can improve the diagnostic reliability of elephant feet radiography.
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NASA Astrophysics Data System (ADS)
Patel, Niravkumar D.; Mehta, Rahul; Ali, Nawab; Soulsby, Michael; Chowdhury, Parimal
2013-04-01
The aim of this study was to determine composition of the leg bone tissue of rats that were exposed to simulated microgravity by Hind-Limb Suspension (HLS) by tail for one week. The leg bones were cross sectioned, cleaned of soft tissues, dried and sputter coated, and then placed horizontally on the stage of a Scanning Electron Microscope (SEM) for analysis. Interaction of a 17.5 keV electron beam, incident from the vertical direction on the sample, generated images using two detectors. X-rays emitted from the sample during electron bombardment were measured with an Energy Dispersive Spectroscopy (EDS) feature of SEM using a liquid-nitrogen cooled Si(Li) detector with a resolution of 144 eV at 5.9 keV (25Mn Kα x-ray). Kα- x-rays from carbon, oxygen, phosphorus and calcium formed the major peaks in the spectrum. Relative percentages of these elements were determined using a software that could also correct for ZAF factors namely Z(atomic number), A(X-ray absorption) and F(characteristic fluorescence). The x-rays from the control groups and from the experimental (HLS) groups were analyzed on well-defined parts (femur, tibia and knee) of the leg bone. The SEM analysis shows that there are definite changes in the hydroxyl or phosphate group of the main component of the bone structure, hydroxyapatite [Ca10(PO4)6(OH)2], due to hind limb suspension. In a separate experiment, entire leg bones (both from HLS and control rats) were subjected to mechanical stress by mean of a variable force. The stress vs. strain graph was fitted with linear and polynomial function, and the parameters reflecting the mechanical strength of the bone, under increasing stress, were calculated. From the slope of the linear part of the graph the Young's modulus for HLS bones were calculated and found to be 2.49 times smaller than those for control bones.
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Büeler, Ariela Rosenzweig; Merbl, Yael; Kushnir, Yishai; Chai, Orit; Aizenberg, Itzhak; Horowitz, Igal; Matalon, Einat; Tam, Doron; Shamir, Merav H
2016-12-01
A 19-yr-old captive male Syrian bear ( Ursus arctos syriacus) presented with a right hind limb lameness that progressed to nonambulatory paraparesis over the course of 2 wk. When night enclosure confinement and a short course of glucocorticoids and antibiotics did not lead to improvement, radiographs were performed, followed by cerebrospinal fluid analysis and myelography, revealing a dynamic spinal cord compression at the level of T2-T3. Dorsal laminectomy of both T2 and T3 was performed to allow decompression. The bear recovered uneventfully with first sign of neurological improvement apparent at 10 days postoperatively. Following 6 mo of rehabilitation the bear was walking and using his hind limbs normally.
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Claw and limb disorders in 12 Norwegian beef-cow herds
Fjeldaas, Terje; Nafstad, Ola; Fredriksen, Bente; Ringdal, Grethe; Sogstad, Åse M
2007-01-01
Background The main aim of the study was to assess the prevalence of claw and limb disorders in Norwegian beef-cow herds. Methods Twenty-six herds with ≥15 cow-years were selected by computerized systematic assignment from the three most beef cattle-dense regions of Norway. The study population consisted of 12 herds with 28 heifers and 334 cows. The animals were trimmed and examined once by claw trimmers during the late winter and spring of 2003. The seven claw trimmers had been taught diagnosing and recording of claw lesions. Environment, feeding and management routines, age and breed, culling and carcass characteristics were also recorded. Results Lameness was recorded in 1.1% of the animals, and only in hind claws. Pericarpal swellings were recorded in one animal and peritarsal lesions in none. In total, claw and limb disorders including lameness were recorded in 29.6% of the animals, 4.1% with front and 28.2% with hind limb disorders, respectively. Most lesions were mild. Laminitis-related claw lesions were recorded in 18.0% of the animals and infectious lesions in 16.6%. The average claw length was 84 mm in front claws and 89 mm in hind claw. Both laminitis-related and infectious claw lesions were more prevalent with increasing age. Carcasses from animals with claw and limb disorders were on average 34 kg heavier than carcasses from animals without such disorders (p = 0.02). Our results also indicate association between some management factors and claw lesions. Conclusion The study shows that the prevalence of lameness was low in 12 Norwegian beef-cow herds compared to beef-cattle herds in other countries and also that there were less claw and limb disorders in these herds compared to foreign dairy-cattle herds. The prevalence of lameness and white-line fissures was approximately the same as in Norwegian dairy herds whereas less dermatitis, heel-horn erosions, haemorrhages of the sole and the white line and sole ulcers were recorded. PMID:17892582
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Bell, Marshall T.; Reece, T. Brett; Smith, Phillip D.; Mares, Joshua; Weyant, Michael J.; Cleveland, Joseph C.; Freeman, Kirsten A.; Fullerton, David A.; Puskas, Ferenc
2014-01-01
Background Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury. The current model demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion. Methods Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery. Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr. Results Mice that underwent sham surgery showed no observable hind limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post operative mortality. Conclusion Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved. PMID:24637534
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Bell, Marshall T; Reece, T Brett; Smith, Phillip D; Mares, Joshua; Weyant, Michael J; Cleveland, Joseph C; Freeman, Kirsten A; Fullerton, David A; Puskas, Ferenc
2014-03-03
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury. The current model demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion. Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery. Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr. Mice that underwent sham surgery showed no observable hind limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post operative mortality. Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved.
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Kamada, Takahito; Hashimoto, Masayuki; Murakami, Masazumi; Shirasawa, Hiroshi; Sakao, Seiichiro; Ino, Hidetoshi; Yoshinaga, Katsunori; Koshizuka, Shuhei; Moriya, Hideshige; Yamazaki, Masashi
2007-01-01
The aim of this study was to evaluate the efficacy in adult rat completely transected spinal cord of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to bone marrow stromal cells (BMSC). BMSC were infected with adenovirus vectors carrying β-galactosidase (AxCALacZ) or BDNF (AxCABDNF) genes. The T8 segment of spinal cord was removed and replaced by graft containing Matrigel alone (MG group) or Matrigel and BMSC infected by AxCALacZ (BMSC-LacZ group) or AxCABDNF (BMSC-BDNF group). Axons in the graft were evaluated by immunohistochemistry and functional recovery was assessed with BBB locomotor scale. In the BMSC-BDNF group, the number of fibers positive for growth associated protein-43, tyrosine hydroxylase, and calcitonin gene-related peptide was significantly larger than numbers found for the MG and BMSC-LacZ groups. Rats from BMSC-BDNF and BMSC-LacZ groups showed significant recovery of hind limb function compared with MG rats; however, there was no significant difference between groups in degree of functional recovery. These findings demonstrate that adenovirus vector-mediated ex vivo gene transfer of BDNF enhances the capacity of BMSC to promote axonal regeneration in this completely transected spinal cord model; however, BDNF failed to enhance hind limb functional recovery. Further investigation is needed to establish an optimal combination of cell therapy and neurotrophin gene transfer for cases of spinal cord injury. PMID:17885772
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NASA Astrophysics Data System (ADS)
Poole, Kristin M.; Patil, Chetan A.; Nelson, Christopher E.; McCormack, Devin R.; Madonna, Megan C.; Duvall, Craig L.; Skala, Melissa C.
2014-03-01
Peripheral arterial disease (PAD) is an atherosclerotic disease of the extremities that leads to high rates of myocardial infarction and stroke, increased mortality, and reduced quality of life. PAD is especially prevalent in diabetic patients, and is commonly modeled by hind limb ischemia in mice to study collateral vessel development and test novel therapies. Current techniques used to assess recovery cannot obtain quantitative, physiological data non-invasively. Here, we have applied hyperspectral imaging and swept source optical coherence tomography (OCT) to study longitudinal changes in blood oxygenation and vascular morphology, respectively, intravitally in the diabetic mouse hind limb ischemia model. Additionally, recommended ranges for controlling physiological variability in blood oxygenation with respect to respiration rate and body core temperature were determined from a control animal experiment. In the longitudinal study with diabetic mice, hyperspectral imaging data revealed the dynamics of blood oxygenation recovery distally in the ischemic footpad. In diabetic mice, there is an early increase in oxygenation that is not sustained in the long term. Quantitative analysis of vascular morphology obtained from Hessian-filtered speckle variance OCT volumes revealed temporal dynamics in vascular density, total vessel length, and vessel diameter distribution in the adductor muscle of the ischemic limb. The combination of hyperspectral imaging and speckle variance OCT enabled acquisition of novel functional and morphological endpoints from individual animals, and provides a more robust platform for future preclinical evaluations of novel therapies for PAD.
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Anitua, Eduardo; Pelacho, Beatriz; Prado, Roberto; Aguirre, José Javier; Sánchez, Mikel; Padilla, Sabino; Aranguren, Xabier L; Abizanda, Gloria; Collantes, María; Hernandez, Milagros; Perez-Ruiz, Ana; Peñuelas, Ivan; Orive, Gorka; Prosper, Felipe
2015-03-28
PRGF is a platelet concentrate within a plasma suspension that forms an in situ-generated fibrin-matrix delivery system, releasing multiple growth factors and other bioactive molecules that play key roles in tissue regeneration. This study was aimed at exploring the angiogenic and myogenic effects of PRGF on in vitro endothelial cells (HUVEC) and skeletal myoblasts (hSkMb) as well as on in vivo mouse subcutaneously implanted matrigel and on limb muscles after a severe ischemia. Human PRGF was prepared and characterized. Both proliferative and anti-apoptotic responses to PRGF were assessed in vitro in HUVEC and hSkMb. In vivo murine matrigel plug assay was conducted to determine the angiogenic capacity of PRGF, whereas in vivo ischemic hind limb model was carried out to demonstrate PRGF-driven vascular and myogenic regeneration. Primary HUVEC and hSkMb incubated with PRGF showed a dose dependent proliferative and anti-apoptotic effect and the PRGF matrigel plugs triggered an early and significant sustained angiogenesis compared with the control group. Moreover, mice treated with PRGF intramuscular infiltrations displayed a substantial reperfusion enhancement at day 28 associated with a fibrotic tissue reduction. These findings suggest that PRGF-induced angiogenesis is functionally effective at expanding the perfusion capacity of the new vasculature and attenuating the endogenous tissue fibrosis after a severe-induced skeletal muscle ischemia. Copyright © 2015 Elsevier B.V. All rights reserved.
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Effects of spaceflight and simulated weightlessness on longitudinal bone growth
NASA Technical Reports Server (NTRS)
Sibonga, J. D.; Zhang, M.; Evans, G. L.; Westerlind, K. C.; Cavolina, J. M.; Morey-Holton, E.; Turner, R. T.
2000-01-01
Indirect measurements have suggested that spaceflight impairs bone elongation in rats. To test this possibility, our laboratory measured, by the fluorochrome labeling technique, bone elongation that occurred during a spaceflight experiment. The longitudinal growth rate (LGR) in the tibia of rats in spaceflight experiments (Physiological Space Experiments 1, 3, and 4 and Physiological-Anatomical Rodent Experiment 3) and in two models of skeletal unloading (hind-limb elevation and unilateral sciatic neurotomy) were calculated. The effects of an 11 day spaceflight on gene expression of cartilage matrix proteins in rat growth plates were also determined by northern analysis and are reported for the first time in this study. Measurements of longitudinal growth indicate that skeletal unloading generally did not affect LGR, regardless of age, strain, gender, duration of unloading, or method of unloading. There was, however, one exception with 34% suppression in LGR detected in slow-growing, ovariectomized rats skeletally unloaded for 8 days by hind-limb elevation. This detection of reduced LGR by hind-limb elevation is consistent with changes in steady-state mRNA levels for type II collagen (-33%) and for aggrecan (-53%) that were detected in rats unloaded by an 11 day spaceflight. The changes detected in gene expression raise concern that spaceflight may result in changes in the composition of extracellular matrix, which could have a negative impact on conversion of growth-plate cartilage into normal cancellous bone by endochondral ossification.
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Lee, Dongwon; Bae, Soochan; Ke, Qingen; Lee, Jiyoo; Song, Byungjoo; Karumanchi, S Ananth; Khang, Gilson; Choi, Hak Soo; Kang, Peter M
2013-12-28
The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the generation of high level of hydrogen peroxide (H2O2). In this study, we report a novel diagnostic and therapeutic strategy for I/R injury based on H2O2-activatable copolyoxalate nanoparticles using a murine model of hind limb I/R injury. The nanoparticles are composed of hydroxybenzyl alcohol (HBA)-incorporating copolyoxalate (HPOX) that, in the presence of H2O2, degrades completely into three known and safe compounds, cyclohexanedimethanol, HBA and CO2. HPOX effectively scavenges H2O2 in a dose-dependent manner and hydrolyzes to release HBA which exerts intrinsic antioxidant and anti-inflammatory activities both in vitro and in vivo models of hind limb I/R. HPOX nanoparticles loaded with fluorophore effectively and robustly image H2O2 generated in hind limb I/R injury, demonstrating their potential for bioimaging of H2O2-associated diseases. Furthermore, HPOX nanoparticles loaded with anti-apoptotic drug effectively release the drug payload after I/R injury, exhibiting their effectiveness for a targeted drug delivery system for I/R injury. We anticipate that multifunctional HPOX nanoparticles have great potential as H2O2 imaging agents, therapeutics and drug delivery systems for H2O2-associated diseases. © 2013.
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Raisis, A L; Young, L E; Taylor, P M; Walsh, K P; Lekeux, P
2000-03-01
To use Doppler ultrasonography and single-fiber laser Doppler flowmetry (LDF) to evaluate blood flow in the dependent and nondependent hind limbs of anesthetized horses and to evaluate changes in femoral arterial blood flow and microvascular skeletal muscle perfusion in response to administration of phenylephrine hydrochloride or dobutamine hydrochloride. 6 healthy adult horses. Horses were anesthetized and positioned in left lateral recumbency. Doppler ultrasonography was used to measure velocity and volumetric flow in the femoral vessels. Single-fiber LDF was used to measure relative microvascular perfusion at a single site in the semimembranosus muscles. Phenylephrine or dobutamine was then administered to decrease or increase femoral arterial blood flow, and changes in blood flow and microvascular perfusion were recorded. Administration of phenylephrine resulted in significant decreases in femoral arterial and venous blood flows and cardiac output and significant increases in mean aortic blood pressure, systemic vascular resistance, and PCV. Administration of dobutamine resulted in significant increases in femoral arterial blood flow, mean aortic blood pressure, and PCV. Significant changes in microvascular perfusion were not detected. Results suggest that Doppler ultrasonography and single-fiber LDF can be used to study blood flows in the hind limbs of anesthetized horses. However, further studies are required to determine why changes in femoral arterial blood flows were not associated with changes in microvascular perfusion.
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Rothenberg, Alexis B; Berdon, Walter E; Woodard, J Carroll; Cowles, Robert A
2007-12-01
Vitamin A toxicity in the infant, which now occurs rarely from dietary overdosage, was recognized in the 1940s as painful periostitis with rare progression to premature closure of the lower limb epiphyses. Decades later, most cases of vitamin A-induced premature epiphyseal closure (physeal obliteration) occur in pediatric dermatologic patients given vitamin A analogues. This phenomenon resembles a strange disease discovered in more recent years in calves with closed epiphyses of the hind limbs, known as hyena disease. This was a mystery until proved to be caused by vitamin A toxicity from enriched grain that causes the calves to have short hind limbs that resemble those of a hyena and gait disturbance. This historical review links the human and veterinary literature in terms of vitamin A-induced epiphyseal closure using a case report format of a 16-month-old human infant with closed knee epiphyses and gait disturbance that is reminiscent of hyena disease seen in calves.
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Management of bilateral patellar luxation in an alpaca.
Abuja, Gustavo A; Kowaleski, Michael P; García-López, José M
2014-05-01
To report surgical management bilateral lateral patellar luxation in a mature alpaca using a combination of trochlear wedge recession (TWR), tibial tuberosity transposition (TTT), and joint capsule imbrication. Clinical case report. 9-year-old castrated male Alpaca. Bilateral, grade III/IV, lateral patellar luxation was identified by palpation, lameness examination and confirmed with radiography and ultrasonography. Surgical procedures were staged, with the left stifle treated first. Bilateral TWR, TTT, and joint capsule imbrication were performed. Outcome was assessed by radiography and follow up lameness examinations. An immediate improvement in weight bearing occurred after surgery of the left hind limb. Five months after initial surgery, right hind limb patella luxation was corrected. After surgery on the 2nd limb, the alpaca had progressive improvement in weight bearing during hospitalization. At 12 months, there were no signs of lameness and the alpaca had resumed normal activities. For bilateral lateral patellar luxation, a combination of TWR, TTT, and joint capsule imbrication resulted in excellent long-term outcome. © Copyright 2014 by The American College of Veterinary Surgeons.
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McCracken, K.G.; Harshman, J.; Mcclellan, D.A.; Afton, A.D.
1999-01-01
The unwitting inclusion of convergent characters in phylogenetic estimates poses a serious problem for efforts to recover phylogeny. Convergence is not inscrutable, however, particularly when one group of characters tracks phylogeny and another set tracks adaptive history. In such cases, convergent characters may be correlated with one or a few functional anatomical units and readily identifiable by using comparative methods. Stifftail ducks (Oxyurinae) offer one such opportunity to study correlated character evolution and function in the context of phylogenetic reconstruction. Morphological analyses place stifftail ducks as part of a large clade of diving ducks that includes the sea ducks (Mergini), Hymenolaimus, Merganetta, and Tachyeres, and possibly the pochards (Aythyini). Molecular analyses, on the other hand, place stifftails far from other diving ducks and suggest, moreover, that stifftails are polyphyletic. Mitochondrial cytochrome b gene sequences of eight stifftail species traditionally supposed to form a clade were compared with each other and with sequences from 50 other anseriform and galliform species. Stifftail ducks are not the sister group of sea ducks but lie outside the typical ducks (Anatinae). Of the four traditional stifftail genera, monophyly of Oxyura and its sister group relationship with Nomonyx are strongly supported. Heteronetta probably is the sister group of that clade, but support is weak. Biziura is not a true stifftail. Within Oxyura, Old World species (O. australis, O. leucocephala, O. mnccoa) appear to form a clade, with New World species (O. jamaicensis, O. vittata) branching basally. Incongruence between molecules and morphology is interpreted to be the result of adaptive specialization and functional convergence in the hind limbs of Biziura and true stifftails. When morphological characters are divided into classes, only hind-limb characters are significantly in conflict with the molecular tree. Likewise, null models of synonymous and nonsynonymous substitution based on patterns of codon-degeneracy and chemical dissimilarity indicate that the nucleotide and amino acid changes postulated by the molecular tree are more plausible than those postulated by the morphological tree. These findings teach general lessons about the utility of highly adaptive characters (in particular those related to foraging ecology) and underscore the problems that convergence can pose for attempts to recover phylogeny. They also demonstrate how the concept of natural data partitions and simple models of evolution (e.g., parsimony, likelihood, neutrality) can be used to test the accuracy of independent phylogenetic estimates and provide arguments in favor of one tree topology over another.
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Acute intraparenchymal spinal cord injury in a cat due to high-rise syndrome.
Cruz-Arámbulo, Robert; Nykamp, Stephanie
2012-03-01
A 9-year-old spayed female Bengal Red cat was evaluated for high-rise syndrome. The cat had paraplegia of the hind limbs, intact reflexes and pain perception, and hyperesthesia in the caudal thoracic area. Mentation, cranial nerve function, forelimb proprioceptive responses, and spinal reflexes were normal. There were no abnormalities on radiographs or computed tomography scan, but magnetic resonance imaging revealed a hyperintense intraparenchymal spinal cord lesion on T2-weighted and T2 fat saturation images.
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Thoracolumbar vertebral osteochondroma in a young dog.
Santen, D R; Payne, J T; Pace, L W; Kroll, R A; Johnson, G C
1991-10-15
Osteosarcoma was diagnosed in a 7-month-old female German Shepherd Dog with hind limb paresis. Radiography revealed a circumscribed calcified mass in the dorsal vertebral lamina at T13-L1 resulting in extradural compression of the spinal cord. Surgical excision of the mass resulted in gradual return to normal neurologic function. Four weeks after surgery, the dog became severely atactic after rolling onto its back. A chip fracture of T13 was identified, and the dog was euthanatized at the owners' request.
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Aversi-Ferreira, Roqueline A. G. M. F.; de Abreu, Tainá; Pfrimer, Gabriel A.; Silva, Sylla F.; Ziermann, Janine M.; Carneiro-e-Silva, Frederico O.; Tomaz, Carlos; Tavares, Maria Clotilde H.; Maior, Rafael S.; Aversi-Ferreira, Tales A.
2013-01-01
Capuchin monkeys are known to exhibit sporadic bipedalism while performing specific tasks, such as cracking nuts. The bipedal posture and locomotion cause an increase in the metabolic cost and therefore increased blood supply to lower limbs is necessary. Here, we present a detailed anatomical description of the capuchin arteries and veins of the pelvic limb of Sapajus libidinosus in comparison with other primates. The arterial pattern of the bearded capuchin hind limb is more similar to other quadrupedal Cebus species. Similarities were also found to the pattern observed in the quadruped Papio, which is probably due to a comparable pelvis and the presence of the tail. Sapajus' traits show fewer similarities when compared to great apes and modern humans. Moreover, the bearded capuchin showed unique patterns for the femoral and the short saphenous veins. Although this species switches easily from quadrupedal to bipedal postures, our results indicate that the bearded capuchin has no specific or differential features that support extended bipedal posture and locomotion. Thus, the explanation for the behavioral differences found among capuchin genera probably includes other aspects of their physiology. PMID:24396829
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Aversi-Ferreira, Roqueline A G M F; de Abreu, Tainá; Pfrimer, Gabriel A; Silva, Sylla F; Ziermann, Janine M; Carneiro-E-Silva, Frederico O; Tomaz, Carlos; Tavares, Maria Clotilde H; Maior, Rafael S; Aversi-Ferreira, Tales A
2013-01-01
Capuchin monkeys are known to exhibit sporadic bipedalism while performing specific tasks, such as cracking nuts. The bipedal posture and locomotion cause an increase in the metabolic cost and therefore increased blood supply to lower limbs is necessary. Here, we present a detailed anatomical description of the capuchin arteries and veins of the pelvic limb of Sapajus libidinosus in comparison with other primates. The arterial pattern of the bearded capuchin hind limb is more similar to other quadrupedal Cebus species. Similarities were also found to the pattern observed in the quadruped Papio, which is probably due to a comparable pelvis and the presence of the tail. Sapajus' traits show fewer similarities when compared to great apes and modern humans. Moreover, the bearded capuchin showed unique patterns for the femoral and the short saphenous veins. Although this species switches easily from quadrupedal to bipedal postures, our results indicate that the bearded capuchin has no specific or differential features that support extended bipedal posture and locomotion. Thus, the explanation for the behavioral differences found among capuchin genera probably includes other aspects of their physiology.
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Genomic Correlates of Relationship QTL Involved in Fore- versus Hind Limb Divergence in Mice
Pavlicev, Mihaela; Wagner, Günter P.; Noonan, James P.; Hallgrímsson, Benedikt; Cheverud, James M.
2013-01-01
Divergence of serially homologous elements of organisms is a common evolutionary pattern contributing to increased phenotypic complexity. Here, we study the genomic intervals affecting the variational independence of fore- and hind limb traits within an experimental mouse population. We use an advanced intercross of inbred mouse strains to map the loci associated with the degree of autonomy between fore- and hind limb long bone lengths (loci affecting the relationship between traits, relationship quantitative trait loci [rQTL]). These loci have been proposed to interact locally with the products of pleiotropic genes, thereby freeing the local trait from the variational constraint due to pleiotropic mutations. Using the known polymorphisms (single nucleotide polymorphisms [SNPs]) between the parental strains, we characterized and compared the genomic regions in which the rQTL, as well as their interaction partners (intQTL), reside. We find that these two classes of QTL intervals harbor different kinds of molecular variation. SNPs in rQTL intervals more frequently reside in limb-specific cis-regulatory regions than SNPs in intQTL intervals. The intQTL loci modified by the rQTL, in contrast, show the signature of protein-coding variation. This result is consistent with the widely accepted view that protein-coding mutations have broader pleiotropic effects than cis-regulatory polymorphisms. For both types of QTL intervals, the underlying candidate genes are enriched for genes involved in protein binding. This finding suggests that rQTL effects are caused by local interactions among the products of the causal genes harbored in rQTL and intQTL intervals. This is the first study to systematically document the population-level molecular variation underlying the evolution of character individuation. PMID:24065733
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Johnsen, Jacob; Pryds, Kasper; Salman, Rasha; Løfgren, Bo; Kristiansen, Steen Buus; Bøtker, Hans Erik
2016-03-01
Remote ischemic preconditioning (rIPC), induced by cycles of transient limb ischemia and reperfusion (IR), is cardioprotective. The optimal rIPC-algorithm is not established. We investigated the effect of cycle numbers and ischemia duration within each rIPC-cycle and the influence of effector organ mass on the efficacy of cardioprotection. Furthermore, the duration of the early phase of protection by rIPC was investigated. Using a tourniquet tightened at the inguinal level, we subjected C57Bl/6NTac mice to intermittent hind-limb ischemia and reperfusion. The rIPC-protocols consisted of (I) two, four, six or eight cycles, (II) 2, 5 or 10 min of ischemia in each cycle, (III) single or two hind-limb occlusions and (IV) 0.5, 1.5, 2.0 or 2.5 h intervals from rIPC to index cardiac ischemia. All rIPC algorithms were followed by 5 min of reperfusion. The hearts were subsequently exposed to 25 min of global ischemia and 60 min of reperfusion in an ex vivo Langendorff model. Cardioprotection was evaluated by infarct size and post-ischemic hemodynamic recovery. Four to six rIPC cycles yielded significant cardioprotection with no further protection by eight cycles. Ischemic cycles lasting 2 min offered the same protection as cycles of 5 min ischemia, whereas prolonged cycles lasting 10 min abrogated protection. One and two hind-limb preconditioning were equally protective. In our mouse model, the duration of protection by rIPC was 1.5 h. These findings indicate that the number and duration of cycles rather than the tissue mass exposed to rIPC determines the efficacy of rIPC.
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Quadrupedal rodent gait compensations in a low dose monoiodoacetate model of osteoarthritis.
Lakes, Emily H; Allen, Kyle D
2018-06-01
Rodent gait analysis provides robust, quantitative results for preclinical musculoskeletal and neurological models. In prior work, surgical models of osteoarthritis have been found to result in a hind limb shuffle-stepping gait compensation, while a high dose monoiodoacetate (MIA, 3 mg) model resulted in a hind limb antalgic gait. However, it is unknown whether the antalgic gait caused by MIA is associated with severity of degeneration from the high dosage or the whole-joint degeneration associated with glycolysis inhibition. This study evaluates rodent gait changes resulting from a low dose, 1 mg unilateral intra-articular injection of MIA compared to saline injected and naïve rats. Spatiotemporal and dynamic gait parameters were collected from a total of 42 male Lewis rats spread across 3 time points: 1, 2, and 4 weeks post-injection. To provide a detailed analysis of this low dose MIA model, gait analysis was used to uniquely quantify both fore and hind limb gait parameters. Our data indicate that 1 mg of MIA caused relatively minor degeneration and a shuffle-step gait compensation, similar to the compensation observed in prior surgical models. These data from a 1 mg MIA model show a different gait compensation compared to a previously studied 3 mg model. This 1 mg MIA model resulted in gait compensations more similar to a previously studied surgical model of osteoarthritis. Additionally, this study provides detailed 4 limb analysis of rodent gait that includes spatiotemporal and dynamic data from the same gait trial. These data highlight the importance of measuring dynamic data in combination with spatiotemporal data, since compensatory gait patterns may not be captured by spatial, temporal, or dynamic characterizations alone. Copyright © 2018 Elsevier B.V. All rights reserved.
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Reay, Daniel P; Yang, Michele; Watchko, Jon F; Daood, Molly; O'Day, Terrence L; Rehman, Khaleel K; Guttridge, Denis C; Robbins, Paul D; Clemens, Paula R
2011-09-01
The activation of nuclear factor κB (NF-κB) contributes to muscle degeneration that results from dystrophin deficiency in human Duchenne muscular dystrophy (DMD) and in the mdx mouse. In dystrophic muscle, NF-κB participates in inflammation and failure of muscle regeneration. Peptides containing the NF-κB Essential Modulator (NEMO) binding domain (NBD) disrupt the IκB kinase complex, thus blocking NF-κB activation. The NBD peptide, which is linked to a protein transduction domain to achieve in vivo peptide delivery to muscle tissue, was systemically delivered to mdx mice for 4 or 7 weeks to study NF-κB activation, histological changes in hind limb and diaphragm muscle and ex vivo function of diaphragm muscle. Decreased NF-κB activation, decreased necrosis and increased regeneration were observed in hind limb and diaphragm muscle in mdx mice treated systemically with NBD peptide, as compared to control mdx mice. NBD peptide treatment resulted in improved generation of specific force and greater resistance to lengthening activations in diaphragm muscle ex vivo. Together these data support the potential of NBD peptides for the treatment of DMD by modulating dystrophic pathways in muscle that are downstream of dystrophin deficiency. Published by Elsevier Inc.
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Studies on the mechanism of photodynamic-therapy-induced tumor destruction
NASA Astrophysics Data System (ADS)
Fingar, Victor H.; Wieman, Thomas J.
1990-07-01
There exists little doubt that profound changes occur to both tumor and normal tissue microvasculature during photodynamic therapy, and that these changes are important in the process of tumor destruction. We hypothesize that singlet oxygen, produced during light activation of photosensitizer, interacts with cellular membranes and induces the release of arachidonic acid metabolites, notably thromboxane, into the intravascular environment. This leads to vasoconstriction, platelet aggregation, and hemostasis. To test this hypothesis, we have measured the release of thromboxane into serum as a function of porphyrin and light doses used in phototherapy. Sprague Dawley rats bearing chondrosarcoma in the right hind limb were injected with 0-25 mg/kg Photofrin IP'. A catheter was implanted in the carotid artery 24 h later, and the hind limb exposed to 0-135 J/cm2 630 nm light. Immediately after treatment, serum was collected and thromboxane levels were measured by radioimmunoassay. We found significant increases in systemic thromboxane concentrations following phototherapy at the highest porphyrin and light doses, compared to drug and light controls. The administration of indomethacin (10 mg/kg i.p.) prior to treatment suppressed the release of thromboxane from tumor and normal tissues and inhibited hemostasis and tumor response to phototherapy. These studies have reinforced the important role of arachidonic acid metabolites in producing vascular damage during phototherapy.
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Il'ina-Kakueva, E I
2002-01-01
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.
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Bacterial infective arthritis of the coxofemoral joint in dogs with hip dysplasia.
Benzioni, H; Shahar, R; Yudelevitch, S; Milgram, J
2008-01-01
The objective of this study was to describe seven cases of unilateral bacterial infective coxarthritis from a total of 19 cases of bacterial infective arthritis (BIA), presenting over a two year period. We recorded the history, clinical signs, diagnostic process, treatment and clinical outcome in these cases. The data were obtained from medical records, review of the radiographs, and telephone follow-up with the owners. All of the dogs in this study had severe chronic osteoarthritis secondary to hip dysplasia, which caused periodic hind limb lameness. They were all admitted with severe acute hind-limb lameness. Pelvic radiographs were performed under general anaesthesia shortly after presentation, followed immediately by arthrocentesis of the affected joint. The synovial fluid was evaluated microscopically by direct smear and a sample was sent for culture and sensitivity. An attempt was not made to drain or lavage the affected joint during the course of treatment. The initial choice of antibiotics was empiric and subsequently modified, as required, based on the sensitivity results. Four of the dogs showed a rapid return to weight-bearing after the initiation of antibiotic treatment, and all of the patients returned to their pre-BIA level of function. Neither recurrent infections nor any adverse sequela requiring further intervention were reported by the owners on telephone follow-up.
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Takikawa, Makoto; Nakamura, Shingo; Ishihara, Masayuki; Takabayashi, Yuki; Fujita, Masanori; Hattori, Hidemi; Kushibiki, Toshihiro; Ishihara, Miya
2015-06-15
We produced fibroblast growth factor (FGF)-2-containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles (FGF-2 + F/P NPs). The purpose of this study was to evaluate the effectiveness of the local administration of FGF-2 + F/P NPs on repairing crush syndrome (CS)-injured lesions after compression release using a nonlethal and reproducible CS injury rat model. The hind limbs of the anesthetized rats were compressed for 6 h using 3.6 kg blocks, as previously described. The effects of administering FGF-2 + F/P NPs (group A), F/P NPs alone (group B), FGF-2 alone (group C), and saline (control; group D) were examined. Motor function, surface blood flow in the hind limbs, and the wet/dry weight ratio in the tibialis anterior muscle were examined for 1-28 d after the compression release. Histologic analyses were also performed. At the middle and late stages (3-28 d after the compression release), group A had higher scores in the motor function, improved blood flow, increased number of blood vessels, and faster recovered muscle tissue, compared with the other groups. There was no significant difference in enhanced edema in the tibialis anterior muscle among all groups. The local administration of FGF-2 + F/P NPs to a CS-injured lesion was effective in repairing damaged muscle tissue after compression release. Copyright © 2015 Elsevier Inc. All rights reserved.
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Gordon-Evans, Wanda J; Dunning, Diane; Johnson, Ann L; Knap, Kim E
2011-07-01
To determine whether carprofen, a commercially available NSAID, would decrease perceived exertion and signs of pain in dogs and therefore increase muscle mass and hind limb function without decreasing range of motion after lateral fabellar suture stabilization. Randomized, blinded, controlled clinical trial. 35 dogs with cranial cruciate ligament rupture and lateral fabellar suture stabilization followed by rehabilitation. All dogs underwent surgical stabilization of cranial cruciate ligament rupture by placement of a lateral fabellar suture. Dogs received carprofen (2.2 mg/kg [1 mg/lb], PO, q 12 h) for the first 7 days after surgery and underwent concentrated rehabilitation exercises during weeks 3, 5, and 7 after surgery. Eighteen dogs also received carprofen (2.2 mg/kg, PO, q 12 h) during the weeks of concentrated rehabilitation. Outcomes were measured by a single investigator, who was blinded to group assignments, using pressure platform gait analysis, goniometry, thigh circumference, and mean workout speed at a consistent level of exertion. There were no differences between the 2 groups in ground reaction forces, thigh circumference, or exertion (mean workout speed) over time or at any individual time point. However, both groups improved significantly over time for all outcome measures. Providing carprofen to dogs during concentrated rehabilitation after lateral fabellar suture stabilization did not improve hind limb function, range of motion, or thigh circumference, nor did it decrease perceived exertion, compared with control dogs. Carprofen was not a compulsory component of a physical therapy regimen after lateral fabellar suture stabilization.
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Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats.
Ge, Li; Wei, Li-Hua; Du, Chang-Qing; Song, Guo-Hua; Xue, Ya-Zhuo; Shi, Hao-Shen; Yang, Ming; Yin, Xin-Xin; Li, Run-Ting; Wang, Xue-Er; Wang, Zhen; Song, Wen-Gang
2017-06-27
To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11-T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells.
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Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats
Ge, Li; Wei, Li-Hua; Du, Chang-Qing; Song, Guo-Hua; Xue, Ya-Zhuo; Shi, Hao-Shen; Yang, Ming; Yin, Xin-Xin; Li, Run-Ting; Wang, Xue-er; Wang, Zhen; Song, Wen-Gang
2017-01-01
To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11–T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells. PMID:28404953
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Khumsap, S; Clayton, H M; Lanovaz, J L
2001-06-01
To measure the effect of subject velocity on hind limb ground reaction force variables at the walk and to use the data to predict the force variables at different walking velocities in horses. 5 clinically normal horses. Kinematic and force data were collected simultaneously. Each horse was led over a force plate at a range of walking velocities. Stance duration and force data were recorded for the right hind limb. To avoid the effect of horse size on the outcome variables, the 8 force variables were standardized to body mass and height at the shoulders. Velocity was standardized to height at the shoulders and expressed as velocity in dimensionless units (VDU). Stance duration was also expressed in dimensionless units (SDU). Simple regression analysis was performed, using stance duration and force variables as dependent variables and VDU as the independent variable. Fifty-six trials were recorded with velocities ranging from 0.24 to 0.45 VDU (0.90 to 1.72 m/s). Simple regression models between measured variables and VDU were significant (R2 > 0.69) for SDU, first peak of vertical force, dip between the 2 vertical force peaks, vertical impulse, and timing of second peak of vertical force. Subject velocity affects vertical force components only. In the future, differences between the forces measured in lame horses and the expected forces calculated for the same velocity will be studied to determine whether the equations can be used as diagnostic criteria.
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Pressure hyperalgesia in hind limb suspended rats.
Chowdhury, Parimal; Soulsby, Michael E; Jayroe, John; Akel, Nisreen S; Gaddy, Dana; Dobretsov, Maxim
2011-10-01
Spaceflight and simulated microgravity often associate with pain and prediabetes. Streptozotocin (STZ)-induced moderate insulinopenia rat models of prediabetes result in pressure hyperalgesia. The current study was designed to determine whether or not simulated microgravity induced by hind limb suspension (HLS) in rats lead to insulinopenia and pressure hyperalgesia. Adult male rats were divided into HLS (N = 20) and control, non-suspended (N = 16) groups, respectively. Bodyweight and hind limb pressure-pain withdrawal threshold (PPT) were measured at regular 2-5 d intervals for 7 d before and 12-13 d after HLS. Bodyweights and PPT of control and HLS animals measured on the day of suspension were not different. During the experiment, control rats gained 61 +/- 5 g, but maintained their PPT at the baseline level. Suspended rats gained 26 +/- 3 g of weight during the same time period and their PPT declined from 105 +/- 6 g to 84 +/- 6 g. Neither blood glucose nor pancreatic islet density and area were affected by HLS. However, the random plasma insulin of HLS rats was significantly lower than that of control animals (1.6 +/- 0.2 vs. 2.7 +/- 0.2 ng ml(-1)). The observed relationship between insulin and PPT levels in the HLS rats was similar to that observed in rats with STZ-induced insulinopenia. These data suggest that moderate insulinopenia may affect the rat's sensitivity to deep pressure directly, without affecting glucose homeostasis. In addition, our data suggest that HLS rats may develop peripheral neuropathy.
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Leftin, Avigdor; Roussel, Tangi; Frydman, Lucio
2014-01-01
Measuring metabolism's time- and space-dependent responses upon stimulation lies at the core of functional magnetic resonance imaging. While focusing on water's sole resonance, further insight could arise from monitoring the temporal responses arising from the metabolites themselves, in what is known as functional magnetic resonance spectroscopy. Performing these measurements in real time, however, is severely challenged by the short functional timescales and low concentrations of natural metabolites. Dissolution dynamic nuclear polarization is an emerging technique that can potentially alleviate this, as it provides a massive sensitivity enhancement allowing one to probe low-concentration tracers and products in a single-scan. Still, conventional implementations of this hyperpolarization approach are not immediately amenable to the repeated acquisitions needed in real-time functional settings. This work proposes a strategy for functional magnetic resonance of hyperpolarized metabolites that bypasses this limitation, and enables the observation of real-time metabolic changes through the synchronization of stimuli-triggered, multiple-bolus injections of the metabolic tracer 13C1-pyruvate. This new approach is demonstrated with paradigms tailored to reveal in vivo thresholds of murine hind-limb skeletal muscle activation, involving the conversion of 13C1-pyruvate to 13C1-lactate and 13C1-alanine. These functional hind-limb studies revealed that graded skeletal muscle stimulation causes commensurate increases in glycolytic metabolism in a frequency- and amplitude-dependent fashion, that can be monitored on the seconds/minutes timescale using dissolution dynamic nuclear polarization. Spectroscopic imaging further allowed the in vivo visualization of uptake, transformation and distribution of the tracer and products, in fast-twitch glycolytic and in slow-twitch oxidative muscle fiber groups. While these studies open vistas in time and sensitivity for metabolic functional magnetic resonance studies in muscle, the simplicity of our approach makes this technique amenable to a wide range of functional metabolic tracer studies.
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Hilliard, A.; Stott, C.; Wright, S.; Guy, G.; Pryce, G.; Al-Izki, S.; Bolton, C.; Giovannoni, G.
2012-01-01
This study investigated the antispasticity potential of Sativex in mice. Chronic relapsing experimental allergic encephalomyelitis was induced in adult ABH mice resulting in hind limb spasticity development. Vehicle, Sativex, and baclofen (as a positive control) were injected intravenously and the “stiffness” of limbs assessed by the resistance force against hind limb flexion. Vehicle alone caused no significant change in spasticity. Baclofen (5 mg/kg) induced approximately a 40% peak reduction in spasticity. Sativex dose dependently reduced spasticity; 5 mg/kg THC + 5 mg/kg CBD induced approximately a 20% peak reduction; 10 mg/kg THC + 10 mg/kg CBD produced approximately a 40% peak reduction in spasticity. Sativex has the potential to reduce spasticity in an experimental mouse model of multiple sclerosis (MS). Baclofen reduced spasticity and served as a positive control. Sativex (10 mg/kg) was just as effective as baclofen, providing supportive evidence for Sativex use in the treatment of spasticity in MS. PMID:22928118
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Patel, Niravkumar D.; Mehta, Rahul; Ali, Nawab
2013-04-19
The aim of this study was to determine composition of the leg bone tissue of rats that were exposed to simulated microgravity by Hind-Limb Suspension (HLS) by tail for one week. The leg bones were cross sectioned, cleaned of soft tissues, dried and sputter coated, and then placed horizontally on the stage of a Scanning Electron Microscope (SEM) for analysis. Interaction of a 17.5 keV electron beam, incident from the vertical direction on the sample, generated images using two detectors. X-rays emitted from the sample during electron bombardment were measured with an Energy Dispersive Spectroscopy (EDS) feature of SEM usingmore » a liquid-nitrogen cooled Si(Li) detector with a resolution of 144 eV at 5.9 keV ({sub 25}Mn K{sub {alpha}} x-ray). K{sub {alpha}}- x-rays from carbon, oxygen, phosphorus and calcium formed the major peaks in the spectrum. Relative percentages of these elements were determined using a software that could also correct for ZAF factors namely Z(atomic number), A(X-ray absorption) and F(characteristic fluorescence). The x-rays from the control groups and from the experimental (HLS) groups were analyzed on well-defined parts (femur, tibia and knee) of the leg bone. The SEM analysis shows that there are definite changes in the hydroxyl or phosphate group of the main component of the bone structure, hydroxyapatite [Ca{sub 10}(PO{sub 4}){sub 6}(OH){sub 2}], due to hind limb suspension. In a separate experiment, entire leg bones (both from HLS and control rats) were subjected to mechanical stress by mean of a variable force. The stress vs. strain graph was fitted with linear and polynomial function, and the parameters reflecting the mechanical strength of the bone, under increasing stress, were calculated. From the slope of the linear part of the graph the Young's modulus for HLS bones were calculated and found to be 2.49 times smaller than those for control bones.« less
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A Porcine Model for Endolaparoscopic Abdominal Aortic Repair and Endoscopic Training
Zarins, Christopher K.; Daunt, David A.; Coleman, Leslie A.; Saenz, Yamil; Fogarty, Thomas J.; Hermann, George D.; Nezhat, Camran R.; Olsen, Eric K.
2003-01-01
Objective: The goals of this laboratory model were to evaluate the performance of the surgical team and endolaparoscopic techniques in the porcine model of infrarenal abdominal aortic repair. Methods: Twenty-four pigs underwent full endolaparoscopic aorto-aortic graft implantation with voice-activated computerized robotics. The first group of 10 pigs (acute) was sacrificed while under anesthesia at 0.5 hours (5 animals) and 2 hours (5 animals). The second group of 14 pigs (survival) were recovered from anesthesia and maintained for 7 hours (5 pigs) and 7 days (9 pigs) prior to sacrifice. Survival animals were observed for evidence of hind limb dysfunction. All grafts were visually inspected at autopsy. Results: All animals survived the operation. All grafts were successfully implanted, and all were patent with intact anastomoses at autopsy. Mean aortic clamp time for each group was as follows: acute, 92.9±28.04 minutes; survival, 59.6±13.8 minutes; P=0.0008. Total operative time for each group was as follows: acute, 179±39.6 minutes; survival, 164.6±48 minutes; P=0.44 ns. Estimated blood loss for each group was as follows: acute, 214±437.8 mL; survival 169.2±271 mL; P=0.76 ns. The following outcomes were observed: 1 animal died from respiratory arrest; 1 animal suffered motor sensory dysfunction of the hind limbs (spinal cord ischemia); significant bleeding occurred in 6 of 24 pigs; 8 of the 9 seven-day survivors required minimal pain medication and had normal hind limb function. Conclusions: The reduction in aortic clamp time, total operative time, and blood loss as the study progressed indicate the feasibility of this surgical protocol and the maturation of the learning process, which is paramount in prevention of 2 main sources of morbidity: bleeding and spinal cord ischemia. The reduction in aortic clamp time between the acute and survival groups was dramatic and statistically significant. An intensive formal training program combining dry and live surgical laboratories is deemed essential for the development of endoscopic skill sets necessary for this challenging procedure. PMID:12856843
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Bone morphology of the hind limbs in two caviomorph rodents.
de Araújo, F A P; Sesoko, N F; Rahal, S C; Teixeira, C R; Müller, T R; Machado, M R F
2013-04-01
In order to evaluate the hind limbs of caviomorph rodents a descriptive analysis of the Cuniculus paca (Linnaeus, 1766) and Hydrochoerus hydrochaeris (Linnaeus, 1766) was performed using anatomical specimens, radiography, computed tomography (CT) and full-coloured prototype models to generate bone anatomy data. The appendicular skeleton of the two largest rodents of Neotropical America was compared with the previously reported anatomical features of Rattus norvegicus (Berkenhout, 1769) and domestic Cavia porcellus (Linnaeus, 1758). The structures were analyzed macroscopically and particular findings of each species reported. Features including the presence of articular fibular projection and lunulae were observed in the stifle joint of all rodents. Imaging aided in anatomical description and, specifically in the identification of bone structures in Cuniculus paca and Hydrochoerus hydrochaeris. The imaging findings were correlated with the anatomical structures observed. The data may be used in future studies comparing these animals to other rodents and mammalian species. © 2012 Blackwell Verlag GmbH.
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Negredo, Pilar; Rivero, José-Luis L; González, Beatriz; Ramón-Cueto, Almudena; Manso, Rafael
2008-01-01
Paralysed skeletal muscle of rats with spinal cord injury (SCI) undergoes atrophy and a switch in gene expression pattern which leads to faster, more fatigable phenotypes. Olfactory ensheathing glia (OEG) transplants have been reported to promote axonal regeneration and to restore sensory-motor function in animals with SCI. We hypothesized that OEG transplants could attenuate skeletal muscle phenotypic deterioration and that this effect could underlie the functional recovery observed in behavioural tests. A variety of morphological, metabolic and molecular markers were assessed in soleus (SOL) and extensor digitorum longus (EDL) muscles of spinal cord transected (SCT), OEG-transplanted rats 8 months after the intervention and compared with non-transplanted SCT rats and sham-operated (without SCT) controls (C). A multivariate analysis encompassing all the parameters indicated that OEG-transplanted rats displayed skeletal muscle phenotypes intermediate between non-transplanted and sham-operated controls, but different from both. A high correlation was observed between behaviourally tested sensory-motor functional capacity and expression level of slow- and fast-twitch hind limb skeletal muscle phenotypic markers, particularly the histochemical glycerol-3-phosphate dehydrogenase activity (−0.843, P < 0.0001) and the fraction of variant 2s of the slow regulatory myosin light chain isoform (0.848, P < 0.0001) in SOL. Despite the mean overall effect of OEG transplants in patterning skeletal muscle protein expression towards normal, in 6 out of 9 animals they appeared insufficient to overcome fibre type switching and to support a consistent and generalized long-term maintenance of normal skeletal muscle characteristics. The interplay of OEG and exercise-mediated neurotrophic actions is a plausible mechanism underlying OEG transplantation effects on paralysed skeletal muscle. PMID:18372308
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Burgess, M Loring; Schmitt, Daniel; Zeininger, Angel; McFarlin, Shannon C; Zihlman, Adrienne L; Polk, John D; Ruff, Christopher B
2016-09-01
Previous studies suggest that the postures habitually adopted by an animal influence the mechanical loading of its long bones. Relatively extended limb postures in larger animals should preferentially reduce anteroposterior (A-P) relative to mediolateral (M-L) bending of the limb bones and therefore decrease A-P/M-L rigidity. We test this hypothesis by examining growth-related changes in limb bone structure in two primate taxa that differ in ontogenetic patterns of joint posture. Knee and elbow angles of adult and immature vervets (Chlorocebus aethiops, n = 16) were compared to published data for baboons (Papio hamadryas ursinus, n = 33, Patel et al., ). Ontogenetic changes in ratios of A-P/M-L bending rigidity in the femur and humerus were compared in skeletal samples (C. aethiops, n = 28; P. cynocephalus, n = 39). Size changes were assessed with linear regression, and age group differences tested with ANOVA. Only the knee of baboons shows significant postural change, becoming more extended with age and mass. A-P/M-L bending rigidity of the femur decreases during ontogeny in immature and adult female baboons only. Trends in the humerus are less marked. Adult male baboons have higher A-P/M-L bending rigidity of the femur than females. The hypothesized relationship between more extended joints and reduced A-P/M-L bending rigidity is supported by our results for immature and adult female baboon hind limbs, and the lack of significant age changes in either parameter in forelimbs and vervets. Adult males of both species depart from general ontogenetic trends, possibly due to socially mediated behavioral differences between sexes. Am J Phys Anthropol 161:72-83, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Computed tomographic contrast tenography of the digital flexor tendon sheath of the equine hindlimb.
Agass, Rachel; Dixon, Jonathon; Fraser, Barny
2018-05-01
Pre-surgical investigation of digital flexor tendon sheath pathology remains challenging with current standard imaging techniques. The aim of this prospective, anatomical, pilot study was to describe the anatomy of the equine hind limb digital flexor tendon sheath using a combination of computed tomography (CT) and computed tomographic contrast tenography in clinically normal cadaver limbs. Ten pairs of hind limbs with no external abnormalities were examined from the level of the tarsometatarsal joint distally. Limbs initially underwent non-contrast CT examination using 120 kVp, 300 mAs, and 1.5 mm slice thickness. Sixty millilitres of ioversol iodinated contrast media and saline (final concentration 100 mg/ml) were injected using a basilar sesamoidean approach. The computed tomographic contrast tenography examination was then repeated, before dissection of the specimens to compare gross and imaging findings. The combined CT and computed tomographic contrast tenography examinations provided excellent anatomical detail of intra-thecal structures. The borders of the superficial and deep digital flexor tendons, and the manica flexoria were consistently identifiable in all limbs. Detailed anatomy including that of the mesotenons, two of which are previously undescribed, and the plantar annular ligament were also consistently identifiable. Dissection of all 10 pairs of limbs revealed there to be no pathology, in accordance with the imaging findings. In conclusion, the combination of CT and computed tomographic contrast tenography may be useful adjunctive diagnostic techniques to define digital flexor tendon sheath pathology prior to surgical exploration in horses. © 2017 American College of Veterinary Radiology.
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Smith, N Adam; Clarke, Julia A
2014-02-01
Although studies of osteological morphology, gross myology, myological histology, neuroanatomy, and wing-scaling have all documented anatomical modifications associated with wing-propelled diving, the osteohistological study of this highly derived method of locomotion has been limited to penguins. Herein we present the first osteohistological study of the derived forelimbs and hind limbs of wing-propelled diving Pan-Alcidae (Aves, Charadriiformes). In addition to detailing differences between wing-propelled diving charadriiforms and nondiving charadriiforms, microstructural modifications to the humeri, ulnae and femora of extinct flightless pan-alcids are contrasted with those of volant alcids. Histological thin-sections of four species of pan-alcids (Alca torda, †Alca grandis, †Pinguinus impennis, †Mancalla cedrosensis) and one outgroup charadriiform (Stercorarius longicaudus) were compared. The forelimb bones of wing-propelled diving charadriiforms were found to have significantly thicker (∼22%) cortical bone walls. Additionally, as in penguins, the forelimbs of flightless pan-alcids are found to be osteosclerotic. However, unlike the pattern documented in penguins that display thickened cortices in both forelimbs and hind limbs, the forelimb and hind limb elements of pan-alcids display contrasting microstructural morphologies with thickened forelimb cortices and relatively thinner femoral cortices. Additionally, the identification of medullary bone in the sampled †Pinguinus impennis specimen suggests that further osteohistological investigation could provide an answer to longstanding questions regarding sexual dimorphism of Great Auks. Finally, these results suggest that it is possible to discern volant from flightless wing-propelled divers from fragmentary fossil remains. Copyright © 2013 Wiley Periodicals, Inc.
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Local and systemic vasodilatory effects of low molecular weight S-nitrosothiols.
Liu, Taiming; Schroeder, Hobe J; Wilson, Sean M; Terry, Michael H; Romero, Monica; Longo, Lawrence D; Power, Gordon G; Blood, Arlin B
2016-02-01
S-nitrosothiols (SNOs) such as S-nitroso-L-cysteine (L-cysNO) are endogenous compounds with potent vasodilatory activity. During circulation in the blood, the NO moiety can be exchanged among various thiol-containing compounds by S-transnitrosylation, resulting in SNOs with differing capacities to enter the cell (membrane permeability). To determine whether the vasodilating potency of SNOs is dependent upon membrane permeability, membrane-permeable L-cysNO and impermeable S-nitroso-D-cysteine (D-cysNO) and S-nitroso-glutathione (GSNO) were infused into one femoral artery of anesthetized adult sheep while measuring bilateral femoral and systemic vascular conductances. L-cysNO induced vasodilation in the infused hind limb, whereas D-cysNO and GSNO did not. L-cysNO also increased intracellular NO in isolated arterial smooth muscle cells, whereas GSNO did not. The infused SNOs remained predominantly in a low molecular weight form during first-passage through the hind limb vasculature, but were converted into high molecular weight SNOs upon systemic recirculation. At systemic concentrations of ~0.6 μmol/L, all three SNOs reduced mean arterial blood pressure by ~50%, with pronounced vasodilation in the mesenteric bed. Pharmacokinetics of L-cysNO and GSNO were measured in vitro and in vivo and correlated with their hemodynamic effects, membrane permeability, and S-transnitrosylation. These results suggest local vasodilation by SNOs in the hind limb requires membrane permeation, whereas systemic vasodilation does not. The systemic hemodynamic effects of SNOs occur after equilibration of the NO moiety amongst the plasma thiols via S-transnitrosylation. Copyright © 2015 Elsevier Inc. All rights reserved.
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Analgesic efficacy of butorphanol and morphine in bearded dragons and corn snakes.
Sladky, Kurt K; Kinney, Matthew E; Johnson, Stephen M
2008-07-15
To test the hypothesis that administration of butorphanol or morphine induces antinociception in bearded dragons and corn snakes. Prospective crossover study. 12 juvenile and adult bearded dragons and 13 corn snakes. Infrared heat stimuli were applied to the plantar surface of bearded dragon hind limbs or the ventral surface of corn snake tails. Thermal withdrawal latencies (TWDLs) were measured before (baseline) and after SC administration of physiologic saline (0.9% NaCl) solution (equivalent volume to opioid volumes), butorphanol tartrate (2 or 20 mg/kg [0.91 or 9.1 mg/lb]), or morphine sulfate (1, 5, 10, 20, or 40 mg/kg [0.45, 2.27, 4.5, 9.1, or 18.2 mg/lb]). For bearded dragons, butorphanol (2 or 20 mg/kg) did not alter hind limb TWDLs at 2 to 24 hours after administration. However, at 8 hours after administration, morphine (10 and 20 mg/kg) significantly increased hind limb TWDLs from baseline values (mean +/- SEM maximum increase, 2.7+/-0.4 seconds and 2.8+/-0.9 seconds, respectively). For corn snakes, butorphanol (20 mg/kg) significantly increased tail TWDLs at 8 hours after administration (maximum increase from baseline value, 3.0+/-0.8 seconds); the low dose had no effect. Morphine injections did not increase tail TWDLs at 2 to 24 hours after administration. Compared with doses used in most mammalian species, high doses of morphine (but not butorphanol) induced analgesia in bearded dragons, whereas high doses of butorphanol (but not morphine) induced analgesia in corn snakes.
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Understanding hind limb lameness signs in horses using simple rigid body mechanics.
Starke, S D; May, S A; Pfau, T
2015-09-18
Hind limb lameness detection in horses relies on the identification of movement asymmetry which can be based on multiple pelvic landmarks. This study explains the poorly understood relationship between hind limb lameness pointers, related to the tubera coxae and sacrum, based on experimental data in context of a simple rigid body model. Vertical displacement of tubera coxae and sacrum was quantified experimentally in 107 horses with varying lameness degrees. A geometrical rigid-body model of pelvis movement during lameness was created in Matlab. Several asymmetry measures were calculated and contrasted. Results showed that model predictions for tubera coxae asymmetry during lameness matched experimental observations closely. Asymmetry for sacrum and comparative tubera coxae movement showed a strong association both empirically (R(2)≥ 0.92) and theoretically. We did not find empirical or theoretical evidence for a systematic, pronounced adaptation in the pelvic rotation pattern with increasing lameness. The model showed that the overall range of movement between tubera coxae does not allow the appreciation of asymmetry changes beyond mild lameness. When evaluating movement relative to the stride cycle we did find empirical evidence for asymmetry being slightly more visible when comparing tubera coxae amplitudes rather than sacrum amplitudes, although variation exists for mild lameness. In conclusion, the rigidity of the equine pelvis results in tightly linked movement trajectories of different pelvic landmarks. The model allows the explanation of empirical observations in the context of the underlying mechanics, helping the identification of potentially limited assessment choices when evaluating gait. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Chicken-sized oviraptorid dinosaurs from central China and their ontogenetic implications.
Lü, Junchang; Currie, Philip J; Xu, Li; Zhang, Xingliao; Pu, Hanyong; Jia, Songhai
2013-02-01
Oviraptorids are a group of specialized non-avian theropod dinosaurs that were generally one to 8 m in body length. New specimens of baby oviraptorids from the Late Cretaceous of Henan Province are some of the smallest individuals known. They include diagnostic characters such as the relative position of the antorbital fenestra and the external naris, distinct opening in the premaxilla anteroventral to the external naris, antorbital fossa partly bordered by premaxilla posterodorsally, lacrimal process of premaxilla does not contact the anterodorsal process of the lacrimal, parietal almost as long as frontal; in dorsal view, posterior margin forms a straight line between the postzygapophyses in each of the fourth and fifth cervicals; femur longer than ilium. They also elucidate the ontogenetic processes of oviraptorids, including fusion of cranial elements and changes in relative body proportions. Hind limb proportions are constant in oviraptorids, regardless of absolute body size or ontogenetic stage. This suggests a sedentary lifestyle that did not involve the pursuit of similar-sized prey. The functional implications for bite force and therefore dietary preferences are better understood through the study of such small animals. The comparison of the measurements of 115 skeletons indicates that oviraptorids maintain their hind limb proportions regardless of ontogenetic stage or absolute size, which is a pattern seen more commonly in herbivores than in carnivores. This may weakly support the hypothesis that oviraptorids are herbivores rather than active carnivores.
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Chicken-sized oviraptorid dinosaurs from central China and their ontogenetic implications
NASA Astrophysics Data System (ADS)
Lü, Junchang; Currie, Philip J.; Xu, Li; Zhang, Xingliao; Pu, Hanyong; Jia, Songhai
2013-02-01
Oviraptorids are a group of specialized non-avian theropod dinosaurs that were generally one to 8 m in body length. New specimens of baby oviraptorids from the Late Cretaceous of Henan Province are some of the smallest individuals known. They include diagnostic characters such as the relative position of the antorbital fenestra and the external naris, distinct opening in the premaxilla anteroventral to the external naris, antorbital fossa partly bordered by premaxilla posterodorsally, lacrimal process of premaxilla does not contact the anterodorsal process of the lacrimal, parietal almost as long as frontal; in dorsal view, posterior margin forms a straight line between the postzygapophyses in each of the fourth and fifth cervicals; femur longer than ilium. They also elucidate the ontogenetic processes of oviraptorids, including fusion of cranial elements and changes in relative body proportions. Hind limb proportions are constant in oviraptorids, regardless of absolute body size or ontogenetic stage. This suggests a sedentary lifestyle that did not involve the pursuit of similar-sized prey. The functional implications for bite force and therefore dietary preferences are better understood through the study of such small animals. The comparison of the measurements of 115 skeletons indicates that oviraptorids maintain their hind limb proportions regardless of ontogenetic stage or absolute size, which is a pattern seen more commonly in herbivores than in carnivores. This may weakly support the hypothesis that oviraptorids are herbivores rather than active carnivores.
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Hinahon, Erika; Estrada, Christina; Tong, Lin; Won, Deborah S; de Leon, Ray D
2017-08-01
The application of resistive forces has been used during body weight-supported treadmill training (BWSTT) to improve walking function after spinal cord injury (SCI). Whether this form of training actually augments the effects of BWSTT is not yet known. To determine if robotic-applied resistance augments the effects of BWSTT using a controlled experimental design in a rodent model of SCI. Spinally contused rats were treadmill trained using robotic resistance against horizontal (n = 9) or vertical (n = 8) hind limb movements. Hind limb stepping was tested before and after 6 weeks of training. Two control groups, one receiving standard training (ie, without resistance; n = 9) and one untrained (n = 8), were also tested. At the terminal experiment, the spinal cords were prepared for immunohistochemical analysis of synaptophysin. Six weeks of training with horizontal resistance increased step length, whereas training with vertical resistance enhanced step height and movement velocity. None of these changes occurred in the group that received standard (ie, no resistance) training or in the untrained group. Only standard training increased the number of step cycles and shortened cycle period toward normal values. Synaptophysin expression in the ventral horn was highest in rats trained with horizontal resistance and in untrained rats and was positively correlated with step length. Adding robotic-applied resistance to BWSTT produced gains in locomotor function over BWSTT alone. The impact of resistive forces on spinal connections may depend on the nature of the resistive forces and the synaptic milieu that is present after SCI.
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Suppression of morphogenesis in embryonic mouse limbs exposed in vitro to excess gravity.
Duke, J C
1983-06-01
This paper is a report of the first investigation of the effect of excess gravity on in vitro mammalian limb chondrogenesis. Limb buds from mice of various gestational stages were exposed to excess gravity (2.6G) using a culture centrifuge. Both forelimbs and hind limbs were cultured and the development of various limb elements was scored after four to six days. The 2.6G force significantly depressed the development of limb elements when applied during the teratogen-sensitive period of chondrogenesis. There was a proximodistal gradient of sensitivity to excess gravity in the limb with proximal structures being less susceptible than distal ones. In some cases, proximal limb elements present prior to explantation disappeared upon exposure to excess gravity. Hypergravity's teratogenic effect is assumed to operate via changes in tension and/or pressure on the cells, accompanied by alterations in cell morphometry and membrane properties.
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Evaluation of gait kinetics in puppies with coxofemoral joint laxity
Lopez, Mandi J.; Quinn, Margaret M.; Markel, Mark D.
2007-01-01
Objective To characterize ground reaction forces (GRFs) and determine whether there were correlations between forces and passive coxofemoral joint laxity in puppies. Animals Fifty-one 16-week-old hound-breed dogs. Procedure Force-plate gait evaluation and distraction radiographic imaging were performed. Ground reaction forces evaluated included x (mediolateral), y (craniocaudal breaking and propulsion), and z (vertical) peak force and impulse. Z-plane limb loading and unloading rates, loading interval, and weight distribution and y-plane stance time breaking and propulsion percentages were calculated. One-way ANOVA with the Duncan multiple range test was used to evaluate differences in gait variables among limbs. The relationships of left, right, highest, and mean distraction index (DI) with individual limb data of each dog were evaluated with the Spearman rank correlation. Left and right DIs were compared by means of linear regression analysis. Results Mean ± SEM DI was 0.67 ± 0.02. Left and right DIs were strongly correlated, but there were no significant relationships between DIs and gait variables. Most fore- and hind limb gait variables differed significantly, whereas paired fore- and hind limb gait variables did not. Asymmetry was most pronounced in the x- and y-planes. Conclusions and Clinical Relevance GRFs were consistent with those of clinically normal mature dogs, supporting an absence of association between GRF and DI in young dogs. The GRFs and elucidation of the relationship between GRFs and DI may be useful for future studies in immature dogs. PMID:16454627
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Kim, Jongmin; Kazmierczak, Kris A; Breur, Gert J
2011-09-01
To compare temporospatial variables (TSVs) and kinetic variables (KVs) for fore-limbs and hind limbs of small and large dogs of various breeds during walking and to determine associations among body weight (BW), TSVs, and KVs in these groups. 12 adult dogs with no evidence of lameness. Dogs (grouped according to BW as small [< 10 kg; n = 6] or large [> 25 kg; 6]) were walked in a straight line at their preferred velocity on a wooden platform with an embedded pressure-sensing walkway. Five valid trials were analyzed for each dog; mean TSVs and KVs were determined for each group. The TSVs and KVs for forelimbs and hind limbs were compared between groups, and correlations among BW, TSVs, and KVs were determined. Small dogs had significantly smaller TSVs and KVs than did large dogs. Temporal variables of small dogs and absolute vertical force variables of small and large dogs increased as BW increased. However, normalized peak vertical force and weight distribution values among the 4 limbs were similar between groups. Substantial similarities and differences were detected in gait characteristics between small and large dogs. Results indicated TSVs and KVs can be used for comparison of the walking gait between dogs or for comparison of variables between limbs in an individual dog. Use of the pressure-sensing walkway is a simple method for acquisition of TSVs and KVs for large and small dogs.
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A number of species of anuran amphibians from different regions across North America have recently exhibited an increased occurrence of, predominantly, hind limb malformations. Research concerning factors potentially responsible for these malformations has focused extensively on ...
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Patel, Rajendra; Albadawi, Hassan; Steudel, Wolfgang; Hashmi, Faraz F.; Kang, Jeanwan; Yoo, Hyung-Jin; Watkins, Michael T.
2011-01-01
Introduction The purpose of this study was to determine if inhaled carbon monoxide (CO) can ameliorate skeletal muscle injury, modulate endogenous heme oxygenase-1 (HO) expression, improve indices of tissue integrity and inflammation following hind limb ischemia reperfusion(IR). Methods C57BL6 mice inhaling CO (250ppm) or room air were subjected to 1.5 hrs of ischemia followed by limb reperfusion for either 3 or 6 hours (total treatment time of 4.5 or 7.5 hrs). After the initial period of reperfusion, all mice breathed only room air until 24 hours after the onset of ischemia. Mice were sacrificed at either the end of CO treatment or at 24 hours reperfusion. Skeletal muscle was subjected to histologic and biochemical analysis. Results CO treatment for 7.5 hours protected skeletal muscle from histologic and structural evidence of skeletal muscle injury. Serum and tissue cytokines were significantly reduced (p<0.05) in mice treated with CO for 7.5 hours. Tubulin, Heme Oxygenase, and ATP levels were higher in CO treated mice. Conclusions Inhaled CO protected muscle from structural injury and energy depletion following IR. PMID:22450026
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Poloxamer 188 protects against ischemia-reperfusion injury in a murine hind-limb model.
Murphy, Adrian D; McCormack, Michael C; Bichara, David A; Nguyen, John T; Randolph, Mark A; Watkins, Michael T; Lee, Raphael C; Austen, William G
2010-06-01
Ischemia-reperfusion injury can activate pathways generating reactive oxygen species, which can injure cells by creating holes in the cell membranes. Copolymer surfactants such as poloxamer 188 are capable of sealing defects in cell membranes. The authors postulated that a single-dose administration of poloxamer 188 would decrease skeletal myocyte injury and mortality following ischemia-reperfusion injury. Mice underwent normothermic hind-limb ischemia for 2 hours. Animals were treated with 150 microl of poloxamer 188 or dextran at three time points: (1) 10 minutes before ischemia; (2) 10 minutes before reperfusion; and (3) 2 or 4 hours after reperfusion. After 24 hours of reperfusion, tissues were analyzed for myocyte injury (histology) and metabolic dysfunction (muscle adenosine 5'-triphosphate). Additional groups of mice were followed for 7 days to assess mortality. When poloxamer 188 treatment was administered 10 minutes before ischemia, injury was reduced by 84 percent, from 50 percent injury in the dextran group to 8 percent injury in the poloxamer 188 group (p < 0.001). When administered 10 minutes before reperfusion, poloxamer 188 animals demonstrated a 60 percent reduction in injury compared with dextran controls (12 percent versus 29 percent). Treatment at 2 hours, but not at 4 hours, postinjury prevented substantial myocyte injury. Preservation of muscle adenosine 5'-triphosphate paralleled the decrease in myocyte injury in poloxamer 188-treated animals. Poloxamer 188 treatment significantly reduced mortality following injury (10 minutes before, 75 percent versus 25 percent survival, p = 0.0077; 2 hours after, 50 percent versus 8 percent survival, p = 0.032). Poloxamer 188 administered to animals decreased myocyte injury, preserved tissue adenosine 5'-triphosphate levels, and improved survival following hind-limb ischemia-reperfusion injury.
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Lee, Younglim; Pai, Madhavi; Brederson, Jill-Desiree; Wilcox, Denise; Hsieh, Gin; Jarvis, Michael F; Bitner, Robert S
2011-05-20
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. 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. 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.
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NASA Technical Reports Server (NTRS)
Kostenuik, P. J.; Harris, J.; Halloran, B. P.; Turner, R. T.; Morey-Holton, E. R.; Bikle, D. D.
1999-01-01
Skeletal unloading decreases bone formation and osteoblast number in vivo and decreases the number and proliferation of bone marrow osteoprogenitor (BMOp) cells in vitro. We tested the ability of parathyroid hormone (PTH) to stimulate BMOp cells in vivo by treating Sprague Dawley rats (n = 32) with intermittent PTH(1-34) (1 h/day at 8 microg/100 g of body weight), or with vehicle via osmotic minipumps during 7 days of normal weight bearing or hind limb unloading. Marrow cells were flushed from the femur and cultured at the same initial density for up to 21 days. PTH treatment of normally loaded rats caused a 2.5-fold increase in the number of BMOp cells, with similar increases in alkaline phosphatase (ALP) activity and mineralization, compared with cultures from vehicle-treated rats. PTH treatment of hind limb unloaded rats failed to stimulate BMOp cell number, ALP activity, or mineralization. Hind limb unloading had no significant effect on PTH receptor mRNA or protein levels in the tibia. Direct in vitro PTH challenge of BMOp cells isolated from normally loaded bone failed to stimulate their proliferation and inhibited their differentiation, suggesting that the in vivo anabolic effect of intermittent PTH on BMOp cells was mediated indirectly by a PTH-induced factor. We hypothesize that this factor is insulin-like growth factor-I (IGF-I), which stimulated the in vitro proliferation and differentiation of BMOp cells isolated from normally loaded bone, but not from unloaded bone. These results suggest that IGF-I mediates the ability of PTH to stimulate BMOp cell proliferation in normally loaded bone, and that BMOp cells in unloaded bone are resistant to the anabolic effect of intermittent PTH therapy due to their resistance to IGF-I.
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Agarwal, Shailesh; Loder, Shawn; Wood, Sherri; Cederna, Paul S.; Bishop, D. Keith; Wang, Stewart C.; Levi, Benjamin
2015-01-01
Objective The aim of this study was to demonstrate lymphatic isolation in a model of hind limb lymph node (LN) excision, consisting of ipsilateral popliteal and inguinal LN excision and to evaluate the immunologic response to allogeneic skin transplanted onto this region of lymphatic isolation. Methods To study lymphatic flow, C57BL/6 mice underwent lymphadenectomy (n = 5), sham lymphadenectomy (n = 5), or no intervention (n = 5), followed by methylene blue injection. Mice were dissected to determine whether methylene blue traveled to the iliac LN. To study host response to skin transplantation, C57BL/6 mice underwent allogeneic skin transplantation with LN excision (n = 6), allogeneic skin transplantation alone (n = 6), or syngeneic skin transplantation (n = 4). Skin grafts were placed distal to the popliteal fossa and mice were euthanized at day 10. Grafts were stained for endothelial cell and proliferation markers (CD31 and Ki67, respectively). Secondary lymphoid tissues (spleen, ipsilateral axillary LN, and contralateral inguinal LN) were removed and rechallenged with BALB/c alloantigen in vitro with subsequent assay of interferon-γ and interleukin 4 cell expression using ELISPOT technique. Results Mice that underwent LN excision had no evidence of methylene blue in the iliac nodes; mice without surgical intervention or with sham LN excision consistently had methylene blue visible in the ipsilateral iliac nodes. Mice treated with allogeneic skin transplantation and LN excision had lower expression of interferon-γ and interleukin 4 in the secondary lymphoid tissues. Conclusions Lymph node excision completely interrupts lymphatic flow of the hind limb. This model of lymphatic isolation impairs the ability of the transplant recipient to acutely mount a Th1 or Th2 response to allogeneic skin transplants. PMID:24509194
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Park, Ui Jun; Kim, Hyoung Tae; Cho, Won Hyun; Park, Jae Hyoung; Jung, Hye Ra; Kim, Min Young
2016-12-01
Ischemic preconditioning (IPC), including remote IPC (rIPC) and direct IPC (dIPC), is a promising method to decrease ischemia-reperfusion (IR) injury. This study tested the effect of both rIPC and dIPC on the genes for antioxidant enzymes and endoplasmic reticulum (ER) stress-related proteins. Twenty rats were randomly divided into the control and study groups. In the control group (n=10), the right hind limb was sham-operated. The left hind limb (IscR) of the control group underwent IR injury without IPC. In the study group (n=10), the right hind limb received IR injury after 3 cycles of rIPC. The IscR received IR injury after 3 cycles of dIPC. Gene expression was analyzed by Quantitative real-time polymerase chain reaction from the anterior tibialis muscle. The expression of the antioxidant enzyme genes including glutathione peroxidase (GPx), superoxide dismutase (SOD) 1 and catalase (CAT) were significantly reduced in IscR compared with sham treatment. In comparison with IscR, rIPC enhanced the expression of GPx, SOD2, and CAT genes. dIPC enhanced the expression of SOD2 and CAT genes. The expression of SOD2 genes was consistently higher in rIPC than in dIPC, but the difference was only significant for SOD2. The expression of genes for ER stress-related proteins tended to be reduced in IscR in comparison with sham treatment. However, the difference was only significant for C/EBP homologous protein (CHOP). In comparison with IscR, rIPC significantly up-regulated activating transcription factor 4 and CHOP, whereas dIPC up-regulated CHOP. Both rIPC and dIPC enhanced expression of genes for antioxidant enzymes and ER stress-related proteins.
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Bates, Karl T; Maidment, Susannah C R; Allen, Vivian; Barrett, Paul M
2012-01-01
Ornithischia (the ‘bird-hipped’ dinosaurs) encompasses bipedal, facultative quadrupedal and quadrupedal taxa. Primitive ornithischians were small bipeds, but large body size and obligate quadrupedality evolved independently in all major ornithischian lineages. Numerous pelvic and hind limb features distinguish ornithischians from the majority of other non-avian dinosaurs. However, some of these features, notably a retroverted pubis and elongate iliac preacetabular process, appeared convergently in maniraptoran theropods, and were inherited by their avian descendants. During maniraptoran/avian evolution these pelvic modifications led to significant changes in the functions of associated muscles, involving alterations to the moment arms and the activation patterns of pelvic musculature. However, the functions of these features in ornithischians and their influence on locomotion have not been tested and remain poorly understood. Here, we provide quantitative tests of bipedal ornithischian muscle function using computational modelling to estimate 3D hind limb moment arms for the most complete basal ornithischian, Lesothosaurus diagnosticus. This approach enables sensitivity analyses to be carried out to explore the effects of uncertainties in muscle reconstructions of extinct taxa, and allows direct comparisons to be made with similarly constructed models of other bipedal dinosaurs. This analysis supports some previously proposed qualitative inferences of muscle function in basal ornithischians. However, more importantly, this work highlights ambiguities in the roles of certain muscles, notably those inserting close to the hip joint. Comparative analysis reveals that moment arm polarities and magnitudes in Lesothosaurus, basal tetanuran theropods and the extant ostrich are generally similar. However, several key differences are identified, most significantly in comparisons between the moment arms of muscles associated with convergent osteological features in ornithischians and birds. Craniad migration of the iliofemoralis group muscles in birds correlates with increased leverage and use of medial femoral rotation to counter stance phase adduction moments at the hip. In Lesothosaurus the iliofemoralis group maintains significantly higher moment arms for abduction, consistent with the hip abduction mode of lateral limb support hypothesized for basal dinosaurs. Sensitivity analysis highlights ambiguity in the role of musculature associated with the retroverted pubis (puboischiofemoralis externus group) in ornithischians. However, it seems likely that this musculature may have predominantly functioned similarly to homologous muscles in extant birds, activating during the swing phase to adduct the lower limb through lateral rotation of the femur. Overall the results suggest that locomotor muscle leverage in Lesothosaurus (and by inference basal ornithischians in general) was more similar to that of other non-avian dinosaurs than the ostrich, representing what was probably the basal dinosaur condition. This work thereby contradicts previous hypotheses of ornithischian–bird functional convergence. PMID:22211275
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Bates, Karl T; Maidment, Susannah C R; Allen, Vivian; Barrett, Paul M
2012-03-01
Ornithischia (the 'bird-hipped' dinosaurs) encompasses bipedal, facultative quadrupedal and quadrupedal taxa. Primitive ornithischians were small bipeds, but large body size and obligate quadrupedality evolved independently in all major ornithischian lineages. Numerous pelvic and hind limb features distinguish ornithischians from the majority of other non-avian dinosaurs. However, some of these features, notably a retroverted pubis and elongate iliac preacetabular process, appeared convergently in maniraptoran theropods, and were inherited by their avian descendants. During maniraptoran/avian evolution these pelvic modifications led to significant changes in the functions of associated muscles, involving alterations to the moment arms and the activation patterns of pelvic musculature. However, the functions of these features in ornithischians and their influence on locomotion have not been tested and remain poorly understood. Here, we provide quantitative tests of bipedal ornithischian muscle function using computational modelling to estimate 3D hind limb moment arms for the most complete basal ornithischian, Lesothosaurus diagnosticus. This approach enables sensitivity analyses to be carried out to explore the effects of uncertainties in muscle reconstructions of extinct taxa, and allows direct comparisons to be made with similarly constructed models of other bipedal dinosaurs. This analysis supports some previously proposed qualitative inferences of muscle function in basal ornithischians. However, more importantly, this work highlights ambiguities in the roles of certain muscles, notably those inserting close to the hip joint. Comparative analysis reveals that moment arm polarities and magnitudes in Lesothosaurus, basal tetanuran theropods and the extant ostrich are generally similar. However, several key differences are identified, most significantly in comparisons between the moment arms of muscles associated with convergent osteological features in ornithischians and birds. Craniad migration of the iliofemoralis group muscles in birds correlates with increased leverage and use of medial femoral rotation to counter stance phase adduction moments at the hip. In Lesothosaurus the iliofemoralis group maintains significantly higher moment arms for abduction, consistent with the hip abduction mode of lateral limb support hypothesized for basal dinosaurs. Sensitivity analysis highlights ambiguity in the role of musculature associated with the retroverted pubis (puboischiofemoralis externus group) in ornithischians. However, it seems likely that this musculature may have predominantly functioned similarly to homologous muscles in extant birds, activating during the swing phase to adduct the lower limb through lateral rotation of the femur. Overall the results suggest that locomotor muscle leverage in Lesothosaurus (and by inference basal ornithischians in general) was more similar to that of other non-avian dinosaurs than the ostrich, representing what was probably the basal dinosaur condition. This work thereby contradicts previous hypotheses of ornithischian-bird functional convergence. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.
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Severe pruritus and myoclonus following intrathecal morphine administration in a dog
Iff, Isabelle; Valeskini, Karin; Mosing, Martina
2012-01-01
During epidural needle placement in a 32-kg dog the subarachnoid space was punctured and half the intended dose of lidocaine, bupivacaine, and morphine was injected. After recovery from anesthesia the dog showed signs of severe pruritus of the tail base and limbs and myoclonus of the tail and hind limbs. Methadone, acepromazine, ketamine, buprenorphine, and butorphanol were administered to control myoclonus and pruritus, but were unsuccessful. Diazepam was used to control myoclonus until the effects of morphine abated. PMID:23450863
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Moser, Darla K; Schoonover, Mike J; Sippel, Kate M; Dieterly, Alix M; Ritchey, Jerry W; Wall, Corey R
2017-01-01
This report describes fibrous cyst lining injection and extracorporeal shock wave therapy (ESWT) of a medial femoral condyle (MFC) subchondral cystic lesion (SCL) resulting in catastrophic MFC fracture in an Arabian mare. The mare was presented for evaluation of a severe hind limb lameness of approximately 4 months duration. On presentation, a non-weight bearing lameness of the left hind limb with severe effusion and soft tissue swelling of the stifle region was noted. Radiographic evaluation of the stifle revealed a large SCL of the MFC with associated osteoarthritis. Arthroscopic guided intra-lesional injection of the SCL with corticosteroids and autologous bone marrow concentrate was performed followed by ESWT of the MFC. The mare was discharged walking comfortably 48-hours post-operatively. An acute increase in lameness was noted 14 days post-operatively. Imaging revealed catastrophic fracture of the left MFC. Possible mechanisms leading to failure of the MFC secondary to the described treatment are discussed.
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Automated gait analysis in the open-field test for laboratory mice.
Leroy, Toon; Silva, Mitchell; D'Hooge, Rudi; Aerts, Jean-Marie; Berckmans, Daniel
2009-02-01
In this article, an automated and accurate mouse observation method, based on a conventional test for motor function evaluation, is outlined. The proposed measurement technique was integrated in a regular open-field test, where the trajectory and locomotion of a free-moving mouse were measured simultaneously. The system setup consisted of a transparent cage and a camera placed below it with its lens pointing upward, allowing for images to be captured from underneath the cage while the mouse was walking on the transparent cage floor. Thus, additional information was obtained about the position of the limbs of the mice for gait reconstruction. In a first step, the camera was calibrated as soon as it was fixed in place. A linear calibration factor, relating distances in image coordinates to real-world dimensions, was determined. In a second step, the mouse was located and its body contour segmented from the image by subtracting a previously taken "background" image of the empty cage from the camera image. In a third step, the movement of the mouse was analyzed and its speed estimated from its location in the past few images. If the speed was above a 1-sec threshold, the mouse was recognized to be running, and the image was further processed for footprint recognition. In a fourth step, color filtering was applied within the recovered mouse region to measure the position of the mouse's paws, which were visible in the image as small pink spots. Paws that were detected at the same location in a number of subsequent images were kept as footprints-that is, paws in contact with the cage floor. The footprints were classified by their position relative to the mouse's outline as corresponding to the front left or right paw or the hind left or right paw. Finally, eight parameters were calculated from the footprint pattern to describe the locomotion of the mouse: right/left overlap, front/hind base, right/left front limb stride, and right/left hind limb stride. As an application, the system was tested using normal mice and mice displaying pentobarbital-induced ataxia. The footprint parameters measured using the proposed system showed differences of 10% to 20% between normal and ataxic mice.
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Oda, Shinichiro; Nagahama, Ryoji; Nakano, Kaku; Matoba, Tetsuya; Kubo, Mitsuki; Sunagawa, Kenji; Tominaga, Ryuji; Egashira, Kensuke
2010-08-01
We recently demonstrated in a murine model that nanoparticle-mediated delivery of pitavastatin into vascular endothelial cells effectively increased therapeutic neovascularization. For the development of a clinically applicable approach, further investigations are necessary to assess whether this novel system can induce the development of collateral arteries (arteriogenesis) in a chronic ischemia setting in larger animals. Chronic hind limb ischemia was induced in rabbits. They were administered single injections of nanoparticles loaded with pitavastatin (0.05, 0.15, and 0.5 mg/kg) into ischemic muscle. Treatment with pitavastatin nanoparticles (0.5 mg/kg), but not other nanoparticles, induced angiographically visible arteriogenesis. The effects of intramuscular injections of phosphate-buffered saline, fluorescein isothiocyanate (FITC)-loaded nanoparticles, pitavastatin (0.5 mg/kg), or pitavastatin (0.5 mg/kg) nanoparticles were examined. FITC nanoparticles were detected mainly in endothelial cells of the ischemic muscles for up to 4 weeks. Treatment with pitavastatin nanoparticles, but not other treatments, induced therapeutic arteriogenesis and ameliorated exercise-induced ischemia, suggesting the development of functional collateral arteries. Pretreatment with nanoparticles loaded with vatalanib, a vascular endothelial growth factor receptor (VEGF) tyrosine kinase inhibitor, abrogated the therapeutic effects of pitavastatin nanoparticles. Separate experiments with mice deficient for VEGF receptor tyrosine kinase demonstrated a crucial role of VEGF receptor signals in the therapeutic angiogenic effects. The nanotechnology platform assessed in this study (nanoparticle-mediated endothelial cell-selective delivery of pitavastatin) may be developed as a clinically feasible and promising strategy for therapeutic arteriogenesis in patients. Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
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Yu, Zhi-Bin; Gao, Fang; Feng, Han-Zhong; Jin, J-P
2006-01-01
Weight-bearing skeletal muscles change phenotype rapidly in response to unloading. Using the hind limb-suspension rat model, we investigated the regulation of myofilament protein isoforms in correlation to contractility. Four weeks of continuous hind limb unloading produced progressive atrophy and contractility changes in soleus but not extensor digitorum longus (EDL) muscle. The unloaded soleus muscle also had decreased fatigue resistance. Together with the decrease of myosin heavy chain (MHC) isoform I and IIa and increase of MHC IIb and IIx, coordinated regulation of thin filament regulatory protein isoforms were observed: γ- and β-tropomyosin decreased and α-tropomyosin increased, resulting in an α/β ratio similar to that in normal fast twitch skeletal muscle; troponin I and troponin T (TnT) both showed decrease in the slow isoform and increases in the fast isoform. The TnT isoform switching began after 7 days of unloading and TnI isoform showed detectable changes at 14 days while other protein isoform changes were not significant until 28 days of treatment. Correlating to the early changes in contractility, especially the resistance to fatigue, the early response of TnT isoform regulation may play a unique role in the adaptation of skeletal muscle to unloading. When the fast TnT gene expression was up-regulated in the unloaded soleus muscle, alternative RNA splicing switched to produce more high molecular weight acidic isoforms, reflecting a potential compensation for the decrease of slow TnT that is critical to skeletal muscle function. The results demonstrate that differential regulation of TnT isoforms is a sensitive mechanism in muscle adaptation to functional demands. PMID:17108008
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Ogita, Shogo; Endo, Toshiki; Sugiyama, Shinichiro; Saito, Ryuta; Inoue, Tomoo; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Sonoda, Yukihiko; Tominaga, Teiji
2017-05-01
Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier. To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model. Toxicity studies were performed in 42 rats following the administration of 4 μl of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0.1 to 10 mg/ml. Behavioral analyses and histological evaluations were performed to assess ACNU toxicity in the spinal cord. A survival study was performed in 32 rats following the implantation of 9 L cells into the T8 spinal cord. Seven days after the implantation, rats were assigned to four groups: ACNU CED (0.25 mg/ml; n = 8); ACNU intravenous (i.v.) (0.4 mg; n = 8); saline CED (n = 8); saline i.v. (n = 8). Hind limb movements were evaluated daily in all rats for 21 days. Tumor sizes were measured histologically. The maximum tolerated ACNU concentration was 0.25 mg/ml. Preservation of hind limb motor function and tumor growth suppression was observed in the ACNU CED (0.25 mg/ml) and ACNU i.v. groups. Antitumor effects were more prominent in the ACNU CED group especially in behavioral analyses (P < 0.05; log-rank test). ACNU CED had efficacy in controlling tumor growth and preserving neurological function in an experimental spinal cord tumor model. ACNU CED can be a viable treatment option for spinal cord high-grade glioma.
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DIETARY SELENIUM PROTECTS AGAINST SELECTED SIGNS OF AGING AND METHYLMERCURY EXPOSURE
Banna, Kelly M.; Reed, Miranda N.; Pesek, Erin F.; Cole, Nathan; Li, Jun; Newland, M. Christopher
2010-01-01
Acute or short-term exposure to high doses of methylmercury (MeHg) causes a well-characterized syndrome that includes sensory and motor deficits. The environmental threat from MeHg, however, comes from chronic, low-level exposure, the consequences of which are poorly understood. Selenium (Se), an essential nutrient, both increases deposition of mercury (Hg) in neurons and mitigates some of MeHg's neurotoxicity in the short term, but it is unclear whether this deposition produces long-term adverse consequences. To investigate these issues, adult Long Evans rats were fed a diet containing 0.06 or 0.6 ppm of Se as sodium selenite. After 100 days on these diets, the subjects began consuming 0.0, 0.5, 5.0, or 15 ppm of Hg as methylmercuric chloride in their drinking water for 16 months. Somatosensory sensitivity, grip strength, hind-limb cross (clasping reflex), flexion, and voluntary wheel-running in overnight sessions were among the measures examined. MeHg caused a dose- and time-dependent impairment in all measures, No effects appeared in rats consuming 0 or 0.5 ppm of Hg. Somatosensory function, grip strength, and flexion were among the earliest signs of exposure. Selenium significantly delayed or blunted MeHgs effects. Selenium also increased running in unexposed animals as they aged, a novel finding that may have important clinical implications. Nerve pathology studies revealed axonal atrophy or mild degeneration in peripheral nerve fibers, which is consistent with abnormal sensorimotor function in chronic MeHg neurotoxicity. Lidocaine challenge reproduced the somatosensory deficits but not hind-limb cross or flexion. Together, these results quantify the neurotoxicity of long-term MeHg exposure, support the safety and efficacy of Se in ameliorating MeHg's neurotoxicity, and demonstrate the potential benefits of Se during aging. PMID:20079371
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Porcari, Paola; Hall, Matt G; Clark, Chris A; Greally, Elizabeth; Straub, Volker; Blamire, Andrew M
2018-03-01
The investigation of age-related changes in muscle microstructure between developmental and healthy adult mice may help us to understand the clinical features of early-onset muscle diseases, such as Duchenne muscular dystrophy. We investigated the evolution of mouse hind-limb muscle microstructure using diffusion imaging of in vivo and in vitro samples from both actively growing and mature mice. Mean apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined as a function of diffusion time (Δ), age (7.5, 22 and 44 weeks) and diffusion gradient direction, applied parallel or transverse to the principal axis of the muscle fibres. We investigated a wide range of diffusion times with the goal of probing a range of diffusion lengths characteristic of muscle microstructure. We compared the diffusion time-dependent ADC of hind-limb muscles with histology. ADC was found to vary as a function of diffusion time in muscles at all stages of maturation. Muscle water diffusivity was higher in younger (7.5 weeks) than in adult (22 and 44 weeks) mice, whereas no differences were observed between the older ages. In vitro data showed the same diffusivity pattern as in vivo data. The highlighted differences in diffusion properties between young and mature muscles suggested differences in underlying muscle microstructure, which were confirmed by histological assessment. In particular, although diffusion was more restricted in older muscle, muscle fibre size increased significantly from young to adult age. The extracellular space decreased with age by only ~1%. This suggests that the observed diffusivity differences between young and adult muscles may be caused by increased membrane permeability in younger muscle associated with properties of the sarcolemma. Copyright © 2018 John Wiley & Sons, Ltd.
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Poole, KM; Nelson, CE; Joshi, RV; Martin, JR; Gupta, MK; Haws, SC; Kavanaugh, TE; Skala, MC; Duvall, CL
2014-01-01
A new microparticle-based delivery system was synthesized from reactive oxygen species (ROS)-responsive poly(propylene sulfide) (PPS) and tested for “on demand” antioxidant therapy. PPS is hydrophobic but undergoes a phase change to become hydrophilic upon oxidation and thus provides a useful platform for ROS-demanded drug release. This platform was tested for delivery of the promising anti-inflammatory and antioxidant therapeutic molecule curcumin, which is currently limited in use in its free form due to poor pharmacokinetic properties. PPS microspheres efficiently encapsulated curcumin through oil-in-water emulsion and provided sustained, on demand release that was modulated in vitro by hydrogen peroxide concentration. The cytocompatible, curcumin-loaded microspheres preferentially targeted and scavenged intracellular ROS in activated macrophages, reduced in vitro cell death in the presence of cytotoxic levels of ROS, and decreased tissue-level ROS in vivo in the diabetic mouse hind limb ischemia model of peripheral arterial disease. Interestingly, due to the ROS scavenging behavior of PPS, the blank microparticles also showed inherent therapeutic properties that were synergistic with the effects of curcumin in these assays. Functionally, local delivery of curcumin-PPS microspheres accelerated recovery from hind limb ischemia in diabetic mice, as demonstrated using non-invasive imaging techniques. This work demonstrates the potential for PPS microspheres as a generalizable vehicle for ROS-demanded drug release and establishes the utility of this platform for improving local curcumin bioavailability for treatment of chronic inflammatory diseases. PMID:25522975
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MacLellan, M J; Catavitello, G; Ivanenko, Y P; Lacquaniti, F
2017-11-01
Habitual quadrupeds have been shown to display a planar covariance of segment elevation angle waveforms in the fore and hind limbs during many forms of locomotion. The purpose of the current study was to determine if humans generate similar patterns in the upper and lower limbs during hand-foot crawling. Nine healthy young adults performed hand-foot crawling on a treadmill at speeds of 1, 2, and 3 km/h. A principal component analysis (PCA) was applied to the segment elevation angle waveforms for the upper (upper arm, lower arm, and hand) and lower (thigh, shank, and foot) limbs separately. The planarity of the elevation angle waveforms was determined using the sum of the variance explained by the first two PCs and the orientation of the covariance plane was quantified using the direction cosines of the eigenvector orthogonal to the plane, projected upon each of the segmental semi-axes. Results showed that planarity of segment elevation angles was maintained in the upper and lower limbs (explained variance >97%), although a slight decrease was present in the upper limb when crawling at 3 km/h. The orientation of the covariance plane was highly limb-specific, consistent with animal studies and possibly related to the functional neural control differences between the upper and lower limbs. These results may suggest that the motor patterns stored in the central nervous system for quadrupedal locomotion may be retained through evolution and may still be exploited when humans perform such tasks.
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Molecular anatomy of the developing limb in the coquí frog, Eleutherodactylus coqui.
Gross, Joshua B; Kerney, Ryan; Hanken, James; Tabin, Clifford J
2011-01-01
The vertebrate limb demonstrates remarkable similarity in basic organization across phylogenetically disparate groups. To gain further insight into how this morphological similarity is maintained in different developmental contexts, we explored the molecular anatomy of size-reduced embryos of the Puerto Rican coquí frog, Eleutherodactylus coqui. This animal demonstrates direct development, a life-history strategy marked by rapid progression from egg to adult and absence of a free-living, aquatic larva. Nonetheless, coquí exhibits a basal anuran limb structure, with four toes on the forelimb and five toes on the hind limb. We investigated the extent to which coquí limb bud development conforms to the model of limb development derived from amniote studies. Toward this end, we characterized dynamic patterns of expression for 13 critical patterning genes across three principle stages of limb development. As expected, most genes demonstrate expression patterns that are essentially unchanged compared to amniote species. For example, we identified an EcFgf8-expression domain within the apical ectodermal ridge (AER). This expression pattern defines a putatively functional AER signaling domain, despite the absence of a morphological ridge in coquí embryos. However, two genes, EcMeis2 and EcAlx4, demonstrate altered domains of expression, which imply a potential shift in gene function between coquí frogs and amniote model systems. Unexpectedly, several genes thought to be critical for limb patterning in other systems, including EcFgf4, EcWnt3a, EcWnt7a, and EcGremlin, demonstrated no evident expression pattern in the limb at the three stages we analyzed. The absence of EcFgf4 and EcWnt3a expression during limb patterning is perhaps not surprising, given that neither gene is critical for proper limb development in the mouse, based on knockout and expression analyses. In contrast, absence of EcWnt7a and EcGremlin is surprising, given that expression of these molecules appears to be absolutely essential in all other model systems so far examined. Although this analysis substantiates the existence of a core set of ancient limb-patterning molecules, which likely mediate identical functions across highly diverse vertebrate forms, it also reveals remarkable evolutionary flexibility in the genetic control of a conserved morphological pattern across evolutionary time. © 2011 Wiley Periodicals, Inc.
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Drummond, Heather A; Xiang, Lusha; Chade, Alejandro R; Hester, Robert
2017-08-01
Acid-sensing ion channel (ASIC) proteins form extracellular proton-gated, cation-selective channels in neurons and vascular smooth muscle cells and are proposed to act as extracellular proton sensors. However, their importance to vascular responses under conditions associated with extracellular acidosis, such as strenuous exercise, is unclear. Therefore, the purpose of this study was to determine if one ASIC protein, ASIC1a, contributes to extracellular proton-gated vascular responses and exercise tolerance. To determine if ASIC1a contributes to exercise tolerance, we determined peak oxygen (O 2 ) uptake in conscious ASIC1a -/- mice during exhaustive treadmill running. Loss of ASIC1a was associated with a greater peak running speed (60 ± 2 vs. 53 ± 3 m·min -1 , P = 0.049) and peak oxygen (O 2 ) uptake during exhaustive treadmill running (9563 ± 120 vs. 8836 ± 276 mL·kg -1 ·h -1 , n = 6-7, P = 0.0082). There were no differences in absolute or relative lean body mass, as determined by EchoMRI. To determine if ASIC1a contributes to vascular responses during muscle contraction, we measured femoral vascular conductance (FVC) during a stepwise electrical stimulation (0.5-5.0 Hz at 3 V for 60 sec) of the left major hind limb muscles. FVC increased to a greater extent in ASIC1a -/- versus ASIC1a +/+ mice (0.44 ± 0.03 vs. 0.30 ± 0.04 mL·min -1 ·100 g hind limb mass -1 · mmHg -1 , n = 5 each, P = 0.0009). Vasodilation following local application of external protons in the spinotrapezius muscle increased the duration, but not the magnitude, of the vasodilatory response in ASIC1a -/- mice. Finally, we examined hind limb vascular density using micro-CT and found increased density of 0-80 μ m vessels ( P < 0.05). Our findings suggest an increased vascular density and an enhanced vasodilatory response to local protons, to a lesser degree, may contribute to the enhanced vascular conductance and increased peak exercise capacity in ASIC1a -/- mice. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
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Kangaroo rat bone compared to white rat bone after short-term disuse and exercise
Muths, E.; Reichman, O. J.
1996-01-01
Kangaroo rats (Dipodomys ordii) were used to study the effects of confinement on mechanical properties of bone with a long range objective of proposing an alternative to the white rat model for the study of disuse osteoporosis. Kangaroo rats exhibit bipedal locomotion, which subjects their limbs to substantial accelerative forces in addition to the normal stress of weight bearing. We subjected groups of kangaroo rats and white rats (Rattus norvegicus) to one of two confinement treatments or to an exercise regime; animals were exercised at a rate calculated to replicate their (respective) daily exercise patterns. White laboratory rats were used as the comparison because they are currently the accepted model used in the study of disuse osteoporosis. After 6 weeks of treatment, rats were killed and the long bones of their hind limbs were tested mechanically and examined for histomorphometric changes. We found that kangaroo rats held in confinement had less ash content in their hind limbs than exercised kangaroo rats. In general, treated kangaroo rats showed morphometric and mechanical bone deterioration compared to controls and exercised kangaroo rats appeared to have slightly “stronger” bones than confined animals. White rats exhibited no significant differences between treatments. These preliminary results suggest that kangaroo rats may be an effective model in the study of disuse osteoporosis.
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Computed tomographic anatomy of the equine stifle joint.
Vekens, Elke Van der; Bergman, Erik H J; Vanderperren, Katrien; Raes, Els V; Puchalski, Sarah M; Bree, Henri J J van; Saunders, Jimmy H
2011-04-01
To provide a detailed computed tomography (CT) reference of the anatomically normal equine stifle joint. Sample-16 hind limbs from 8 equine cadavers; no horses had evidence of orthopedic disease of the stifle joints. CT of the stifle joint was performed on 8 hind limbs. In all limbs, CT was also performed after intra-articular injection of 60 mL of contrast material (150 mg of iodine/mL) in the lateral and medial compartments of the femorotibial joint and 80 mL of contrast material in the femoropatellar joint (CT arthrography). Reformatted CT images in the transverse, parasagittal, and dorsal plane were matched with corresponding anatomic slices of the 8 remaining limbs. The femur, tibia, and patella were clearly visible. The patellar ligaments, common origin of the tendinous portions of the long digital extensor muscle and peroneus tertius muscle, collateral ligaments, tendinous portion of the popliteus muscle, and cranial and caudal cruciate ligaments could also be consistently evaluated. The cruciate ligaments and the meniscotibial ligaments could be completely assessed in the arthrogram sequences. Margins of the meniscofemoral ligament and the lateral and medial femoropatellar ligaments were difficult to visualize on the precontrast and postcontrast images. CT and CT arthrography were used to accurately identify and characterize osseous and soft tissue structures of the equine stifle joint. This technique may be of value when results from other diagnostic imaging techniques are inconclusive. The images provided will serve as a CT reference for the equine stifle joint.
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Venegas, Pablo J.; Torres-Carvajal, Omar; Duran, Vilma; de Queiroz, Kevin
2013-01-01
Abstract We report the discovery of two sympatric new species of Enyalioides from a montane rainforest of the Río Huallaga basin in northeastern Peru. Among other characters, the first new species is distinguishable from other Enyalioides by the combination of the following characters: strongly keeled ventral scales, more than 37 longitudinal rows of dorsals in a transverse line between the dorsolateral crests at midbody, low vertebral crest on the neck with vertebrals on neck similar in size to those between hind limbs, projecting scales on body or limbs absent, 96 mm maximum SVL in both sexes, and caudals increasing in size posteriorly within each autotomic segment. The second new species differs from other species of Enyalioides in having strongly keeled ventral scales, scales posterior to the superciliaries forming a longitudinal row of strongly projecting scales across the lateral edge of the skull roof in adults of both sexes, 31 or fewer longitudinal rows of strongly keeled dorsals in a transverse line between the dorsolateral crests at midbody, vertebrals on neck more than five times the size of vertebrals between hind limbs in adult males, projecting scales on body or limbs absent, and caudals increasing in size posteriorly within each autotomic segment. We also present an updated molecular phylogenetic tree of hoplocercines including new samples of Enyalioides rudolfarndti, Enyalioides rubrigularis, both species described in this paper, as well as an updated identification key for species of Hoplocercinae. PMID:23794824
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Bacterial diskospondylitis in juvenile mink from 2 Ontario mink farms
Martínez, Jorge; Vidaña, Beatriz; Cruz-Arambulo, Robert; Slavic, Durda; Tapscott, Brian; Brash, Marina L.
2013-01-01
Nine juvenile mink with hind-limb paresis/paralysis from 2 Ontario farms were submitted for necropsy. Diagnostic tests revealed spinal compression and severe thoracic diskospondylitis with intralesional Gram-positive coccoid bacterial colonies. Streptococcus canis, Streptococcus dysgalactiae subsp. equisimilis, and hemolytic Staphylococcus spp. were isolated from vertebral lesions. PMID:24155490
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Bacterial diskospondylitis in juvenile mink from 2 Ontario mink farms.
Martínez, Jorge; Vidaña, Beatriz; Cruz-Arambulo, Robert; Slavic, Durda; Tapscott, Brian; Brash, Marina L
2013-09-01
Nine juvenile mink with hind-limb paresis/paralysis from 2 Ontario farms were submitted for necropsy. Diagnostic tests revealed spinal compression and severe thoracic diskospondylitis with intralesional Gram-positive coccoid bacterial colonies. Streptococcus canis, Streptococcus dysgalactiae subsp. equisimilis, and hemolytic Staphylococcus spp. were isolated from vertebral lesions.
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SURGICAL CORRECTION OF BILATERAL PATELLAR LUXATION IN AN AMERICAN BLACK BEAR CUB (URSUS AMERICANUS).
Bennett, Katarina R; Desmarchelier, Marion R; Bailey, Trina R
2015-06-01
A wild orphaned male American black bear cub ( Ursus americanus ) presented with hind limb gait abnormalities and was found to have bilateral grade 3 laterally luxating patellas. There were no other significant abnormalities detected on neurologic, radiographic, or hematologic examinations. The trochlear grooves were deepened with a chondroplasty, and the redundant soft tissues imbricated. There was a marked improvement in the bear's gait postoperatively, with an apparent full return to function. To the authors' knowledge, patellar luxation has not been reported in the Ursidae family, and the success in this case suggests that this technique may be used in large wild or captive carnivore cubs.
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Egenvall, Agneta; Haubro Andersen, Pia; Pfau, Thilo
2017-01-01
Recent studies evaluating horses in training and considered free from lameness by their owners have identified a large proportion of horses with motion asymmetries. However the prevalence, type and magnitude of asymmetries when trotting in a straight line or on the lunge have not been investigated. The aim of this study was to objectively investigate the presence of motion asymmetries in riding horses in training by identifying the side and quantifying the degree and type (impact, pushoff) of forelimb and hind limb asymmetries found during straight line trot and on the lunge. In a cross-sectional study, vertical head and pelvic movement symmetry was measured in 222 Warmblood type riding horses, all without perceived performance issues and considered free from lameness by their owners. Body-mounted uni-axial accelerometers were used and differences between maximum and minimum head (HDmax, HDmin) and pelvic (PDmax, PDmin) vertical displacement between left and right forelimb and hind limb stances were calculated during straight line trot and on the lunge. Previously reported symmetry thresholds were used. The thresholds for symmetry were exceeded in 161 horses for at least one variable while trotting in a straight line, HDmin (n = 58, mean 14.3 mm, SD 7.1), HDmax (n = 41, mean 12.7 mm, SD 5.5), PDmax (n = 87, mean 6.5 mm, SD 3.10), PDmin (n = 79, mean 5.7 mm, SD 2.1). Contralateral and ipsilateral concurrent forelimb and hind limb asymmetries were detected in 41 and 49 horses, respectively. There was a linear association between the straight line PDmin values and the values on the lunge with the lame limb to the inside of the circle. A large proportion (72.5%) of horses in training which were perceived as free from lameness by their owner showed movement asymmetries above previously reported asymmetry thresholds during straight line trot. It is not known to what extent these asymmetries are related to pain or to mechanical abnormalities. Therefore, one of the most important questions that must be addressed is how objective asymmetry scores can be translated into pain, orthopedic abnormality, or any type of unsoundness. PMID:28441406
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Rhodin, Marie; Egenvall, Agneta; Haubro Andersen, Pia; Pfau, Thilo
2017-01-01
Recent studies evaluating horses in training and considered free from lameness by their owners have identified a large proportion of horses with motion asymmetries. However the prevalence, type and magnitude of asymmetries when trotting in a straight line or on the lunge have not been investigated. The aim of this study was to objectively investigate the presence of motion asymmetries in riding horses in training by identifying the side and quantifying the degree and type (impact, pushoff) of forelimb and hind limb asymmetries found during straight line trot and on the lunge. In a cross-sectional study, vertical head and pelvic movement symmetry was measured in 222 Warmblood type riding horses, all without perceived performance issues and considered free from lameness by their owners. Body-mounted uni-axial accelerometers were used and differences between maximum and minimum head (HDmax, HDmin) and pelvic (PDmax, PDmin) vertical displacement between left and right forelimb and hind limb stances were calculated during straight line trot and on the lunge. Previously reported symmetry thresholds were used. The thresholds for symmetry were exceeded in 161 horses for at least one variable while trotting in a straight line, HDmin (n = 58, mean 14.3 mm, SD 7.1), HDmax (n = 41, mean 12.7 mm, SD 5.5), PDmax (n = 87, mean 6.5 mm, SD 3.10), PDmin (n = 79, mean 5.7 mm, SD 2.1). Contralateral and ipsilateral concurrent forelimb and hind limb asymmetries were detected in 41 and 49 horses, respectively. There was a linear association between the straight line PDmin values and the values on the lunge with the lame limb to the inside of the circle. A large proportion (72.5%) of horses in training which were perceived as free from lameness by their owner showed movement asymmetries above previously reported asymmetry thresholds during straight line trot. It is not known to what extent these asymmetries are related to pain or to mechanical abnormalities. Therefore, one of the most important questions that must be addressed is how objective asymmetry scores can be translated into pain, orthopedic abnormality, or any type of unsoundness.
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Hox gene expression in the specialized limbs of the Iberian mole (Talpa occidentalis).
Bickelmann, Constanze; van der Vos, Wessel; de Bakker, Merijn A G; Jiménez, Rafael; Maas, Saskia; Sánchez-Villagra, Marcelo R
2017-01-01
Fossorial talpid moles use their limbs predominantly for digging, which explains their highly specialized anatomy. The humerus is particularly short and dorsoventrally rotated, with broadened distal and proximal parts where muscles attach and which facilitate powerful abductive movements. The radius and ulna are exceptionally robust and short. The ulna has an expanded olecranon process. The femur is generalized, but the fused tibia-fibula complex is short and robust. To understand the developmental bases of these specializations, we studied expression patterns of four 5' Hox genes in the fossorial Iberian mole (Talpa occidentalis). These genes are known to play major roles in patterning the developing limb skeleton in the mouse, with which comparisons were made (Mus musculus, C57BL/6Jico strain). We find that HoxA9 expression is spatially expanded in the developing stylopodial area in the mole forelimb, compared to the less specialized mouse forelimb and mole hind limb. HoxD9 expression does not extend into the thoracic body wall in the mole forelimb in contrast to the mouse, and is also reduced in the presumptive zeugopodium in mole forelimb, compared to mouse. Expression of HoxD11 is upregulated in the mole in the postaxial area of the hind limb zeugopod, compared to the mouse. On the other hand, HoxD13 is downregulated in the postaxial zeugopodial area in the forelimb of the mole, compared to the mouse. The differences in the expression patterns of these 5' Hox genes between Talpa and Mus are an indication of the developmental changes going hand in hand with anatomical digging adaptations in the mole adult. © 2016 Wiley Periodicals, Inc.
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Effects from fine muscle and cutaneous afferents on spinal locomotion in cats
Kniffki, K.-D.; Schomburg, E. D.; Steffens, H.
1981-01-01
1. The effects of chemically activated fine muscle afferents (groups III and IV) and electrically activated cutaneous afferents on motoneuronal discharges were studied before and during fictive locomotion induced pharmacologically by i.v. administration of nialamide and l-DOPA in high spinal cats. Efferent activity was recorded simultaneously from nerve filaments to ipsi- and contralateral extensor and flexor muscles. In addition, intracellular recordings were made from lumbar α-motoneurones. 2. After nialamide but before treatment with l-DOPA, in some cases, transient locomotor-like discharges were induced by an increased activity in fine muscle afferents. The response pattern in nerves to both hind limbs could be different showing e.g. only transient alternating activity between knee flexor and extensor of one limb but not of the other one. 3. Treatment with l-DOPA did not always cause fictive locomotion. Often not all motoneurone pools showed rhythmic activity. In these cases stimulation of group III and IV muscle afferents usually caused transient periodic activity. In cases with apparent rhythmic activity, algesic stimulation of the gastrocnemius—soleus muscle caused an accentuation of the rhythm by a more abrupt transition from the active phase to the non-active interval. Again, the response patterns on both sides were not uniform in all cases. 4. A second type of response to activation of fine muscle afferents had a quite different character: the rhythmic activity was more or less completely overridden by a strong transient tonic hyperactivity or the rhythm was transiently blocked. These phenomena did not occur in the same way in all nerves. 5. Electrical stimulation of cutaneous nerves of the hind limb generally induced the same response pattern as chemical stimulation of the group III and IV muscle afferents. The effects varied depending on the stimulus strength and the nerve. 6. The results revealed that cutaneous and fine muscle afferents not only have similar functions in the reflex control of a limb but also in evocation and modulation of locomotion. Therefore, it is assumed that both types of afferents may serve together as a peripheral feed-back to the spinal locomotor centre. PMID:7320927
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Woods, Jason B.; Lowery, Nicholas J.; Burns, Patrick R.
2012-01-01
Managing complications after attempted hind foot and ankle arthrodesis with intramedullary nail fixation is a challenge. This situation becomes more problematic in the patient with diabetes mellitus and multiple comorbidities. Infection and subsequent osteomyelitis can be a devastating, limb threatening complication associated with these procedures. The surgeon must manage both the infectious process and the skeletal instability concurrently. This article provides a literature review and detailed management strategies for a modified technique of employing antibiotic impregnated polymethylmethacrylate-coated intramedullary nailing. PMID:22396833
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Study of Hind Limb Tissue Gas Phase Formation in Response to Suspended Adynamia and Hypokinesia
NASA Technical Reports Server (NTRS)
Butler, Bruce D.
1996-01-01
The purpose of this study was to investigate the hypothesis that reduced joint/muscle activity (hypo kinesia) as well as reduced or null loading of limbs (adynamia) in gravity would result in reduced decompression-induced gas phase and symptoms of decompression sickness (DCS). Finding a correlation between the two phenomena would correspond to the proposed reduction in tissue gas phase formation in astronauts undergoing decompression during extravehicular activity (EVA) in microgravity. The observation may further explain the reported low incidence of DCS in space.
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Banks, R W; Hulliger, M; Saed, H H; Stacey, M J
2009-06-01
The encapsulated sensory endings of mammalian skeletal muscles are all mechanoreceptors. At the most basic functional level they serve as length sensors (muscle spindle primary and secondary endings), tension sensors (tendon organs), and pressure or vibration sensors (lamellated corpuscles). At a higher functional level, the differing roles of individual muscles in, for example, postural adjustment and locomotion might be expected to be reflected in characteristic complements of the various end-organs, their sensory endings and afferent nerve fibres. This has previously been demonstrated with regard to the number of muscle-spindle capsules; however, information on the other types of end-organ, as well as the complements of primary and secondary endings of the spindles themselves, is sporadic and inconclusive regarding their comparative provision in different muscles. Our general conclusion that muscle-specific variability in the provision of encapsulated sensory endings does exist demonstrates the necessity for the acquisition of more data of this type if we are to understand the underlying adaptive relationships between motor control and the structure and function of skeletal muscle. The present quantitative and comparative analysis of encapsulated muscle afferents is based on teased, silver-impregnated preparations. We begin with a statistical analysis of the number and distribution of muscle-spindle afferents in hind-limb muscles of the cat, particularly tenuissimus. We show that: (i) taking account of the necessity for at least one primary ending to be present, muscles differ significantly in the mean number of additional afferents per spindle capsule; (ii) the frequency of occurrence of spindles with different sensory complements is consistent with a stochastic, rather than deterministic, developmental process; and (iii) notwithstanding the previous finding, there is a differential distribution of spindles intramuscularly such that the more complex ones tend to be located closer to the main divisions of the nerve. Next, based on a sample of tendon organs from several hind-foot muscles of the cat, we demonstrate the existence in at least a large proportion of tendon organs of a structural substrate to account for multiple spike-initiation sites and pacemaker switching, namely the distribution of sensory terminals supplied by the different first-order branches of the Ib afferent to separate, parallel, tendinous compartments of individual tendon organs. We then show that the numbers of spindles, tendon organs and paciniform corpuscles vary independently in a sample of (mainly) hind-foot muscles of the cat. Grouping muscles by anatomical region in the cat indicated the existence of a gradual proximo-distal decline in the overall average size of the afferent complement of muscle spindles from axial through hind limb to intrinsic foot muscles, but with considerable muscle-specific variability. Finally, we present some comparative data on muscle-spindle afferent complements of rat, rabbit and guinea pig, one particularly notable feature being the high incidence of multiple primary endings in the rat.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Krasnoshtein, F.; Buchwald, M.
1994-09-01
Fanconi anemia (FA) is an autosomal recessive disorder characterized by a variety of congenital and skeletal malformations, progressive pancytopanenia and predisposition to malignancies. FA cells display chromosomal instability and hypersensitivity to DNA-damaging agents. Both the human and the corresponding murine cDNAs have been cloned in our lab. Here we describe the expression of Facc during mouse development, using mRNA in situ hybridization. Our aim is to obtain clues on the possible function of the Facc gene product during development that may help elucidate basic defect(s) in FA. In addition, knowledge of the exact pattern of Facc expression will assist inmore » interpreting the phenotypes of mutant mice, currently being developed. In embryos the gene is diffusely expressed over the entire embryo, with higher hybridization levels in the mesenchyme and in both upper and lower extremities. Specific expression of Facc is seen in the perichondrium and marrow of long bones of hind limbs/hip; long bones of front limbs/shoulder region; developing digits of front and hind paws; and ribs. The signal is also detected in the following regions: cranial/frontal; facial/periorbital and maxillary/mandibular, hair follicles, diaphragm and lung. In addition, generalized Facc expression is seen during these embryonic stages. The pattern of Facc expression is consistent with the known skeletal abnormalities in FA patients, which include radial ray deformities, metacarpal hypoplasia, and abnormalities of lower limbs, ribs, head and face. The signal in the lung is consistent with the lung lobe absence and abnormal pulmonary drainage that have been detected in some FA patients. The sloped forehead and microcephaly in FA patients may have some association with the signal seen in the frontal region of the mouse cranium. Taken together, our results suggest that Facc is directly involved in the development of various embryonic tissues, particularly bone.« less
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Effects of topical oxygen therapy on ischemic wound healing.
Rao, Congqiang; Xiao, Liling; Liu, Hongwei; Li, Shenghong; Lu, Jinqiang; Li, Jiangxuan; Gu, Shixing
2016-01-01
[Purpose] This study evaluated the effects of topical oxygen therapy on the hind limb wounds of rats under ischemic conditions. [Subjects and Methods] Twelve injured rats were treated with topical oxygen on skin wounds located on the hind limb and compared with twelve injured control rats. Indexes including gross morphology of the wound, wound healing time, wound healing rate, and histological and immunohistochemical staining of sections of wound tissue were examined at different time points after intervention. [Results] The wound healing time was shorter in the topical oxygen therapy group than the control group. The wound healing rate and granulation tissue formation in the topical oxygen therapy group showed significant improvement on days 3, 7, and 14. Through van Gieson staining, the accumulation of collagen fiber in the topical oxygen therapy group was found to have improved when compared with the control group on day 7. Through semiquantitative immunohistochemical staining, many more new vessels were found in the topical oxygen therapy group compared with the model control group on day 7. [Conclusion] The results of the experiment showed that topical oxygen therapy improved ischemic wound healing.
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Local and distant trauma after hypervelocity ballistic impact to the pig hind limb.
Chen, Jin; Zhang, Bo; Chen, Wei; Kang, Jian-Yi; Chen, Kui-Jun; Wang, Ai-Min; Wang, Jian-Min
2016-01-01
The development of high-energy weapons could increase the velocity of projectiles to well over 1000 m/s. The nature of the injuries caused by the ballistic impact of projectiles at velocities much faster than 1000 m/s is unclear. This study characterizes the mechanical and biochemical alterations caused by high-speed ballistic impact generated by spherical steel ball to the hind limbs of the pig. That the local and distal injuries caused by hypervelocity ballistic impact to the living body are also identified. It is showed that the severity of the injury was positively correlated with the velocity of the projectile. And 4000 m/s seems to be the critical velocity for the 5.6 mm spherical steel ball, which would cause severe damage to either local or distal organs, as below that speed the projectile penetrated the body while above that speed it caused severe damage to the body. In addition, vaporization prevented the projectile from penetrating the body and the consequent pressure wave seems to be the causal factor for the distant damage.
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Spugnini, Enrico Pierluigi; Bolaffio, Carlo; Scacco, Licia; Baldi, Alfonso
2017-01-01
A twenty-year-old female saddle horse was referred for evaluation of a seven month, non-healing erosive lesion of the right hind hoof with proliferation and bleeding of the underlying soft tissues. This lesion had been twice surgically treated as a canker but rapidly recurred. Histological examination of the second excision revealed a well-differentiated squamous cell carcinoma. At presentation, the horse was mildly depressed, lame and partially non-weight-bearing on the right hind leg, which exhibited a 10 x 10 cm erosive and proliferative lesion remodeling the hoof. After completing staging procedures, the lesion was approached with surgery and intraoperative electrochemotherapy (ECT) administration of bleomycin in isolated limb perfusion. A second session of surgery and ECT was performed one month later, followed by three additional monthly sessions of ECT. During periodic recheck, the mare showed continuous improvement. One year after presentation, the mare was in complete remission and her gait markedly improved. ECT was well-tolerated and resulted in improved local control of a tumor in a challenging anatomical district.
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Firouzi, Matin Sadat; Firouzi, Masoumeh; Nabian, Mohammad Hossein; Zanjani, Leila Oryadi; Zadegan, Shayan Abdollah; Kamrani, Reza Shahryar; Rahimi-Movaghar, Vafa
2015-04-01
Denervation of the hind limb is a technique used to study peripheral nerve regeneration. Autotomy or autophagia is an undesirable response to denervation in such studies. Application of a commercially available lotion used to deter nail biting in humans reduced autotomy in rats after denervation but did not completely prevent it. In this study, this authors evaluated the application of picric acid to prevent autotomy in rats in peripheral nerve experiments. They carried out sciatic nerve transection in 41 adult female Wistar rats and then applied either bite-deterrent lotion (n = 26) or saturated picric acid solution (n = 15) topically to the affected hind limb immediately after surgery and every day for 1 month. Autotomy scores were lower for rats treated with picric acid than for rats treated with bite-deterrent lotion 1 week and 2 weeks after surgery but were not different between the two groups 4 weeks after surgery. The authors conclude that application of picric acid could be used as an alternative strategy to prevent autotomy in peripheral nerve studies.
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RESISTANCE TO X-IRRADIATION BY EMBRYONIC CELLS OF THE LIMB-BUDS OF TADPOLES
DOE Office of Scientific and Technical Information (OSTI.GOV)
Allen, B.M.; Ewell, L.M.
1959-01-01
Both total-body irradiation and shielding of the trunk were used to study the effects of x irradiation from 1000 to 30000 r upon the limb-buds of Bufo boreas and Hyla regilla tadpoles. The object was to test the view that the younger the cells the more sensitive they are to irradiation. The answer is negative. If there is any special susceptibility of these undifferentiated cells it should appear at levels far below the 30000 r maximum employed. A sharp distinction is made between the very susceptible mitotic cells and the resistant non-dividing embryonic cells that have been accumulated in suchmore » numbers that they may rapidly differentiate into the characteristic limb tissues under the stimulus of the thyroid hormone. Many irradiated ectoderm cells were changed to form bizarre excrescences but were not destroyed. Unicellular cuthneous gland cells continued to arise even after the heaviest irradiation. Irradiated tadpoles with hind limb-buds from 0.6 mm down to 0.2 mm length were unable to develop normal limbs. This capacity was propontional to the number of non-dividing embryonic cells stored at the time of irradiation. Irradiation of 5000, equal degree but the rapidity was greatest in the cases of higher dosage. Not only did these levels of irradiation fail to destroy the non-dividing embryonic cells but they did not effect their pre-deterrmined specificity nor modify their capacity for subsequent differentiation and growth. Exposure to a thyroxin solution caused the hind limb-buds without visible differentiation of cells to grow from a length of 0.8 or 0.9 mm or 1.0 mm at the time of irradiation to a length of as much as 5.0 mm in the course of 7 days. Development of thigh, shank, ankle, and toes was complete. Microscopic studies showed characteristic tissues such as cartilage, connective tissue, and muscle, developed to a comparable degree in control and irradiated specimens. (auth)« less
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Klotzsche - von Ameln, Anne; Cremer, Sebastian; Hoffmann, Jedrzej; Schuster, Peggy; Khedr, Sherif; Korovina, Irina; Troulinaki, Maria; Neuwirth, Ales; Sprott, David; Chatzigeorgiou, Antonios; Economopoulou, Matina; Orlandi, Alessia; Hain, Andreas; Zeiher, Andreas M.; Deussen, Andreas; Hajishengallis, George; Dimmeler, Stefanie; Chavakis, Triantafyllos; Chavakis, Emmanouil
2017-01-01
We have recently identified endothelial cell-secreted developmental endothelial locus-1 (Del-1) as an endogenous inhibitor of β2-integrin–dependent leukocyte infiltration. Del-1 was previously also implicated in angiogenesis. Here, we addressed the role of endogenously produced Del-1 in ischemia-related angiogenesis. Intriguingly, Del-1–deficient mice displayed increased neovascularization in two independent ischemic models (retinopathy of prematurity and hind-limb ischemia), as compared to Del-1–proficient mice. On the contrary, angiogenic sprouting in vitro or ex vivo (aortic ring assay) and physiological developmental retina angiogenesis were not affected by Del-1 deficiency. Mechanistically, the enhanced ischemic neovascularization in Del-1-deficiency was linked to higher infiltration of the ischemic tissue by CD45+ hematopoietic and immune cells. Moreover, Del-1-deficiency promoted β2-integrin–dependent adhesion of hematopoietic cells to endothelial cells in vitro, and the homing of hematopoietic progenitor cells and of immune cell populations to ischemic muscles in vivo. Consistently, the increased hind limb ischemia-related angiogenesis in Del-1 deficiency was completely reversed in mice lacking both Del-1 and the β2-integrin LFA-1. Additionally, enhanced retinopathy-associated neovascularization in Del-deficient mice was reversed by LFA-1 blockade. Our data reveal a hitherto unrecognized function of endogenous Del-1 as a local inhibitor of ischemia-induced angiogenesis by restraining LFA-1–dependent homing of pro-angiogenic hematopoietic cells to ischemic tissues. Our findings are relevant for the optimization of therapeutic approaches in the context of ischemic diseases. PMID:28447099
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Wang, Kaiyun; Li, Zicong; Li, Yang; Zeng, Jinyong; He, Chang; Yang, Jinzeng; Liu, Dewu; Wu, Zhenfang
2013-10-01
Myostatin is a well-known negative regulator of skeletal muscle growth. Inhibition of myostatin activity results in increased muscle mass. Myostatin propeptide, as a myostatin antagonist, could be applied to promote meat production in livestock such as pigs. In this study, we generated a transgenic mouse model expressing porcine myostatin propeptide under the control of muscle-specific regulatory elements. The mean body weight of transgenic mice from a line expressing the highest level of porcine myostatin propeptide was increased by 5.4 % (P = 0.023) and 3.2 % (P = 0.031) in males and females, respectively, at 8 weeks of age. Weight of carcass, fore limb and hind limb was respectively increased by 6.0 % (P = 0.038), 9.0 % (P = 0.014), 8.7 % (P = 0.036) in transgenic male mice, compared to wild-type male controls at the age of 9 weeks. Similarly, carcass, fore limb and hind limb of transgenic female mice was 11.4 % (P = 0.002), 14.5 % (P = 0.006) and 14.5 % (P = 0.03) respectively heavier than that of wild-type female mice. The mean cross-section area of muscle fiber was increased by 17 % (P = 0.002) in transgenic mice, in comparison with wild-type controls. These results demonstrated that porcine myostatin propeptide is effective in enhancement of muscle growth. The present study provided useful information for future study on generation of transgenic pigs overexpressing porcine myostatin propeptide for improvement of muscle mass.
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Zhuang, Mingna V.; Higham, Timothy E.
2016-01-01
By using adhesion, geckos can move through incredibly challenging habitats. However, continually changing terrain may necessitate modulation of the adhesive apparatus in order to maximize its effectiveness over a range of challenges. Behaviorally modulating how the adhesive system is applied can occur by altering the alignment of the foot relative to the long axis of the body and/or the angles between the digits (interdigital angle). Given the directionality of the adhesive system, geckos likely vary the application of the system via these mechanisms as they run. We quantified 3D movements (using high-speed video) of the day gecko, Phelsuma madagascariensis, running on a range of ecologically relevant inclines (0°, 45°, 90°) and perch diameters (1.5 cm, 10 cm and broad). We measured the instantaneous sum of interdigital angles and foot alignment relative to the body, as well as other kinematic variables, throughout each stride and across treatments. Modulation of foot alignment at 45° and 90° was similar between the forelimb and hind limb, but differed at 0°, suggesting that P. madagascariensis is able to exert an adhesive force using multiple strategies. Both the sum of interdigital angles and alignment in the fore- and hind foot were modulated. Differences in modulation between the limbs are likely related to the underlying morphology. The modulation of interdigital angle and foot alignment suggests that aspects other than the mechanism of adhesion, such as joint morphology, are important for arboreal movement in geckos. Our study of foot usage in arboreal locomotion reveals patterns that may be widespread across pad-bearing lizards. In addition to understanding the constraints exerted by the adhesive apparatus, we highlight how biomechanical traits may respond to the evolution of novel adaptations and morphologies. PMID:27145027
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Vasukutty, N; Jawalkar, H; Anugraha, A; Chekuri, R; Ahluwalia, R; Kavarthapu, V
2017-04-28
Corrective fusion for the unstable deformed hind foot and mid foot in Charcot Neuroarthropathy (CN) is quite challenging and is best done in tertiary centres under the supervision of multidisciplinary teams. We present a follow up to our initial report with a series of 42 hind foot corrections in 40 patients from a tertiary level teaching hospital in the United Kingdom. The mean patient age was 59 (33-82). 17 patients had type1diabetes mellitus, 23 had type 2. 23 feet in 22 patients had chronic ulceration despite offloading. 17 patients were ASA 2 and 23 were ASA grade 3. All patients had hind foot nail fusion performed through a standard technique by the senior author and managed perioperatively by the multidisciplinary team. At a mean follow up of 42 months (12-99) we achieved 100% limb salvage initially and a 97% fusion rate. One patient with persisting non-union of ankle and subtalar joint with difficulty in bracing has been offered below-knee amputation. We achieved deformity correction in 100% and ulcer healing in 83%. 83% patients are able to mobilize and manage independent activities of daily living. There were 11 patients with one or more complications including metal work failure, infection and ulcer reactivation. There have been nine repeat procedures including one revision fixation and one vascular procedure. Single stage corrective fusion for hind foot deformity in CN is an effective procedure when delivered by a skilled multidisciplinary team. Copyright © 2017. Published by Elsevier Ltd.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Palena, Luis Mariano, E-mail: marianopalena@hotmail.com; Brocco, Enrico; Manzi, Marco
2013-05-09
Charcot neuroarthropathy is a low-incidence complication of diabetic foot and is associated with ankle and hind foot deformity. Patients who have not developed deep ulcers are managed with offloading and supportive bracing or orthopedic arthrodesis. In patients who have developed ulcers and severe ankle instability and deformity, below-the-knee amputation is often indicated, especially when deformity and cutaneous involvement result in osteomyelitis. Ischemic association has not been described but can be present as a part of peripheral arterial disease in the diabetic population. In this extreme and advanced stage of combined neuroischemic diabetic foot disease, revascularization strategies can support surgical andmore » orthopedic therapy, thus preventing osteomyelitis and leading to limb and foot salvage.« less
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Duncan, Jennifer S; Singer, Ellen R; Devaney, Jane; Oultram, Joanne W H; Walby, Anna J; Lester, Bridie R; Williams, Helen J
2013-03-01
The aim of this project was to develop a detailed, accessible set of reference images of the normal radiographic anatomy of the ovine digit up to and including the metacarpo/metatatarsophalangeal joints. The lower front and hind limbs of 5 Lleyn ewes were radiographed using portable radiography equipment, a digital image processer and standard projections. Twenty images, illustrating the normal radiographic anatomy of the limb were selected, labelled and presented along with a detailed description and corresponding images of the bony skeleton. These images are aimed to be of assistance to veterinary surgeons, veterinary students and veterinary researchers by enabling understanding of the normal anatomy of the ovine lower limb, and allowing comparison with the abnormal.
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Experiment K-314: Fetal and neonatal rat bone and joint development following in Utero spaceflight
NASA Technical Reports Server (NTRS)
Sabelman, E. E.; Holton, E. M.; Arnaud, C. D.
1981-01-01
Infant rat limb specimens from Soviet and U.S. ground-based studies were examined by radiography, macrophotography, histologic sectioning and staining and scanning electron microscopy. A comparison was conducted between vivarium and flight-type diets suggesting that nutritional obesity may adversely affect pregnancy. Data were obtained on maturation of ossification centers, orientation of collagen fibers in bone, tendon and ligaments, joint surface texture and spatial relationships of bones of the hind limb. Computer reconstructions of the knee and hip show promise as a means of investigating the etiology of congenital hip dislocation.
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Ren, Jing; Bai, Ming; Yang, Xing-Ke; Zhang, Run-Zhi; Ge, Si-Qin
2017-01-01
The success of beetles is mainly attributed to the possibility to hide the hindwings under the sclerotised elytra. The acquisition of the transverse folding function of the hind wing is an important event in the evolutionary history of beetles. In this study, the morphological and functional variances in the hind wings of 94 leaf beetle species (Coleoptera: Chrysomelinae) is explored using geometric morphometrics based on 36 landmarks. Principal component analysis and Canonical variate analysis indicate that changes of apical area, anal area, and middle area are three useful phylogenetic features at a subtribe level of leaf beetles. Variances of the apical area are the most obvious, which strongly influence the entire venation variance. Partial least squares analysis indicates that the proximal and distal parts of hind wings are weakly associated. Modularity tests confirm that the proximal and distal compartments of hind wings are separate modules. It is deduced that for leaf beetles, or even other beetles, the hind wing possibly exhibits significant functional divergences that occurred during the evolution of transverse folding that resulted in the proximal and distal compartments of hind wings evolving into separate functional modules.
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Endo, Toshiki; Spenger, Christian; Tominaga, Teiji; Brené, Stefan; Olson, Lars
2007-11-01
Cortical sensory maps can reorganize in the adult brain in an experience-dependent manner. We monitored somatosensory cortical reorganization after sensory deafferentation using functional magnetic resonance imaging (fMRI) in rats subjected to complete transection of the mid-thoracic spinal cord. Cortical representation in response to spared forelimb stimulation was observed to enlarge and invade adjacent sensory-deprived hind limb territory in the primary somatosensory cortex as early as 3 days after injury. Functional MRI also demonstrated long-term cortical plasticity accompanied by increased thalamic activation. To support the notion that alterations of cortical neuronal circuitry after spinal cord injury may underlie the fMRI changes, we quantified transcriptional activities of several genes related to cortical plasticity including the Nogo receptor (NgR), its co-receptor LINGO-1 and brain derived neurotrophic factor (BDNF), using in situ hybridization. We demonstrate that NgR and LINGO-1 are down-regulated specifically in cortical areas deprived of sensory input and in adjacent cortex from 1 day after injury, while BDNF is up-regulated. Our results demonstrate that cortical neurons react to sensory deprivation by decreasing transcriptional activities of genes encoding the Nogo receptor components in the sensory deprived and the anatomically adjacent non-deprived area. Combined with the BDNF up-regulation, these changes presumably allow structural changes in the neuropil. Our observations therefore suggest an involvement of Nogo signalling in cortical activity-dependent plasticity in the somatosensory system. In spinal cord injury, cortical reorganization as shown here can become a disadvantage, much like the situation in amblyopia or phantom sensation. Successful strategies to repair sensory pathways at the spinal cord level may not lead to proper reestablishment of cortical connections, once deprived hind limb cortical areas have been reallocated to forelimb use. In such situations, methods to control cortical plasticity, possibly by targeting Nogo signalling, may become helpful.
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Ren, Chuancheng; Gao, Xuwen; Steinberg, Gary K.; Zhao, Heng
2009-01-01
Remote ischemic preconditioning is an emerging concept for stroke treatment, but its protection against focal stroke has not been established. We tested whether remote preconditioning, performed in the ipsilateral hind limb, protects against focal stroke and explored its protective parameters. Stroke was generated by a permanent occlusion of the left distal middle cerebral artery (MCA) combined with a 30 minute occlusion of the bilateral common carotid arteries (CCA) in male rats. Limb preconditioning was generated by 5 or 15 minute occlusion followed with the same period of reperfusion of the left hind femoral artery, and repeated for 2 or 3 cycles. Infarct was measured 2 days later. The results showed that rapid preconditioning with 3 cycles of 15 minutes performed immediately before stroke reduced infarct size from 47.7±7.6% of control ischemia to 9.8±8.6%; at 2 cycles of 15 minutes, infarct was reduced to 24.7±7.3%; at 2 cycles of 5 minutes, infarct was not reduced. Delayed preconditioning with 3 cycles of 15 minutes conducted 2 days before stroke also reduced infarct to 23.0 ±10.9%, but with 2 cycles of 15 minutes it offered no protection. The protective effects at these two therapeutic time windows of remote preconditioning are consistent with those of conventional preconditioning, in which the preconditioning ischemia is induced in the brain itself. Unexpectedly, intermediate preconditioning with 3 cycles of 15 minutes performed 12 hours before stroke also reduced infarct to 24.7±4.7%, which contradicts the current dogma for therapeutic time windows for the conventional preconditioning that has no protection at this time point. In conclusion, remote preconditioning performed in one limb protected against ischemic damage after focal cerebral ischemia. PMID:18201834
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Femoral head and neck excision arthroplasty in a leopard tortoise (Stigmochelys pardalis).
Naylor, Adam D
2013-12-01
Cases of femoral head and neck excision arthroplasty are infrequently reported in reptiles, and details of surgical technique and clinical outcome in chelonia are lacking. An adult female leopard tortoise (Stigmochelys pardalis) was presented with chronic non-weight-bearing lameness of the left hind limb. Examination and radiography were consistent with coxofemoral luxation, and as a result of the chronic presentation, surgical intervention was recommended. A cranial approach to the joint via the prefemoral fossa afforded good surgical exposure. A depressed lytic acetabular lesion was noted during the procedure, postulated to be a result of abnormal wear from the luxated femoral head. A fiberglass prop was used during recovery to allow extension of the limb without full weight-bearing. Lameness persisted postoperatively, but limb usage significantly improved.
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Vaccine-associated fibrosarcoma with keloidal differentiation in a cat.
Gumber, Sanjeev; Wakamatsu, Nobuko
2011-09-01
A 6-year-old Domestic Shorthair cat was presented with a history of subcutaneous mass of the lateral left hind limb. The subcutaneous mass developed over a period of approximately 16 months subsequent to administration of Feline leukemia virus vaccines. Based on the histopathological and immunohistochemical examination, the subcutaneous mass was diagnosed as vaccine-associated fibrosarcoma with keloidal differentiation.
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A comparison of rat myosin from fast and slow skeletal muscle and the effect of disuse
NASA Technical Reports Server (NTRS)
Unsworth, B. R.; Witzmann, F. A.; Fitts, R. H.
1981-01-01
Certain enzymatic and structural features of myosin, purified from rat skeletal muscles representative of the fast twitch glycolytic (type IIb), the fast twitch oxidative (type IIa), and the slow twitch oxidative (type I) fiber, were determined and the results were compared with the measured contractile properties. Good correlation was found between the shortening velocities and Ca(2+)-activated ATPase activity for each fiber type. Short term hind limb immobilization caused prolongation of contraction time and one-half relaxation time in the fast twitch muscles and a reduction of these contractile properties in slow twitch soleus. Furthermore, the increased maximum shortening velocity in the immobilized soleus could be correlated with increased Ca(2+)-ATPase, but no change was observed in the enzymatic activity of the fast twitch muscles. No alteration in light chain distribution with disuse was observed in any of the fiber types. The myosin from slow twitch soleus could be distinguished from fast twitch myosins on the basis of the pattern of peptides generated by proteolysis of the heavy chains. Six weeks of hind limb immobilization resulted in both an increased ATPase activity and an altered heavy chain primary structure in the slow twitch soleus muscle.
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Gardner, Christina L.; Burke, Crystal W.; Higgs, Stephen T.; Klimstra, William B.; Ryman, Kate D.
2012-01-01
In humans, chikungunya virus (CHIKV) infection causes fever, rash, and acute and persisting polyarthalgia/arthritis associated with joint swelling. We report a new CHIKV disease model in adult mice that distinguishes the wild-type CHIKV-LR strain from the live-attenuated vaccine strain (CHIKV-181/25). Although eight-week old normal mice inoculated in the hind footpad developed no hind limb swelling with either virus, CHIKV-LR replicated in musculoskeletal tissues and caused detectable inflammation. In mice deficient in STAT1-dependent interferon (IFN) responses, CHIKV-LR caused significant swelling of the inoculated and contralateral limbs and dramatic inflammatory lesions, while CHIKV-181/25 vaccine and another arthritogenic alphavirus, Sindbis, failed to induce swelling. IFN responses suppressed CHIKV-LR and CHIKV-181/25 replication equally in dendritic cells in vitro whereas macrophages were refractory to infection independently of STAT1-mediated IFN responses. Glycosaminoglycan (GAG) binding may be a CHIKV vaccine attenuation mechanism as CHIKV-LR infectivity was not dependent upon GAG, while CHIKV-181/25 was highly dependent. PMID:22305131
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Occurrence of Wounds in Nigerian Horses.
Agina, Onyinyechukwu A; Ihedioha, John I
2017-01-01
This study investigated the occurrence of wounds in Nigerian horses. The study population was 1,621 horses sold at the Obollo Afor horse lairage in Enugu State, Nigeria, during a 6-month period: 3 months of dry season and 3 months of rainy season (February-April and June-August 2012). A total of 207 horses were systematically sampled and subjected to a comprehensive physical examination. Those with wounds were marked, recorded, and clinically examined. Of the 207 horses sampled, 21 (10.1%) had wounds. The body distribution of the wounds was 9.5% head, 9.5% forelimbs, 19.1% hind limbs, 4.8% tail, 14.3% flank, 9.5% loin, 19.1% hip, 9.5% barrel, and 4.8% croup. The occurrence of the wounds was not significantly associated with sex or season, but the occurrence in adults was significantly (p < .05) higher than that in the young and aged horses. It was concluded that the occurrence of wounds is relatively high (10.1%), and mainly the hind limbs, hip, and flank of adult horses are affected. It was recommended that horse guardians and handlers should be properly educated on the care of horses.
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Harris, L K; Whay, H R; Murrell, J C
2018-04-01
This study investigated the effects of osteoarthritis (OA) on somatosensory processing in dogs using mechanical threshold testing. A pressure algometer was used to measure mechanical thresholds in 27 dogs with presumed hind limb osteoarthritis and 28 healthy dogs. Mechanical thresholds were measured at the stifles, radii and sternum, and were correlated with scores from an owner questionnaire and a clinical checklist, a scoring system that quantified clinical signs of osteoarthritis. The effects of age and bodyweight on mechanical thresholds were also investigated. Multiple regression models indicated that, when bodyweight was taken into account, dogs with presumed osteoarthritis had lower mechanical thresholds at the stifles than control dogs, but not at other sites. Non-parametric correlations showed that clinical checklist scores and questionnaire scores were negatively correlated with mechanical thresholds at the stifles. The results suggest that mechanical threshold testing using a pressure algometer can detect primary, and possibly secondary, hyperalgesia in dogs with presumed osteoarthritis. This suggests that the mechanical threshold testing protocol used in this study might facilitate assessment of somatosensory changes associated with disease progression or response to treatment. Copyright © 2017. Published by Elsevier Ltd.
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Field, Cara L; Beaufrère, Hugues; Wakamatsu, Nobuko; Rademacher, Nathalie; MacLean, Robert
2012-12-01
A 22-year-old female African black-footed penguin (Spheniscus demersus), housed indoors with other African and rockhopper penguins, was presented acutely with lethargy, ataxia, and hind limb weakness after a molt. The penguin would assume a hunched position and, when resting, sat on its hocks or lay on its keel. Physical and neurologic examination revealed hind limb paraparesis, proprioceptive deficits, and tiptoe walking. Results of a complete blood cell count and biochemical analysis revealed mild heterophilic leukocytosis, anemia, mild hypoalbuminemia, hypokalemia, and hyperuricemia. Results of whole-body radiographs and coelioscopy were unremarkable. Two computed tomographies of the spine at a 3-month interval revealed a lesion at the mobile thoracic vertebra proximal to the synsacrum with associated spinal cord compression. The penguin was treated with itraconazole, doxycycline, and meloxicam, and it initially improved with return to near normal gait and behavior. However, 5 months after the onset of clinical signs, the penguin was euthanatized after a relapse with worsening of the neurologic signs. Postmortem and histopathologic examination revealed focal granulomatous discospondylitis at the penultimate mobile thoracic vertebra, with intralesional bacteria from which Staphylococcus aureus was cultured.
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Mineral distribution in rat skeletons after exposure to a microgravity model
NASA Technical Reports Server (NTRS)
Arnaud, Sara B.; Harper, Jennifer S.; Navidi, Meena
1995-01-01
Exposure to space flight models induces changes in the distribution of bone mineral in the human skeleton that has the features of a gravitational gradient. Regional bone mineral measurements with dual energy x-ray absorptiometry (DEXA) in male adults exposed to head-down tilt bed rest for 30 days shown non-significant decrements in the pelvis and legs with 10% increases in the head region. Horizontal bed rest for 17 weeks reveals losses of bone mineral ranging from 2.2 to 10.4% from the lumbar spine to the calcaneus and an increase of 3.4% in the skull. Investigation of this phenomena would be most definitively carried out in an animal model. One candidate is the flight simulation model in the rat which removes body weight from the hind limbs and induces a cephalad fluid shift by suspending the animal by the tail. Weanling rats exposed to this model showed bone mineral to be lower in the hind limbs and higher in the skull after 3 weeks. These finds are similar in older 200 g animals after 2 weeks tail suspension. The purpose of this study was to determine the effect of age on the distribution of skeletal mineral in this model.
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Tseng, Shih-Ya; Chao, Ting-Hsing; Li, Yi-Heng; Liu, Ping-Yen; Lee, Cheng-Han; Cho, Chung-Lung; Wu, Hua-Lin; Chen, Jyh-Hong
2016-04-01
Cilostazol is an antiplatelet agent with vasodilatory effects that works by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP). This study investigated the effects of cilostazol in preventing high glucose (HG)-induced impaired angiogenesis and examined the potential mechanisms involving activation of AMP-activated protein kinase (AMPK). Assays for colony formation, adhesion, proliferation, migration, and vascular tube formation were used to determine the effect of cilostazol in HG-treated endothelial progenitor cells (EPCs) or human umbilical vein endothelial cells (HUVECs). Animal-based assays were performed in hyperglycemic ICR mice undergoing hind limb ischemia. An immnunoblotting assay was used to identify the expression and activation of signaling molecules in vitro and in vivo. Cilostazol treatment significantly restored endothelial function in EPCs and HUVECs through activation of AMPK/acetyl-coenzyme A carboxylase (ACC)-dependent pathways and cAMP/protein kinase A (PKA)-dependent pathways. Recovery of blood flow in the ischemic hind limb and the population of circulating CD34(+) cells were significantly improved in cilostazol-treated mice, and these effects were abolished by local AMPK knockdown. Cilostazol increased the phosphorylation of AMPK/ACC and Akt/endothelial nitric oxide synthase signaling molecules in parallel with or downstream of the cAMP/PKA-dependent signaling pathway in vitro and in vivo. Cilostazol prevents HG-induced endothelial dysfunction in EPCs and HUVECs and enhances angiogenesis in hyperglycemic mice by interactions with a broad signaling network, including activation of AMPK/ACC and probably cAMP/PKA pathways. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
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Thompson, Melissa D; Mei, Yu; Weisbrod, Robert M; Silver, Marcy; Shukla, Praphulla C; Bolotina, Victoria M; Cohen, Richard A; Tong, Xiaoyong
2014-07-18
The sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) is key to Ca(2+) homeostasis and is redox-regulated by reversible glutathione (GSH) adducts on the cysteine (C) 674 thiol that stimulate Ca(2+) uptake activity and endothelial cell angiogenic responses in vitro. We found that mouse hind limb muscle ischemia induced S-glutathione adducts on SERCA in both whole muscle tissue and endothelial cells. To determine the role of S-glutathiolation, we used a SERCA 2 C674S heterozygote knock-in (SKI) mouse lacking half the key thiol. Following hind limb ischemia, SKI animals had decreased SERCA S-glutathione adducts and impaired blood flow recovery. We studied SKI microvascular endothelial cells in which total SERCA 2 expression was unchanged. Cultured SKI microvascular endothelial cells showed impaired migration and network formation compared with wild type (WT). Ca(2+) studies showed decreased nitric oxide (·NO)-induced (45)Ca(2+) uptake into the endoplasmic reticulum (ER) of SKI cells, while Fura-2 studies revealed lower Ca(2+) stores and decreased vascular endothelial growth factor (VEGF)- and ·NO-induced Ca(2+) influx. Adenoviral overexpression of calreticulin, an ER Ca(2+) binding protein, increased ionomycin-releasable stores, VEGF-induced Ca(2+) influx and endothelial cell migration. Taken together, these data indicate that the redox-sensitive Cys-674 thiol on SERCA 2 is required for normal endothelial cell Ca(2+) homeostasis and ischemia-induced angiogenic responses, revealing a novel redox control of angiogenesis via Ca(2+) stores. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
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Bischofberger, Andrea S; Ringer, Simone K; Geyer, Hans; Imboden, Isabel; Ueltschi, Gottlieb; Lischer, Christoph J
2006-04-01
To determine via histologic examination and scintigraphy the effect of focused extracorporeal shock wave therapy (ESWT) on normal bone and the bone-ligament interface in horses. 6 horses without lameness. Origins of the suspensory ligament at the metacarpus (35-mm probe depth) and fourth metatarsal bone (5-mm probe depth) were treated twice (days 0 and 16) with 2,000 shocks (energy flux density, 0.15 mJ/mm2). One forelimb and 1 hind limb were randomly treated, and the contralateral limbs served as nontreated controls. Bone scans were performed on days -1 (before ESWT), 3, 16, and 19. Histomorphologic studies of control and treated tissues were performed on day 30. ESWT significantly increased the number of osteoblasts but caused no damage to associated soft tissue structures and did not induce cortical microfractures. A significant correlation between osteoblast numbers and radiopharmaceutical uptake was noticed on lateral views of the hind limb on days 3 and 16 and on caudal views of the forelimb on day 3. Results suggested that ESWT has the potential to increase osteoblast numbers in horses. The correlation between increased osteoblast numbers and radio-pharmaceutical uptake 3 days and 16 days after the first ESWT suggested that stimulation of osteogenesis occurred soon after ESWT. No damage to bone or the bone-ligament interface should occur at the settings used in this study, and ESWT can therefore be administered safely in horses.
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Holfeld, Johannes; Tepeköylü, Can; Blunder, Stefan; Lobenwein, Daniela; Kirchmair, Elke; Dietl, Marion; Kozaryn, Radoslaw; Lener, Daniela; Theurl, Markus; Paulus, Patrick; Kirchmair, Rudolf; Grimm, Michael
2014-01-01
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.
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Bourke, Ca
2009-03-01
Fenugreek staggers has occurred in sheep in Victoria, as both an acute and a chronic syndrome. Signs included quadraparesis, a high stepping fore limb gait and a 'bunny-hopping' hind limb gait. Changes consistent with acute oedema were found in the brain and spinal cord of acute cases, and Wallerian degeneration in the peripheral nerves of chronic cases. Kangaroo gait occurred in ewes in New South Wales, and the clinical signs and microscopic changes were remarkably similar to those of fenugreek staggers. Although the diet associated with each is different the causal agent may be the same.
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Effects of stretching and disuse on amino acids in muscles of rat hind limbs
NASA Technical Reports Server (NTRS)
Jaspers, Stephen R.; Henriksen, Erik J.; Satarug, Soisungwan; Tischler, Marc E.
1989-01-01
The effects of disuse and passive stretch on the concentrations of amino acids and ammonia in the unloaded soleus muscle was investigated in hindquarter-suspended (for six days by casting one foot in dorsiflexion) tail-casted rats. For a comparison with the condition of unloading, amino acids and ammonia were also measured in shortened extensor digitorum longus in the same casted limb and in denervated leg muscles. The results obtained suggest that passive stretch diminishes some of the characteristic alterations of amino acid concentrations due to unloading. This effect of stretch is considered to be due to the maintenance of muscle tension.
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NASA Astrophysics Data System (ADS)
Kamimura, Hermes; Wang, Shutao; Chen, Hong; Wang, Qi; Aurup, Christian; Fan, Kathtleen; Carneiro, Antonio; Konofagou, Elisa
Ultrasound neurostimulation has been proven capable of eliciting motor responses. However, the studies in sedated rodents presented problems with target specificity due to the use of low ultrasound frequencies (<700 kHz). Here, we show that focused ultrasound (FUS) in mega-Hz range was able to evoke motor responses in mice under deep anesthesia. Contralateral movements of the hind limbs were observed when sonications were carried out at +2 mm of Lambda and ±2 mm lateral of midline in three mice. Moreover, stimulating other regions of the somatosensory and cerebellum induced trunk and ipsilateral limb movements in all six mice.
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Use of Methyl Salicylates As a Trialing Chemical Agent Simulant
1990-05-01
phocomelia of the hind-limbs were frequently seen after injection on day 11. Hydronephrosis , ectoplc kidneys, and exencephaly were occasionally observed...Oapparent hydronephrosis " late in gestition. This apparent abnormality decreases by steady lengthening of the renal papilla with advancing fetal anw...treated fetuses at weaning., This persistent condition, suggestive, of hydronephrosis or hypoplasia, was not noted in control fetuses. Monie (1970
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Progressive ataxia in a Charolais bull.
Zicker, S C; Kasari, T R; Scruggs, D W; Read, W K; Edwards, J F
1988-06-01
A 20-month-old Charolais bull was referred for evaluation of progressive hind limb ataxia. Clinical findings suggested a neuroanatomic lesion caudal to T2. Postmortem histologic examination revealed multifocal, acellular, pale, eosinophilic plaques throughout the cerebellum, which were diagnostic for the disease progressive ataxia of Charolais cattle. This disease is presumed to have a hereditary transmission and is not commonly recognized in the United States.
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2009-01-01
H12 Swollen forelimb (a) and hind limb (b)....................................................................................58 H13 Predator...tortoises have been impacted by incidental take permits issued to developers in the past 14 years (J. Berish, pers. comm.). The inherent impacts of...respect to the potential infectious diseases present within wild populations, the impact of disease status on relocation or reproduction of species
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Effects of Hind Limb Unloading on Pharmacokinetics of Procainamide in Mice
NASA Technical Reports Server (NTRS)
Risin, Semyon A.; Dasgupta, Amitava; Ramesh, Govindarajan T.; Risin, Diana
2007-01-01
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-life time in the HLU mice points towards slower drug elimination from the circulation.
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NASA Astrophysics Data System (ADS)
Walb, M. C.; Black, P. J.; Payne, V. S.; Munley, M. T.; Willey, J. S.
2015-07-01
Exposure to the spaceflight environment has long been known to be a health challenge concerning many body systems. Both microgravity and/or ionizing radiation can cause acute and chronic effects in multiple body systems. The hind limb unloaded (HLU) rodent model is a ground-based analogue for microgravity that can be used to simulate and study the combined biologic effects of reduced loading with spaceflight radiation exposure. However, studies delivering radiation to rodents during periods of HLU are rare. Herein we report the development of an irradiation protocol using a clinical linear accelerator that can be used with hind limb unloaded, unanesthetized rodents that is capable of being performed at most academic medical centers. A 30.5 cm × 30.5 cm × 40.6 cm rectangular chamber was constructed out of polymethyl methacrylate (PMMA) sheets (0.64 cm thickness). Five centimeters of water-equivalent material were placed outside of two PMMA inserts on either side of the rodent that permitted the desired radiation dose buildup (electronic equilibrium) and helped to achieve a flatter dose profile. Perforated aluminum strips permitted the suspension dowel to be placed at varying heights depending on the rodent size. Radiation was delivered using a medical linear accelerator at an accelerating potential of 10 MV. A calibrated PTW Farmer ionization chamber, wrapped in appropriately thick tissue-equivalent bolus material to simulate the volume of the rodent, was used to verify a uniform dose distribution at various regions of the chamber. The dosimetry measurements confirmed variances typically within 3%, with maximum variance <10% indicated through optically stimulated luminescent dosimeter (OSLD) measurements, thus delivering reliable spaceflight-relevant total body doses and ensuring a uniform dose regardless of its location within the chamber. Due to the relative abundance of LINACs at academic medical centers and the reliability of their dosimetry properties, this method may find great utility in the implementation of future ground-based studies that examine the combined spaceflight challenges of reduced loading and radiation while using the HLU rodent model.
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Miles, C A; Fursey, G A; Fisher, A V; Page, S J
1991-01-01
The application of the velocity of sound (VOS) technique to lamb carcasses in a previous study (Fisher & Page, 1986) measured composition at a hind limb and neck site but was not as precise as fat scores in predicting lean proportion. This study examines VOS measurements made at sites in the hind limbs and along the vertebral column in live sheep and carcasses. A group (A) comprising five breeds of males and females (n = 61) and a sub-group (B) of Scottish Blackface castrated males (n = 34) were studied, and the reciprocal velocity of ultrasound (RV) was measured on the live sheep immediately behind the shoulder and over the last rib using a fixed-distance transducer assembly operating at 5 MHz, and in the hind limbs at 2·25 MHz using the apparatus described by Miles et al. (1984). Corresponding measurements were made on the carcasses which were classified by a Meat and Livestock Commission fatstock officer and then dissected. Standard deviations of lean proportion were 4·48% (A) and 3·39% (B). The residual standard deviations (rsds) for groups A and B respectively were obtained using the following predictors: live mass (LM) 4·27% and 2·96%; LM + breed (B) 3·08% (group A only); LM + mean RV 2·36% and 2·07%; LM + B + mean RV 1·99% (group A only). Using carcass measurements: carcass mass (CM) 4·25% and 2·90%; CM + MLC fat score 2·99% and 2·12%; CM + RV last rib 2·89% and 2·02%. These data show that VOS measurements through dorsal sites of live sheep provide encouragingly precise estimates of carcass lean proportion. For carcasses, dorsal sites provide a less precise estimate of carcass lean but when carcass mass is included in multiple regression the precision of the correlation is comparable with that of multiple regression of fat score with carcass mass. Copyright © 1991. Published by Elsevier Ltd.
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The effects of L-carnitine on spinal cord ischemia/reperfusion injury in rabbits.
Tetik, O; Yagdi, T; Islamoglu, F; Calkavur, T; Posacioglu, H; Atay, Y; Ayik, F; Canpolat, L; Yuksel, M
2002-02-01
Paraplegia after distal aortic aneurysm repair remains a persistent clinical problem. We hypothesized that the tolerance of the spinal cord to an ischemic period could be improved with hypothermic Ringer's Lactate containing L-Carnitine. Twenty-eight New Zealand white rabbits were used as spinal cord ischemia models. We separated rabbits into four equal groups and clamped each animal's abdominal aorta distal to the left renal artery. We occluded the aortas above the iliac bifurcation for 30 minutes. In group I, the infrarenal aorta was clamped without infusing any solution. In group II, Ringer's Lactate solution was infused at + 25degrees C for 3 minutes at a rate of 5 ml/min into the isolated aortic segments immediately after cross-clamping and the last 3 minutes of ischemia. In group III, Ringer's Lactate solution at +3 degrees C was given in the same method as that of group II. In group IV, Ringer's Lactate solution at +3 degrees C plus 100 mg/kg of L-carnitine was infused using the same technique. We assessed the neurological status of the hind limbs 24 and 48 hours after operation according to Tarlov's criteria. All animals were sacrificed and spinal cords were harvested for histological analyses. The neurological status in groups III and IV was significantly superior to that of groups I and II. All the animals in group I had complete hind-limb paraplegia. Complete hind-limb paraplegia occurred in 5 rabbits in group II. Two of the 7 animals in group III had spastic paraplegia, and none at all in group IV. Histological analysis of the cross-clamped segments of the rabbits with paraplegia in group I, II and III revealed changes consistent with ischemic injury, while findings were normal for the normal animals in group III and IV. In this model, the infusion of hypothermic Ringer's Lactate contained L-carnitine provided sufficient spinal cord protection against ischemia. Clinically, this may be a useful adjunct for prevention of paraplegia during surgery of the descending aorta.
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Papastefanaki, Florentia; Jakovcevski, Igor; Poulia, Nafsika; Djogo, Nevena; Schulz, Florian; Martinovic, Tamara; Ciric, Darko; Loers, Gabrielle; Vossmeyer, Tobias; Weller, Horst; Schachner, Melitta; Matsas, Rebecca
2015-06-01
Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.
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Proteomic analysis of blastema formation in regenerating axolotl limbs
2009-01-01
Background Following amputation, urodele salamander limbs reprogram somatic cells to form a blastema that self-organizes into the missing limb parts to restore the structure and function of the limb. To help understand the molecular basis of blastema formation, we used quantitative label-free liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)-based methods to analyze changes in the proteome that occurred 1, 4 and 7 days post amputation (dpa) through the mid-tibia/fibula of axolotl hind limbs. Results We identified 309 unique proteins with significant fold change relative to controls (0 dpa), representing 10 biological process categories: (1) signaling, (2) Ca2+ binding and translocation, (3) transcription, (4) translation, (5) cytoskeleton, (6) extracellular matrix (ECM), (7) metabolism, (8) cell protection, (9) degradation, and (10) cell cycle. In all, 43 proteins exhibited exceptionally high fold changes. Of these, the ecotropic viral integrative factor 5 (EVI5), a cell cycle-related oncoprotein that prevents cells from entering the mitotic phase of the cell cycle prematurely, was of special interest because its fold change was exceptionally high throughout blastema formation. Conclusion Our data were consistent with previous studies indicating the importance of inositol triphosphate and Ca2+ signaling in initiating the ECM and cytoskeletal remodeling characteristic of histolysis and cell dedifferentiation. In addition, the data suggested that blastema formation requires several mechanisms to avoid apoptosis, including reduced metabolism, differential regulation of proapoptotic and antiapoptotic proteins, and initiation of an unfolded protein response (UPR). Since there is virtually no mitosis during blastema formation, we propose that high levels of EVI5 function to arrest dedifferentiated cells somewhere in the G1/S/G2 phases of the cell cycle until they have accumulated under the wound epidermis and enter mitosis in response to neural and epidermal factors. Our findings indicate the general value of quantitative proteomic analysis in understanding the regeneration of complex structures. PMID:19948009
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Regeneration of limb joints in the axolotl (Ambystoma mexicanum).
Lee, Jangwoo; Gardiner, David M
2012-01-01
In spite of numerous investigations of regenerating salamander limbs, little attention has been paid to the details of how joints are reformed. An understanding of the process and mechanisms of joint regeneration in this model system for tetrapod limb regeneration would provide insights into developing novel therapies for inducing joint regeneration in humans. To this end, we have used the axolotl (Mexican Salamander) model of limb regeneration to describe the morphology and the expression patterns of marker genes during joint regeneration in response to limb amputation. These data are consistent with the hypothesis that the mechanisms of joint formation whether it be development or regeneration are conserved. We also have determined that defects in the epiphyseal region of both forelimbs and hind limbs in the axolotl are regenerated only when the defect is small. As is the case with defects in the diaphysis, there is a critical size above which the endogenous regenerative response is not sufficient to regenerate the joint. This non-regenerative response in an animal that has the ability to regenerate perfectly provides the opportunity to screen for the signaling pathways to induce regeneration of articular cartilage and joints.
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Regeneration of Limb Joints in the Axolotl (Ambystoma mexicanum)
Lee, Jangwoo; Gardiner, David M.
2012-01-01
In spite of numerous investigations of regenerating salamander limbs, little attention has been paid to the details of how joints are reformed. An understanding of the process and mechanisms of joint regeneration in this model system for tetrapod limb regeneration would provide insights into developing novel therapies for inducing joint regeneration in humans. To this end, we have used the axolotl (Mexican Salamander) model of limb regeneration to describe the morphology and the expression patterns of marker genes during joint regeneration in response to limb amputation. These data are consistent with the hypothesis that the mechanisms of joint formation whether it be development or regeneration are conserved. We also have determined that defects in the epiphyseal region of both forelimbs and hind limbs in the axolotl are regenerated only when the defect is small. As is the case with defects in the diaphysis, there is a critical size above which the endogenous regenerative response is not sufficient to regenerate the joint. This non-regenerative response in an animal that has the ability to regenerate perfectly provides the opportunity to screen for the signaling pathways to induce regeneration of articular cartilage and joints. PMID:23185640
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Heterochrony in the regulation of the developing marsupial limb.
Chew, Keng Yih; Shaw, Geoffrey; Yu, Hongshi; Pask, Andrew J; Renfree, Marilyn B
2014-02-01
At birth, marsupial neonates have precociously developed forelimbs. The development of the tammar wallaby (Macropus eugenii) hindlimbs lags significantly behind that of the forelimbs. This differs from the grey short-tailed opossum, Monodelphis domestica, which has relatively similar fore- and hindlimbs at birth. This study examines the expression of the key patterning genes TBX4, TBX5, PITX1, FGF8, and SHH in developing limb buds in the tammar wallaby. All genes examined were highly conserved with orthologues from opossum and mouse. TBX4 expression appeared earlier in development than in the mouse, but later than in the opossum. SHH expression is restricted to the zone of polarising activity, while TBX5 (forelimb) and PITX1 (hindlimb) showed diffuse mRNA expression. FGF8 is specifically localised to the apical ectodermal ridge, which is more prominent than in the opossum. The most marked divergence in limb size in marsupials occurs in the kangaroos and wallabies. The faster development of the fore limb compared to that of the hind limb correlates with the early timing of the expression of the key patterning genes in these limbs. Copyright © 2013 Wiley Periodicals, Inc.
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Kostereva, Nataliya V; Wang, Yong; Fletcher, Derek R; Unadkat, Jignesh V; Schnider, Jonas T; Komatsu, Chiaki; Yang, Yang; Stolz, Donna B; Davis, Michael R; Plock, Jan A; Gorantla, Vijay S
2016-01-01
Impaired nerve regeneration and inadequate recovery of motor and sensory function following peripheral nerve repair remain the most significant hurdles to optimal functional and quality of life outcomes in vascularized tissue allotransplantation (VCA). Neurotherapeutics such as Insulin-like Growth Factor-1 (IGF-1) and chondroitinase ABC (CH) have shown promise in augmenting or accelerating nerve regeneration in experimental models and may have potential in VCA. The aim of this study was to evaluate the efficacy of low dose IGF-1, CH or their combination (IGF-1+CH) on nerve regeneration following VCA. We used an allogeneic rat hind limb VCA model maintained on low-dose FK506 (tacrolimus) therapy to prevent rejection. Experimental animals received neurotherapeutics administered intra-operatively as multiple intraneural injections. The IGF-1 and IGF-1+CH groups received daily IGF-1 (intramuscular and intraneural injections). Histomorphometry and immunohistochemistry were used to evaluate outcomes at five weeks. Overall, compared to controls, all experimental groups showed improvements in nerve and muscle (gastrocnemius) histomorphometry. The IGF-1 group demonstrated superior distal regeneration as confirmed by Schwann cell (SC) immunohistochemistry as well as some degree of extrafascicular regeneration. IGF-1 and CH effectively promote nerve regeneration after VCA as confirmed by histomorphometric and immunohistochemical outcomes.
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Tröster, Philip; Haseleu, Julia; Petersen, Jonas; Drees, Oliver; Schmidtko, Achim; Schwaller, Frederick; Lewin, Gary R.; Ter-Avetisyan, Gohar; Winter, York; Peters, Stefanie; Feil, Susanne; Feil, Robert; Rathjen, Fritz G.; Schmidt, Hannes
2018-01-01
A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI (Npr2fl/fl;Wnt1Cre and cGKIKO/fl;Wnt1Cre) that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice. Cholera toxin labeling in digits of the hind paw demonstrated an altered shape of sensory neuron termination fields in the spinal cord of conditional Npr2 mouse mutants. Behavioral testing of both sexes indicated that noxious heat sensation and nociception induced by chemical irritants are impaired in the mutants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are not affected. Recordings from C-fiber nociceptors in the hind limb skin showed that Npr2 function was not required to maintain normal heat sensitivity of peripheral nociceptors. Thus, the altered behavioral responses to noxious heat found in Npr2fl/fl;Wnt1Cre mice is not due to an impaired C-fiber function. Overall, these data point to a critical role of axonal bifurcation for the processing of pain induced by heat or chemical stimuli. PMID:29472841
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Carter, Edward A; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A; Jung, Walter; Tompkins, Ronald G; Fischman, Alan J
2014-01-01
Burn trauma to the extremities can produce marked systemic effects in mice. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism ([18F] 2-fluoro-2-deoxy-D-glucose [18FDG] uptake) by brown adipose tissue (BAT) and nuclear factor (NF)-κB activity in several tissues including skeletal muscle. This study examined the effect of a single hind limb burn in mice on 18FDG uptake by NF-κB activity in vivo, and blood flow was determined by laser Doppler techniques. Male NF-κB luciferase reporter mice (28-30 g) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham-treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 mL, i.p.). The individual animals were placed in wire bottom cages with no food and free access to water. After 24 hours, the animals were imaged with laser Doppler for measuring blood flow in the hind limb. The animals were then unanesthetized with 50 μCi of FDG or luciferin (1.0 mg, i.v.) via tail vein. Five minutes after luciferin injection, NF-κB mice were studied by bioluminescence imaging with a charge-coupled device camera. One hour after 18FDG injection, the animals were killed with carbon dioxide overdose, and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full-thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than that in the contralateral limb. Similarly, luciferase activity and blood flow in the burned leg were lower than those in the contralateral leg. 18FDG uptake by BAT and heart increased, whereas that by brain decreased. In conclusion, the present study suggests that burn injury to a single leg decreased FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression compared with the contralateral leg and the uninjured skeletal muscle of the sham but activated NF-κB expression in a number of other organs. These findings are consistent with the hypothesis that burn trauma to the extremities can produce marked systemic effects, including activation of NF-κB expression and activation of 18FDG uptake by BAT.
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Positioning Vascularized Composite Allotransplantation in the Spectrum of Transplantation
2015-10-01
composite allograft (VCA) survival without a need for maintenance immunosuppression. 12th Congress of the International Hand and Composite Tissue ...14. ABSTRACT We have continued our studies of the immune mechanisms contributing to rejection of vascularized composite allografts (VCA) in murine...models, and how these may be overcome to promote long-term allograft survival. We have now firmly established an orthotopic hind limb VCA model in our
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Acute hind limb paralysis secondary to an extradural spinal cord Cryptococcus gattii lesion in a dog
Kurach, Lindsey; Wojnarowicz, Chris; Wilkinson, Tom; Sereda, Colin
2013-01-01
A 2-year-old, spayed female, German short-haired pointer was presented with a 1-day history of non-ambulatory paraplegia with absent deep pain perception. A computed tomography scan revealed an irregular eighth thoracic vertebral body and an extradural compressive lesion. Decompression was performed and abnormal tissues were submitted for analysis. Findings were consistent with a Cryptococcus gattii infection. PMID:24155428
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Focal thoracolumbar spinal cord lymphosarcoma in a ferret (Mustela putorius furo)
Ingrao, Joelle C.; Eshar, David; Vince, Andrew; Lee-Chow, Bridget; Nykamp, Stephanie; DeLay, Josepha; Smith, Dale
2014-01-01
A 6-year-old, castrated male domestic ferret (Mustela putorius furo) was euthanized following progressive hind limb paresis and atonia of the bladder of 1-year duration. Neurological evaluation localized the lesion to the thoracolumbar spinal region, and magnetic resonance imaging showed a focal intramedullary spinal cord lesion. Histopathology revealed an extensive, unencapsulated, poorly demarcated mass within the thoracolumbar spinal cord, diagnosed as lymphosarcoma. PMID:24982519
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Synergistic Actions of Pyridostigmine Bromide and Insecticides on Muscle and Vascular Nociceptors
2012-07-01
biceps femoris muscles (right hind limb; PAM, Ugo Basile ). To complement pressure pain testing, activity levels (movement distance, rest time) were...Permethrin on Skin, Muscle and Vascular Nociceptors During the brief course of the Gulf war, GW veterans were exposed to 13 or more pesticides (DOD...Environmental Exposure Report: Pesticides , 2003). Some of these pesticides have direct interactions with the pain system (pyrethroids: permethrin
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Khunakornvichaya, Arada; Lekmeechai, Sujinna; Pham, Phi Phuong; Himakoun, Wanwisa; Pitaksuteepong, Tasana; Morales, Noppawan Phumala; Hemstapat, Warinkarn
2016-01-01
This study was designed to investigate the anti-nociceptive effect of Morus alba stem extract as well as its cartilage protective effect in the anterior cruciate ligament transection (ACLT)-induced rat model of osteoarthritis (OA). The anti-nociceptive effect of this plant extract was determined by measuring hind limb weight bearing, while the severity of cartilage damage to the knee joints was evaluated using the modified Mankin grading system. Oral administration of M. alba stem extract (56 and 560 mg/kg) significantly attenuated joint pain as indicated by a significant (p < 0.05) increase in the values of percent weight borne on the operated hind limb for the OA-induced groups that received M. alba stem extract at 56 and 560 mg/kg when compared to those of the vehicle-treated OA-induced group. In addition, a significant improvement in the Mankin score was also observed in rats treated with 560 mg/kg M. alba stem extract, which was in agreement with its pain-relieving effect. The results showed that M. alba stem extract exhibited an anti-nociceptive effect as well as cartilage protection in the ACLT-induced rat model of OA, supporting its potential use as a therapeutic treatment for OA. © 2016 S. Karger AG, Basel.
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Tumor necrosis factor-alpha induced enhancement of cryosurgery
NASA Astrophysics Data System (ADS)
Goel, Raghav; Paciotti, Guilio F.; Bischof, John C.
2008-02-01
Local recurrence of cancer after cryosurgery is related to the inability to monitor and predict destruction of cancer (temperatures > -40°C) within an iceball. We previously reported that a cytokine adjuvant TNF-α could be used to achieve complete cancer destruction at the periphery of an iceball (0 to -40°C). This study is a further development of that work in which cryosurgery was performed using cryoprobes operating at temperatures > -40°C. LNCaP Pro 5 tumor grown in a dorsal skin fold chamber (DSFC) was frozen at -6°C after TNF-α incubation for 4 or 24 hours. Tumors grown in the hind limb were frozen with a probe tip temperature of -40°C, 4 or 24 hours after systemic injection with TNF-α. Both cryosurgery alone or TNF-α treatment alone caused only a minimal damage to the tumor tissue at the conditions used in the study. The combination of TNF-α and cryosurgery produced a significant damage to the tumor tissue in both the DSFC and the hind limb model system. This augmentation in cryoinjury was found to be time-dependent with 4-hour time period between the two treatments being more effective than 24-hour. These results suggests the possibility of cryotreatment at temperatures > -40°C with the administration of TNF-α.
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Schuster, Frank; Johannsen, Stephan; Roewer, Norbert; Anetseder, Martin
2013-04-01
We hypothesized that the phosphodiesterase-III-inhibitor milrinone and the non-specific G-protein activator sodium fluoride increase the skeletal muscular lactate levels as a sign of a hypermetabolic response. With approval of the local animal care committee Sprague-Dawley rats were killed and artificially perfused either with Ringer's solution or sodium fluoride 110 mM, while milrinone 1.32 mM or Ringer's solution at 1 μl/min was applied via microdialysis probes in both hind limbs. Lactate was measured spectrophotometrically in the dialysate. Baseline lactate levels before drug application did not differ between hind limbs. Local infusion of milrinone via microdialysis did not significantly increase intramuscular lactate concentrations compared with the Ringer control group. Muscular perfusion with sodium fluoride resulted in a significant increase of lactate and was potentiated by combination with local milrinone. Phosphodiesterase-III-inhibition alone does not significantly influence the lactate levels in skeletal muscle of sacrificed rats. Sodium fluoride infusion leads to an intramuscular lactate increase, which was further potentiated by local inhibition of phosphodiesterase-III. The fluoride-mediated hypermetabolic response following sodium fluoride could be a possible explanation for the observed myotoxic adverse effects in individuals treated by fluoride-containing agents. © 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.
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NASA Astrophysics Data System (ADS)
Ahad, M. A.; Rutkove, S. B.
2010-04-01
Tetrapolar surface electrical impedance methods are sensitive to changes in muscle status and can therefore provide a means for studying neuromuscular disease noninvasively. In order to better understand the relationship between surface impedance measurements and the actual muscle electrical properties, we performed measurements on 20 adult Wistar rats, 8 of which underwent sciatic nerve crush. Surface impedance measurements were performed on the left hind limb both before injury and out to 2 weeks after injury. In addition, both normal and sciatic crush animals were sacrificed and the dielectric properties of the extracted gastrocnemius muscle measured. We found that 50 kHz conductivities were greater in the animals that underwent crush than in the animals that did not. The permittivities in both directions, however, showed non-significant differences. In order to analyze the effect of these changes as well as the accompanying reduction in muscle volume, a finite element model of the hind limb was developed based on computerized tomographic imaging. The model successfully predicted the surface impedance values in the animals after crush injury and, by its inverse application, may be used to help determine the underlying electrical properties of muscle in various neuromuscular diseases based on surface impedance data.
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Morphological changes in hind limb muscles elicited by adjuvant-induced arthritis of the rat knee.
Ozawa, J; Kurose, T; Kawamata, S; Yamaoka, K
2010-02-01
We investigated qualitative and quantitative changes in rat hind limb muscles caused by complete Freund's adjuvant (CFA)-induced knee joint pain. One week after CFA injection, muscle atrophy was induced only on the CFA-injected side. Wet weight of the rectus femoris (RF) and soleus (SOL) muscles were significantly decreased by 20% and 19%, respectively. The reduction in cross-sectional areas by CFA was similar for fast and slow muscle fibers in the RF (10% vs 15%, respectively) and SOL muscles (16% vs 16%, respectively). At the light microscopic level, pathological changes were not found in the RF muscles on both sides, although the infiltration of mononuclear cells and muscle regeneration were found in the SOL muscles on CFA-injected and contralateral control sides. On the other hand, electron microscopy revealed degenerative changes in the RF and SOL muscles on the CFA-injected side. Interestingly, sarcomere hypercontraction, indicating overexercise, was observed to a limited extent in the SOL muscles on the control side. In conclusions, knee joint pain can trigger the rapid development of muscle atrophy with degenerative changes not only in thigh but also calf muscles. This indicates that early interventions to inhibit joint pain or inflammation may prevent muscle atrophy.
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The response of Dahl salt-sensitive and salt-resistant female rats to a space flight model
NASA Technical Reports Server (NTRS)
Thierry-Palmer, Myrtle; Cephas, Stacy; Cleek, Tammy; Sayavongsa, Phouyong; Arnaud, Sara B.
2003-01-01
Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have tested the hypothesis that differences in vitamin D metabolism would render the Dahl S rat more susceptible than the Dahl R rat to the effects of a space flight model. Dahl female rats were tail suspended (hind limb unloaded) for 28 days, while fed a low salt (3 g/kg sodium chloride) diet. Plasma 25-OHD concentrations of S rats were significantly lower than that of R rats. Plasma 1,25-(OH)2D concentration was 50% lower in unloaded than in loaded S rats, but was unaffected in unloaded R rats. The left soleus muscle weight and breaking strength of the left femur (torsion test) were 50% and 25% lower in unloaded than in loaded S and R rats. The mineral content of the left femur, however, was significantly lower (by 11%) only in unloaded S rats. We conclude that female S rats are more vulnerable than female R rats to decreases in plasma 1,25-(OH)2D concentration and femur mineral content during hind limb unloading, but equally vulnerable to muscle atrophy and reduced breaking strength of the femur.
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Mice with cancer-induced bone pain show a marked decline in day/night activity.
Majuta, Lisa A; Guedon, Jean-Marc G; Mitchell, Stefanie A T; Kuskowski, Michael A; Mantyh, Patrick W
2017-09-01
Cancer-induced bone pain (CIBP) is the most common type of pain with cancer. In humans, this pain can be difficult to control and highly disabling. A major problem with CIBP in humans is that it increases on weight-bearing and/or movement of a tumor-bearing bone limiting the activity and functional status of the patient. Currently, there is less data concerning whether similar negative changes in activity occur in rodent models of CIBP. To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Osteosarcoma cells were injected and confined to 1 femur of the adult male mouse. Every 7 days, spontaneous horizontal and vertical activities were assessed over a 20-hour day and night period using automated activity boxes. Mechanical hypersensitivity of the hind paw skin was assessed using von Frey testing. As the tumor cells grew within the femur, there was a significant decline in horizontal and vertical activity during the times of the day/night when the mice are normally most active. Mice also developed significant hypersensitivity in the skin of the hind paw in the tumor-bearing limb. Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status.
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Initial evaluation of a canine stifle arthrotomy post-operative pain model.
Tomas, A; Bledsoe, D; Wall, S; Davidson, G; Lascelles, B D X
2015-06-01
Most models of acute post-operative orthopedic pain involve the injection of a clinically irrelevant pro-inflammatory agent. The ideal model should, however, be clinically relevant and allow full functional recovery of enrolled animals after research is completed. This study explored the validity of a model employing arthrotomy and objectively measured limb use. Six purpose-bred Beagles underwent arthrotomies on each stifle with a washout period in between. Using a randomized crossover design, each dog received placebo and an extended-release buprenorphine (ER-Bup) preparation. Static and dynamic ground reaction forces (GRFs) were measured prior to and for 72 h following surgery using a pressure sensitive walkway (PSW). GRFs for each hind limb were compared using difference (delta), and symmetry indices (SI). The effects of surgery and of treatment were analyzed using repeated measures ANCOVA. The results indicated significantly decreased limb use compared to baseline for placebo, and significantly increased limb use in the ER-Bup group over placebo at all times for % bodyweight distribution (%BWdistrib), peak vertical force (PVF) and vertical impulse (VI). There was a significant treatment by time interaction for velocity (P = 0.03) and %BWdistrib (P = 0.01, 0.003). Overall, the data show that reduced limb use was present for at least 72 h following arthrotomy. In addition, the use of the ER-Bup analgesic decreased lameness, confirming the validity of this approach as a model of post-operative pain. Subjective assessments did not detect the pain-inducing effects of arthrotomy or pain-alleviating effects of treatment, and subjective measures of procedural pain in research dogs need to be developed. Copyright © 2015 Elsevier Ltd. All rights reserved.
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A simple behavioral test for locomotor function after brain injury in mice.
Tabuse, Masanao; Yaguchi, Masae; Ohta, Shigeki; Kawase, Takeshi; Toda, Masahiro
2010-11-01
To establish a simple and reliable test for assessing locomotor function in mice with brain injury, we developed a new method, the rotarod slip test, in which the number of slips of the paralytic hind limb from a rotarod is counted. Brain injuries of different severity were created in adult C57BL/6 mice, by inflicting 1-point, 2-point and 4-point cryo-injuries. These mice were subjected to the rotarod slip test, the accelerating rotarod test and the elevated body swing test (EBST). Histological analyses were performed to assess the severity of the brain damage. Significant and consistent correlations between test scores and severity were observed for the rotarod slip test and the EBST. Only the rotarod slip test detected the mild hindlimb paresis in the acute and sub-acute phase after injury. Our results suggest that the rotarod slip test is the most sensitive and reliable method for assessing locomotor function after brain damage in mice. Copyright © 2010 Elsevier Ltd. All rights reserved.
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Vibration-induced muscle injury. An experimental model and preliminary findings.
Necking, L E; Dahlin, L B; Fridén, J; Lundborg, G; Lundström, R; Thornell, L E
1992-06-01
The hind paws of rats were subjected to vibration at a frequency of 80 Hz., an acceleration of 32 m./s.2 rms (i.e. ah.w approximately 6.3 m./s.2 rms) for five hours daily during five consecutive days. Morphological, histochemical and immunohistochemical analyses of the soleus, extensor digitorum longus and the plantar muscles in the vibrated limb and the contralateral control limb were performed. No changes were seen in the soleus or extensor digitorum longus muscles but different degrees of degeneration of the muscle fibres were seen in the plantar muscle sections as well as signs of regeneration. No changes were observed in the contralateral unexposed limb. It is concluded that it is not only nervous tissue but also muscle tissue that can be affected by vibration. The changes seem to be confined to muscles close to the vibration exciter.
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Thromboxane A2 moderates permeability after limb ischemia.
Lelcuk, S; Alexander, F; Valeri, C R; Shepro, D; Hechtman, H B
1985-01-01
Reperfusion after limb ischemia results in muscle edema as well as excess secretion of thromboxane A2 (TxA2), an agent associated with permeability increase in other settings. This study tests whether TxA2 moderates the permeability following limb ischemia. A tourniquet inflated to 300 mmHg was applied for 2 hours around the hind limb of four groups of dogs. In untreated animals (N = 25), 2 hours following tourniquet release, plasma TxB2 values rose from 320 pg/ml to 2416 pg/ml (p less than 0.001), and popliteal lymph values rose from 378 pg/ml to 1046 pg/ml (p less than 0.001). Platelet TxB2 was unaltered and plasma 6-keto-PGF1 alpha levels did not vary. Following ischemia, lymph flow (QL) increased from 0.07 to 0.37 ml/h (p less than 0.05), while the lymph/plasma (L/P) protein ratio was unchanged at 0.41. These measurements indicate increased permeability since increase in hydrostatic pressure in a second group by tourniquet inflation to 50 mmHg (N = 7) led to a rise in QL from 0.07 to 0.22 ml/h, but a fall in the L/P ratio to 0.32, a value lower than the ischemic group (p less than 0.05). Pretreatment with the imidazole derivative ketoconazole (N = 11) reduced platelet Tx synthesis from 42 ng to 2 ng/10(9) platelets, but lymph TxB2 levels rose to 1703 pg/ml after ischemia, indicating an extravascular or vessel wall site of synthesis not inhibited by ketoconazole. Pretreatment with a lower molecular weight imidazole derivative OKY 046 (N = 9) inhibited all Tx synthesis after ischemia. Prior to tourniquet inflation, both OKY 046 and ketoconazole lowered plasma TxB2 levels as well as the L/P ratio (p less than 0.05). After ischemia, OKY 046, but not ketoconazole, maintained the L/P ratio at 0.33, a value below that of untreated animals (p less than 0.05). These results indicate that nonplatelet-derived TxA2 modulates both baseline and ischemia-induced increases in microvascular permeability in the dog hind limb. PMID:3840349
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Feed forward and feedback control for over-ground locomotion in anaesthetized cats
NASA Astrophysics Data System (ADS)
Mazurek, K. A.; Holinski, B. J.; Everaert, D. G.; Stein, R. B.; Etienne-Cummings, R.; Mushahwar, V. K.
2012-04-01
The biological central pattern generator (CPG) integrates open and closed loop control to produce over-ground walking. The goal of this study was to develop a physiologically based algorithm capable of mimicking the biological system to control multiple joints in the lower extremities for producing over-ground walking. The algorithm used state-based models of the step cycle each of which produced different stimulation patterns. Two configurations were implemented to restore over-ground walking in five adult anaesthetized cats using intramuscular stimulation (IMS) of the main hip, knee and ankle flexor and extensor muscles in the hind limbs. An open loop controller relied only on intrinsic timing while a hybrid-CPG controller added sensory feedback from force plates (representing limb loading), and accelerometers and gyroscopes (representing limb position). Stimulation applied to hind limb muscles caused extension or flexion in the hips, knees and ankles. A total of 113 walking trials were obtained across all experiments. Of these, 74 were successful in which the cats traversed 75% of the 3.5 m over-ground walkway. In these trials, the average peak step length decreased from 24.9 ± 8.4 to 21.8 ± 7.5 (normalized units) and the median number of steps per trial increased from 7 (Q1 = 6, Q3 = 9) to 9 (8, 11) with the hybrid-CPG controller. Moreover, within these trials, the hybrid-CPG controller produced more successful steps (step length ≤ 20 cm ground reaction force ≥ 12.5% body weight) than the open loop controller: 372 of 544 steps (68%) versus 65 of 134 steps (49%), respectively. This supports our previous preliminary findings, and affirms that physiologically based hybrid-CPG approaches produce more successful stepping than open loop controllers. The algorithm provides the foundation for a neural prosthetic controller and a framework to implement more detailed control of locomotion in the future.
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Feed forward and feedback control for over-ground locomotion in anaesthetized cats
Mazurek, K A; Holinski, B J; Everaert, D G; Stein, R B; Etienne-Cummings, R; Mushahwar, V K
2012-01-01
The biological central pattern generator (CPG) integrates open and closed loop control to produce over-ground walking. The goal of this study was to develop a physiologically based algorithm capable of mimicking the biological system to control multiple joints in the lower extremities for producing over-ground walking. The algorithm used state-based models of the step cycle each of which produced different stimulation patterns. Two configurations were implemented to restore over-ground walking in five adult anaesthetized cats using intramuscular stimulation (IMS) of the main hip, knee and ankle flexor and extensor muscles in the hind limbs. An open loop controller relied only on intrinsic timing while a hybrid-CPG controller added sensory feedback from force plates (representing limb loading), and accelerometers and gyroscopes (representing limb position). Stimulation applied to hind limb muscles caused extension or flexion in the hips, knees and ankles. A total of 113 walking trials were obtained across all experiments. Of these, 74 were successful in which the cats traversed 75% of the 3.5 m over-ground walkway. In these trials, the average peak step length decreased from 24.9 ± 8.4 to 21.8 ± 7.5 (normalized units) and the median number of steps per trial increased from 7 (Q1=6, Q3 = 9) to 9 (8, 11) with the hybrid-CPG controller. Moreover, these trials, the hybrid-CPG controller produced more successful steps (step length ≤ 20 cm; ground reaction force ≥ 12.5% body weight) than the open loop controller: 372 of 544 steps (68%) versus 65 of 134 steps (49%), respectively. This supports our previous preliminary findings, and affirms that physiologically based hybrid-CPG approaches produce more successful stepping than open loop controllers. The algorithm provides the foundation for a neural prosthetic controller and a framework to implement more detailed control of locomotion in the future. PMID:22328615
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Effects of VX on Acoustic Startle Response and Acquisition of Operant Behavior in Rats
2008-02-01
spontaneous motor activity , fore- and hind-limb grip strength, thermal sensitivity (paw-lick latency), rectal temperature, acoustic startle response, and...whereas spontaneous motor activity and avoidance responding were affected at doses at or above 123 µg/kg, and acoustic startle response was affected...The 60- and 70-dB stimuli were stimulus control conditions presented to ensure that there was not significant activity within the recording chamber
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Papageorges, M.; Lussier, S.; Breton, L.; Gosselin, Y.; Teuscher, E.
1982-01-01
A pulmonary anaplastic epithelioma in a bitch An anaplastic epithelioma of the lungs was diagnosed in a 26 month old female Airedale. The authors describe signs of bronchopneumonia and lameness involving the right fore and hind limbs. The lameness occurred following metastases to the long bones. The clinical signs, the radiological appearance, the postmortem lesions encountered with that neoplasm and differential diagnosis are discussed. ImagesFigure 1.Figure 2.Figure 3.Figure 4a,b.Figure 5.Figure 6. PMID:17422120
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2017-06-12
REBOA.Methods: 12 swine were anesthetized, instrumented, then underwent 15 blood volume hemorrhage. Animals were randomized to hypothermia or...normothermia followed by 4 hours of zone III REBOA, resuscitation with shed blood , and 3 hours of critical care. Physiologic parameters were continuously...significant differences between groups at baseline or after hemorrhage. No histologic differences were observed in hind limb skeletal muscle. Maximum
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Rubenson, Jonas; Lloyd, David G; Besier, Thor F; Heliams, Denham B; Fournier, Paul A
2007-07-01
Although locomotor kinematics in walking and running birds have been examined in studies exploring many biological aspects of bipedalism, these studies have been largely limited to two-dimensional analyses. Incorporating a five-segment, 17 degree-of-freedom (d.f.) kinematic model of the ostrich hind limb developed from anatomical specimens, we quantified the three-dimensional (3-D) joint axis alignment and joint kinematics during running (at approximately 3.3 m s(-1)) in the largest avian biped, the ostrich. Our analysis revealed that the majority of the segment motion during running in the ostrich occurs in flexion/extension. Importantly, however, the alignment of the average flexion/extension helical axes of the knee and ankle are rotated externally to the direction of travel (37 degrees and 21 degrees , respectively) so that pure flexion and extension at the knee will act to adduct and adbuct the tibiotarsus relative to the plane of movement, and pure flexion and extension at the ankle will act to abduct and adduct the tarsometatarsus relative to the plane of movement. This feature of the limb anatomy appears to provide the major lateral (non-sagittal) displacement of the lower limb necessary for steering the swinging limb clear of the stance limb and replaces what would otherwise require greater adduction/abduction and/or internal/external rotation, allowing for less complex joints, musculoskeletal geometry and neuromuscular control. Significant rotation about the joints' non-flexion/extension axes nevertheless occurs over the running stride. In particular, hip abduction and knee internal/external and varus/valgus motion may further facilitate limb clearance during the swing phase, and substantial non-flexion/extension movement at the knee is also observed during stance. Measurement of 3-D segment and joint motion in birds will be aided by the use of functionally determined axes of rotation rather than assumed axes, proving important when interpreting the biomechanics and motor control of avian bipedalism.
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Rupture of the gastrocnemius muscle in six foals.
Jesty, Sophy A; Palmer, Jonathan E; Parente, Eric J; Schaer, Thomas P; Wilkins, Pamela A
2005-12-15
Rupture of the gastrocnemius muscle and subsequent disruption of the reciprocal mechanism of the hind limb was diagnosed in 6 foals examined at 7 hours to 3 weeks of age. In 2 foals, the musculoskeletal injury was detected as an ancillary finding to clinical signs of neurologic dysfunction ascribed to hypoxic ischemic insult during delivery, whereas in the other 4 foals, musculoskeletal injury, manifested as inability to rise or stand unsupported, was the chief complaint at admission. Five foals had a history of dystocia and assisted delivery. Common clinical signs were inability to rise, disruption of the reciprocal mechanism, swelling in the caudal aspect of the thigh, instability of the stifle joint, and stifle joint effusion. For mild gastrocnemius injury, exercise restriction via forced recumbency, with minimal or no bandaging, may be sufficient treatment. For more severe disruption of the muscle, limb stabilization via splinting and intensive nursing and monitoring are necessary. Four foals had important concurrent problems, including musculoskeletal deformations (joint contractures), hypoxic ischemic disease, and failure of passive transfer and associated problems (ie, sepsis, polyarthritis, and pneumonia). Moderate to severe gastrocnemius muscle injury is difficult to treat successfully, and the long-term prognosis for athletic function should be regarded as guarded.
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Do all frogs swim alike? The effect of ecological specialization on swimming kinematics in frogs.
Robovska-Havelkova, Pavla; Aerts, Peter; Rocek, Zbynek; Prikryl, Tomas; Fabre, Anne-Claire; Herrel, Anthony
2014-10-15
Frog locomotion has attracted wide scientific interest because of the unusual and derived morphology of the frog pelvic girdle and hind limb. Previous authors have suggested that the design of the frog locomotor system evolved towards a specialized jumping morphology early in the radiation of the group. However, data on locomotion in frogs are biased towards a few groups and most of the ecological and functional diversity remains unexplored. Here, we examine the kinematics of swimming in eight species of frog with different ecologies. We use cineradiography to quantify movements of skeletal elements from the entire appendicular skeleton. Our results show that species with different ecologies do differ in the kinematics of swimming, with the speed of limb extension and especially the kinematics of the midfoot being different. Our results moreover suggest that this is not a phylogenetic effect because species from different clades with similar ecologies converge on the same swimming kinematics. We conclude that it is important to analyze frog locomotion in a broader ecological and evolutionary context if one is to understand the evolutionary origins of this behavior. © 2014. Published by The Company of Biologists Ltd.
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The effects of topical oxygen therapy on equine distal limb dermal wound healing.
Tracey, Alexandra K; Alcott, Cody J; Schleining, Jennifer A; Safayi, Sina; Zaback, Peter C; Hostetter, Jesse M; Reinertson, Eric L
2014-12-01
Topical oxygen therapy (TOT) has been used in human medicine to promote healing in chronic wounds. To test the efficacy and safety of TOT in horses, an experimental wound model was created by making 1 standardized dermal wound on each limb of 4 healthy horses (n = 16). Each wound was fitted with an oxygen delivery cannula and covered with a bandage. One limb of each front and hind pair was randomly assigned to the treatment group (fitted with an oxygen concentrator device), with the contralateral limb assigned to the control group (no device). Wound area, epithelial area, and contraction were measured every 3 to 4 d. Biopsy samples and culture swabs were taken on days 16 and 32 to evaluate angiogenesis, fibroplasia, epithelial hyperplasia, inflammation and bacterial growth. Mean healing time in treated wounds (45 d, range: 38 to 52 d) was not significantly different from that in the paired control wounds (50 d, range: 38 to 62 d). Topical oxygen therapy had little effect on dermal wound healing in this experimental wound model in healthy horses.
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Tsuka, T; Ooshita, K; Sugiyama, A; Osaki, T; Okamoto, Y; Minami, S; Imagawa, T
2012-01-01
Computed tomography (CT) was performed on 400 claws (200 inner and 200 outer claws) of 100 pairs of bovine hind limbs to investigate the etiological theory that an exacerbating factor for ulceration is exostosis of the tuberculum flexorium within the distal phalanx. A variety of morphological changes of the tuberculum flexorium of bovine hind limb claws was visualized by 3-dimensional CT, and the geometry of these claws suggested a growth pattern of bone development with respect to the assumed daily loading patterns. This growth occurs initially at the abaxial caudal aspect of the distal phalanx and is followed by horizontal progression toward the axial aspect. The length of downward bone development on the solar face of the distal phalanx was 2.73±1.32 mm in the outer claws, significantly greater than in the inner claws (2.38±0.96 mm). Ratios of downward (vertical) bone development to the thickness of the subcutis and the corium (VerBD ratios) did not differ between the outer and inner claws (36.7 vs. 38.3%, respectively). Ratios of horizontal bone development to the axial-to-abaxial line of the tuberculum flexorium (HorBD ratios) were approximately 60% for both outer and inner claws. These quantitative measures regarding horizontal and vertical bone development within the distal phalanx were positively correlated with age and VerBD ratios (r=0.53 and r=0.36 for the inner and outer claws, respectively). Correlations between claw width of the outer claw and length of vertical bone development (r=0.43), the HorBD ratio (r=0.51), and the VerBD ratio (r=0.42) suggested that the relative size difference between the inner and outer claws enhances bone development in the outer claw. Correlation coefficients between VerBD and HorBD ratios (r=0.52 and 0.63 for the inner and outer claws, respectively) suggested that horizontal and vertical bone development occurs as a synchronized process within the tuberculum flexorium. This age-related progress of bone development within the tuberculum flexorium is associated with increased exposure to several exacerbating factors and the laminitic process. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
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In vivo characterization of regenerative peripheral nerve interface function
NASA Astrophysics Data System (ADS)
Ursu, Daniel C.; Urbanchek, Melanie G.; Nedic, Andrej; Cederna, Paul S.; Gillespie, R. Brent
2016-04-01
Objective. Regenerative peripheral nerve interfaces (RPNIs) are neurotized free autologous muscle grafts equipped with electrodes to record myoelectric signals for prosthesis control. Viability of rat RPNI constructs have been demonstrated using evoked responses. In vivo RPNI characterization is the next critical step for assessment as a control modality for prosthetic devices. Approach. Two RPNIs were created in each of two rats by grafting portions of free muscle to the ends of divided peripheral nerves (peroneal in the left and tibial in the right hind limb) and placing bipolar electrodes on the graft surface. After four months, we examined in vivo electromyographic signal activity and compared these signals to muscular electromyographic signals recorded from autologous muscles in two rats serving as controls. An additional group of two rats in which the autologous muscles were denervated served to quantify cross-talk in the electrode recordings. Recordings were made while rats walked on a treadmill and a motion capture system tracked the hind limbs. Amplitude and periodicity of signals relative to gait were quantified, correlation between electromyographic and motion recording were assessed, and a decoder was trained to predict joint motion. Main Results. Raw RPNI signals were active during walking, with amplitudes of 1 mVPP, and quiet during standing, with amplitudes less than 0.1 mVPP. RPNI signals were periodic and entrained with gait. A decoder predicted bilateral ankle motion with greater than 80% reliability. Control group signal activity agreed with literature. Denervated group signals remained quiescent throughout all evaluations. Significance. In vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Signal contamination from muscles adjacent to the RPNI is minimal, as demonstrated by the low amplitude signals obtained from the Denervated group. The periodicity and entrainment to gait of RPNI recordings suggests the transduced signals were generated via central nervous system control.
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Handrigan, Gregory R; Wassersug, Richard J
2007-02-01
Anurans (frogs, toads, and their larvae) are among the most morphologically derived of vertebrates. While tightly conserved across the order, the anuran Bauplan (body plan) diverges widely from that of other vertebrates, particularly with respect to the skeleton. Here we address the adaptive, ontogenetic, and genetic bases of three such hallmark anuran features: (1) the absence of discrete caudal vertebrae, (2) a truncated axial skeleton, and (3) elongate hind limbs. We review the functional significance of each as it relates to the anuran lifestyle, which includes locomotor adaptations to both aquatic and terrestrial environments. We then shift our focus to the proximal origins of each feature, namely, ontogeny and its molecular regulation. Drawing on relatively limited data, we detail the development of each character and then, by extrapolating from comparative vertebrate data, propose molecular bases for these processes. Cast in this light, the divergent morphology of anurans emerges as a product of evolutionary modulation of the generalised vertebrate developmental machinery. Specifically, we hypothesise that: (1) the formation of caudal vertebrae is precluded due to a failure of sclerotomes to form cartilaginous condensations, perhaps resulting from altered expression of a suite of genes, including Pax1, Pax9, Msx1, Uncx-4.1, Sonic hedgehog, and noggin; (2) anteriorised Hox gene expression in the paraxial mesoderm has led to a rostral shift of morphological boundaries of the vertebral column; and, (3) spatial and temporal shifts in Hox expression may underlie the expanded tarsal elements of the anuran hind limb. Technology is currently in place to investigate each of these scenarios in the African clawed frog Xenopus. Experimental corroboration will further our understanding of the molecular regulation of the anuran Bauplan and provide insight into the origin of vertebrate morphological diversity as well as the role of development in evolution.
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Positioning Vascularized Composite Allotransplantation within the Spectrum of Transplantation
2016-10-01
In the third year of this grant, we made significant progress using our rat osteomyocutaneous flap model to study the effect of rejection on...submitted in the first quarter of year 4. We have also made significant progress in using the Vevo 2100 in imaging vasculopathy in the rat model, as...transplant biopsy timepoints, with multiple slides per timepoint to scan, as well as selected slides of the rat hind-limb project that are designated for
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Wagner, Robert A
2009-01-01
Cardiac disease in pet ferrets is common and includes dilated cardiomyopathy, arrhythmias, and acquired valvular disease. Clinical presentation of cardiac disease in ferrets may be similar to dog or cats, although hind limb weakness may be a prominent feature. Radiography, ECG, and ultrasound are all useful tools in the diagnosis of cardiac disease in ferrets. Therapeutics for cardiac disease in ferrets is based on recommendations for dogs and cats. The prognosis for cardiac disease in ferrets varies from fair to guarded, depending on underlying disease.
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Nerve Growth Factor Dependent Changes in Electrophysiology Measured in a Neurotrophic Electrode
2001-10-25
required for neuroprosthetic systems is developing rapidly. We have systems capable of simultaneously recording 10s of channels of neuronal data, computers...on the face, on the shoulder or torso, and a few on the hind limb . To date, we have recorded from a single implant 3 of 4 Fig. 3 Comparison of non...producing neurite extension in a chick DRG preparation. IV. DISCUSSION One of the important advances required before neuroprosthetics can become a
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Rahman, M. H.; Hossain, M. M.; Rahman, S. M. E.; Amin, M. R.; Oh, Deog-Hwan
2015-01-01
This study was performed to explore the deterioration of physicochemical quality of beef hind limb during frozen storage at −20℃, affected by repeated freeze-thaw cycles. The effects of three successive freeze-thaw cycles on beef hind limb were investigated comparing with unfrozen beef muscle for 80 d by keeping at −20±1℃. The freeze-thaw cycles were subjected to three thawing methods and carried out to select the best one on the basis of deterioration of physicochemical properties of beef. As the number of repeated freeze-thaw cycles increased, drip loss decreased and water holding capacity (WHC) increased (p<0.05) till two cycles and then decreased. Cooking loss increased in cycle one and three but decreased in cycle two. Moreover, drip loss, WHC and cooking loss affected (p<0.05) by thawing methods within the cycles. However, pH value decreased (p<0.05), but peroxide value (p<0.05), free fatty acids value (p<0.05) and TBARS value increased (p<0.05) significantly as the number of repeated freeze-thaw cycles increased. Moreover, significant (p<0.05) interactive effects were found among the thawing methods and repeated cycles. As a result, freeze-thaw cycles affected the physicochemical quality of beef muscle, causing the degradation of its quality. PMID:26877637
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Servo-controlled hind-limb electrical stimulation for short-term arterial pressure control.
Kawada, Toru; Shimizu, Shuji; Yamamoto, Hiromi; Shishido, Toshiaki; Kamiya, Atsunori; Miyamoto, Tadayoshi; Sunagawa, Kenji; Sugimachi, Masaru
2009-05-01
Autonomic neural intervention is a promising tool for modulating the circulatory system thereby treating some cardiovascular diseases. In 8 pentobarbital-anesthetized cats, it was examined whether the arterial pressure (AP) could be controlled by acupuncture-like hind-limb electrical stimulation (HES). With a 0.5-ms pulse width, HES monotonically reduced AP as the stimulus current increased from 1 to 5 mA, suggesting that the stimulus current could be a primary control variable. In contrast, the depressor effect of HES showed a nadir approximately 10 Hz in the frequency range between 1 and 100 Hz. Dynamic characteristics of the AP response to HES approximated a second-order low-pass filter with dead time (gain: -10.2 +/- 1.6 mmHg/mA, natural frequency: 0.040 +/- 0.004 Hz, damping ratio 1.80 +/- 0.24, dead time: 1.38 +/- 0.13 s, mean +/- SE). Based on these dynamic characteristics, a servo-controlled HES system was developed. When a target AP value was set at 20 mmHg below the baseline AP, the time required for the AP response to reach 90% of the target level was 38 +/- 10 s. The steady-state error between the measured and target AP values was 1.3 +/- 0.1 mmHg. Autonomic neural intervention by acupuncture-like HES might provide an additional modality to quantitatively control the circulatory system.
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Koga, Hiroyasu; Nanjoh, Yasuko; Toga, Tetsuo; Pillai, Radhakrishnan; Jo, William; Tsuboi, Ryoji
2016-01-01
To compare drug concentrations in the stratum corneum following daily application of luliconazole and terbinafine cream in a guinea pig tinea pedis model. Luliconazole 1% cream or terbinafine 1% cream were topically applied once daily to hind limbs of guinea pigs for 14 days. Drug concentration in stratum corneum of plantar skin was measured by HPLC-UV on days 1, 3, 7, 10, and 14. Separately, creams were applied daily for 5 days to the hind limbs of guinea pigs and skin drug release determined. In addition, drug retention in the stratum corneum was assessed by infecting guinea pigs with Trichophyton mentagrophytes, 14 and 21 days after a single application of luliconazole or terbinafine creams. Luliconazole stratum corneum concentrations were higher than those of terbinafine throughout the study. Concentrations of luliconazole and terbinafine were 71.6μg/g and 36.6μg/g, respectively, after a single application (P<.05), reaching steady state after 10 days. Cumulative release of luliconazole from the stratum corneum was 4.5 times greater than with terbinafine. Unlike terbinafine, no fungal invasion of the stratum corneum was seen 14 days post-treatment with luliconazole. Drug concentrations of luliconazole in the stratum corneum and subsequent release are greater than those achieved with terbinafine and may contribute to clinical efficacy. Luliconazole may also provide greater protection against disease recurrence.
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Three new species of woodlizards (Hoplocercinae, Enyalioides) from northwestern South America
Torres-Carvajal, Omar; Venegas, Pablo J.; de Queiroz, Kevin
2015-01-01
Abstract The discovery of three new species of Enyalioides from the tropical Andes in Ecuador and northern Peru is reported. Enyalioides altotambo sp. n. occurs in northwestern Ecuador and differs from other species of Enyalioides in having dorsal scales that are both smooth and homogeneous in size, a brown iris, and in lacking enlarged, circular and keeled scales on the flanks. Enyalioides anisolepis sp. n. occurs on the Amazonian slopes of the Andes in southern Ecuador and northern Peru and can be distinguished from other species of Enyalioides by its scattered, projecting large scales on the dorsum, flanks, and hind limbs, as well as a well-developed vertebral crest, with the vertebrals on the neck at least three times higher than those between the hind limbs. Enyalioides sophiarothschildae sp. n. is from the Amazonian slopes of the Cordillera Central in northeastern Peru; it differs from other species of Enyalioides in having caudal scales that are relatively homogeneous in size on each caudal segment, a white gular region with a black medial patch and several turquoise scales in males, as well as immaculate white labials and chin. A molecular phylogenetic tree of 18 species of hoplocercines is presented, including the three species described in this paper and Enyalioides cofanorum, as well as an updated identification key for species of Hoplocercinae. PMID:25901116
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A mouse model for chronic pain-induced increase in ethanol consumption.
Butler, Ryan K; Knapp, Darin J; Ulici, Veronica; Longobardi, Lara; Loeser, Richard F; Breese, George R
2017-03-01
Chronic pain conditions are often comorbid with alcohol abuse. "Self-medication" with alcohol introduces a host of problems associated with the abuse of alcohol which over time has the potential of exacerbating the painful condition. Despite the prevalence of chronic pain being associated with alcohol abuse, rodent models which mimic the comorbid conditions are lacking. In this study, we model osteoarthritis (OA) in C57BL/6J mice by surgically destabilizing the medial meniscus (DMM). Sham-operated mice served as controls. Thirteen weeks after surgery, DMM but not sham-operated mice exhibited pronounced incapacitance of the surgically manipulated hind limb compared with the nonsurgically manipulated hind limb. At this time, the mice were exposed to the 2-bottle ethanol choice, beginning with 2.5% with a gradual increasing to 20%. Compared with sham controls, DMM mice consumed more EtOH and preferred EtOH over water at the 20% EtOH concentration. Histological analysis verified that the DMM mice exhibited significant damage to the articular cartilage and osteophyte growth compared with sham controls and these measures of the severity of OA correlated with the amount of ethanol intake. Thus, the combination of the DMM model of OA with the enhanced two-bottle ethanol choice is a potential preclinical approach in mice by which the basis of the comorbid association of alcohol abuse and chronic pain conditions can be explored.
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Mice with cancer-induced bone pain show a marked decline in day/night activity
Majuta, Lisa A.; Guedon, Jean-Marc G.; Mitchell, Stefanie A.T.; Kuskowski, Michael A.; Mantyh, Patrick W.
2017-01-01
Abstract Introduction: Cancer-induced bone pain (CIBP) is the most common type of pain with cancer. In humans, this pain can be difficult to control and highly disabling. A major problem with CIBP in humans is that it increases on weight-bearing and/or movement of a tumor-bearing bone limiting the activity and functional status of the patient. Currently, there is less data concerning whether similar negative changes in activity occur in rodent models of CIBP. Objectives: To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Methods: Osteosarcoma cells were injected and confined to 1 femur of the adult male mouse. Every 7 days, spontaneous horizontal and vertical activities were assessed over a 20-hour day and night period using automated activity boxes. Mechanical hypersensitivity of the hind paw skin was assessed using von Frey testing. Results: As the tumor cells grew within the femur, there was a significant decline in horizontal and vertical activity during the times of the day/night when the mice are normally most active. Mice also developed significant hypersensitivity in the skin of the hind paw in the tumor-bearing limb. Conclusion: Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status. PMID:29392229
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Venous Shunt Versus Venous Ligation for Vascular Damage Control: The Immunohistochemical Evidence.
Góes Junior, Adenauer Marinho de Oliveira; Abib, Simone de Campos Vieira; Alves, Maria Teresa de Seixas; Ferreira, Paulo Sérgio Venerando da Silva; Andrade, Mariseth Carvalho de
2017-05-01
To evaluate the expression of immunohistochemical markers of tissue ischemia (iNOS, eNOS, and HSP70) in a vascular damage control experimental model to determine if a venous temporary vascular shunt insertion leads to a better limb perfusion when compared with the ligature of the injured vein. Experimental study in male Sus Scrofa weighting 40 Kg. Animals were distributed into 5 groups: group 1 animals were submitted to right external iliac artery (EIA) shunting and right external iliac vein (EIV) ligation; group 2 animals were submitted to right EIA shunting and right EIV shunting; group 3 animals were submitted to right EIV ligation; group 4 animals were submitted to right EIV shunting; group 5 animals were not submitted to vascular shunting or venous ligation. Transonic Systems flowmeters were used to measure vascular flow on right and left external iliac vessels, and i-STAT (Abbot) portable blood analyzer was used for EIVs blood biochemical analysis. An initial baseline register of invasive arterial pressure, iliac vessels flow, and venous blood analysis was performed. Arterial pressure and iliac vessels flow were taken immediately after right iliac vessels shunting or ligation. Then, hemorrhagic shock was induced by continuous 20 mL/min blood withdraw from the external right jugular vein whereas arterial blood pressure and iliac vessels flow registers were taken every 10 min, and blood samples from EIVs were obtained every 30 min until the vascular flow through right EIA (or through the shunt inserted into the right EIV for group 4 animals) became inexistent or until the animal's death. After the end of the experiments, bilateral hind limb's biopsies were obtained for immunohistochemical analysis. Using image editing and analysis software, the expression of iNOS, eNOS, and HSP70 (3 well-known ischemic associated immunohistochemical markers) was assessed. The mean expression of each marker in the right hind limb was compared between groups. For statistical analysis, Microsoft Office Excel 2007 and BioEstat 5.0 (2007) were used. Immunohistochemical analysis showed no difference regarding the iNOS expression; nevertheless, both eNOS and HSP70 expression were statistically more intense (P < 0.05) on group 1 (eNOS = 1.32; HSP70 = 15.05) than on group 2 (eNOS = 0.018; HSP70 = 8.56). The higher expression of eNOS and HSP70 in the right hind limbs of group 1 animals (arterial shunt and venous ligature) than group 2 animals (arterial shunt and venous shunt) suggests that venous ligation is associated with more intense ischemic histological findings than venous shunting. Copyright © 2017 Elsevier Inc. All rights reserved.
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SUDSUKH, Apichaya; TAYA, Kazuyoshi; WATANABE, Gen; WAJJWALKU, Worawidh; THONGPHAKDEE, Ampika; THONGTIP, Nikorn
2016-01-01
To clarify the reproductive cycle of female Rusa deer (Rusa timorensis), the fecal concentrations of progesterone and 17β-estradiol metabolites were measured. Fecal samples were collected on a weekly basis for one year (between October, 2012 and September, 2013) from five healthy adult hinds in Thailand. At the beginning of the study, three hinds were pregnant. Two hinds delivered one healthy offspring, and one hind delivered a stillborn calf. The mating period of Rusa hinds in Thailand is from November to April. In pregnant hinds, fecal progesterone metabolite concentration was high in late pregnancy and abruptly declined to the baseline around parturition, suggesting that the placenta secretes a large amount of progesterone. Fecal 17β-estradiol metabolite concentration remained elevated around the day of parturition. Both concentrations of fecal progesterone and 17β-estradiol metabolites in non-lactating hinds were significantly higher than those in lactating hinds, indicating that ovarian activity of lactating hinds is suppressed by the suckling stimulus of fawn during lactation. The present study demonstrated that monitoring of fecal steroid hormones is useful method for assessing ovarian function in this species. PMID:27570098
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Retinal angiogenesis suppression through small molecule activation of p53
Chavala, Sai H.; Kim, Younghee; Tudisco, Laura; Cicatiello, Valeria; Milde, Till; Kerur, Nagaraj; Claros, Nidia; Yanni, Susan; Guaiquil, Victor H.; Hauswirth, William W.; Penn, John S.; Rafii, Shahin; De Falco, Sandro; Lee, Thomas C.; Ambati, Jayakrishna
2013-01-01
Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3–mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels in the adult mouse retina, suggesting that only proliferating retinal vessels are sensitive to Nutlin-3. Furthermore, Nutlin-3 inhibited angiogenesis in nonretinal models such as the hind limb ischemia model. Our work demonstrates that Nutlin-3 functions through an antiproliferative pathway with conceivable advantages over existing cytokine-targeted antiangiogenesis therapies. PMID:24018558
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Pedicled Sensate Composite Calcaneal Flap in Children With Congenital Tibial Pseudoarthrosis.
Mongon, Mauricio L D; Ribera, Fernando C; de Souza, Antonio M A; Sposito, Aurelio L; Belangero, William D; Livani, Bruno
2017-06-01
The preservation and functionality of a limb affected by a malformation (such as congenital pseudoarthrosis of the tibia) or a severely mangled lower limb in children, despite modern reconstructive techniques, remains challenging, often eventually requiring amputation to achieve a better outcome. The classical Syme and Boyd procedures are functionally better than transtibial (TT) amputation, but are not feasible for congenital tibial pseudoarthrosis. TT amputation delivers an excellent, effective, and functional stump that usually leads, after prosthetization, to a functional gait. Unfortunately, in some situations, particularly when amputation is performed conventionally, the stump is also associated with complications. Future surgical revisions are often needed, particularly in children, because of stump overgrowth. Between 2008 and 2010, three patients diagnosed with congenital pseudoarthrosis of the tibia associated with neurofibromatosis who were indicated for TT amputation with calcaneal flap after failure of all previous surgical reconstructive procedures were selected. The chosen method for osteosynthesis was an external fixator of Ilizarov. At 12 weeks of follow-up, the stump had healed in all three patients, and tibiocalcaneal fusion was achieved without complications. All patients were prosthetized and had an asymptomatic gait. After a minimum follow-up of 6 years, all three cases with the pedicled sensate composite calcaneal flap still had a strong, full weight-bearing surface and have adapted easily to the conventional prosthesis, providing a painless stump with excellent functionality. With a 0 rate of needed revisions, all 3 cases with the pedicled sensate composite calcaneal flap preserving the hind foot still have a strong, full weight-bearing surface and have easily adapted to the conventional prosthesis, providing a painless and excellent functional stump that could last a lifetime. Level IV.
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NASA Technical Reports Server (NTRS)
Deaver, D. R.; Amann, R. P.; Hammerstedt, R. H.; Ball, R.; Veeramachaneni, D. N. R.; Musacchia, X. J.
1992-01-01
A variety of biologic processes are perturbed when exposed to microgravity (space flight) for more than 7 days, including testicular function. Suspension of rats in a special harness (caudal elevation) to induce thoracic pooling of blood fluids and remove the support function of the hind limbs is used to mimic, on earth, the effects of microgravity encountered during space flight. Typically, this induces cryptorchidism in male rats. Three experiments were conducted to differentiate the effects of caudal elevation (30 deg angle) and anatomic location of testes on spermatogenesis and steroidogenesis. Rats were subjected to caudal elevation for 7 days using either a tail harness or a whole-body harness. Testes of rats fell into the abdominal cavity when a tail harness was used, but ligation of the iguinal canal prevented this repositioning. For rats with abdominal testes, testicular weight was reduced (P less than 0.05) and histology of testes was abnormal; the number of spermatids per gram parenchyma was lower (P less than 0.05) in tail-suspended rats compared with control rats.
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Radiographic features of the limbs of juvenile and subadult loggerhead sea turtles (Caretta caretta)
Valente, Ana Luisa; Marco, Ignasi; Zamora, Maria Angeles; Parga, Maria Luz; Lavín, Santiago; Alegre, Ferran; Cuenca, Rafaela
2007-01-01
This study aimed to provide the normal radiographic anatomic appearance of the limbs of the loggerhead sea turtle, Caretta caretta. Dorsopalmar and dorsoplantar radiographs were taken of the forelimbs and hindlimbs of 15 juvenile and 15 subadult loggerhead sea turtles, 17 alive and 13 dead. For comparison, computed tomographic, gross anatomic, osteologic, and histologic studies were performed on the limbs of 5 of the sea turtles. Bones from the distal part of the fore and hind flippers were seen in detail with a mammographic film–screen combination. The pectoral and pelvic girdles, superimposed by the carapace, were better seen on standard radiographs with the use of rare-earth intensifying screens. Mammographic radiographs of the manus of 5 small juvenile turtles showed active growth zones. Visualization of bone contours in the distal part of the limbs was clearer than in mammals owing to the very few superimpositions. The presence of a substantial amount of cartilage in the epiphyses produced better visibility of limb ends. We conclude that use of a mammography film–screen combination is the best way to evaluate the bony and joint structures of the limbs of sea turtles. Radiography provides reliable images for clinical purposes. Considering the low cost and logistics of this technique, it is a practical ancillary test for marine animal rehabilitation centers to use. PMID:17955906
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2014-01-01
Background To gain insight into what differences might restrict the capacity for limb regeneration in Xenopus froglets, we used High Performance Liquid Chromatography (HPLC)/double mass spectrometry to characterize protein expression during fibroblastema formation in the amputated froglet hindlimb, and compared the results to those obtained previously for blastema formation in the axolotl limb. Results Comparison of the Xenopus fibroblastema and axolotl blastema revealed several similarities and significant differences in proteomic profiles. The most significant similarity was the strong parallel down regulation of muscle proteins and enzymes involved in carbohydrate metabolism. Regenerating Xenopus limbs differed significantly from axolotl regenerating limbs in several ways: deficiency in the inositol phosphate/diacylglycerol signaling pathway, down regulation of Wnt signaling, up regulation of extracellular matrix (ECM) proteins and proteins involved in chondrocyte differentiation, lack of expression of a key cell cycle protein, ecotropic viral integration site 5 (EVI5), that blocks mitosis in the axolotl, and the expression of several patterning proteins not seen in the axolotl that may dorsalize the fibroblastema. Conclusions We have characterized global protein expression during fibroblastema formation after amputation of the Xenopus froglet hindlimb and identified several differences that lead to signaling deficiency, failure to retard mitosis, premature chondrocyte differentiation, and failure of dorsoventral axial asymmetry. These differences point to possible interventions to improve blastema formation and pattern formation in the froglet limb. PMID:25063185
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Lin, Yi-Wen; Huang, Chun-Yao; Chen, Yung-Hsiang; Shih, Chun-Ming; Tsao, Nai-Wen; Lin, Cheng-Yen; Chang, Nen-Chung; Tsai, Chien-Sung; Tsai, Hsiao-Ya; Tsai, Jui-Chi; Huang, Po-Hsun; Li, Chi-Yuan; Lin, Feng-Yen
2013-01-01
The number and function of endothelial progenitor cells (EPCs) are sensitive to hyperglycemia, hypertension, and smoking in humans, which are also associated with the development of atherosclerosis. GroEL1 from Chlamydia pneumoniae has been found in atherosclerotic lesions and is related to atherosclerotic pathogenesis. However, the actual effects of GroEL1 on EPC function are unclear. In this study, we investigate the EPC function in GroEL1-administered hind limb-ischemic C57BL/B6 and C57BL/10ScNJ (a toll-like receptor 4 (TLR4) mutation) mice and human EPCs. In mice, laser Doppler imaging, flow cytometry, and immunohistochemistry were used to evaluate the degree of neo-vasculogenesis, circulating level of EPCs, and expression of CD34, vWF, and endothelial nitric oxide synthase (eNOS) in vessels. Blood flow in the ischemic limb was significantly impaired in C57BL/B6 but not C57BL/10ScNJ mice treated with GroEL1. Circulating EPCs were also decreased after GroEL1 administration in C57BL/B6 mice. Additionally, GroEL1 inhibited the expression of CD34 and eNOS in C57BL/B6 ischemic muscle. In vitro, GroEL1 impaired the capacity of differentiation, mobilization, tube formation, and migration of EPCs. GroEL1 increased senescence, which was mediated by caspases, p38 MAPK, and ERK1/2 signaling in EPCs. Furthermore, GroEL1 decreased integrin and E-selectin expression and induced inflammatory responses in EPCs. In conclusion, these findings suggest that TLR4 and impaired NO-related mechanisms could contribute to the reduced number and functional activity of EPCs in the presence of GroEL1 from C. pneumoniae.
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Converse, K.A.; Mattsson, J.; Eaton-Poole, L.
2000-01-01
The national distribution of information on the discovery of malformations in Minnesota frogs in 1995 stimulated collection and examination of newly metamorphosed frogs during 1996. By late summer and early fall of 1996, malformed frogs and toads were reported on U.S. Fish and Wildlife Service (USFWS) lands in Vermont (Northeast, Region 5) and Minnesota (Midwest, Region 3). In response to these reports, biologists in USFWS Regions 3 and 5 conducted a survey, during the summer of 1997 to determine the distribution and type of malformations in frogs and toads on selected federal lands. Region 3 personnel surveyed 38 field stations at National Wildlife Refuges (NWR's) and Wetland Management Districts. Malformed frogs and toads were collected at 23 (61%) of the Region 3 sites. External malformations were detected in 110 of 6632 individuals representing seven of 13 frog species and one of three toad species examined for an overall of 1.7% affected (percentages for affected species ranged from 0.4-5.2%). In Region 5, 17 NWR's and one National Park were surveyed. Malformed frogs were collected at 10 (56%) of the Region 5 sites. External malformations were detected in 58 of 2267 individuals representing six of 11 frog species and one of two toad species examined for an overall total of 2.6% affected (percentages for affected species ranged from 1.8-15.6%). The majority of malformations observed in frogs and toads collected in Regions 3 and 5 were partially or completely missing hind limbs and digits (50%)or malformed hind limbs and digits (14%). A few individuals had an extra limb or toe, missing or malformed front limb, missing eye, or malformation of the mandible. Despite small sample sizes at some sites, malformations were confirmed to be present in eight species of frogs and two species of toads on Federal lands in USFWS Regions 3 and 5. Further study is needed to determine the extent and distribution of amphibian malformations in these Regions. Data from this study were provided to the national database on distribution of malformed amphibians.
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Sensory and motor neuropathy in a Border Collie.
Harkin, Kenneth R; Cash, Walter C; Shelton, G Diane
2005-10-15
A 5-month-old female Border Collie was evaluated because of progressive hind limb ataxia. The predominant clinical findings suggested a sensory neuropathy. Sensory nerve conduction velocity was absent in the tibial, common peroneal, and radial nerves and was decreased in the ulnar nerve; motor nerve conduction velocity was decreased in the tibial, common peroneal, and ulnar nerves. Histologic examination of nerve biopsy specimens revealed considerable nerve fiber depletion; some tissue sections had myelin ovoids, foamy macrophages, and axonal degeneration in remaining fibers. Marked depletion of most myelinated fibers within the peroneal nerve (a mixed sensory and motor nerve) supported the electrodiagnostic findings indicative of sensorimotor neuropathy. Progressive deterioration in motor function occurred over the following 19 months until the dog was euthanatized. A hereditary link was not established, but a littermate was similarly affected. The hereditary characteristic of this disease requires further investigation.
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TREATMENT OF CHRONIC HERPESVIRAL DERMATITIS IN A CAPTIVE CHEETAH (ACINONYX JUBATUS) IN NAMIBIA.
Flacke, Gabriella L; Schmidt-Küntzel, Anne; Marker, Laurie
2015-09-01
A 9-yr-old male cheetah (Acinonyx jubatus) housed at the Cheetah Conservation Fund in Namibia developed cutaneous lesions consisting of alopecia, erythema, ulceration, and crusting on the left fore and hind limbs. Histopathology of skin biopsies in conjunction with indirect fluorescent antibody and polymerase chain reaction testing confirmed a diagnosis of feline herpesvirus-1 dermatitis; microbial culture indicated secondary bacterial infection. Therapy included targeted systemic antimicrobial and antiviral treatment, topical medications, and repeated cryotherapy. Lesions exhibited varying degrees of clinical improvement but, overall, progressed in extent, size, and severity during the subsequent 2.5 yr of intense treatment. The cheetah was ultimately euthanized due to a guarded prognosis and concerns about poor quality of life. Potential factors initiating or contributing (or both) to the severity and nonhealing nature of the cutaneous lesions include chronic unidentified stress, altered immune system function, and other environmental influences.
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The influence of rat suspension-hypokinesia on the gastrocnemius muscle
NASA Technical Reports Server (NTRS)
Templeton, G. H.; Padalino, M.; Manton, J.; Leconey, T.; Hagler, H.; Glasberg, M.
1984-01-01
Hind-limb hypokinesia was induced in rats by the Morey method to characterize the response of the gastrocnemius muscle. A comparison of rats suspended for 2 weeks with weight, sex, and litter-matched control rats indicate no difference in gastrocnemius wet weight, contraction, or one-half relaxation times, but less contractile function as indicated by lowered dP/dt. Myosin ATPase staining identified uniform Type I (slow-twitch) and II (fast-twitch) atrophy in the muscles from 4 of 10 rats suspended for 2 weeks and 1 of 12 rats suspended for 4 weeks; muscles from three other rats of the 4-week group displayed greater Type I atrophy. Other histochemical changes were characteristic of a neuropathy. These data together with recently acquired soleus data (29) indicate the Morey model, like space flight, evokes greater changes in the Type I or slow twitch fibers of the gastrocnemius and soleus muscles.
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The validity of an animal model for experiments related to weightlessness
NASA Technical Reports Server (NTRS)
Musacchia, X. J.; Steffen, J. M.
1983-01-01
Animal evolution has witnessed morphological and physiological adaptations to gravitational forces. In the rat, hind limb muscles can be used to illustrate a range of load bearing functions: soleus - gastrocnemius = plantaris - extensor digitorum longus (EDL). A harness suspension apparatus is used to induce hypokinesia and hypodynamia (H&H) and to simulate responses comparable to those seen in weightlessness (i.e., COSMOS experiments). After one and two weeks of suspension H&H, there is muscle atrophy with a loss in muscle mass; the result of loss in muscle protein. Concommitantly, there is a decrease in RNA, but not in DNA content. The effects are greatest in the soleus and least in the EDL. These recent findings, in concert with earlier reports of increased nitrogenous excretion, suggest that both decreased protein synthesis and increased protein catabolism are characteristic of muscle atrophy. Recovery is seen in terms of reversal of these effects after removal from suspension.
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Orthotopic Transplantation of Achilles Tendon Allograft in Rats
Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun
2018-01-01
The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at −80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully appreciate the functional benefits of MSCs. PMID:29637821
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Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun
2018-02-01
The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at -80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully appreciate the functional benefits of MSCs.
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Lederis, K.; Medaković, M.
1974-01-01
1 Intravenous injections of urotensin I regularly caused a long-lasting, dose-related, lowering of blood pressure and an increase in heart rate in conscious rats, or a reduction in perfusion pressure in the isolated hind limb of the rat. 2 After subcutaneous administration, the hypotensive effect of urotensin I was greater in extent and in duration (> 24 hours). 3 Anaesthesia with ether, chloralose, pentobarbitone and thiobarbitone caused a decrease in blood pressure and only slightly diminished the hypotensive effect of urotensin. 4 Mecamylamine, hexamethonium, atropine, phenoxybenzamine, propranolol and diphenhydramine did not alter the effect of urotensin in conscious rats or in the isolated hind limb, although the effects of the respective agonists, i.e. nicotine, acetylcholine, noradrenaline, isoprenaline and histamine were inhibited. 5 In conscious rats, pressor effects of adrenaline, noradrenaline, nicotine and angiotensin II, and depressor effects of acetylcholine and bradykinin, were decreased or inhibited, whereas the hypotensive effect of phenoxybenzamine was potentiated by previous administration of urotensin I. Carotid occlusion reflex was partially inhibited by lower doses of urotensin and abolished by higher doses in rats lightly anaesthetized with chloralose. Urotensin elicited postural hypotension in rats anaesthetized with pentobarbitone. 6 The increase in heart rate produced by urotensin was not affected by phenoxybenzamine, but was abolished by propranolol or ganglion blocking agents (mecamylamine or hexamethonium). 7 It is concluded that urotensin elicits hypotension in the rat by a direct dilatory action on the resistance vessels causing a simultaneous reflex tachycardia. PMID:4375526
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NASA Astrophysics Data System (ADS)
Blottner, Dieter; Shenkman, Boris; Salanova, Michele
Exposure to microgravity results in various structural, biochemical and molecular changes of the skeletal neuromuscular system. The BION Joint Flight Proposal between the Charité Berlin Center of Space Medicine (www.zwmb.de) in Berlin, and the Institute of Biomedical Problem (IMBP) in Moscow, provided an exciting opportunity for a more detailed analysis of neuromuscular changes in mice (C57/bl6) exposed to real microgravity housed for 30 days in a BION M1 biosatellite on orbit. The mice from the BION flight group (n=5) were compared to three different on-ground control groups (Flight control, BION-ground and Vivarium, each n=5 mice). We started to analyse various skeletal muscles from the hind limbs or trunk. Apart from routine structural and biochemical analysis (fiber size and type distribution, slow/fastMyHC) we test the hypothesis for the presence of a microgravity-induced sarcolemma-cytosolic protein shift of nitric oxide synthase (NOS) and partial loss in neuromuscular synapse scaffold protein (Homer) immunoexpression known to be prone to disuse in mice or humans (hind limb unloading, bed rest) as previously shown (Sandonà D et al., PLoS One, 2012, Salanova M et al., FASEB J, 2011). National Sponsors: Federal Ministry of Economics and Technology (BMWi) via the German AeroSpace Board, DLR e.V., Bonn-Oberkassel, Germany (#50WB1121); Contract RAS-IMBP/Charité Berlin # Bion-M1/2013
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Meng, Fan Xing; Hou, Jing Ming; Sun, Tian Sheng
2017-02-08
Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent oxidative stress in the remodeling of the brain after SCI. We established a rat model of central pain after SCI. Rats were divided randomly into four groups: SCI, sham operation, SCI plus deferoxamine (DFX) intervention, and SCI plus nitric oxide synthase (NOS) inhibitor treatment. Pain behavior was observed and thermal pain threshold was measured regularly, and brain levels of iron, transferrin receptor 1 (TfR1), ferritin (Fn), and lactoferrin (Lf), were detected in the different groups 12 weeks after establishment of the model. Rats demonstrated self-biting behavior after SCI. Furthermore, the latent period of thermal pain was reduced and iron levels in the hind limb sensory area, hippocampus, and thalamus increased after SCI. Iron-regulatory protein (IRP) 1 levels increased in the hind limb sensory area, while Fn levels decreased. TfR1 mRNA levels were also increased and oxidative stress was activated. Oxidative stress could be inhibited by ferric iron chelators and NOS inhibitors. SCI may cause intracranial iron overload through the NOS-iron-responsive element/IRP pathway, resulting in central pain mediated by the oxidative stress response. Iron chelators and oxidative stress inhibitors can effectively relieve SCI-associated central pain.
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Remote effects of extracorporeal shock wave therapy on cutaneous microcirculation.
Kisch, Tobias; Sorg, Heiko; Forstmeier, Vinzent; Knobloch, Karsten; Liodaki, Eirini; Stang, Felix; Mailänder, Peter; Krämer, Robert
2015-11-01
Extracorporeal shock wave treatment (ESWT) has proven its clinical benefits in different fields of medicine. Tissue regeneration and healing is improved after shock wave treatment. Even in the case of burn wounds angiogenesis and re-epithelialization is accelerated, but ESWT in extensive burn wounds is impracticable. High energy ESWT influences cutaneous microcirculation at body regions remote from application site. Eighteen Sprague Dawley rats were randomly assigned to two groups and received either high energy ESWT (Group A: total 1000 impulses, 10 J) or placebo shock wave treatment (Group B: 0 impulses, 0 J), applied to the dorsal lower leg of the hind limb. Ten minutes later microcirculatory effects were assessed at the contralateral lower leg of the hind limb (remote body region) by combined Laser-Doppler-Imaging and Photospectrometry. In Group A cutaneous capillary blood velocity was significantly increased by 152.8% vs. placebo ESWT at the remote body location (p = 0.01). Postcapillary venous filling pressure remained statistically unchanged (p > 0.05), while cutaneous tissue oxygen saturation increased by 12.7% in Group A (p = 0.220). High energy ESWT affects cutaneous hemodynamics in body regions remote from application site in a standard rat model. The results of this preliminary study indicate that ESWT might be beneficial even in disseminated and extensive burn wounds by remote shock wave effects and should therefore be subject to further scientific evaluation. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.
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Rana, Kesha; Chiu, Maria W S; Russell, Patricia K; Skinner, Jarrod P; Lee, Nicole K L; Fam, Barbara C; Zajac, Jeffrey D; MacLean, Helen E
2016-08-01
The aim of this study was to investigate the direct muscle cell-mediated actions of androgens by comparing two different mouse lines. The cre-loxP system was used to delete the DNA-binding activity of the androgen receptor (AR) in mature myofibers (MCK mAR(ΔZF2)) in one model and the DNA-binding activity of the AR in both proliferating myoblasts and myofibers (α-actin mAR(ΔZF2)) in another model. We found that hind-limb muscle mass was normal in MCK mAR(ΔZF2) mice and that relative mass of only some hind-limb muscles was reduced in α-actin mAR(ΔZF2) mice. This suggests that myoblasts and myofibers are not the major cellular targets mediating the anabolic actions of androgens on male muscle during growth and development. Levator ani muscle mass was decreased in both mouse lines, demonstrating that there is a myofiber-specific effect in this unique androgen-dependent muscle. We found that the pattern of expression of genes including c-myc, Fzd4 and Igf2 is associated with androgen-dependent changes in muscle mass; therefore, these genes are likely to be mediators of anabolic actions of androgens. Further research is required to identify the major targets of androgen actions in muscle, which are likely to include indirect actions via other tissues. © 2016 Society for Endocrinology.
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Altered cellular kinetics in growth plate according to alterations in weight bearing.
Park, Hoon; Kong, Sun Young; Kim, Hyun Woo; Yang, Ick Hwan
2012-05-01
To examine the effects of change in weight bearing on the growth plate metabolism, a simulated animal model of weightlessness was introduced and the chondrocytes' cellular kinetics was evaluated. Unloading condition on the hind-limb of Sprague-Dawley rats was created by fixing a tail and lifting the hind-limb. Six rats aged 6 weeks old were assigned to each group of unloading, reloading, and control groups of unloading or reloading. Unloading was maintained for three weeks, and then reloading was applied for another one week thereafter. Histomorphometry for the assessment of vertical length of the growth plate, 5-bromo-2'-deoxyuridin immunohistochemistry for cellular kinetics, and biotin nick end labeling transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay for chondrocytes apoptosis in the growth plate were performed. The vertical length of the growth plate and the proliferative potential of chondrocytes were decreased in the unloading group compared to those of control groups. Inter-group differences were more significant in the proliferative and hypertrophic zones. Reloading increased the length of growth plate and proliferative potential of chondrocytes. However, apoptotic changes in the growth plate were not affected by the alterations of weight bearing. Alterations in the weight bearing induced changes in the chondrocytic proliferative potential of the growth plate, however, had no effects on the apoptosis. This may explain why non-weight bearing in various clinical situations hampers normal longitudinal bone growth. Further studies on the factors for reversibility of chondrocytic proliferation upon variable mechanical stresses are needed.
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Mechanisms Mediating Vibration-induced Chronic Musculoskeletal Pain Analyzed in the Rat
Dina, Olayinka A.; Joseph, Elizabeth K.; Levine, Jon D.; Green, Paul G.
2009-01-01
While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and re-exposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60–80 Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a pro-inflammatory cytokine or re-exposure to vibration. Exposure of a hind limb to vibration produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for ~2 weeks. When nociceptive thresholds had returned to baseline, exposure to a pro-inflammatory cytokine or re-exposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia induced by vibration was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cε, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-α (TNFα) receptor. Finally, in TNFα-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. Perspective These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFα and the second messenger PKCε as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. PMID:19962353
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Mechanisms mediating vibration-induced chronic musculoskeletal pain analyzed in the rat.
Dina, Olayinka A; Joseph, Elizabeth K; Levine, Jon D; Green, Paul G
2010-04-01
While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and reexposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60-80Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a proinflammatory cytokine or reexposure to vibration. Exposure of a hind limb to vibration-produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for approximately 2 weeks. When nociceptive thresholds had returned to baseline, exposure to a proinflammatory cytokine or reexposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cepsilon, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-alpha (TNFalpha) receptor. Finally, in TNFalpha-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFalpha and the second messenger protein kinase Cepsilon as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. Copyright 2010 American Pain Society. All rights reserved.
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Sparling, D.W.
1998-01-01
During the summer of 1997 we repeatedly sprayed Altosid, a formulation of 4% methoprene used for mosquito control, on six constructed macrocosms. Six additional macrocosms were sprayed with Abate4E, containing the organophosphate pesticide temephos, and six were sprayed with water (controls). The wetlands were created on an impermeable foundation for research purposes and averaged 215 m2 in area and 0.5 m deep. Application rates and frequency of Abate4E and Altosid followed label directions and mimicked procedures for mosquito control in National Wildlife Refuges. In early September juvenile frogs and metamorphing tadpoles were collected with dip nets from each pond and examined for deformities. In all, 91 juveniles and metamorph southern leopard frogs (Rana utricularia) were collected from Altosid sprayed wetlands with 14 (15%) demonstrating deformities. Seventyseven juveniles and metamorphs were collected from control wetlands with three (4%) showing deformities. Only six juveniles and metamorphs were collected from Abate4E wetlands and none showed deformities. Deformities included missing or deformed hind limbs (9 of 10 involving only the right hind limb), missing eyes, and abnormal color. The differences in rate of deformities was dependent on treatment (X2=6.44, p< 0.02). The number of leopard frogs caught per unit effort (tadpoles and juveniles) differed among treatments (p=0.032) with Abate4E wetlands producing fewer individuals per capture effort than either Altosid or control wetlands.
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Human spinal cord injury: motor unit properties and behaviour.
Thomas, C K; Bakels, R; Klein, C S; Zijdewind, I
2014-01-01
Spinal cord injury (SCI) results in widespread variation in muscle function. Review of motor unit data shows that changes in the amount and balance of excitatory and inhibitory inputs after SCI alter management of motoneurons. Not only are units recruited up to higher than usual relative forces when SCI leaves few units under voluntary control, the force contribution from recruitment increases due to elevation of twitch/tetanic force ratios. Force gradation and precision are also coarser with reduced unit numbers. Maximal unit firing rates are low in hand muscles, limiting voluntary strength, but are low, normal or high in limb muscles. Unit firing rates during spasms can exceed voluntary rates, emphasizing that deficits in descending drive limit force production. SCI also changes muscle properties. Motor unit weakness and fatigability seem universal across muscles and species, increasing the muscle weakness that arises from paralysis of units, motoneuron death and sensory impairment. Motor axon conduction velocity decreases after human SCI. Muscle contractile speed is also reduced, which lowers the stimulation frequencies needed to grade force when paralysed muscles are activated with patterned electrical stimulation. This slowing does not necessarily occur in hind limb muscles after cord transection in cats and rats. The nature, duration and level of SCI underlie some of these species differences, as do variations in muscle function, daily usage, tract control and fibre-type composition. Exploring this diversity is important to promote recovery of the hand, bowel, bladder and locomotor function most wanted by people with SCI. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
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Central control of interlimb coordination and speed‐dependent gait expression in quadrupeds
Danner, Simon M.; Wilshin, Simon D.; Shevtsova, Natalia A.
2016-01-01
Key points Quadrupeds express different gaits depending on speed of locomotion.Central pattern generators (one per limb) within the spinal cord generate locomotor oscillations and control limb movements. Neural interactions between these generators define interlimb coordination and gait.We present a computational model of spinal circuits representing four rhythm generators with left–right excitatory and inhibitory commissural and fore–hind inhibitory interactions within the cord.Increasing brainstem drive to all rhythm generators and excitatory commissural interneurons induces an increasing frequency of locomotor oscillations accompanied by speed‐dependent gait changes from walk to trot and to gallop and bound.The model closely reproduces and suggests explanations for multiple experimental data, including speed‐dependent gait transitions in intact mice and changes in gait expression in mutants lacking certain types of commissural interneurons. The model suggests the possible circuit organization in the spinal cord and proposes predictions that can be tested experimentally. Abstract As speed of locomotion is increasing, most quadrupeds, including mice, demonstrate sequential gait transitions from walk to trot and to gallop and bound. The neural mechanisms underlying these transitions are poorly understood. We propose that the speed‐dependent expression of different gaits results from speed‐dependent changes in the interactions between spinal circuits controlling different limbs and interlimb coordination. As a result, the expression of each gait depends on (1) left–right interactions within the spinal cord mediated by different commissural interneurons (CINs), (2) fore–hind interactions on each side of the spinal cord and (3) brainstem drives to rhythm‐generating circuits and CIN pathways. We developed a computational model of spinal circuits consisting of four rhythm generators (RGs) with bilateral left–right interactions mediated by V0 CINs (V0D and V0V sub‐types) providing left–right alternation, and conditional V3 CINs promoting left–right synchronization. Fore and hind RGs mutually inhibited each other. We demonstrate that linearly increasing excitatory drives to the RGs and V3 CINs can produce a progressive increase in the locomotor speed accompanied by sequential changes of gaits from walk to trot and to gallop and bound. The model closely reproduces and suggests explanations for the speed‐dependent gait expression observed in vivo in intact mice and in mutants lacking V0V or all V0 CINs. Specifically, trot is not expressed after removal of V0V CINs, and only bound is expressed after removal of all V0 CINs. The model provides important insights into the organization of spinal circuits and neural control of locomotion. PMID:27633893
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Pharmacological Inhibitors of the Proteosome in Atrophying Muscles
NASA Technical Reports Server (NTRS)
Goldberg, Alfred
1999-01-01
It is now clear that the marked loss of muscle mass that occurs with disuse, denervation or in many systemic diseases (cancer cachexia, sepsis, acidosis, various endocrine disorders) is due primarily to accelerated degradation of muscle proteins, especially myofibrillar components. Recent work primarily in Dr. Goldberg's laboratory had suggested that in these diverse conditions, the enhancement of muscle proteolysis results mainly from activation of the Ub-proteasome degradative pathway. In various experimental models of atrophy, rat muscles show a common series of changes indicative of activation of this pathway, including increases in MRNA for Ub and proteasome subunits, content of ubiquitinated proteins, and sensitivity to inhibitors of the proteasome. In order to understand the muscle atrophy seen in weightlessness, Dr. Goldberg's laboratory is collaborating with Dr. Baldwin in studies to define the changes in these parameters upon hind-limb suspension. Related experiments will explore the effects on this degradative system of exercise regimens and also of glucocorticoids, which are known to rise in space personnel and to promote muscle, especially in inactive muscles. The main goals will be: (A) to define the enzymatic changes leading to enhanced activity of the Ub-proteasome pathway in inactive muscles upon hind-limb suspension, and the effects on this system of exposure to glucocorticoids or exercise; and (B) to learn whether inhibitors of the Ub-proteasome pathway may be useful in retarding the excessive proteolysis in atrophying muscles. Using muscle extracts, Dr. Goldberg's group hopes to define the rate-limiting, enzymatic changes that lead to the accelerated Ub-conjugation and protein degradation. They have recently developed cell-free preparations from atrophying rat muscles, in which Ub-conjugation to muscle proteins is increased above control levels. Because these new preparations seem to reproduce the changes occurring in vivo, they will analyze in depth extracts from normal and atrophying muscles to compare the activities of the Ub-activating enzyme (El), the various LTh-carrier proteins (E2s), and Ub-protein ligases (E3s). Recent studies of other types of muscle wasting -suggest a very important role in muscle proteolysis of certain ubiquitination enzymes, E214k and E3-alpha(i.e. components of the "N-end pathway"). Future studies will focus in understanding their role and test whether they are in fact critical for muscle atrophy in vivo. Since weightlessness leads to a specific loss of contractile proteins and to a switching of myosin isotypes, Dr. Goldberg's group will attempt to identify the ubiquitination enzymes specifically involved in myosin degradation both in normal muscle and after hind-limb suspension.
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Directionally compliant legs influence the intrinsic pitch behaviour of a trotting quadruped
Lee, David V; Meek, Sanford G
2005-01-01
Limb design is well conserved among quadrupeds, notably, the knees point forward (i.e. cranial inclination of femora) and the elbows point back (i.e. caudal inclination of humeri). This study was undertaken to examine the effects of joint orientation on individual leg forces and centre of mass dynamics. Steady-speed trotting was simulated in two quadrupedal models. Model I had the knee and elbow orientation of a quadruped and model II had a reversed leg configuration in which knees point back and elbows point forward. The model's legs showed directional compliance determined by the orientation of the knee/elbow. In both models, forward pointing knees/elbows produced a propulsive force bias, while rearward pointing knees/elbows produced a braking force bias. Hence, model I showed the same pattern of hind-leg propulsion and fore-leg braking observed in trotting animals. Simulations revealed minimal pitch oscillations during steady-speed trotting of model I, but substantially greater and more irregular pitch oscillations of model II. The reduced pitch oscillation of model I was a result of fore-leg and hind-leg forces that reduced pitching moments during early and late stance, respectively. This passive mechanism for reducing pitch oscillations was an emergent property of directionally compliant legs with the fore–hind configuration of model I. Such intrinsic stability resulting from mechanical design can simplify control tasks and lead to more robust running machines. PMID:15817430
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Wang, Xiao Hong; Lu, Gang; Hu, Xiang; Tsang, Kam Sze; Kwong, Wing Hang; Wu, Feng Xia; Meng, Hai Wei; Jiang, Shu; Liu, Shu Wei; Ng, Ho Keung; Poon, Wai Sang
2012-11-14
Gait deficits are important clinical symptoms of Parkinson's disease (PD). However, existing behavioral tests for the detection of motor impairments in rodents with systemic dopamine depletion only measure akinesia and dyskinesia, and data focusing on gait are scarce. We evaluated gait changes in the methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced C57BL/6 murine model of PD by using a computer-assisted CatWalk system. Correlations of gait parameters with tyrosine hydroxylase (TH) protein levels in the substantia nigra (SN) were also investigated. The gait readouts, including the walking duration, variation of walking speed, step cycle, duty cycle, stance, initial dual stance, terminal dual stance, three- and four-point supports, and the base of support between hind limbs was noted to increase significantly one week after MPTP injection. In contrast, values of the stride length, cadence, swing speed, and diagonal dual support decreased substantially following MPTP treatment (p < 0.05). All of these changes lasted for three weeks after the last MPTP administration. Except for the stance in the fore limbs and the swing speed in the hind limbs, the gait variability in the PD mice showed a closer correlation with the protein levels of TH in the SN than the walking distances in the conventional open field test. Coordination parameters of the regularity index and step pattern were not affected in mice treated with MPTP. Data of the study suggest that the computer-assisted CatWalk system can provide reliable and objective criteria to stratify gait changes arising from MPTP-induced bilateral lesions in C57/BL6 mice. The extent of gait changes was noted to correlate with the expression of the biomarker for dopaminergic neurons. This novel analytical method may hold promise in the study of disease progression and new drug screening in a murine PD model.
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2012-01-01
Background Gait deficits are important clinical symptoms of Parkinson’s disease (PD). However, existing behavioral tests for the detection of motor impairments in rodents with systemic dopamine depletion only measure akinesia and dyskinesia, and data focusing on gait are scarce. We evaluated gait changes in the methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced C57BL/6 murine model of PD by using a computer-assisted CatWalk system. Correlations of gait parameters with tyrosine hydroxylase (TH) protein levels in the substantia nigra (SN) were also investigated. Results The gait readouts, including the walking duration, variation of walking speed, step cycle, duty cycle, stance, initial dual stance, terminal dual stance, three- and four-point supports, and the base of support between hind limbs was noted to increase significantly one week after MPTP injection. In contrast, values of the stride length, cadence, swing speed, and diagonal dual support decreased substantially following MPTP treatment (p < 0.05). All of these changes lasted for three weeks after the last MPTP administration. Except for the stance in the fore limbs and the swing speed in the hind limbs, the gait variability in the PD mice showed a closer correlation with the protein levels of TH in the SN than the walking distances in the conventional open field test. Coordination parameters of the regularity index and step pattern were not affected in mice treated with MPTP. Conclusion Data of the study suggest that the computer-assisted CatWalk system can provide reliable and objective criteria to stratify gait changes arising from MPTP-induced bilateral lesions in C57/BL6 mice. The extent of gait changes was noted to correlate with the expression of the biomarker for dopaminergic neurons. This novel analytical method may hold promise in the study of disease progression and new drug screening in a murine PD model. PMID:23151254
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Offerman, Steven R; Barry, J David; Richardson, William H; Tong, Tri; Tanen, Dave; Bush, Sean P; Clark, Richard F
2009-01-01
This study was designed to investigate whether the local, subcutaneous injection of Crotaline Fab antivenom (CroFab) at the rattlesnake envenomation site would result in less extremity edema when compared to intravenous (i.v.) antivenom infusion alone. This is a randomized, three-arm laboratory experiment using a porcine model. Each animal was anesthetized, intubated, and maintained on mechanical ventilation. About 6 mg/kg of Crotalus atrox venom was injected subcutaneously at the hock of the right hind leg. Animals were then randomized to immediately receive subcutaneous and i.v. antivenom (SC/IV), i.v. antivenom only, or saline control. SC/IV animals received two vials of CroFab subcutaneously at the envenomation site and two vials intravenously. IV animals received four vials of CroFab intravenously. Limb edema was tracked by serial circumference and volumetric measurements over an 8-h period. Limb circumference was measured at four pre-determined locations hourly. Limb volume was measured by a water displacement method at baseline, 4, and 8 h. Twenty-six animals were randomized to the three treatment groups. The SC/IV and IV arms included nine animals each. Two animals in the SC/IV group died suddenly during the study, leaving seven animals for data analysis. There were eight controls. Increasing limb edema was observed in all groups. No differences were detected in limb circumferences or limb volumes between control and either treatment arms. In this porcine model of crotaline envenomation, no differences in limb edema were found between animals treated with SC/IV or IV CroFab when compared to saline controls.
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Methods for Teratogenic Screening of Air Force Chemicals
1978-01-01
7 2 4 3 2.3 7 8 2 1 7 2.6 8 5 1 1 4 2.5 20 0 10 22 8 1 1 7 2.8 26 6 5 2 4 2.4 3 Gross Abnormalities Number of Fetuses with Abnormality Anophthalmia ...meningoencephalocoele), anophthalmia , cleft palate, cleft lip, misplaced ears, clubbed hind limbs, fused vertebrae, fused ribs, split centra and scoliosis.* In...experimentation with hydroxyurea in Fisher 344 rats, at 250 mg/kg on day nine of pregnancy, our results showed anophthalmia , brain abnormalities
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Effect of the Intermittent Hypoxia on the Bone Tissue State After Microgravitation Modeling
NASA Astrophysics Data System (ADS)
Berezovskiy, V. A.; Litovka, I. G.; Chaka, H. G.; Magomedov, S.; Mehed, N. V.
The authors studied the influence of low PO2 under normal atmospheric pressure on the Ca and P metabolism, bone remodeling markers, and biomechanical properties of the femura bone in rats with their hind limbs unloaded. A hypoxic gas mixture (HGM) was given in intermittent regime A and B for 8 hours/day during 28 days. It was shown that regime A slows down the development of osteopenia and may be used in complex with other rehabilitation procedures for preventing the unloading osteopenia.
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Cold-Induced Changes in Arterial Sensitivity
1991-05-01
muscle contraction . The in vitro exposure of femoral arteries from rabbits and pigs to cold resulted in a progressive loss of sensitivity to agonist. Femoral arteries isolated from hypothermic pigs (core temp = 25 C for 2 hours) were no more sensitive to NEPI in vitro than arteries from normothermic animals. However, the in situ hind limb arterial bed of the hypothermic pig was ten times more sensitive to arterial injection of NEPI than the arterial bed of the normothermic pig. The sensitivity of porcine vascular smooth muscle to NEPI does not appear to be affected by
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Arthroscopically accessible anatomy of the tarsal collateral ligaments in the horse.
Kümmerle, Jan M; Kummer, Martin R
2013-04-01
To describe the arthroscopically accessible anatomy of the tarsal collateral ligaments in the horse. Descriptive study. Cadaveric equine hind limbs (n = 24) obtained from horses without tarsal disease. Two pairs of tarsal joints were used to obtain silicone models of the tarsocrural joint and dissect the tarsal collateral ligaments (CLs). Ten pairs of tarsocrural joints had arthroscopic exploration and the accessible parts of the tarsal CLs were marked with an arthroscopic hook knife. Subsequently, the limbs were dissected and the marked positions were allocated to the specific parts of the CLs. Ipsilateral arthroscope and instrument portals were used in each pouch of the tarsocrural joint. Via the plantaromedial pouch, the superficial (2/20 limbs), middle (7), deep (6) or both middle and deep (3) short medial CL and the long medial CL (14) were reached. Access via the plantarolateral pouch allowed manipulation of the deep short lateral CL (20/20 limbs) and the long lateral CL (20). Dorsally, arthroscopy via the dorsomedial pouch gave access to the deep short medial CL (20/20 limbs), while the superficial (9) or middle (10) or both superficial and middle (1) short lateral CL could be reached via the dorsolateral joint recess. Limited parts of the tarsal CLs can be observed or manipulated arthroscopically in normal equine tarsocrural joints. © Copyright 2013 by The American College of Veterinary Surgeons.
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The Role of Spatially Controlled Cell Proliferation in Limb Bud Morphogenesis
Boehm, Bernd; Westerberg, Henrik; Lesnicar-Pucko, Gaja; Raja, Sahdia; Rautschka, Michael; Cotterell, James; Swoger, Jim; Sharpe, James
2010-01-01
Although the vertebrate limb bud has been studied for decades as a model system for spatial pattern formation and cell specification, the cellular basis of its distally oriented elongation has been a relatively neglected topic by comparison. The conventional view is that a gradient of isotropic proliferation exists along the limb, with high proliferation rates at the distal tip and lower rates towards the body, and that this gradient is the driving force behind outgrowth. Here we test this hypothesis by combining quantitative empirical data sets with computer modelling to assess the potential role of spatially controlled proliferation rates in the process of directional limb bud outgrowth. In particular, we generate two new empirical data sets for the mouse hind limb—a numerical description of shape change and a quantitative 3D map of cell cycle times—and combine these with a new 3D finite element model of tissue growth. By developing a parameter optimization approach (which explores spatial patterns of tissue growth) our computer simulations reveal that the observed distribution of proliferation rates plays no significant role in controlling the distally extending limb shape, and suggests that directional cell activities are likely to be the driving force behind limb bud outgrowth. This theoretical prediction prompted us to search for evidence of directional cell orientations in the limb bud mesenchyme, and we thus discovered a striking highly branched and extended cell shape composed of dynamically extending and retracting filopodia, a distally oriented bias in Golgi position, and also a bias in the orientation of cell division. We therefore provide both theoretical and empirical evidence that limb bud elongation is achieved by directional cell activities, rather than a PD gradient of proliferation rates. PMID:20644711
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Barkl-Luke, Mallory E.; Ngo, Shyuan T.; Thomas, Nicola K.; McDonald, Tanya S.; Borges, Karin
2016-01-01
There is increasing evidence that energy metabolism is disturbed in Amyotrophic Lateral Sclerosis (ALS) patients and animal models. Treatment with triheptanoin, the triglyceride of heptanoate, is a promising approach to provide alternative fuel to improve oxidative phosphorylation and aid ATP generation. Heptanoate can be metabolized to propionyl-CoA, which after carboxylation can produce succinyl-CoA and thereby re-fill the tricarboxylic acid (TCA) cycle (anaplerosis). Here we tested the hypothesis that treatment with triheptanoin prevents motor neuron loss and delays the onset of disease symptoms in female mice overexpressing the mutant human SOD1G93A (hSOD1G93A) gene. When oral triheptanoin (35% of caloric content) was initiated at P35, motor neuron loss at 70 days of age was attenuated by 33%. In untreated hSOD1G93A mice, the loss of hind limb grip strength began at 16.7 weeks. Triheptanoin maintained hind limb grip strength for 2.8 weeks longer (p<0.01). Loss of balance on the rotarod and reduction of body weight were delayed by 13 and 11 days respectively (both p<0.01). Improved motor function occurred in parallel with alterations in the expression of genes associated with muscle metabolism. In gastrocnemius muscles, the mRNA levels of pyruvate, 2-oxoglutarate and succinate dehydrogenases and methyl-malonyl mutase were reduced by 24–33% in 10 week old hSOD1G93A mice when compared to wild-type mice, suggesting that TCA cycling in skeletal muscle may be slowed in this ALS mouse model at a stage when muscle strength is still normal. At 25 weeks of age, mRNA levels of succinate dehydrogenases, glutamic pyruvic transaminase 2 and the propionyl carboxylase β subunit were reduced by 69–84% in control, but not in triheptanoin treated hSOD1G93A animals. Taken together, our results suggest that triheptanoin slows motor neuron loss and the onset of motor symptoms in ALS mice by improving TCA cycling. PMID:27564703
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Costa, Marina; Cerqueira, Mariana T; Santos, Tírcia C; Sampaio-Marques, Belém; Ludovico, Paula; Marques, Alexandra P; Pirraco, Rogério P; Reis, Rui L
2017-06-01
Current vascularization strategies for Tissue Engineering constructs, in particular cell sheet-based, are limited by time-consuming and expensive endothelial cell isolation and/or by the complexity of using extrinsic growth factors. Herein, we propose an alternative strategy using angiogenic cell sheets (CS) obtained from the stromal vascular fraction (SVF) of adipose tissue that can be incorporated into more complex constructs. Cells from the SVF were cultured in normoxic and hypoxic conditions for up to 8days in the absence of extrinsic growth factors. Immunocytochemistry against CD31 and CD146 revealed spontaneous organization in capillary-like structures, more complex after hypoxic conditioning. Inhibition of HIF-1α pathway hindered capillary-like structure formation in SVF cells cultured in hypoxia, suggesting a role of HIF-1α. Moreover, hypoxic SVF cells showed a trend for increased secretion of angiogenic factors, which was reflected in increased network formation by endothelial cells cultured on matrigel using that conditioned medium. In vivo implantation of SVF CS in a mouse hind limb ischemia model revealed that hypoxia-conditioned CS led to improved restoration of blood flow. Both in vitro and in vivo data suggest that SVF CS can be used as simple and cost-efficient tools to promote functional vascularization of TE constructs. Neovascularization after implantation is a major obstacle for producing clinically viable cell sheet-based tissue engineered constructs. Strategies using endothelial cells and extrinsic angiogenic growth factors are expensive and time consuming and may raise concerns of tumorigenicity. In this manuscript, we describe a simplified approach using angiogenic cell sheets fabricated from the stromal vascular fraction of adipose tissue. The strong angiogenic behavior of these cell sheets, achieved without the use of external growth factors, was further stimulated by low oxygen culture. When implanted in an in vivo model of hind limb ischemia, the angiogenic cell sheets contributed to blood flux recovery. These cell sheets can therefore be used as a straightforward tool to increase the neovascularization of cell sheet-based thick constructs. Copyright © 2017. Published by Elsevier Ltd.
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Evolution of the hominoid vertebral column: The long and the short of it.
Williams, Scott A; Russo, Gabrielle A
2015-01-01
The postcranial axial skeleton exhibits considerable morphological and functional diversity among living primates. Particularly striking are the derived features in hominoids that distinguish them from most other primates and mammals. In contrast to the primitive catarrhine morphotype, which presumably possessed an external (protruding) tail and emphasized more pronograde trunk posture, all living hominoids are characterized by the absence of an external tail and adaptations to orthograde trunk posture. Moreover, modern humans evolved unique vertebral features that satisfy the demands of balancing an upright torso over the hind limbs during habitual terrestrial bipedalism. Our ability to identify the evolutionary timing and understand the functional and phylogenetic significance of these fundamental changes in postcranial axial skeletal anatomy in the hominoid fossil record is key to reconstructing ancestral hominoid patterns and retracing the evolutionary pathways that led to living apes and modern humans. Here, we provide an overview of what is known about evolution of the hominoid vertebral column, focusing on the currently available anatomical evidence of three major transitions: tail loss and adaptations to orthograde posture and bipedal locomotion. © 2015 Wiley Periodicals, Inc.
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Modeling of skin cooling, blood flow, and optical properties in wounds created by electrical shock
NASA Astrophysics Data System (ADS)
Nguyen, Thu T. A.; Shupp, Jeffrey W.; Moffatt, Lauren T.; Jordan, Marion H.; Jeng, James C.; Ramella-Roman, Jessica C.
2012-02-01
High voltage electrical injuries may lead to irreversible tissue damage or even death. Research on tissue injury following high voltage shock is needed and may yield stage-appropriate therapy to reduce amputation rate. One of the mechanisms by which electricity damages tissue is through Joule heating, with subsequent protein denaturation. Previous studies have shown that blood flow had a significant effect on the cooling rate of heated subcutaneous tissue. To assess the thermal damage in tissue, this study focused on monitoring changes of temperature and optical properties of skin next to high voltage wounds. The burns were created between left fore limb and right hind limb extremities of adult male Sprague-Dawley rats by a 1000VDC delivery shock system. A thermal camera was utilized to record temperature variation during the exposure. The experimental results were then validated using a thermal-electric finite element model (FEM).
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NASA Astrophysics Data System (ADS)
Xu, Xiaorong; Zhu, Wen; Padival, Vikram; Xia, Mengna; Cheng, Xuefeng; Bush, Robin; Christenson, Linda; Chan, Tim; Doherty, Tim; Iatridis, Angelo
2003-07-01
Photonify"s tissue spectrometer uses Near-Infrared Spectroscopy for real-time, noninvasive measurement of hemoglobin concentration and oxygen saturation [SO2] of biological tissues. The technology was validated by a series of ex vivo and animal studies. In the ex vivo experiment, a close loop blood circulation system was built, precisely controlling the oxygen saturation and the hemoglobin concentration of a liquid phantom. Photonify"s tissue spectrometer was placed on the surface of the liquid phantom for real time measurement and compared with a gas analyzer, considered the gold standard to measure oxygen saturation and hemoglobin concentration. In the animal experiment, the right hind limb of each dog accepted onto the study was surgically removed. The limb was kept viable by connecting the femoral vein and artery to a blood-primed extracorporeal circuit. Different concentrations of hemoglobin were obtained by adding designated amount of saline solution into the perfusion circuit. Photonify"s tissue spectrometers measured oxygen saturation and hemoglobin concentration at various locations on the limb and compared with gas analyzer results. The test results demonstrated that Photonify"s tissue spectrometers were able to detect the relative changes in tissue oxygen saturation and hemoglobin concentration with a high linear correlation compared to the gas analyzer
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Magdoom, Kulam Najmudeen; Pishko, Gregory L.; Rice, Lori; Pampo, Chris; Siemann, Dietmar W.; Sarntinoranont, Malisa
2014-01-01
Systemic drug delivery to solid tumors involving macromolecular therapeutic agents is challenging for many reasons. Amongst them is their chaotic microvasculature which often leads to inadequate and uneven uptake of the drug. Localized drug delivery can circumvent such obstacles and convection-enhanced delivery (CED) - controlled infusion of the drug directly into the tissue - has emerged as a promising delivery method for distributing macromolecules over larger tissue volumes. In this study, a three-dimensional MR image-based computational porous media transport model accounting for realistic anatomical geometry and tumor leakiness was developed for predicting the interstitial flow field and distribution of albumin tracer following CED into the hind-limb tumor (KHT sarcoma) in a mouse. Sensitivity of the model to changes in infusion flow rate, catheter placement and tissue hydraulic conductivity were investigated. The model predictions suggest that 1) tracer distribution is asymmetric due to heterogeneous porosity; 2) tracer distribution volume varies linearly with infusion volume within the whole leg, and exponentially within the tumor reaching a maximum steady-state value; 3) infusion at the center of the tumor with high flow rates leads to maximum tracer coverage in the tumor with minimal leakage outside; and 4) increasing the tissue hydraulic conductivity lowers the tumor interstitial fluid pressure and decreases the tracer distribution volume within the whole leg and tumor. The model thus predicts that the interstitial fluid flow and drug transport is sensitive to porosity and changes in extracellular space. This image-based model thus serves as a potential tool for exploring the effects of transport heterogeneity in tumors. PMID:24619021
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Impact of Chiropractic Manipulation on Bone and Skeletal Muscle of Ovariectomized Rats.
López-Herradón, A; Fujikawa, R; Gómez-Marín, M; Stedile-Lovatel, J P; Mulero, F; Ardura, J A; Ruiz, P; Muñoz, I; Esbrit, P; Mahíllo-Fernández, I; Ortega-de Mues, A
2017-11-01
Evidence suggests that chiropractic manipulation might exert positive effects in osteoporotic patients. The aim of this study was to evaluate the effects of chiropractic manipulation on bone structure and skeletal muscle in rats with bone loss caused by ovariectomy (OVX). The 6-month old Sprague-Dawley rats at 10 weeks following OVX or sham operation (Sh) did not suffer chiropractic manipulation (NM group) or were submitted to true chiropractic manipulation using the chiropractic adjusting instrument Activator V ® three times/week for 6 weeks as follows: Force 1 setting was applied onto the tibial tubercle of the rat right hind limb (TM group), whereas the corresponding left hind limb received a false manipulation (FM group) consisting of ActivatorV ® firing in the air and slightly touching the tibial tubercle. Bone mineral density (BMD) and bone mineral content (BMC) were determined in long bones and L3-L4 vertebrae in all rats. Femora and tibia were analyzed by μCT. Mechano growth factor (MGF) was detected in long bones and soleus, quadriceps and tibial muscles by immunohistochemistry and Western blot. The decrease of BMD and BMC as well as trabecular bone impairment in the long bones of OVX rats vs Sh controls was partially reversed in the TM group versus FM or NM rats. This bone improvement by chiropractic manipulation was associated with an increased MGF expression in the quadriceps and the anterior tibial muscle in OVX rats. These findings support the notion that chiropractic manipulation can ameliorate osteoporotic bone at least partly by targeting skeletal muscle.
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Role of blood and vascular smooth muscle in the vasoactivity of nitrite.
Liu, Taiming; Schroeder, Hobe J; Barcelo, Lisa; Bragg, Shannon L; Terry, Michael H; Wilson, Sean M; Power, Gordon G; Blood, Arlin B
2014-10-01
Recent evidence from humans and rats indicates that nitrite is a vasodilator under hypoxic conditions by reacting with metal-containing proteins to produce nitric oxide (NO). We tested the hypothesis that near-physiological concentrations of nitrite would produce vasodilation in a hypoxia- and concentration-dependent manner in the hind limb of sheep. Anesthetized sheep were instrumented to measure arterial blood pressure and femoral blood flows continuously in both hind limbs. Nitrite was infused into one femoral artery to raise the nitrite concentration in the femoral vein by 10 to 15-fold while the sheep breathed 50%, 14% or 12% oxygen in inspired air. In contrast to reports in humans and rats, the nitrite infusion had no measurable effect on mean femoral blood flows or vascular conductances, regardless of inspired O2 levels. In vitro experiments showed no significant difference in the release of NO from nitrite in sheep and human red blood cells. Further experiments demonstrated nitrite is converted to NO in rat artery homogenates faster than sheep arteries, and that this source of NO production is attenuated in the presence of a heme oxidizer. Finally, western blots indicate that concentrations of the heme-containing protein cytoglobin, but not myoglobin, are markedly lower in sheep arteries compared with rats. Overall, the results demonstrate that nitrite is not a physiological vasodilator in sheep. This is likely due to a lack of conversion of nitrite to NO within the vascular smooth muscle, perhaps due to deficient amounts of the heme-containing protein cytoglobin. Copyright © 2014 the American Physiological Society.
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Brown, D C; Boston, R C; Farrar, J T
2013-01-01
Lameness assessment using force plate gait analysis (FPGA) and owner assessment of chronic pain using the Canine Brief Pain Inventory (CBPI) are valid and reliable methods of evaluating canine osteoarthritis. There are no studies comparing these 2 outcome measures. Evaluate the relationship between CBPI pain severity (PS) and interference (PI) scores with the vertical forces of FPGA as efficacy measures in canine osteoarthritis. Sixty-eight client-owned dogs with osteoarthritis (50 hind limb and 18 forelimb). Double-blind, randomized. Owners completed the CBPI, and dogs underwent FPGA on days 0 and 14. Dogs received carprofen or placebo on days 1 through 14. The change in PS and PI scores from day 0 to 14 were compared to the change in peak vertical force (PVF) and vertical impulse (VI). PS and PI scores significantly decreased in carprofen- compared with placebo-treated dogs (P = .002 and P = .03, respectively). PVF and VI significantly increased in carprofen- compared with placebo-treated dogs (P = .006 and P = .02, respectively). There was no correlation or concordance between the PS or PI score changes and change in PVF or VI. In these dogs with hind limb or forelimb osteoarthritis, owner assessment of chronic pain using the CBPI and assessment of lameness using FPGA detected significant improvement in dogs treated with carprofen. The lack of correlation or concordance between the change in owner scores and vertical forces suggests that owners were focused on behaviors other than lameness when making efficacy evaluations in their dogs. Copyright © 2012 by the American College of Veterinary Internal Medicine.
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Lauer, Susanne K; Hillman, Robert B; Li, Li; Hosgood, Giselle L
2009-05-01
To evaluate the effect of treadmill incline on muscle activity and joint range of motion (ROM) in hind limbs of dogs. 8 purpose-bred healthy adult hounds. Activities of the hamstring (semimembranosus, semitendinosus, and biceps femoris muscles), gluteal (superficial, middle, and deep gluteal muscles), and quadriceps (femoris, vastus lateralis, vastus intermedius, and vastus medialis muscles) muscle groups and hip and stifle joint ROM were measured with surface electrogoniometric and myographic sensors in hounds walking on a treadmill at 0.54 m/s at inclines of 5%, 0%, and -5% in random order. Mean electromyographic activities and mean ROMs at each inclination were compared for swing and stance phases. Treadmill inclination did not affect duration of the stance and swing phases or the whole stride. When treadmill inclination was increased from -5% to 5%, hip joint ROM increased and the degree of stifle joint extension decreased significantly. In the beginning of the stance phase, activity of the hamstring muscle group was significantly increased when walking at a 5% incline versus a 5% decline. In the end of the stance phase, that activity was significantly increased when walking at a 5% incline versus at a 5% decline or on a flat surface. Activity of the gluteal and quadriceps muscle groups was not affected when treadmill inclination changed. Treadmill inclination affected joint kinematics only slightly. Walking on a treadmill at a 5% incline had more potential to strengthen the hamstring muscle group than walking on a treadmill with a flat or declined surface.
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Role of blood and vascular smooth muscle in the vasoactivity of nitrite
Liu, Taiming; Schroeder, Hobe J.; Barcelo, Lisa; Bragg, Shannon L.; Terry, Michael H.; Wilson, Sean M.; Power, Gordon G.
2014-01-01
Recent evidence from humans and rats indicates that nitrite is a vasodilator under hypoxic conditions by reacting with metal-containing proteins to produce nitric oxide (NO). We tested the hypothesis that near-physiological concentrations of nitrite would produce vasodilation in a hypoxia- and concentration-dependent manner in the hind limb of sheep. Anesthetized sheep were instrumented to measure arterial blood pressure and femoral blood flows continuously in both hind limbs. Nitrite was infused into one femoral artery to raise the nitrite concentration in the femoral vein by 10 to 15-fold while the sheep breathed 50%, 14% or 12% oxygen in inspired air. In contrast to reports in humans and rats, the nitrite infusion had no measurable effect on mean femoral blood flows or vascular conductances, regardless of inspired O2 levels. In vitro experiments showed no significant difference in the release of NO from nitrite in sheep and human red blood cells. Further experiments demonstrated nitrite is converted to NO in rat artery homogenates faster than sheep arteries, and that this source of NO production is attenuated in the presence of a heme oxidizer. Finally, western blots indicate that concentrations of the heme-containing protein cytoglobin, but not myoglobin, are markedly lower in sheep arteries compared with rats. Overall, the results demonstrate that nitrite is not a physiological vasodilator in sheep. This is likely due to a lack of conversion of nitrite to NO within the vascular smooth muscle, perhaps due to deficient amounts of the heme-containing protein cytoglobin. PMID:25108012
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Effective robotic assistive pattern of treadmill training for spinal cord injury in a rat model
Zhao, Bo-Lun; Li, Wen-Tao; Zhou, Xiao-Hua; Wu, Su-Qian; Cao, Hong-Shi; Bao, Zhu-Ren; An, Li-Bin
2018-01-01
The purpose of the present study was to establish an effective robotic assistive stepping pattern of body-weight-supported treadmill training based on a rat spinal cord injury (SCI) model and assess the effect by comparing this with another frequently used assistive stepping pattern. The recorded stepping patterns of both hind limbs of trained intact rats were edited to establish a 30-sec playback normal rat stepping pattern (NRSP). Step features (step length, step height, step number and swing duration), BBB scores, latencies, and amplitudes of the transcranial electrical motor-evoked potentials (tceMEPs) and neurofilament 200 (NF200) expression in the spinal cord lesion area during and after 3 weeks of body-weight-supported treadmill training (BWSTT) were compared in rats with spinal contusion receiving NRSP assistance (NRSPA) and those that received manual assistance (MA). Hind limb stepping performance among rats receiving NRSPA during BWSTT was greater than that among rats receiving MA in terms of longer step length, taller step height, and longer swing duration. Furthermore a higher BBB score was also indicated. The rats in the NRSPA group achieved superior results in the tceMEPs assessment and greater NF200 expression in the spinal cord lesion area compared with the rats in the MA group. These findings suggest NRSPA was an effective assistive pattern of treadmill training compared with MA based on the rat SCI model and this approach could be used as a new platform for animal experiments for better understanding the mechanisms of SCI rehabilitation. PMID:29545846
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Expression of heat shock protein 72 in atrophied rat skeletal muscles
NASA Technical Reports Server (NTRS)
Oishi, Y.; Ishihara, A.; Talmadge, R. J.; Ohira, Y.; Taniguchi, K.; Matsumoto, H.; Roy, R. R.; Edgerton, V. R.
2001-01-01
Changes in the expression of heat shock protein 72 (HSP72) in response to atrophic-inducing perturbations of muscle involving chronic mechanical unloading and denervation were determined. Adult male Wistar rats were assigned randomly to a sedentary cage control (CON), hind limb unloading (HU, via tail suspension), HU plus tenotomy (HU + TEN), HU plus denervation (HU + DEN), or HU + TEN + DEN group. Tenotomy and DEN involved cutting the Achilles tendon and removing a segment of the sciatic nerve, respectively. After 5 days, HSP72 levels in the soleus of the HU + DEN and HU + TEN + DEN groups were 42 (P < 0.05) and 53% (P < 0.01) less than CON, respectively. Soleus weight decreased in both groups. Heat shock protein 72 levels in the plantaris of the HU + TEN, HU + DEN, and HU + TEN + DEN groups were 31, 25, and 30% lower than CON, respectively (P < 0.05). Plantaris weight decreased in the HU + DEN and HU + TEN + DEN, but not in the HU + TEN group. Hind limb unloading alone had little effect on the HSP72 level in either muscle. Reduced levels of HSP72 were associated with a decreased soleus (r=0.62, P < 0.01) and plantaris (r=0.78, P < 0.001) weight. These results indicate that the levels of HSP72 in both a slow and a fast rat plantarflexor are responsive to a chronic decrease in the levels of loading and/or activation and suggest that the neuromuscular activity level and the presence of innervation of a muscle are important factors that induce HSP72 expression.
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Gasior, M; Borowicz, K; Kleinrok, Z; Starownik, R; Czuczwar, S J
1997-04-01
This study was designed to investigate the influence of the calcium (Ca2+) channel inhibitors nicardipine, nifedipine, and flunarizine on the protective action of MK-801, LY 235959 [N-methyl-D-aspartate (NMDA) receptor antagonists], and GYKI 52466 (a non-NMDA receptor antagonist) against electroconvulsions in mice. Unlike nicardipine (15 mg/kg) or flunarizine (10 mg/kg) nifedipine (7.5 and 15 mg/kg) potentiated the protective potency of MK-801 (0.05 mg/kg), as reflected by significant elevation of the convulsive threshold (a CS50 value of the current strength in mA producing tonic hind limb extension in 50% of the animals). The protective activity of LY 235959 and GYKI 52466 was reflected by their ED50 values in mg/kg, at which the drugs were expected to protect 50% of mice against maximal electroshock-induced tonic extension of the hind limbs. Nicardipine (3.75 15 mg/kg), nifedipine (0.94-15 mg/kg), and flunarizine (2.5-10 mg/kg) in a dose-dependent manner markedly potentiated the antiseizure efficacy of LY 235959. Flunarizine (5 and 10 mg/kg) was the only Ca2+ channel inhibitor to enhance the protective action of GYKI 52466 against electroconvulsions. Except with MK-801 + flunarizine (motor performance) or GYKI 52466 + flunarizine (long-term memory), combination of NMDA or non-NMDA receptor antagonists with Ca2+ channel inhibitors produced an impairment of motor performance (evaluated in the chimney test) and long-term memory acquisition (measured in the passive avoidance task) as compared with vehicle treatment.
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Adams, Rick A.; Snode, Emily R.; Shaw, Jason B.
2012-01-01
Historically, studies concerning bat flight have focused primarily on the wings. By analyzing high-speed video taken on 48 individuals of five species of vespertilionid bats, we show that the capacity to flap the tail-membrane (uropatagium) in order to generate thrust and lift during takeoffs and minimal-speed flight (<1 m s−1) was largely underestimated. Indeed, bats flapped the tail-membrane by extensive dorso-ventral fanning motions covering as much as 135 degrees of arc consistent with thrust generation by air displacement. The degree of dorsal extension of the tail-membrane, and thus the potential amount of thrust generated during platform launches, was significantly correlated with body mass (P = 0.02). Adduction of the hind limbs during upstrokes collapsed the tail-membrane thereby reducing its surface area and minimizing negative lift forces. Abduction of the hind limbs during the downstroke fully expanded the tail-membrane as it was swept ventrally. The flapping kinematics of the tail-membrane is thus consistent with expectations for an airfoil. Timing offsets between the wings and tail-membrane during downstrokes was as much as 50%, suggesting that the tail-membrane was providing thrust and perhaps lift when the wings were retracting through the upstoke phase of the wing-beat cycle. The extent to which the tail-membrane was used during takeoffs differed significantly among four vespertilionid species (P = 0.01) and aligned with predictions derived from bat ecomorphology. The extensive fanning motion of the tail membrane by vespertilionid bats has not been reported for other flying vertebrates. PMID:22393378
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Effect of recovery mode following hind-limb suspension on soleus muscle composition in the rat
NASA Technical Reports Server (NTRS)
McNulty, A. L.; Otto, A. J.; Kasper, C. E.; Thomas, D. P.
1992-01-01
The purpose of this study was to compare the effects of two different recovery modes from hind-limb suspension-induced hypodynamia on whole body and muscle (soleus) growth as well as soleus composition and size changes of different fiber types within this same muscle. Following 28 days of tail-suspension, rats were returned to their cages and sedentarily recovered (HS), or were exercised by running on a treadmill 5 days/wk, at progressively increasing workloads (HR) for one month. Sedentary and running control groups of animals (CS, CR) were also evaluated for comparative purposes. The exercise program, which was identical for CR and HR groups, had no effect on body wt., soleus wt., soleus muscle composition or fiber size in CR rats. Atrophied soleus muscle and reduced soleus wt./body wt. ratio (both 60% of control) had returned to control values by day 7 of recovery in both suspended groups despite the fact that whole body wt. gain was significantly reduced (p less than 0.05) in HR as compared to HS rats. Atrophied soleus Type I fiber mean cross-sectional area in both HR and HS groups demonstrated similar and significant (p less than 0.01) increases during recovery. Increases in Type IIa and IIc fiber area during this same period were significant only in the HR group. While the percentage area of muscle composed of Type I fibers increased in both hypodynamic groups during recovery, the reduction in area percentage of muscle made up of Type IIa fibers was again only significant in the HR group.(ABSTRACT TRUNCATED AT 250 WORDS).
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Evaluation of arterial digital blood flow using Doppler ultrasonography in healthy dairy cows.
Müller, H; Heinrich, M; Mielenz, N; Reese, S; Steiner, A; Starke, A
2017-06-06
Local circulatory disturbances have been implicated in the development of foot disorders in cattle. The goals of this study were to evaluate the suitability of the interdigital artery in the pastern region in both hind limbs using pulsed-wave (PW) Doppler ultrasonography and to investigate quantitative arterial blood flow variables at that site in dairy cows. An Esaote MyLabOne ultrasound machine with a 10-MHz linear transducer was used to assess blood flow in the interdigital artery in the pastern region in both hind limbs of 22 healthy German Holstein cows. The cows originated from three commercial farms and were restrained in a standing hoof trimming chute without sedation. A PW Doppler signal suitable for analysis was obtained in 17 of 22 cows. The blood flow profiles were categorised into four curve types, and the following quantitative variables were measured in three uniform cardiac cycles: vessel diameter, pulse rate, maximum systolic velocity, maximum diastolic velocity, end-diastolic velocity, reverse velocity, maximum time-averaged mean velocity, blood flow rate, resistance index and persistence index. The measurements did not differ among cows from the three farms. Maximum systolic velocity, vessel diameter and pulse rate did not differ but other variables differed significantly among blood flow profiles. Differences in weight-bearing are thought to be responsible for the normal variability of blood flow profiles in healthy cows. The scanning technique used in this report for evaluation of blood flow in the interdigital artery appears suitable for further investigations in healthy and in lame cows.
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Novel Model of Somatosensory Nerve Transfer in the Rat.
Paskal, Adriana M; Paskal, Wiktor; Pelka, Kacper; Podobinska, Martyna; Andrychowski, Jaroslaw; Wlodarski, Pawel K
2018-05-09
Nerve transfer (neurotization) is a reconstructive procedure in which the distal denervated nerve is joined with a proximal healthy nerve of a less significant function. Neurotization models described to date are limited to avulsed roots or pure motor nerve transfers, neglecting the clinically significant mixed nerve transfer. Our aim was to determine whether femoral-to-sciatic nerve transfer could be a feasible model of mixed nerve transfer. Three Sprague Dawley rats were subjected to unilateral femoral-to-sciatic nerve transfer. After 50 days, functional recovery was evaluated with a prick test. At the same time, axonal tracers were injected into each sciatic nerve distally to the lesion site, to determine nerve fibers' regeneration. In the prick test, the rats retracted their hind limbs after stimulation, although the reaction was moderately weaker on the operated side. Seven days after injection of axonal tracers, dyes were visualized by confocal microscopy in the spinal cord. Innervation of the recipient nerve originated from higher segments of the spinal cord than that on the untreated side. The results imply that the femoral nerve axons, ingrown into the damaged sciatic nerve, reinnervate distal targets with a functional outcome.
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Farmer, Nicholas A.; Karnauskas, Mandy
2013-01-01
There is broad interest in the development of efficient marine protected areas (MPAs) to reduce bycatch and end overfishing of speckled hind (Epinephelus drummondhayi) and warsaw grouper (Hyporthodus nigritus) in the Atlantic Ocean off the southeastern U.S. We assimilated decades of data from many fishery-dependent, fishery-independent, and anecdotal sources to describe the spatial distribution of these data limited stocks. A spatial classification model was developed to categorize depth-grids based on the distribution of speckled hind and warsaw grouper point observations and identified benthic habitats. Logistic regression analysis was used to develop a quantitative model to predict the spatial distribution of speckled hind and warsaw grouper as a function of depth, latitude, and habitat. Models, controlling for sampling gear effects, were selected based on AIC and 10-fold cross validation. The best-fitting model for warsaw grouper included latitude and depth to explain 10.8% of the variability in probability of detection, with a false prediction rate of 28–33%. The best-fitting model for speckled hind, per cross-validation, included latitude and depth to explain 36.8% of the variability in probability of detection, with a false prediction rate of 25–27%. The best-fitting speckled hind model, per AIC, also included habitat, but had false prediction rates up to 36%. Speckled hind and warsaw grouper habitats followed a shelf-edge hardbottom ridge from North Carolina to southeast Florida, with speckled hind more common to the north and warsaw grouper more common to the south. The proportion of habitat classifications and model-estimated stock contained within established and proposed MPAs was computed. Existing MPAs covered 10% of probable shelf-edge habitats for speckled hind and warsaw grouper, protecting 3–8% of speckled hind and 8% of warsaw grouper stocks. Proposed MPAs could add 24% more probable shelf-edge habitat, and protect an additional 14–29% of speckled hind and 20% of warsaw grouper stocks. PMID:24260126
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Perfect polydactylism in hind feet of a gray squirrel
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dunaway, P.B.
1969-01-01
An adult gray squirrel from an isolated natural population had seven toes and nine plantar tubercles on each hind foot. The extra digits were articulated with supernumerary cuneiforms and appeared to have been functional. Polydactylism in wild adult rodents is probably a rare anomaly. 6 references, 2 figures.
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López-Dolado, Elisa; Lucas-Osma, Ana M.
2013-01-01
Abstract Incomplete cervical lesion is the most common type of human spinal cord injury (SCI) and causes permanent paresis of arm muscles, a phenomenon still incompletely understood in physiopathological and neuroanatomical terms. We performed spinal cord hemisection in adult rats at the caudal part of the segment C6, just rostral to the bulk of triceps brachii motoneurons, and analyzed the forces and kinematics of locomotion up to 4 months postlesion to determine the nature of motor function loss and recovery. A dramatic (50%), immediate and permanent loss of extensor force occurred in the forelimb but not in the hind limb of the injured side, accompanied by elbow and wrist kinematic impairments and early adaptations of whole-body movements that initially compensated the balance but changed continuously over the follow-up period to allow effective locomotion. Overuse of both contralateral legs and ipsilateral hind leg was evidenced since 5 days postlesion. Ipsilateral foreleg deficits resulted mainly from interruption of axons that innervate the spinal cord segments caudal to the lesion, because chronic loss (about 35%) of synapses was detected at C7 while only 14% of triceps braquii motoneurons died, as assessed by synaptophysin immunohistochemistry and retrograde neural tracing, respectively. We also found a large pool of propriospinal neurons projecting from C2–C5 to C7 in normal rats, with topographical features similar to the propriospinal premotoneuronal system of cats and primates. Thus, concurrent axotomy at C6 of brain descending axons and cervical propriospinal axons likely hampered spontaneous recovery of the focal neurological impairments. PMID:23249275
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Dysplastic lesions and abnormalities in amphibians associated with environmental conditions.
Mizgireuv, I V; Flax, N L; Borkin, L J; Khudoley, V V
1984-01-01
High incidence of developmental anomaly and tumor-like dysplasia of osteochondrous tissue of hind limbs has been detected in frogs and toads the larval development of which has taken place in water, contaminated with sewage. Correlation between frequency of dysplasia and the level of water oxidation has been noted. Study on histogenesis of the marked tumor-like dysplasia were performed. It is assumed that the major mechanism responsible for anomaly consists in cytotoxic effect of teratogenic agent and that the differentiation lesion of cartilaginous tissue is caused by blocking of maturation and death of chondrocytes.
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Experimental skeletal teratogenesis in the frog tadpole.
Roth, M
1978-01-01
Severe deformities of the hind limb skeleton such as shortening, abnormal curvatures, terminal expansions, curled toes and joint dislocations were produced in frog tadpoles by the osteolathyrogenic principle. Gross-anatomical features of the deformed skeleton and of the respective nervous trunks were studied in specimens cleared according to WILLIAMS' technique. The findings support the previously suggested osteo-neural concept: Experimental skeletal deformities represent adaptations of the bone growth at the organ level to the inadequate extensive growth of the nervous trunks. The neural growth appears to be more severely affected by the teratogen than the bone growth proper.
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Morphological changes in neurons of the hind limb reflex arc during long term immobilization
NASA Technical Reports Server (NTRS)
Tkachenko, Z. Y.
1980-01-01
Twelve adult rabbits were immobilized for 9 to 31 days, followed by histological study of the nerve processes of lumbar vertebra 7 and sacral vertebra 1, the sciatic nerve and the motor endings of the thigh muscles. In the spinal ganglia, dystrophic changes of increasing severity with immobilization time were found, including pericellular edema, vacuolized neuroplasm, pycnotic changes, cytolysis and destruction. Chromatophilic matter decreased and was partly bleached, and amitotic division occurred. A portion of the sciatic nerve fibers were argentophilic, and some fragmentary decomposition occurred. Considerable dystrophic changes occurred in the motor nerve endings.
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NASA Technical Reports Server (NTRS)
Lowry, O. H.; Ilyina-Kakueva, E. I.; Krasnov, I. B.; Carter, J. G.; Chi, M. M.-Y.; Choksi, R.; Manchester, J. K.; McDougal, D. B.; Nemeth, P. M.; Pusateri, M. E.
1994-01-01
Individual fibers of any given muscle vary widely in enzyme composition, a fact obscured when enzyme levels of whole muscle are measured. Therefore, the purpose of this part of the study was to assess the effects of microgravity and hind limb suspension on the enzyme patterns within a slow twitch muscle (soleus) and a fast twitch muscle (tibialis anterior).
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NASA Technical Reports Server (NTRS)
Kogan, B. I.; Antipov, Y. S.
1980-01-01
Inbred 1 month old males of C57B 1/6, CBA, CC57Br/Mw interlinear hybrid mice of the first generation and rats of the August and Wistar lines were subjected to conditions of hypo-, normo- and hyperdynamia for 2 months. The statistically reliable dependence is shown between mechanical underloadings and overloadings and macro microscopic changes in the hind limb skeleton of animals. Genetic determination of growth and formation of the forelimb skeleton is established. Hereditary susceptibility and the phenomenon of heterosis are preserved under all motor conditions.
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Synovial T-cell lymphoma of the stifle in a dog.
Lahmers, Sunshine M; Mealey, Katrina L; Martinez, Steven A; Haldorson, Gary J; Sellon, Rance K; Cambridge, Anthony J
2002-01-01
A 6-year-old, 43-kg, spayed female rottweiler was presented for a 1-month history of progressive, left hind-limb lameness. Upon physical examination, a cranial drawer sign and joint distention were present in the left stifle. Radiographically, the stifle had evidence of effusion, remodeling of the patella, and an enlarged popliteal lymph node. Marked synovial thickening and an intact cranial cruciate ligament were noted during surgery. Despite finding a nonspecific, mixed inflammatory response on joint fluid cytopathology, histopathology demonstrated T-cell lymphoma of the synovium. Lameness may be the sole presenting clinical sign in canine lymphoma.
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Bone Density and High Salt Diets in a Space Flight Model
NASA Technical Reports Server (NTRS)
Arnaud, S. B.; Navidi, M.; Liang, M. T. C.; Wolinsky, I.
1999-01-01
High salt diets accelerate bone loss with aging in patients with postmenopausal osteoporosis except when calcium supplementation is provided. We have observed that the decrease in mineral content of growing femurs in juvenile rats, exposed to a space flight model which unloads the hind limbs , is substantially less in animals fed excess salt. To determine whether excess dietary salt has the same effect on the skeleton of the mature animal whose response to unloading is increased resorption and bone loss rather than impaired growth, we carried out a metabolic study in mature rats with hindlimbs unloaded by tailsuspension.
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Ivermectin toxicosis in a dog.
Hopkins, K D; Marcella, K L; Strecker, A E
1990-07-01
A 5-year-old male Doberman Pinscher was examined after ingesting an equine paste dewormer containing approximately 115 mg of ivermectin. Clinical signs consisted of profound hypothermia, mild dehydration, dilated unresponsive pupils, localized muscle group fasciculations around the face and hind limbs, and no response to any external stimuli. Twelve days after parenteral administration of isotonic fluids and IV administration of dexamethasone and dimethyl sulfoxide, the dog returned to a clinically normal neurologic state. Ivermectin toxicosis has been reported frequently in Collies; however, other breeds may have idiosyncratic reactions to low doses. Patients with severe toxicosis should eventually recover completely if given appropriate intensive care.
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Cathepsin L is required for endothelial progenitor cell-induced neovascularization
DOE Office of Scientific and Technical Information (OSTI.GOV)
Urbich, Carmen; Heeschen, Christopher; Aicher, Alexandra
Infusion of endothelial progenitor cells (EPCs), but not of mature endothelial cells (ECs), promotes neovascularization after ischemia. We performed a gene expression profiling of EPCs and ECs to identify genes, which might be important for the neovascularization capacity of EPCs. Intriguingly, the protease cathepsin L (CathL) was highly expressed in EPCs as opposed to ECs and is essential for matrix degradation and invasion by EPCs in vitro. CathL deficient mice showed impaired functional recovery after hind limb ischemia supporting the concept for an important role of CathL in postnatal neovascularization. Infused CathL deficient progenitor cells failed to home to sitesmore » of ischemia and to augment neovascularization. In contrast, over expression of CathL in mature ECs significantly enhanced their invasive activity and induced their neovascularization capacity in vivo. Taken together, CathL plays a crucial role for the integration of circulating EPCs into the ischemic tissue and is required for neovascularization mediated by EPCs.« less
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Trunk orientation causes asymmetries in leg function in small bird terrestrial locomotion.
Andrada, Emanuel; Rode, Christian; Sutedja, Yefta; Nyakatura, John A; Blickhan, Reinhard
2014-12-22
In contrast to the upright trunk in humans, trunk orientation in most birds is almost horizontal (pronograde). It is conceivable that the orientation of the heavy trunk strongly influences the dynamics of bipedal terrestrial locomotion. Here, we analyse for the first time the effects of a pronograde trunk orientation on leg function and stability during bipedal locomotion. For this, we first inferred the leg function and trunk control strategy applied by a generalized small bird during terrestrial locomotion by analysing synchronously recorded kinematic (three-dimensional X-ray videography) and kinetic (three-dimensional force measurement) quail locomotion data. Then, by simulating quail gaits using a simplistic bioinspired numerical model which made use of parameters obtained in in vivo experiments with real quail, we show that the observed asymmetric leg function (left-skewed ground reaction force and longer leg at touchdown than at lift-off) is necessary for pronograde steady-state locomotion. In addition, steady-state locomotion becomes stable for specific morphological parameters. For quail-like parameters, the most common stable solution is grounded running, a gait preferred by quail and most of the other small birds. We hypothesize that stability of bipedal locomotion is a functional demand that, depending on trunk orientation and centre of mass location, constrains basic hind limb morphology and function, such as leg length, leg stiffness and leg damping. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
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Messner, Franka; Hautz, Theresa; Blumer, Michael J F; Bitsche, Mario; Pechriggl, Elisabeth J; Hermann, Martin; Zelger, Bettina; Zelger, Bernhard; Öfner, Dietmar; Schneeberger, Stefan
2017-09-01
We herein investigate critical ischemia times and the effect of novel preservation solutions such as new histidine-tryptophan-ketoglutarate (HTK-N) and TiProtec on the individual tissues of a rat limb isograft. Orthotopic hind-limb transplantations were performed in male Lewis rats after 2 hours, 6 hours, or 10 hours of cold ischemia (CI). Limbs were flushed and stored in HTK-N, TiProtec, HTK, or saline solution. Muscle, nerve, vessel, skin, and bone samples were procured on day 10 for histology, immunohistochemistry, confocal and electron microscopy, and quantitative real-time polymerase chain reaction analysis. Histomorphology of the muscle showed a mainly perivascular inflammatory infiltrate, fibrotic degeneration, and neovascularization after 6 hours and 10 hours of CI. However, centrally aligned nuclei observed in muscle fibers suggest for muscle regeneration in these samples. In addition to Wallerian degeneration, nerve injury was significantly aggravated (P = 0.032) after prolonged CI. Proinflammatory and regulatory cytokines were most significantly upregulated after 2-hour CI. Our data suggest no superiority of novel perfusates HTK-N and TiProtec in terms of tissue preservation, compared with HTK and saline. Limiting CI time for less than 6 hours is the most significant factor to reduce tissue damage in vascularized tissue transplantation. Signs of muscle regeneration give rise that ischemic muscle damage in limb transplantation might be reversible to a certain extent.
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Real-time control of walking using recordings from dorsal root ganglia.
Holinski, B J; Everaert, D G; Mushahwar, V K; Stein, R B
2013-10-01
The goal of this study was to decode sensory information from the dorsal root ganglia (DRG) in real time, and to use this information to adapt the control of unilateral stepping with a state-based control algorithm consisting of both feed-forward and feedback components. In five anesthetized cats, hind limb stepping on a walkway or treadmill was produced by patterned electrical stimulation of the spinal cord through implanted microwire arrays, while neuronal activity was recorded from the DRG. Different parameters, including distance and tilt of the vector between hip and limb endpoint, integrated gyroscope and ground reaction force were modelled from recorded neural firing rates. These models were then used for closed-loop feedback. Overall, firing-rate-based predictions of kinematic sensors (limb endpoint, integrated gyroscope) were the most accurate with variance accounted for >60% on average. Force prediction had the lowest prediction accuracy (48 ± 13%) but produced the greatest percentage of successful rule activations (96.3%) for stepping under closed-loop feedback control. The prediction of all sensor modalities degraded over time, with the exception of tilt. Sensory feedback from moving limbs would be a desirable component of any neuroprosthetic device designed to restore walking in people after a spinal cord injury. This study provides a proof-of-principle that real-time feedback from the DRG is possible and could form part of a fully implantable neuroprosthetic device with further development.
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Liu, C; Zhang, L F; Zhang, L N; Ni, H Y; Zhang, Y Q; Sun, L
2000-12-01
Objective. To study the efficacy of intermittent + Gz (45 degrees head-up tilt, HUT) exposures in preventing or alleviating atrophic changes in hind limb muscles induced by simulated weightlessness. Method. Male Sprague-Dawley (SD) rats were assigned randomly to one of three groups: simultaneous control (CON), simulated weightlessness (SUS), and SUS plus 6 h/d HUT (SUS + HUT). Muscles examined included soleus (SOL), medial gastrocnemius (correction from grastrocnemius) (MG), lateral gastrocnemius (LG) and extensor digitorum longus (EDL). Sections were treated with an adenosinetriphosphatase (ATPase) stain or alkaline phosphatase stain. The cross-sectional areas (CSA) of fibers, the relative proportion of type I fiber and the ratio of capillaries/fibers (C/F) were measured using Leica image analysis system. Result. Compared with CON, the wet weight of hind limb muscles in SUS were significantly reduced. The changes of wet weight in different groups were various. The C/F ratios of all muscles were significantly reduced. SUS + HUT rats showed significant increases in SOL and MG wet weight, and the relative counter-effects of intermittent HUT were 93.4% and 34.8%, respectively. In SUS + HUT group, the CSA of both type I and II fibers and relative proportion of type I fibers were completely recovered in SOL, and partially recovered in MG, while the counter-effects were much less obvious in the fibers of LG and EDL. However, HUT resulted in a significant recovery of the C/F ratios in all muscles. Conclusion. The present study demonstrated that intermittent HUT is effective in counteracting the atrophy induced by simulated weightlessness. The result that reactivity to HUT varied among different muscles suggests that the intermittent artificial gravity should be complemented with other countermeasures.
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Crawford, Robert S.; Albadawi, Hassan; Atkins, Marvin D.; Jones, John J.; Conrad, Mark F.; Austen, William G.; Fink, Mitchell P.; Watkins, Michael T.
2011-01-01
Introduction Experiments were designed to investigate the effects of ethyl pyruvate (EP) in a murine model of hind-limb ischemia-reperfusion (IR) injury. Methods C57BL6 mice underwent 90 minutes of unilateral ischemia followed by 24 hours of reperfusion using two treatment protocols. For the preischemic treatment (pre-I) protocol, mice (n = 6) were given 300 mg/kg EP before ischemia, followed by 150 mg/kg of EP just before reperfusion and at 6 hours and 12 hours after reperfusion. In a postischemic treatment (post-I) protocol, mice (n = 7) were treated with 300 mg/kg EP at the end of the ischemic period, then 15 minutes later, and 2 hours after reperfusion and 150 mg/kg of EP at 4 hours, 6 hours, 10 hours, 16 hours, and 22 hours after reperfusion. Controls mice for both protocols were treated with lactated Ringers alone at time intervals identical to EP. Skeletal muscle levels of adenosine triphosphate (ATP), interleukin-1β, keratinocyte chemoattractant protein, and thrombin antithrombin-3 complex were measured. Skeletal muscle architectural integrity was assessed microscopically. Results ATP levels were higher in mice treated with EP compared with controls under the both treatment protocols (p = 0.02). Interleukin-1β, keratinocyte chemoattractant protein, thrombin antithrombin-3 complex (p < 0.05), and the percentage of injured fibers (p < 0.0001) were significantly decreased in treated versus control mice under the both protocols. Conclusion Muscle fiber injury and markers of tissue thrombosis and inflammation were reduced, and ATP was preserved with EP in pre-I and post-I protocols. Further investigation of the efficacy of EP to modulate IR injury in a larger animal model of IR injury is warranted. PMID:21217488
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KHAN, NADEEM; MUPPARAJU, SRIRAM P.; MINTZOPOULOS, DIONYSSIOS; KESARWANI, MEENU; RIGHI, VALERIA; RAHME, LAURENCE G.; SWARTZ, HAROLD M.; TZIKA, A. ARIA
2010-01-01
Using a mouse model, we tested the hypotheses that severe burn trauma causes metabolic disturbances in skeletal muscle, and that these can be measured and repeatedly followed by in vivo electron paramagnetic resonance (EPR). We used a 1.2-GHz (L-band) EPR spectrometer to measure partial pressure of oxygen (pO2) levels, redox status and oxidative stress following a non-lethal burn trauma model to the left hind limbs of mice. Results obtained in the burned mouse gastrocnemius muscle indicated a significant decrease in tissue pO2 immediately (P=0.032) and at 6 h post burn (P=0.004), compared to the gastrocnemius of the unburned hind limb. The redox status of the skeletal muscle also peaked at 6 h post burn (P=0.027) in burned mice. In addition, there was an increase in the EPR signal of the nitroxide produced by oxidation of the hydroxylamine (CP-H) probe at 12 h post burn injury, indicating a burn-induced increase in mitochondrial reactive oxygen species (ROS). The nitroxide signal continued to increase between 12 and 24 h, suggesting a further increase in ROS generation post burn. These results confirm genomic results, which indicate a downregulation of antioxidant genes and therefore strongly suggest the dysfunction of the mitochondrial oxidative system. We believe that the direct measurement of tissue parameters such as pO2, redox and ROS by EPR may be used to complement measurements by nuclear magnetic resonance (NMR) in order to assess tissue damage and the therapeutic effectiveness of antioxidant agents in severe burn trauma. PMID:21179378
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Multiloculated solitary (unicameral) bone cyst in a young dog.
Roode, Sarah C; Shive, Heather R; Hoorntje, Willemijn; Bernard, Jennifer; Stowe, Devorah M; Pool, Roy R; Grindem, Carol B
2018-05-21
A 20-month-old female spayed Staffordshire Terrier (22.3 kg) presented to the Orthopedic Surgery Service at North Carolina State University Veterinary Teaching Hospital for evaluation of a 6-week history of toe-touching to nonweight-bearing lameness in the right hind limb. Radiographs of the right stifle revealed a multiloculated lytic lesion of the distal femur, with a large open lytic zone centrally, numerous osseous septations peripherally, and focal areas of cortical thinning and loss. An aspirate of the right distal femoral lesion yielded mildly cloudy serosanguineous fluid. Cytologic examination of the fluid revealed a pleomorphic population of discrete cells that exhibited marked anisocytosis and anisokaryosis and a variable nucleus to cytoplasm (N:C) ratio, which were interpreted as probable neoplastic cells, with few macrophages, and evidence of hemorrhage. Given the clinical signs of pain, lesion size, and concern for malignant neoplasia, amputation of the right hind limb was performed. Histologically, the lesion had undulating walls 1-3 mm thick with a continuous outer layer of dense fibrous tissue and an inner layer composed of reactive cancellous bone with no cortical compacta remaining. Remnants of thin fibrous or fibro-osseous septa projected from the bony wall into the cyst lumen. The final histologic diagnosis was a benign multiloculated solitary (unicameral) bone cyst of the distal right femur. Based on the histopathologic findings, it was speculated that the cells identified on cytology were a mixture of developing osteoclasts, osteoblasts, endothelial, and stromal cells. This is the first report describing the cytologic examination of a solitary bone cyst in veterinary medicine. © 2018 American Society for Veterinary Clinical Pathology.
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Preston, Stephanie A; Brown, Murray P; Trumble, Troy N; Chmielewski, Terese L; Zimmel, Dana N; Hernandez, Jorge A
2012-12-01
To determine the effects of various presale radiographic findings for Thoroughbreds sold at a yearling sale on 2-year-old racing performance of those horses. 397 Thoroughbreds. Cohort study. Thoroughbreds offered for sale at a Thoroughbred sales facility in Kentucky were selected via a randomization procedure. Effects of various presale radiographic findings on the following measures of 2-year-old racing performance were determined: having started a race and having placed (ie, finished in first, second, or third place) in a race at least once, total amount of money earned, and amount of money earned per start. Of the 397 horses, 192 (48%) started in at least 1 race during the 2-year-old racing year. The odds of failure to start a race as a 2-year-old were 1.78 times as great for horses with forelimb proximal sesamoid bone osteophytes or enthesophytes as for horses without this finding (95% confidence interval, 1.01 to 3.16). The odds of failure to start a race as a 2-year-old were 2.02 times as great for horses with hind limb proximal phalanx osteochondral fragments as for horses without this finding (95% confidence interval, 0.95 to 4.31), although this result was not significant. Radiographic findings did not have an effect on total amount of money earned, amount of money earned per start, or whether horses placed in a race. Presale radiographic detection of forelimb proximal sesamoid bone osteophytes or enthesophytes or hind limb proximal phalanx osteochondral fragments in yearlings were associated with failure to start a race during the 2-year-old racing year in study horses.
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NEUROLOGICAL DEFICITS IN THE RAT RESULTING FROM X IRRADIATION IN UTERO
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sikov, M.R.; Resta, C.F.; Lofstrom, J.E.
1962-02-01
The effects of prenatal irradiation were investigated by exposure of pregnant rats to 20 or 100 r after 10 days of gestation or 50 or 185 r after 15 days. The incidence and severity of neurological deficits was greatest in the rats treated with 185 r after 15 days of gestation. The incidence was lower in the remaining groups, but of statistical significance in some cases. A higher percentage of defects was found among female than male offspring. In some animals, evidence of altered behavior was first seen at birth, while others appeared normal until more mature. The resulting neurologicalmore » syndrome included loss of righting reflex or impairment of placing and hopping reactions. Some displayed hypersensitivity, manifested as exaggerated myoclonic jerks in response to sensory stimuli. Spasticity of hind limbs was found only in the 15-day, 185-r rats; at times this was accompanied by a hind-limb ataxia, which was also noted in other groups. Some animals displayed a convulsive disorder similar to the Jacksonian seizure of man. Other neurological deficits noted were gait defects, backing-up, and forced circling. At the time of puberty, many males developed priapism, which persisted until death. The neurological deficits correlate well with the morphological lesions. Radiation at 15 days of gestation produced a number of morphological abnormalities of the cerebrum, which included reduction in size, absence of certain structures, defective cell formations, as well as heterotopic development of various areas. It is suggested that radiation during embryonic life may act to produce biochemical alterations with associated metabolic defects, which are not necessarily associated with cell loss but may be associated wlth or result in malformations. (TCO)« less
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Kobulnik, Jeremy; Kuliszewski, Michael A; Stewart, Duncan J; Lindner, Jonathan R; Leong-Poi, Howard
2009-10-27
This study was designed to compare the efficacy of angiogenic gene delivery by ultrasound-mediated (UM) destruction of intravenous carrier microbubbles to direct intramuscular (IM) injections. Current trials of gene therapy for angiogenesis remain limited by suboptimal, invasive delivery techniques. Hind-limb ischemia was produced by iliac artery ligation in 99 rats. In 32 rats, UM delivery of green fluorescent protein (GFP)/vascular endothelial growth factor-165 (VEGF(165)) plasmid deoxyribonucleic acid was performed. Thirty-five animals received IM injections of VEGF(165)/GFP plasmid. Remaining rats received no treatment. Before delivery (day 14 after ligation) and at days 17, 21, and 28 and week 8 after ligation, microvascular blood volume and microvascular blood flow to the proximal hind limbs were assessed by contrast-enhanced ultrasound (n = 8 per group). Total transfection was assessed by reverse transcriptase-polymerase chain reaction, and localization of transfection was determined by immunohistochemistry. By day 28, both IM and UM delivery of VEGF(165) produced significant increases in microvascular blood volume and microvascular blood flow. Whereas increases in microvascular blood volume were similar between treatment groups, microvascular blood flow was greater (p < 0.005) in UM-treated animals as compared with IM-treated animals, persisting to week 8. The VEGF(165)/GFP messenger ribonucleic acid expression was greater (p < 0.05) for IM-treated animals. A strong GFP signal was detected for both groups and was localized to focal perivascular regions and myocytes around injection sites for IM and to the vascular endothelium of arterioles/capillaries in a wider distribution for UM delivery. Despite lower transfection levels, UM delivery of VEGF(165) is as effective as IM injections. The UM delivery results in directed vascular transfection over a wider distribution, which may account for the more efficient angiogenesis.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kinsella, T.J.; DeLuca, A.M.; Barnes, M.
1991-04-01
Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers andmore » perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy.« less
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Management of Candida guilliermondii joint infection in a dog.
Bufalari, Antonello; Maggio, Chiara; Moretti, Giulia; Crovace, Alberto; Stefanetti, Valentina; Straubinger, Reinhard Konrad; Passamonti, Fabrizio
2016-07-08
Candida spp. are dimorphic fungi in the family Cryptococcaceae. Infections with Candida spp. are usually rare conditions in dogs, but immunocompromised patients have a higher risk for developing invasive candidal infections. A 5-year-old male Boxer, positive to Leishmania infantum, was referred to the Veterinary Teaching Hospital of the Department of Veterinary Medicine, University of Perugia, Italy for examination of a non-weight bearing left hind limb lameness of a duration of at least 3 months. During this period, treatment involved systemic anti-inflammatory medications and intra-articular corticosteroid administration. On presentation, clinical examination and radiographic findings were suggestive of cranial cruciate ligament deficiency. To support this diagnosis a stifle arthroscopy was performed: it confirmed a partial rupture of cranial cruciate ligament. Samples culture of synovial fluid and membrane was routinely collected as well, and revealed Candida guilliermondii joint infection. Treatment for the C. guilliermondii joint infection involved systemic anti-fungal therapy, joint lavage and intra-articular administration of antifungal drugs. Lameness improved markedly during this treatment, but lameness did not resolve completely, probably due to cranial cruciate ligament deficiency. Tibial tuberosity advancement (TTA) was chosen in order to treat stifle instability and was performed 4 weeks following cessation of treatment of the C. guilliermondii joint infection. Six month after TTA the dog showed a completely recovery with no lameness. To the authors' knowledge, this is the first case of Candida spp. joint infection reported in dogs. The cause of the progression of the joint C. guilliermondii infection remains unclear but it may be associated with leishmaniasis or intra-articular corticosteroid injections. Treatment with systemic and intra-articular anti-fungal therapies was successful. In the evaluation of hind limb lameness in a chronically immunocompromised dog, it would be advisable to consider also an intra-articular Candida spp.
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Niehoff, Anja; Lechner, Philipp; Ratiu, Oana; Reuter, Sven; Hamann, Nina; Brüggemann, Gert-Peter; Schönau, Eckhard; Bloch, Wilhelm; Beccard, Ralf
2014-04-01
Botulinum toxin A (BTX)-induced muscle paralysis results in pronounced bone degradation with substantial bone loss. We hypothesized that whole-body vibration (WBV) and insulin-like growth factor-I (IGF-I) treatment can counteract paralysis-induced bone degradation following BTX injections by activation of the protein kinase B (Akt) signaling pathway. Female C57BL/6 mice (n = 60, 16 weeks) were assigned into six groups (n = 10 each): SHAM, BTX, BTX+WBV, BTX+IGF-I, BTX+WBV+IGF-I, and a baseline group, which was killed at the beginning of the study. Mice received a BTX (1.0 U/0.1 mL) or saline (SHAM) injection in the right hind limb. The BTX+IGF-I and BTX+WBV+IGF-I groups obtained daily subcutaneous injections of human IGF-I (1 μg/day). The BTX+WBV and BTX+WBV+IGF-I groups underwent WBV (25 Hz, 2.1 g, 0.83 mm) for 30 min/day, 5 days/week for 4 weeks. Femora were scanned by pQCT, and mechanical properties were determined. On tibial sections TRAP staining, static histomorphometry, and immunohistochemical staining against Akt, phospho-Akt, IGF-IR (IGF-I receptor), and phospho-IGF-IR were conducted. BTX injection decreased trabecular and cortical bone mineral density. The WBV and WBV+IGF-I groups showed no difference in trabecular bone mineral density compared to the SHAM group. The phospho-IGF-IR and phospho-Akt stainings were not differentially altered in the injected hind limbs between groups. We found that high-frequency, low-magnitude WBV can counteract paralysis-induced bone loss following BTX injections, while we could not detect any effect of treatment with IGF-I.
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Quek, Hazel; Luff, John; Cheung, KaGeen; Kozlov, Sergei; Gatei, Magtouf; Lee, C Soon; Bellingham, Mark C; Noakes, Peter G; Lim, Yi Chieh; Barnett, Nigel L; Dingwall, Steven; Wolvetang, Ernst; Mashimo, Tomoji; Roberts, Tara L; Lavin, Martin F
2017-04-01
Mutations in the ataxia-telangiectasia (A-T)-mutated ( ATM ) gene give rise to the human genetic disorder A-T, characterized by immunodeficiency, cancer predisposition, and neurodegeneration. Whereas a series of animal models recapitulate much of the A-T phenotype, they fail to present with ataxia or neurodegeneration. We describe here the generation of an Atm missense mutant [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat by intracytoplasmic injection (ICSI) of mutant sperm into oocytes. Atm -mutant rats ( Atm L2262P/L2262P ) expressed low levels of ATM protein, suggesting a destabilizing effect of the mutation, and had a significantly reduced lifespan compared with Atm +/+ Whereas these rats did not show cerebellar atrophy, they succumbed to hind-limb paralysis (45%), and the remainder developed tumors. Closer examination revealed the presence of both dsDNA and ssDNA in the cytoplasm of cells in the hippocampus, cerebellum, and spinal cord of Atm L2262P/L2262P rats. Significantly increased levels of IFN-β and IL-1β in all 3 tissues were indicative of DNA damage induction of the type 1 IFN response. This was further supported by NF-κB activation, as evidenced by p65 phosphorylation (P65) and translocation to the nucleus in the spinal cord and parahippocampus. Other evidence of neuroinflammation in the brain and spinal cord was the loss of motor neurons and the presence of increased activation of microglia. These data provide support for a proinflammatory phenotype that is manifested in the Atm mutant rat as hind-limb paralysis. This mutant represents a useful model to investigate the importance of neuroinflammation in A-T. © Society for Leukocyte Biology.
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Sexual selection targets cetacean pelvic bones
Dines, J. P.; Otárola-Castillo, E.; Ralph, P.; Alas, J.; Daley, T.; Smith, A. D.; Dean, M. D.
2014-01-01
Male genitalia evolve rapidly, probably as a result of sexual selection. Whether this pattern extends to the internal infrastructure that influences genital movements remains unknown. Cetaceans (whales and dolphins) offer a unique opportunity to test this hypothesis: since evolving from land-dwelling ancestors, they lost external hind limbs and evolved a highly reduced pelvis which seems to serve no other function except to anchor muscles that maneuver the penis. Here we create a novel morphometric pipeline to analyze the size and shape evolution of pelvic bones from 130 individuals (29 species) in the context of inferred mating system. We present two main findings: 1) males from species with relatively intense sexual selection (inferred by relative testes size) have evolved relatively large penises and pelvic bones compared to their body size, and 2) pelvic bone shape diverges more quickly in species pairs that have diverged in inferred mating system. Neither pattern was observed in the anterior-most pair of vertebral ribs, which served as a negative control. This study provides evidence that sexual selection can affect internal anatomy that controls male genitalia. These important functions may explain why cetacean pelvic bones have not been lost through evolutionary time. PMID:25186496
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Tibial and fibular nerves evaluation using intraoperative electromyography in rats.
Nepomuceno, André Coelho; Politani, Elisa Landucci; Silva, Eduardo Guandelini da; Salomone, Raquel; Longo, Marco Vinicius Losso; Salles, Alessandra Grassi; Faria, José Carlos Marques de; Gemperli, Rolf
2016-08-01
To evaluate a new model of intraoperative electromyographic (EMG) assessment of the tibial and fibular nerves, and its respectives motor units in rats. Eight Wistar rats underwent intraoperative EMG on both hind limbs at two different moments: week 0 and week 12. Supramaximal electrical stimulation applied on sciatic nerve, and compound muscle action potential recorded on the gastrocnemius muscle (GM) and the extensor digitorum longus muscle (EDLM) through electrodes at specifics points. Motor function assessment was performaced through Walking Track Test. Exposing the muscles and nerves for examination did not alter tibial (p=0.918) or fibular (p=0.877) function between the evaluation moments. Electromyography of the GM, innervated by the tibial nerve, revealed similar amplitude (p=0.069) and latency (p=0.256) at week 0 and at 12 weeks, creating a standard of normality. Meanwhile, electromyography of the EDLM, innervated by the fibular nerve, showed significant differences between the amplitudes (p=0.003) and latencies (p=0.021) at the two different moments of observation. Intraoperative electromyography determined and quantified gastrocnemius muscle motor unit integrity, innervated by tibial nerve. Although this study was not useful to, objectively, assess extensor digitorum longus muscle motor unit, innervated by fibular nerve.
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Isaacs, Jonathan; Feher, Joseph; Shall, Mary; Vota, Scott; Fox, Michael A; Mallu, Satya; Razavi, Ashkon; Friebe, Ilvy; Shah, Sagar; Spita, Nathalie
2013-10-01
Suboptimal recovery following repair of major peripheral nerves has been partially attributed to denervation atrophy. Administration of anabolic steroids in conjunction with neurotization may improve functional recovery of chronically denervated muscle. The purpose of this study was to evaluate the effect of the administration of nandrolone on muscle recovery following prolonged denervation in a rat model. Eight groups of female Sprague-Dawley rats (15 rats per group, 120 in all) were divided into 3- or 6-month denervated hind limb and sham surgery groups and, then, nandrolone treatment groups and sham treatment groups. Evaluation of treatment effects included nerve conduction, force of contraction, comparative morphology, histology (of muscle fibers), protein electrophoresis (for muscle fiber grouping), and immunohistochemical evaluation. Although a positive trend was noted, neither reinnervated nor normal muscle showed a statistically significant increase in peak muscle force following nandrolone treatment. Indirect measures, including muscle mass (weight and diameter), muscle cell size, muscle fiber type, and satellite cell counts, all failed to support significant anabolic effect. There does not seem to be a functional benefit from nandrolone treatment following reinnervation of either mild or moderately atrophic muscle (related to prolonged denervation) in a rodent model.
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Glycogen supercompensation in rat soleus muscle during recovery from nonweight bearing
NASA Technical Reports Server (NTRS)
Henriksen, Erik J.; Kirby, Christopher R.; Tischler, Marc E.
1989-01-01
Events leading to the normalization of the glycogen metabolism in the soleus muscle of rat, altered by 72-h three days of hind-limb suspension, were investigated during the 72-h recovery period when the animals were allowed to bear weight on all four limbs. Relative importance of the factors affecting glycogen metabolism in skeletal muscle during the recovery period was also examined. Glycogen concentration was found to decrease within 15 min and up to 2 h of recovery, while muscle glucose 6-phosphate, and the fractional activities of glycogen phosphorylase and glycogen synthase increased. From 2 to 4 h, when the glycogen synthase activity remained elevated and the phosphorylase activity declined, glycogen concentration increased, until it reached maximum values at about 24 h, after which it started to decrease, reaching control values by 72 h. At 12 and 24 h, the inverse relationship between glycogen concentration and the synthase activity ratio was lost, indicating that the reloading transiently uncoupled glycogen control of this enzyme.
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Protein synthesis rates in atrophied gastrocnemius muscles after limb immobilization
NASA Technical Reports Server (NTRS)
Tucker, K. R.; Seider, M. J.; Booth, F. W.
1981-01-01
Noting that protein synthesis declines in the gastrocnemius 6 hr after immobilization, the study sought to detect an increase of protein synthesis when the limb was freed, and to examine the effects of exercise on the rate of increase. Rats were used as subjects, with their hind legs in plaster of Paris in plantar flexion to eliminate strain on the gastrocnemius. Periods of immobilization were varied and samples of blood from the muscle were taken to track protein synthesis rates for different groups in immobilization and exercise regimens (running and weightlifting). Synthesis rates declined 3.6% during time in the cast, then increased 6.3%/day after the casts were removed. Both running and weightlifting were found to increase the fractional rate of protein formation in the gastrocnemius muscle when compared with contralateral muscles that were not exercised and were used as controls, suggesting that the mechanism controlling protein synthesis in skeletal muscles is rapidly responsive to changes in muscular contractile activity.
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Size and metabolic properties of single muscle fibers in rat soleus after hindlimb suspension
NASA Technical Reports Server (NTRS)
Hauschka, Edward O.; Roy, Roland R.; Edgerton, V. Reggie
1987-01-01
The effect of 28-day-long hind-limb suspension (HS) combined with 10 daily forceful lengthening contractions of the limb on the morphological and metabolic properties of individual fibers of the soleus was studied in rats, using quantitative histochemical techniques. Compared with nonsuspended controls (CON), soleus wet weights of HS rats were decreased by 49 percent; the fibers staining lightly for myosin ATPase ('light-ATPase' fibers) atrophied more than the 'dark-ATPase' fibers. Single-fiber alpha-glycerophosphate dehydrogenase (GPD) and succinate dehydrogenase (SDH) activities were higher in HS than in CON rats. Daily forceful lengthening contractions did not prevent the HS-induced changes. The results support the view that the soleus fibers can change from a slow-twitch oxidative to a fast-twitch oxidative-glycolytic profile, but rarely to a fast-twitch glycolytic one, and that the SDH and GPD activities per volume of tissue can be increased even when there are severe losses of contractile proteins.
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Intraspinal Microstimulation Produces Over-ground Walking in Anesthetized Cats
Holinski, B.J.; Mazurek, K.A.; Everaert, D.G.; Toossi, A.; Lucas-Osma, A.M.; Troyk, P.; Etienne-Cummings, R.; Stein, R.B.; Mushahwar, V.K.
2016-01-01
Objective Spinal cord injury causes a drastic loss of motor, sensory and autonomic function. The goal of this project was to investigate the use of intraspinal microstimulation (ISMS) for producing long distances of walking over ground. ISMS is an electrical stimulation method developed for restoring motor function by activating spinal networks below the level of an injury. It produces movements of the legs by stimulating the ventral horn of the lumbar enlargement using fine penetrating electrodes (≤ 50µm diameter). Approach In each of five adult cats (4.2–5.5kg), ISMS was applied through 16 electrodes implanted with tips targeting lamina IX in the ventral horn bilaterally. A desktop system implemented a physiologically-based control strategy that delivered different stimulation patterns through groups of electrodes to evoke walking movements with appropriate limb kinematics and forces corresponding to swing and stance. Each cat walked over an instrumented 2.9m walkway and limb kinematics and forces were recorded. Main Results Both propulsive and supportive forces were required for over-ground walking. Cumulative walking distances ranging from 609m to 835m (longest tested) were achieved in three animals. In these three cats, the mean peak supportive force was 3.5±0.6N corresponding to full-weight-support of the hind legs, while the angular range of the hip, knee, and ankle joints were 23.1±2.0°, 29.1±0.2°, and 60.3±5.2°, respectively. To further demonstrate the viability of ISMS for future clinical use, a prototype implantable module was successfully implemented in a subset of trials and produced comparable walking performance. Significance By activating inherent locomotor networks within the lumbosacral spinal cord, ISMS was capable of producing bilaterally coordinated and functional over-ground walking with current amplitudes <100 µA. These exciting results suggest that ISMS may be an effective intervention for restoring functional walking after spinal cord injury. PMID:27619069
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Hyperglycemia, hypernatremia, and hyperosmolarity in 6 neonatal llamas and alpacas.
Cebra, C K
2000-12-01
Neonatal camelids can develop hyperglycemia, hypernatremia, and hyperosmolarity in response to a combination of stress and inadequate water intake. Clinical signs of this syndrome include a fine head tremor, ataxia, and a base-wide stance of the hind limbs, but biochemical analyses are necessary to confirm the diagnosis. Camelids appear to be susceptible to this syndrome because of a poor insulin response to hyperglycemia; hypernatremia results from free water loss associated with glucose diuresis. Water loss associated with glucose diuresis may necessitate a higher rate of fluid administration in camelids with this syndrome than is typically used for treatment of hypernatremia in calves.
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Problems in analysis of data from muscles of rats flow in space
NASA Technical Reports Server (NTRS)
Tischler, Marc E.; Henriksen, Erik; Jacob, Stephan; Satarug, Soisungwan; Cook, Paul
1988-01-01
Comparison of hind-limb muscles of rats flown on Spacelab-3 or tail-traction-suspended showed that 11-17 h reloading postflight might have altered the results. Soleus atrophied; plantaris, gastrocnemius, and extensor digitorum longus grew slower; and tibialis anteiror grew normally. In both flight and simulated soleus and plantaris, higher tyrosine and greater glutamine/glutamate ratio indicated negative protein balance and increased glutamine production, respectively, relative to controls. Aspartate was lower in these muscles. Reloading generally decreased tyrosine, but increased aspartate and glutamine/glutamate. These data showed that 12 h of reloading after flight is characterized by reversal, to varying extents, of the effects of unloading.
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Clinical Perspectives of Digital Dermatitis in Dairy and Beef Cattle.
Plummer, Paul J; Krull, Adam
2017-07-01
Digital dermatitis is a polybacterial disease process of dairy and beef cattle. Lesions are most commonly identified on the plantar aspect of the interdigital cleft of the hind limbs. Treponema spp are routinely present in large numbers of active lesions. Lesions are painful to the touch and can result in clinical lameness. The infectious nature generally results in endemic infection of cattle herds and management requires a comprehensive and integrated multipronged approach. This article provides current perspectives regarding management and treatment of digital dermatitis on dairy and beef cattle operations and provides a review for clinicians dealing with a clinical outbreak. Copyright © 2017 Elsevier Inc. All rights reserved.
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Pitcher, Mark H; Tarum, Farid; Rauf, Imran Z; Low, Lucie A; Bushnell, Catherine
2017-06-01
Aerobic exercise improves outcomes in a variety of chronic health conditions, yet the support for exercise-induced effects on chronic pain in humans is mixed. Although many rodent studies have examined the effects of exercise on persistent hypersensitivity, the most used forced exercise paradigms that are known to be highly stressful. Because stress can also produce analgesic effects, we studied how voluntary exercise, known to reduce stress in healthy subjects, alters hypersensitivity, stress, and swelling in a rat model of persistent hind paw inflammation. Our data indicate that voluntary exercise rapidly and effectively reduces hypersensitivity as well as stress-related outcomes without altering swelling. Moreover, the level of exercise is unrelated to the analgesic and stress-reducing effects, suggesting that even modest amounts of exercise may impart significant benefit in persistent inflammatory pain states. Modest levels of voluntary exercise reduce pain- and stress-related outcomes in a rat model of persistent inflammatory pain, independently of the amount of exercise. As such, consistent, self-regulated activity levels may be more relevant to health improvement in persistent pain states than standardized exercise goals. Published by Elsevier Inc.
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Effects of Plantar Vibration on Bone and Deep Fascia in a Rat Hindlimb Unloading Model of Disuse
Huang, Yunfei; Fan, Yubo; Salanova, Michele; Yang, Xiao; Sun, Lianwen; Blottner, Dieter
2018-01-01
The deep fascia of the vertebrate body comprises a biomechanically unique connective cell and tissue layer with integrative functions to support global and regional strain, tension, and even muscle force during motion and performance control. However, limited information is available on deep fascia in relation to bone in disuse. We used rat hindlimb unloading as a model of disuse (21 days of hindlimb unloading) to study biomechanical property as well as cell and tissue changes to deep fascia and bone unloading. Rats were randomly divided into three groups (n = 8, each): hindlimb unloading (HU), HU + vibration (HUV), and cage-control (CON). The HUV group received local vibration applied to the plantar of both hind paws. Micro-computed tomography analyzed decreased bone mineral density (BMD) of vertebra, tibia, and femur in HU vs. CON. Biomechanical parameters (elastic modulus, max stress, yield stress) of spinal and crural fascia in HU were always increased vs. CON. Vibration in HUV only counteracted HU-induced tibia bone loss and crural fascia mechanical changes but failed to show comparable changes in the vertebra and spinal fascia on lumbar back. Tissue and cell morphometry (size and cell nuclear density), immunomarker intensity levels of anti-collagen-I and III, probed on fascia cryosections well correlated with biomechanical changes suggesting crural fascia a prime target for plantar vibration mechano-stimulation in the HU rat. We conclude that the regular biomechanical characteristics as well as tissue and cell properties in crural fascia and quality of tibia bone (BMD) were preserved by local plantar vibration in disuse suggesting common mechanisms in fascia and bone adaptation to local mechanovibration stimulation following hind limb unloading in the HUV rat. PMID:29875702
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Effects of Plantar Vibration on Bone and Deep Fascia in a Rat Hindlimb Unloading Model of Disuse.
Huang, Yunfei; Fan, Yubo; Salanova, Michele; Yang, Xiao; Sun, Lianwen; Blottner, Dieter
2018-01-01
The deep fascia of the vertebrate body comprises a biomechanically unique connective cell and tissue layer with integrative functions to support global and regional strain, tension, and even muscle force during motion and performance control. However, limited information is available on deep fascia in relation to bone in disuse. We used rat hindlimb unloading as a model of disuse (21 days of hindlimb unloading) to study biomechanical property as well as cell and tissue changes to deep fascia and bone unloading. Rats were randomly divided into three groups ( n = 8, each): hindlimb unloading (HU), HU + vibration (HUV), and cage-control (CON). The HUV group received local vibration applied to the plantar of both hind paws. Micro-computed tomography analyzed decreased bone mineral density (BMD) of vertebra, tibia, and femur in HU vs. CON. Biomechanical parameters (elastic modulus, max stress, yield stress) of spinal and crural fascia in HU were always increased vs. CON. Vibration in HUV only counteracted HU-induced tibia bone loss and crural fascia mechanical changes but failed to show comparable changes in the vertebra and spinal fascia on lumbar back. Tissue and cell morphometry (size and cell nuclear density), immunomarker intensity levels of anti-collagen-I and III, probed on fascia cryosections well correlated with biomechanical changes suggesting crural fascia a prime target for plantar vibration mechano-stimulation in the HU rat. We conclude that the regular biomechanical characteristics as well as tissue and cell properties in crural fascia and quality of tibia bone (BMD) were preserved by local plantar vibration in disuse suggesting common mechanisms in fascia and bone adaptation to local mechanovibration stimulation following hind limb unloading in the HUV rat.
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Reconstruction of long digital extensor tendon by cranial tibial muscle fascia graft in a dog.
Sabiza, Soroush; Khajeh, Ahmad; Naddaf, Hadi
2016-01-01
Tendon rupture in dogs is generally the result of a direct trauma. This report described the use of adjacent muscle autogenic fascial graft for reconstruction of distal rupture of long digital extensor tendon in a dog. A two-year-old male mix breed dog, was presented with a non-weight bearing lameness of the right hind limb and a deep rupture of lateral side of right tarsus. History taking revealed that this rupture appeared without any apparent cause, when walking around the farm, three days before. Radiography was done and no fracture was observed. Hyperextension of right tarsal joint compared to left limb was observed. Under general anesthesia, after dissections of the ruptured area, complete rupture of long digital extensor tendon was revealed. Then, we attempted to locate the edge of the tendon, however, the tendon length was shortened approximately 1 cm. Hence, a strip of 1 cm length from fascia of cranial tibial muscle was harvested to fill the defect. The graft was sutured to the two ends of tendon using locking loop pattern. Subcutaneous layers and the skin were sutured routinely. Ehmer sling bandage was applied to prevent weight bearing on the surgical region. Re-examination and phone contact with the owner eight weeks and six months postoperatively revealed a poor lameness and excellent function of the dog, respectively. It could be concluded that the fascia of adjacent muscles can be used as an autogenic graft for reconstruction of some tendon ruptures.
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Reconstruction of long digital extensor tendon by cranial tibial muscle fascia graft in a dog
Sabiza, Soroush; Khajeh, Ahmad; Naddaf, Hadi
2016-01-01
Tendon rupture in dogs is generally the result of a direct trauma. This report described the use of adjacent muscle autogenic fascial graft for reconstruction of distal rupture of long digital extensor tendon in a dog. A two-year-old male mix breed dog, was presented with a non-weight bearing lameness of the right hind limb and a deep rupture of lateral side of right tarsus. History taking revealed that this rupture appeared without any apparent cause, when walking around the farm, three days before. Radiography was done and no fracture was observed. Hyperextension of right tarsal joint compared to left limb was observed. Under general anesthesia, after dissections of the ruptured area, complete rupture of long digital extensor tendon was revealed. Then, we attempted to locate the edge of the tendon, however, the tendon length was shortened approximately 1 cm. Hence, a strip of 1 cm length from fascia of cranial tibial muscle was harvested to fill the defect. The graft was sutured to the two ends of tendon using locking loop pattern. Subcutaneous layers and the skin were sutured routinely. Ehmer sling bandage was applied to prevent weight bearing on the surgical region. Re-examination and phone contact with the owner eight weeks and six months postoperatively revealed a poor lameness and excellent function of the dog, respectively. It could be concluded that the fascia of adjacent muscles can be used as an autogenic graft for reconstruction of some tendon ruptures. PMID:27872726
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Zihlman, Adrienne L; McFarland, Robin K; Underwood, Carol E
2011-11-01
Great apes diversified during the Miocene in Old World forests. Two lineages, gorillas in Africa and orangutans in Asia, have sexual dimorphisms of super-sized males, though they presumably diverged from a smaller common ancestor. We test the hypothesis that they increased in body mass independently and convergently, and that their many postcranial differences reflect locomotor differences. Whole body dissections of five adult male gorillas and four adult male orangutans allowed quantification of body mass distribution to limb segments, of body composition (muscle, bone, skin, and fat relative to total body mass), and of muscle distribution and proportions. Results demonstrate that gorilla forelimb anatomy accommodates shoulder joint mobility for vertical climbing and reaching while maintaining joint stability during quadrupedal locomotion. The heavily muscled hind limbs are equipped for propulsion and weight-bearing over relatively stable substrates on the forest floor. In contrast, orangutan forelimb length, muscle mass, and joint construction are modified for strength and mobility in climbing, bridging, and traveling over flexible supports through the forest canopy. Muscles of hip, knee, and ankle joints provide rotational and prehensile strength essential for moving on unstable and discontinuous branches. We conclude that anatomical similarities are due to common ancestry and that differences in postcranial anatomy reflect powerful selection for divergent locomotor adaptations. These data further support the evolutionary conclusion that gorillas fall with chimpanzees and humans as part of the African hominoid radiation; orangutans are a specialized outlier. Copyright © 2011 Wiley-Liss, Inc.
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Bertram, John E.A.; Gutmann, Anne
2008-01-01
Mammals use two distinct gallops referred to as the transverse (where landing and take-off are contralateral) and rotary (where landing and take-off are ipsilateral). These two gallops are used by a variety of mammals, but the transverse gallop is epitomized by the horse and the rotary gallop by the cheetah. In this paper, we argue that the fundamental difference between these gaits is determined by which set of limbs, fore or hind, initiates the transition of the centre of mass from a downward–forward to upward–forward trajectory that occurs between the main ballistic (non-contact) portions of the stride when the animal makes contact with the ground. The impulse-mediated directional transition is a key feature of locomotion on limbs and is one of the major sources of momentum and kinetic energy loss, and a main reason why active work must be added to maintain speed in locomotion. Our analysis shows that the equine gallop transition is initiated by a hindlimb contact and occurs in a manner in some ways analogous to the skipping of a stone on a water surface. By contrast, the cheetah gallop transition is initiated by a forelimb contact, and the mechanics appear to have much in common with the human bipedal run. Many mammals use both types of gallop, and the transition strategies that we describe form points on a continuum linked even to functionally symmetrical running gaits such as the tölt and amble. PMID:18854295
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Sadagatullah, Abdul Nawfar; Halim, Ahmad Sukari; Bathusha, Mohd Shakir; Ramachandran, Anantha Kumar
2017-12-01
Background The possibility of a person who had undergone surgery to be exposed to the ill effects of cigarette smoke is high, more so if the person lives with a smoker. With increasing popularity of reverse sural fasciocutaneous flaps, a surgeon may have to manage a person who lives with a smoker or is exposed to cigarette smoke. A clear understanding of the effects of exposure to cigarette smoke on reverse sural fasciocutaneous flaps is necessary. This study was performed to establish a clearer understanding of the effects of smoking on reverse sural fasciocutaneous flaps and evidence for preoperative patient counseling about smoking and smoke exposure. Objective The study investigated effects of exposure to cigarette smoke on the survival of the reverse sural fasciocutaneous flap. Methods This was an experimental observational study conducted at the Laboratory for Animal Research Unit in the Health Campus of Universiti Sains Malaysia. Twelve adult White New Zealand rabbits ( Oryctolagus cuniculus ) were divided into two groups of six. All 12 rabbits had a 2.5- × 2.5-cm reverse sural fasciocutaneous flap raised on both its hind limbs. The group exposed to cigarette smoke underwent 4 weeks of smoke exposure for 2 hours daily prior to surgery. This was then continued until analysis of the results. The control group had no intervention. All flaps were analyzed on the seventh postoperative day, after tracing on transparent plastic sheets with the necrotic area marked followed by 2D planimetry done on a grid paper. The flaps were assessed on the total flap area and survival area percentage. It was recorded as mean ± SD. The presence or absence of infection and hematoma was also noted. Results Twelve flaps were analyzed in each group. Total mean flap area and survival area percentage of the control group were 120.33 ± 31.03 mm 2 and 80.12 ± 15.75%, respectively, whereas in the cigarette smoke-exposed group, it was 121.83 ± 17.93 mm 2 and 62.04 ± 34.01%, respectively. The control group had two infections and one hematoma, and the smoking-exposed group had six infections and nine hematomas. The comparison between the groups was made in terms of total flap area, survival percentage, presence of infection, and hematoma for which the p values were 0.886, 0.115, 0.083, and 0.003, respectively. The differences between right and left hind limbs were also analyzed ( p = 0.414). Conclusion There was no statistical difference in the results from the right and left hind limbs. There was no statistical difference in the survival of reverse sural fasciocutaneous flap between the control and smoking-exposed groups.
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Wong, Kah-Hui; Naidu, Murali; David, Pamela; Abdulla, Mahmood Ameen; Abdullah, Noorlidah; Kuppusamy, Umah Rani; Sabaratnam, Vikineswary
2011-01-01
Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this mushroom in the treatment of injured nerve. Functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI) was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control) group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the regeneration of injured rat peroneal nerve in the early stage of recovery. PMID:21941586
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Morphology and the gradient of a symmetric potential predict gait transitions of dogs.
Wilshin, Simon; Haynes, G Clark; Porteous, Jack; Koditschek, Daniel; Revzen, Shai; Spence, Andrew J
2017-08-01
Gaits and gait transitions play a central role in the movement of animals. Symmetry is thought to govern the structure of the nervous system, and constrain the limb motions of quadrupeds. We quantify the symmetry of dog gaits with respect to combinations of bilateral, fore-aft, and spatio-temporal symmetry groups. We tested the ability of symmetries to model motion capture data of dogs walking, trotting and transitioning between those gaits. Fully symmetric models performed comparably to asymmetric with only a [Formula: see text] increase in the residual sum of squares and only one-quarter of the parameters. This required adding a spatio-temporal shift representing a lag between fore and hind limbs. Without this shift, the symmetric model residual sum of squares was [Formula: see text] larger. This shift is related to (linear regression, [Formula: see text], [Formula: see text]) dog morphology. That this symmetry is respected throughout the gaits and transitions indicates that it generalizes outside a single gait. We propose that relative phasing of limb motions can be described by an interaction potential with a symmetric structure. This approach can be extended to the study of interaction of neurodynamic and kinematic variables, providing a system-level model that couples neuronal central pattern generator networks and mechanical models.
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Time Course of Peri-Implant Bone Regeneration around Loaded and Unloaded Implants in a Rat Model
Jariwala, Shailly H.; Wee, Hwabok; Roush, Evan P.; Whitcomb, Tiffany L.; Murter, Christopher; Kozlansky, Gery; Lakhtakia, Akhlesh; Kunselman, Allen R.; Donahue, Henry J.; Armstrong, April D.; Lewis, Gregory S.
2018-01-01
The time-course of cancellous bone regeneration surrounding mechanically loaded implants affects implant fixation, and is relevant to determining optimal rehabilitation protocols following orthopaedic surgeries. We investigated the influence of controlled mechanical loading of titanium-coated polyether-ether ketone (PEEK) implants on osseointegration using time-lapsed, non-invasive, in vivo micro-computed tomography (micro-CT) scans. Implants were inserted into proximal tibial metaphyses of both limbs of eight female Sprague-Dawley rats. External cyclic loading (60 μm or 100 μm displacement, 1 Hz, 60 seconds) was applied every other day for 14 days to one implant in each rat, while implants in contralateral limbs served as the unloaded controls. Hind limbs were imaged with high-resolution micro-CT (12.5 μm voxel size) at 2, 5, 9, and 12 days post-surgery. Trabecular changes over time were detected by 3D image registration allowing for measurements of bone-formation rate (BFR) and bone-resorption rate (BRR). At day 9, mean %BV/TV for loaded and unloaded limbs were 35.5 ± 10.0 % and 37.2 ± 10.0 %, respectively, and demonstrated significant increases in bone volume compared to day 2. BRR increased significantly after day 9. No significant differences between bone volumes, BFR, and BRR were detected due to implant loading. Although not reaching significance (p = 0.16), an average 119 % increase in pull-out strength was measured in the loaded implants. PMID:27381807
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Real-time control of walking using recordings from dorsal root ganglia
NASA Astrophysics Data System (ADS)
Holinski, B. J.; Everaert, D. G.; Mushahwar, V. K.; Stein, R. B.
2013-10-01
Objective. The goal of this study was to decode sensory information from the dorsal root ganglia (DRG) in real time, and to use this information to adapt the control of unilateral stepping with a state-based control algorithm consisting of both feed-forward and feedback components. Approach. In five anesthetized cats, hind limb stepping on a walkway or treadmill was produced by patterned electrical stimulation of the spinal cord through implanted microwire arrays, while neuronal activity was recorded from the DRG. Different parameters, including distance and tilt of the vector between hip and limb endpoint, integrated gyroscope and ground reaction force were modelled from recorded neural firing rates. These models were then used for closed-loop feedback. Main results. Overall, firing-rate-based predictions of kinematic sensors (limb endpoint, integrated gyroscope) were the most accurate with variance accounted for >60% on average. Force prediction had the lowest prediction accuracy (48 ± 13%) but produced the greatest percentage of successful rule activations (96.3%) for stepping under closed-loop feedback control. The prediction of all sensor modalities degraded over time, with the exception of tilt. Significance. Sensory feedback from moving limbs would be a desirable component of any neuroprosthetic device designed to restore walking in people after a spinal cord injury. This study provides a proof-of-principle that real-time feedback from the DRG is possible and could form part of a fully implantable neuroprosthetic device with further development.
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Real-time control of walking using recordings from dorsal root ganglia
Holinski, B J; Everaert, D G; Mushahwar, V K; Stein, R B
2013-01-01
Objective The goal of this study was to decode sensory information from the dorsal root ganglia (DRG) in real time, and to use this information to adapt the control of unilateral stepping with a state-based control algorithm consisting of both feed-forward and feedback components. Approach In five anesthetized cats, hind limb stepping on a walkway or treadmill was produced by patterned electrical stimulation of the spinal cord through implanted microwire arrays, while neuronal activity was recorded from the dorsal root ganglia. Different parameters, including distance and tilt of the vector between hip and limb endpoint, integrated gyroscope and ground reaction force were modeled from recorded neural firing rates. These models were then used for closed-loop feedback. Main Results Overall, firing-rate based predictions of kinematic sensors (limb endpoint, integrated gyroscope) were the most accurate with variance accounted for >60% on average. Force prediction had the lowest prediction accuracy (48±13%) but produced the greatest percentage of successful rule activations (96.3%) for stepping under closed-loop feedback control. The prediction of all sensor modalities degraded over time, with the exception of tilt. Significance Sensory feedback from moving limbs would be a desirable component of any neuroprosthetic device designed to restore walking in people after a spinal cord injury. This study provides a proof-of-principle that real-time feedback from the DRG is possible and could form part of a fully implantable neuroprosthetic device with further development. PMID:23928579
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NASA Technical Reports Server (NTRS)
Tipton, Charles M.
1991-01-01
The primary purpose of this research is to study the physiological mechanisms associated with the exercise performance of rats subjected to conditions of simulated weightlessness. A secondary purpose is to study related physiological changes associated with other systems. To facilitate these goals, a rodent suspension model was developed (Overton-Tipton) and a VO2 max testing procedure was perfected. Three methodological developments occurred during this past year deserving of mention. The first was the refinement of the tail suspension model so that (1) the heat dissipation functions of the caudal artery can be better utilized, and (2) the blood flow distribution to the tail would have less external constriction. The second was the development on a one-leg weight bearing model for use in simulated weightlessness studies concerned with change in muscle mass, muscle enzyme activity, and hind limb blood flow. The chemical body composition of 30 rats was determined and used to develop a prediction equation for percent fat using underwater weighing procedures to measure carcass specific gravity and to calculate body density, body fat, and fat free mass.
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Behavioral and Physiological Effects of Hindlimb Unloading in Rats
NASA Technical Reports Server (NTRS)
Fox, Robert A.
1998-01-01
The overarching objective of this project was to identify changes in neural and biochemical systems of the central and peripheral nervous systems (the CNS and PNS) that are related to disruptions of functional motor responses, or motor control. The identification of neural and biochemical changes that are related to sensory-motor adaptation elicited as animals react to changes in the gravitational field was of particular interest. Thus, the major objective of this work was to study disruptions of motor responses that arise after (sic. due to) chronic exposure to altered gravity (G). To do this, parallel studies investigating changes in neural, sensory, and neuromuscular systems were conducted after animals (rats) experienced chronic exposure to conditions of altered-G. Conditions of altered-G included hyper-G produced by centrifugation, micro-G produced by orbital flight, and simulated micro-G produced by hind limb suspension. A second major interest was to examine the contribution of putative changes in sensory systems to disruptions of motor responses. To do this, motor responses and reflexes of rats were studied following chronic treatment with streptomycin sulfate (STP, an ototoxic chemical) to damage the vestibular hair cells.
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NASA Astrophysics Data System (ADS)
Ramirez, Joaquin; Periyakaruppan, Adaikkappan; Sarkar, Shubhashish; Ramesh, Govindarajan T.; Sharma, S. Chidananda
2014-02-01
Gravity supports all the life activities present on earth. Microgravity environments have effect on the biological functions and physiological status of an individual. The present study was undertaken to investigate the effect of simulated microgravity on important regulatory enzymes of carbohydrate metabolism in liver using HLS mice model. Following hind limb unloading of mice for 11 days the animal's average body weights were found to be not different, while the liver weights were decreased and found to be significantly different ( p < 0.05) from control mice. Further, in liver the specific activity of hexokinase enzyme was reduced ( p < 0.02) and the phosphoenolpyruvate carboxykinase activity was significantly increased in simulated microgravity subjected mice compared to control ( p < 0.003). Immunoblot analysis show decreased phosphofructokinase-2 activity in HLS mice compared to control. Liver lactate dehydrogenase activity significantly reduced in simulated microgravity subjected mice ( p < 0.005). Thus in our study the rodents have adapted to simulated microgravity conditions, with decreased glycolysis and increased gluconeogenesis in liver and reciprocally regulated.
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Ryu, Jae Choon; Davidson, Brian P; Xie, Aris; Qi, Yue; Zha, Daogang; Belcik, J Todd; Caplan, Evan S; Woda, Juliana M; Hedrick, Catherine C; Hanna, Richard N; Lehman, Nicholas; Zhao, Yan; Ting, Anthony; Lindner, Jonathan R
2013-02-12
Stem cells are thought to enhance vascular remodeling in ischemic tissue in part through paracrine effects. Using molecular imaging, we tested the hypothesis that treatment of limb ischemia with multipotential adult progenitor cells (MAPCs) promotes recovery of blood flow through the recruitment of proangiogenic monocytes. Hind-limb ischemia was produced in mice by iliac artery ligation, and MAPCs were administered intramuscularly on day 1. Optical imaging of luciferase-transfected MAPCs indicated that cells survived for 1 week. Contrast-enhanced ultrasound on days 3, 7, and 21 showed a more complete recovery of blood flow and greater expansion of microvascular blood volume in MAPC-treated mice than in controls. Fluorescent microangiography demonstrated more complete distribution of flow to microvascular units in MAPC-treated mice. On ultrasound molecular imaging, expression of endothelial P-selectin and intravascular recruitment of CX(3)CR-1-positive monocytes were significantly higher in MAPC-treated mice than in the control groups at days 3 and 7 after arterial ligation. Muscle immunohistology showed a >10-fold-greater infiltration of monocytes in MAPC-treated than control-treated ischemic limbs at all time points. Intravital microscopy of ischemic or tumor necrosis factor-α-treated cremaster muscle demonstrated that MAPCs migrate to perimicrovascular locations and potentiate selectin-dependent leukocyte rolling. In vitro migration of human CD14(+) monocytes was 10-fold greater in response to MAPC-conditioned than basal media. In limb ischemia, MAPCs stimulate the recruitment of proangiogenic monocytes through endothelial activation and enhanced chemotaxis. These responses are sustained beyond the MAPC lifespan, suggesting that paracrine effects promote flow recovery by rebalancing the immune response toward a more regenerative phenotype.
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Revascularization and Muscle Adaptation to Limb Demand Ischemia in Diet Induced Obese Mice
Albadawi, Hassan; Tzika, Aria; Rask-Madsen, Christian; Crowley, Lindsey M.; Koulopoulos, Michael W.; Yoo, Hyung-Jin; Watkins, Michael T.
2016-01-01
Background Obesity and type 2 diabetes are major risk factors for peripheral arterial disease (PAD) in humans which can result in lower limb demand ischemia and exercise intolerance. Exercise triggers skeletal muscle adaptation including increased vasculogenesis. The goal of this study was to determine whether demand ischemia modulates revascularization, fiber size, and signaling pathways in the ischemic hind limb muscles of mice with diet-induced obesity (DIO). Materials and Methods DIO mice (n=7) underwent unilateral femoral artery ligation (FAL) and recovered for 2-weeks followed by 4-weeks with daily treadmill exercise to induce demand ischemia. A parallel sedentary ischemia group (n=7) had FAL without exercise. The contralateral limb muscles of sedentary ischemia served as control. Muscles were examined for capillary density, myofiber cross-sectional area (CSA), cytokine levels, and phosphorylation of STAT3 and ERK1/2. Results Exercise significantly enhanced capillary density (p<0.01) and markedly lowered CSA (p<0.001) in demand ischemia compared to sedentary ischemia. These findings coincided with a significant increase in G-CSF (p<0.001) and IL-7 (p<0.01) levels. In addition, phosphorylation of STAT3 and ERK1/2 (p<0.01) were increased while UCP-1 and MCP-1 protein levels were lower (p<0.05) without altering VEGF and TNFα protein levels. Demand ischemia increased the PGC1α mRNA (p<0.001) without augmenting PGC1α protein levels. Conclusions Exercise induced limb demands ischemia in the setting of DIO causes myofiber atrophy despite an increase in muscle capillary density. The combination of persistent increase in TNFα, lower VEGF and failure to increase PGC1α protein may reflect a deficient adaption to demand ischemia in DIO. PMID:27620999
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García-Gutiérrez, Javier; Escalona, Moisés; Mora, Andrés; Díaz De Pascual, Amelia; Fermin, Gustavo
2013-01-01
In this article, a new species of salamander of the genus Bolitoglossa (Eladinea) from the cloud forest near La Mucuy in Sierra Nevada de Mérida, Venezuelan Andes, is described. Bolitoglossa mucuyensis sp. nov. differs from all Venezuelan salamanders, except B. orestes, by a larger SVL/TL ratio, and from La Culata salamander B. orestes by a reduced webbing extension of the front and hind limbs. Additionally, B. mucuyensis sp. nov. and B. orestes diverge 3.12% in terms of the nucleotide sequence of the 16S rRNA gene, as previously reported, and in 8.1% for the cytb gene as shown in this study.
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NASA Technical Reports Server (NTRS)
Jaspers, Stephen R.; Henriksen, Erik; Jacob, Stephan; Tischler, Marc E.
1989-01-01
The effects of muscle unloading, adrenalectomy, and cortisol treatment on the metabolism of branched-chain amino acids in the soleus and extensor digitorum longus of tail-cast suspended rats were investigated using C-14-labeled lucine, isoleucine, and valine in incubation studies. It was found that, compared to not suspended controls, the degradation of branched-chain amino acids in hind limb muscles was accelerated in tail-cast suspended rats. Adrenalectomy was found to abolish the aminotransferase flux and to diminish the dehydrogenase flux in the soleus. The data also suggest that cortisol treatment increases the rate of metabolism of branched-chain amino acids at the dehydrogenase step.
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A critical survey of vestigial structures in the postcranial skeletons of extant mammals
Moch, John G.
2015-01-01
In the Mammalia, vestigial skeletal structures abound but have not previously been the focus of study, with a few exceptions (e.g., whale pelves). Here we use a phylogenetic bracketing approach to identify vestigial structures in mammalian postcranial skeletons and present a descriptive survey of such structures in the Mammalia. We also correct previous misidentifications, including the previous misidentification of vestigial caviid metatarsals as sesamoids. We also examine the phylogenetic distribution of vestigiality and loss. This distribution indicates multiple vestigialization and loss events in mammalian skeletal structures, especially in the hand and foot, and reveals no correlation in such events between mammalian fore and hind limbs. PMID:26623192
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The effects of catecholamines and adrenoceptor blocking drugs on the canine peripheral lymph flow.
De Micheli, P; Glässer, A H
1975-01-01
Blood flow through the femoral artery, lymph flow in a lymphatic vessel in the femoral triangle and metatarsal distal venous pressure were measured simultaneously in a canine moving hind limb. 2. Low intra-arterial doses of adrenaline and noradrenaline increased lymph flow even in the presence of marked arterial vasoconstriction. In contrast, isoprenaline increased arterial blood flow without affecting lymph flow rate. 3. Phenoxybenzamine, dihydroergotoxine, and nicergoline did not inhibit the lymphatic flow increase induced by adrenaline at doses active on arterial or venous vascular alpha-adrenoceptors. 4. Propranolol given intra-arterially into animals pretreated with alpha-adrenoceptor blocking agents restored the vasoconstrictor effect of adrenaline (reversal of adrenaline reversal). PMID:238702
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NASA Astrophysics Data System (ADS)
Duke, P.; Oakley, C.; Montufar-Solis, D.
The embryonic mammalian limb is sensitive both in vivo and in vitro to changes in gravitational force. Hypergravity of centrifugation and microgravity of space decreased size of elements due to precocious or delayed chondrogenesis respectively. In recapitulating spaceflight experiments, premetatarsals were cultured in suspension in a low stress, low sheer rotating bioreactor, and found to be shorter than those cultured in standard culture dishes, and cartilage development was delayed. This study only measured length of the metatarsals, and did not account for possible changes in width and/or in form of the skeletal elements. Shorter cartilage elements in limbbuds cultured in the bioreactor may be due to the ability of the system to reproduce a more in vivo 3D shape than traditional organ cultures. Tissues subjected to traditional organ cultures become flattened by their own weight, attachment to the filter, and restrictions imposed by nutrient diffusion. The purpose of the current experiment was to determine if entire limb buds could be successfully cultured in the bioreactor, and to compare the effects on 3D shape with that of culturing in a culture dish system. Fore and hind limbs from E11-E13 ICR mouse embryos were placed either in the bioreactor, in Trowell culture, or fixed as controls. Limbbuds were cultured for six days, fixed, and processed either as whole mounts or embedded for histology. Qualitative analysis revealed that the Trowell culture specimens were flattened, while bioreactor culture specimens had a more in vivo-like 3D limb shape. Sections of limbbuds from both types of cultures had excellent cartilage differentiation, with apparently more cell maturation, and hypertrophy in the specimens cultured in the bioreactor. Morphometric quantitation of the cartilaginous elements for comparisons of the two culture systems was complicated due to some limb buds fusing together during culture. This problem was especially noticeable in the younger limbs, and may be rectified by embedding the limbs in a matrix (e.g. alginate) to maintain integrity of the tissue while in culture in the bioreactor. The bioreactor supported differentiation of skeletal elements in entire limbs, and maintained better external limb morphology than did the Trowell system. Supported by NIH/NIDCR Training Grant T358DE07252-08.
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Z. Sacharuk, Viviane; A. Lovatel, Gisele; Ilha, Jocemar; Marcuzzo, Simone; Severo do Pinho, Alexandre; L. Xavier, Léder; A. Zaro, Milton; Achaval, Matilde
2011-01-01
INTRODUCTION: Peripheral nerves are often damaged by direct mechanical injury, diseases, and tumors. The peripheral nerve injuries that result from these conditions can lead to a partial or complete loss of motor, sensory, and autonomic functions, which in turn are related to changes in skin temperature, in the involved segments of the body. The aim of this study was to evaluate the changes in hind paw skin temperature after sciatic nerve crush in rats in an attempt to determine whether changes in skin temperature correlate with the functional recovery of locomotion. METHODS: Wistar rats were divided into three groups: control (n = 7), sham (n = 25), and crush (n = 25). All groups were subjected to thermographic, functional, and histological assessments. RESULTS: ΔT in the crush group was different from the control and sham groups at the 1st, 3rd and 7rd postoperative days (p<0.05). The functional recovery from the crush group returned to normal values between the 3rd and 4th week post-injury, and morphological analysis of the nerve revealed incomplete regeneration at the 4th week after injury. DISCUSSION: This study is the first demonstration that sciatic nerve crush in rats induces an increase in hind paw skin temperature and that skin temperature changes do not correlate closely with functional recovery PMID:21876984
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Berndt, Rouven; Hummitzsch, Lars; Heß, Katharina; Albrecht, Martin; Zitta, Karina; Rusch, Rene; Sarras, Beke; Bayer, Andreas; Cremer, Jochen; Faendrich, Fred; Groß, Justus
2018-04-27
Employing growth factor-induced partial reprogramming in vitro, peripheral human blood monocytes can acquire a state of plasticity along with expression of various markers of pluripotency. These so-called programmable cells of monocytic origin (PCMO) hold great promise in regenerative therapies. The aim of this translational study was to explore and exploit the functional properties of PCMO for allogeneic cell transplantation therapy in critical limb ischemia (CLI). Using our previously described differentiation protocol, murine and human monocytes were differentiated into PCMO. We examined paracrine secretion of pro-angiogenic and tissue recovery-associated proteins under hypoxia and induction of angiogenesis by PCMO in vitro. Allogeneic cell transplantation of PCMO was performed in a hind limb ischemia mouse model in comparison to cell transplantation of native monocytes and a placebo group. Moreover, we analyzed retrospectively four healing attempts with PCMO in patients with peripheral artery disease (PAD; Rutherford classification, stage 5 and 6). Statistical analysis was performed by using one-way ANOVA, Tukey's test or the Student's t test, p < 0.05. Cell culture experiments revealed good resilience of PCMO under hypoxia, enhanced paracrine release of pro-angiogenic and tissue recovery-associated proteins and induction of angiogenesis in vitro by PCMO. Animal experiments demonstrated significantly enhanced SO 2 saturation, blood flow, neoangiogenesis and tissue recovery after treatment with PCMO compared to treatment with native monocytes and placebo. Finally, first therapeutic application of PCMO in humans demonstrated increased vascular collaterals and improved wound healing in patients with chronic CLI without exaggerated immune response, malignant processes or extended infection after 12 months. In all patients minor and/or major amputations of the lower extremity could be avoided. In summary, PCMO improve angiogenesis and tissue recovery in chronic ischemic muscle and first clinical results promise to provide an effective and safe treatment of CLI.
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NASA Astrophysics Data System (ADS)
Montufar-Solis, D.; Oakley, C. R.; Jefferson, Y.; Duke, P. J.
2003-10-01
Mechanisms involved in development of the embryonic limb have remained the same throughout eons of genetic and environmental evolution under Earth gravity (lg). During the spaceflight era it has been of interest to explore the ancient theory that form of the skeleton develops in response to gravity, and that changes in gravitational forces can change the developmental pattern of the limb. This has been shown in vivo and in vitro, allowing the hypergravity of centrifugation and microgravity of space to be used as tools to increase our knowledge of limb development. In recapitulations of spaceflight experiments, premetatarsals were cultured in suspension in a bioreactor, and found to be shorter and less differentiated than those cultured in standard culture dishes. This study only measured length of the metatarsals, and did not account for possible changes due to the skeletal elements having a more in vivo 3D shape while in suspension vs. flattened tissues compressed by their own weight. A culture system with an outcome closer to in vivo and that supports growth of younger limb buds than traditional systems will allow studies of early Hox gene expression, and contribute to the understanding of very early stages of development. The purpose of the current experiment was to determine if entire limb buds could be cultured in the bioreactor, and to compare the growth and differentiation with that of culturing in a culture dish system. Fore and hind limbs from E11-E13 ICR mouse embryos were cultured for six days, either in the bioreactor or in center-well organ culture dishes, fixed, and embedded for histology. E13 specimens grown in culture dishes were flat, while bioreactor culture specimens had a more in vivo-like 3D limb shape. Sections showed excellent cartilage differentiation in both culture systems, with more cell maturation, and hypertrophy in the specimens cultured in the bioreactor. Younger limb buds fused together during culture, so an additional set of El 1.5 limb buds was cultured with and without encapsulation in alginate prior to culturing in the bioreactor. Encapsulated limbs grown in the bioreactor did not fuse together, but developed only the more proximal elements while limbs grown in culture dishes formed proximal and distal elements. Alginate encapsulation may have reduced oxygenation to the progress zone of the developing limb bud resulting in lack of development of the more distal elements. These results show that the bioreactor supports growth and differentiation of skeletal elements in entire E13 limb buds, and that a method to culture younger limb buds without fusing together needs to be developed if any morphometric analysis is to be performed.
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Behavioural characterisation of the alpha-mannosidosis guinea pig.
Robinson, A J; Crawley, A C; Auclair, D; Weston, P F; Hirte, C; Hemsley, K M; Hopwood, J J
2008-01-25
alpha-Mannosidosis is a lysosomal storage disorder resulting from a functional deficiency of the lysosomal enzyme alpha-mannosidase. This deficiency results in the accumulation of various oligosaccharides in the lysosomes of affected individuals, causing somatic pathology and progressive neurological degeneration that results in cognitive deficits, ataxia, and other neurological symptoms. We have a naturally occurring guinea pig model of this disease which exhibits a deficiency of lysosomal alpha-mannosidase and has a similar clinical presentation to human alpha-mannosidosis. Various tests were developed in the present study to characterise and quantitate the loss of neurological function in alpha-mannosidosis guinea pigs and to follow closely the progression of the disease. General neurological examinations showed progressive differences in alpha-mannosidosis animals from approximately 1 month of age. Significant differences were observed in hind limb gait width from 2 months of age and significant cognitive (memory and learning) deficits were observed from 3 months of age. Evoked response tests showed an increase in somatosensory P1 peak latency in alpha-mannosidosis guinea pigs from approximately 2 months of age, as well as progressive hearing loss using auditory brainstem evoked responses. The alpha-mannosidosis guinea pig therefore appears to exhibit many of the characteristics of the human disease, and will be useful in evaluating therapies for treatment of central nervous system pathology.
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Schwarz, A.; Pick, C.; Harrach, R.; Stein, G.; Bendella, H.; Ozsoy, O.; Ozsoy, U.; Schoenau, E.; Jaminet, P.; Sarikcioglu, L.; Dunlop, S.; Angelov, D.N.
2015-01-01
Traumatic spinal cord injury (SCI) causes a loss of locomotor function with associated compromise of the musculo-skeletal system. Whole body vibration (WBV) is a potential therapy following SCI, but little is known about its effects on the musculo-skeletal system. Here, we examined locomotor recovery and the musculo-skeletal system after thoracic (T7-9) compression SCI in adult rats. Daily WBV was started at 1, 7, 14 and 28 days after injury (WBV1-WBV28 respectively) and continued over a 12-week post-injury period. Intact rats, rats with SCI but no WBV (sham-treated) and a group that received passive flexion and extension (PFE) of their hind limbs served as controls. Compared to sham-treated rats, neither WBV nor PFE improved motor function. Only WBV14 and PFE improved body support. In line with earlier studies we failed to detect signs of soleus muscle atrophy (weight, cross sectional diameter, total amount of fibers, mean fiber diameter) or bone loss in the femur (length, weight, bone mineral density). One possible explanation is that, despite of injury extent, the preservation of some axons in the white matter, in combination with quadripedal locomotion, may provide sufficient trophic and neuronal support for the musculoskeletal system. PMID:26032204
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Schwarz, A; Pick, C; Harrach, R; Stein, G; Bendella, H; Ozsoy, O; Ozsoy, U; Schoenau, E; Jaminet, P; Sarikcioglu, L; Dunlop, S; Angelov, D N
2015-06-01
Traumatic spinal cord injury (SCI) causes a loss of locomotor function with associated compromise of the musculo-skeletal system. Whole body vibration (WBV) is a potential therapy following SCI, but little is known about its effects on the musculo-skeletal system. Here, we examined locomotor recovery and the musculo-skeletal system after thoracic (T7-9) compression SCI in adult rats. Daily WBV was started at 1, 7, 14 and 28 days after injury (WBV1-WBV28 respectively) and continued over a 12-week post-injury period. Intact rats, rats with SCI but no WBV (sham-treated) and a group that received passive flexion and extension (PFE) of their hind limbs served as controls. Compared to sham-treated rats, neither WBV nor PFE improved motor function. Only WBV14 and PFE improved body support. In line with earlier studies we failed to detect signs of soleus muscle atrophy (weight, cross sectional diameter, total amount of fibers, mean fiber diameter) or bone loss in the femur (length, weight, bone mineral density). One possible explanation is that, despite of injury extent, the preservation of some axons in the white matter, in combination with quadripedal locomotion, may provide sufficient trophic and neuronal support for the musculoskeletal system.
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Mees, Barend; Récalde, Alice; Loinard, Céline; Tempel, Dennie; Godinho, Marcia; Vilar, José; van Haperen, Rien; Lévy, Bernard; de Crom, Rini; Silvestre, Jean-Sébastien
2011-01-01
Bone marrow-derived mononuclear cells (BMMNCs) enhance postischemic neovascularization, and their therapeutic use is currently under clinical investigation. However, cardiovascular risk factors, including diabetes mellitus and hypercholesterolemia, lead to the abrogation of BMMNCs proangiogenic potential. NO has been shown to be critical for the proangiogenic function of BMMNCs, and increased endothelial NO synthase (eNOS) activity promotes vessel growth in ischemic conditions. We therefore hypothesized that eNOS overexpression could restore both the impaired neovascularization response and decreased proangiogenic function of BMMNCs in clinically relevant models of diabetes and hypercholesterolemia. Transgenic eNOS overexpression in diabetic, atherosclerotic, and wild-type mice induced a 1.5- to 2.3-fold increase in postischemic neovascularization compared with control. eNOS overexpression in diabetic or atherosclerotic BMMNCs restored their reduced proangiogenic potential in ischemic hind limb. This effect was associated with an increase in BMMNC ability to differentiate into cells with endothelial phenotype in vitro and in vivo and an increase in BMMNCs paracrine function, including vascular endothelial growth factor A release and NO-dependent vasodilation. Moreover, although wild-type BMMNCs treatment resulted in significant progression of atherosclerotic plaque in ischemic mice, eNOS transgenic atherosclerotic BMMNCs treatment even had antiatherogenic effects. Cell-based eNOS gene therapy has both proangiogenic and antiatherogenic effects and should be further investigated for the development of efficient therapeutic neovascularization designed to treat ischemic cardiovascular disease. PMID:21224043
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Carroll, G L; Narbe, R; Peterson, K; Kerwin, S C; Taylor, L; DeBoer, M
2008-10-01
Sodium urate (SU) synovitis was evaluated as a model for feline arthritic pain using a placebo- and positive-controlled (meloxicam) randomized blinded controlled single crossover design. Monosodium urate crystals [20 mg (1 mL) rod-shaped] were injected into alternate stifles of trained anesthetized cats (n = 3) with a 28 day washout. During the first trial phase, two cats received meloxicam (0.1 mg/kg, PO), a nonsteroidal anti-inflammatory drug (NSAID), for three days before and on the day of SU injection; the third cat received placebo. Treatments and stifles were switched for the second trial. Total force, contact pressure and area of the fore and hind limbs were measured using a pressure mat one day and 0.5 h before, and 2, 4, 6, 8, 10, 24, and 30 h post-SU injection. Skin temperature, joint circumference, analgesia, lameness, and visual analogue scale (VAS) pain scores, were measured at the same times. Comparisons were made for each time and for areas under the curve (AUC) using original and change from baseline; P < 0.05 was significant. Significant differences in force mat data and subjective data were found for the hind limb data (total force and total contact pressure at 6, 10, and 30 h; analgesia and VAS for pain at 4 h; lameness at 10, 24, and 30 h) and for AUC(0)-->(24h) and AUC(0)-->(30 h) (total force, total contact pressure, and mean lameness score) and for differences from BL AUC(0)-->(10h) (total contact area) and AUC(0)-->(24h) (total contact area and mean lameness score) and AUC(0)-->(30 h) (total force, total contact area, and mean lameness). No cats required rescue analgesia. Injection of 1 mL of monosodium urate into the stifle of a cat causes moderate transitory pain and was suitable for assessing analgesic efficacy of an NSAID with a pressure mat and subjective criteria.
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Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats.
Boban Blagaic, Alenka; Blagaic, Vladimir; Mirt, Mirela; Jelovac, Nikola; Dodig, Goran; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Anic, Tomislav; Dubovecak, Miroslav; Staresinic, Mario; Seiwerth, Sven; Sikiric, Predrag
2005-04-11
Serotonin syndrome commonly follows irreversible monoamine oxidase (MAO)-inhibition and subsequent serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake, hypothermia followed by hyperthermia). A stable gastric pentadecapeptide BPC 157 with very safe profile (inflammatory bowel disease clinical phase II, PL-10, PLD-116, PL-14736, Pliva) reduced the duration of immobility to a greater extent than imipramine, and, given peripherally, has region specific influence on brain 5-HT synthesis (alpha-[14C]methyl-L-tryptophan autoradiographic measurements) in rats, different from any other serotonergic drug. Thereby, we investigate this peptide (10 microg, 10 ng, 10 pg/kg i.p.) in (i) full serotonin syndrome in rat combining pargyline (irreversible MAO-inhibition; 75 mg/kg i.p.) and subsequent L-tryptophan (5-HT precursor; 100 mg/kg i.p.; BPC 157 as a co-treatment), or (ii, iii) using pargyline or L-tryptophan given separately, as a serotonin-substrate with (ii) pargyline (BPC 157 as a 15-min posttreatment) or as a potential serotonin syndrome inductor with (iii) L-tryptophan (BPC 157 as a 15 min-pretreatment). In all experiments, gastric pentadecapeptide BPC 157 contrasts with serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a serotonin substrate (counteraction of pargyline), nor an inductor for serotonin syndrome (no influence on L-tryptophan challenge)). Indicatively, severe serotonin syndrome in pargyline + L-tryptophan rats is considerably inhibited even by lower pentadecapeptide BPC 157 doses regimens (particularly disturbances such as hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in pargyline rats (mild hypothermia, feeble hind limbs abduction). Thereby, in severe serotonin syndrome, gastric pentadecapeptide BPC 157 (alone, no behavioral or temperature effect) has a beneficial activity, which is likely, particular, and mostly related to a rather specific counteraction of 5-HT2A receptors phenomena.
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Rosová, Ivana; Dao, Mo; Capoccia, Ben; Link, Daniel; Nolta, Jan A.
2010-01-01
Mesenchymal stem cells (MSC) are adult multipotent cells found in bone marrow, adipose tissue, and other adult tissues. MSC have been shown to improve regeneration of injured tissues in vivo, but the mechanisms remain unclear. Typically, MSC are cultured under ambient, or normoxic, conditions (21% oxygen). However, the physiological niches for MSC in the bone marrow and other sites have much lower oxygen tension. When used as a therapeutic tool to repair tissue injuries, MSC cultured in standard conditions must adapt from 21% oxygen in culture to less than 1% oxygen in the ischemic tissue. We therefore examined the effects of preculturing human bone marrow-derived MSC in hypoxic conditions (1%–3% oxygen) to elucidate the best conditions that enhance their tissue regenerative potential. We demonstrated that MSC cultured in hypoxia activate the Akt signaling pathway while maintaining their viability and cell cycle rates. We also showed that MSC cultured in hypoxia induced expression of cMet, the major receptor for hepatocyte growth factor (HGF), and enhanced cMet signaling. MSC cultured in hypoxic conditions increased their migration rates. Since migration and HGF responsiveness are thought to be key mediators of MSC recruitment and/or activation in vivo, we next examined the tissue regenerative potential of MSC cultured under hypoxic conditions, using a murine hind limb ischemia model. We showed that local expression of HGF is increased in ischemic muscle in this model. Intra-arterial injection of MSC cultured in either normoxic or hypoxic conditions 24 hours after surgical induction of hind limb ischemia enhanced revascularization compared with saline controls. However, restoration of blood flow was observed significantly earlier in mice that had been injected with hypoxic preconditioned MSC. Collectively, these data suggest that preculturing MSC under hypoxic conditions prior to transplantation improves their tissue regenerative potential. PMID:18511601
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Trumble, Troy N; Billinghurst, R Clark; Bendele, Alison M; McIlwraith, C Wayne
2005-01-01
To determine whether decreases in peak vertical force of the hind limb after transection of the cranial cruciate ligament (CrCL) would be indicative of medial meniscal damage in dogs. 39 purpose-bred adult male Walker Hounds. The right CrCL was transected arthroscopically. Force plate measurements of the right hind limb were made prior to and 2, 4, 10, and 18 weeks after transection of the CrCL. Only dogs with > or =10% decreases in peak vertical force after week 2 were considered to have potential meniscal damage. Dogs that did not have > or =10% decreases in peak vertical force at any time point after week 2 were assigned to group 1. Group 2 dogs had > or =10% decreases in peak vertical force from weeks 2 to 4 only. Group 3 and 4 dogs had > or =10% decreases in peak vertical force from weeks 4 to 10 only or from weeks 10 to 18 only, respectively. Damage to menisci and articular cartilage was graded at week 18, and grades for groups 2 to 4 were compared with those of group 1. The percentage change in peak vertical force and impulse area was significantly different in groups 2 (n = 4), 3 (4), and 4 (4) at the end of each measurement period (weeks 4, 10, and 18, respectively) than in group 1 (27). The meniscal grade for groups 2 to 4 was significantly higher than for group 1. A > or =10% decrease in peak vertical force had sensitivity of 52% and accuracy of 72% for identifying dogs with moderate to severe medial meniscal damage. In dogs with transected or ruptured CrCLs, force plate analysis can detect acute exacerbation of lameness, which may be the result of secondary meniscal damage, and provide an objective noninvasive technique that delineates the temporal pattern of medial meniscal injury.
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Roberts, Michael D; Holland, A Maleah; Kephart, Wesley C; Mobley, C Brooks; Mumford, Petey W; Lowery, Ryan P; Fox, Carlton D; McCloskey, Anna E; Shake, Joshua J; Mesquita, Paulo; Patel, Romil K; Martin, Jeffrey S; Young, Kaelin C; Kavazis, Andreas N; Wilson, Jacob M
2016-05-15
We examined whether acute and/or chronic skeletal muscle anabolism is impaired with a low-carbohydrate diet formulated to elicit ketosis (LCKD) vs. a mixed macronutrient Western diet (WD). Male Sprague-Dawley rats (9-10 wk of age, 300-325 g) were provided isoenergetic amounts of a LCKD or a WD for 6 wk. In AIM 1, basal serum and gastrocnemius assessments were performed. In AIM 2, rats were resistance exercised for one bout and were euthanized 90-270 min following exercise for gastrocnemius analyses. In AIM 3, rats voluntarily exercised daily with resistance-loaded running wheels, and hind limb muscles were analyzed for hypertrophy markers at the end of the 6-wk protocol. In AIM 1, basal levels of gastrocnemius phosphorylated (p)-rps6, p-4EBP1, and p-AMPKα were similar between diets, although serum insulin (P < 0.01), serum glucose (P < 0.001), and several essential amino acid levels (P < 0.05) were lower in LCKD-fed rats. In AIM 2, LCKD- and WD-fed rats exhibited increased postexercise muscle protein synthesis levels (P < 0.0125), but no diet effect was observed (P = 0.59). In AIM 3, chronically exercise-trained LCKD- and WD-fed rats presented similar increases in relative hind limb muscle masses compared with their sedentary counterparts (12-24%, P < 0.05), but there was no between-diet effects. Importantly, the LCKD induced "mild" nutritional ketosis, as the LCKD-fed rats in AIM 2 exhibited ∼1.5-fold greater serum β-hydroxybutyrate levels relative to WD-fed rats (diet effect P = 0.003). This study demonstrates that the tested LCKD in rodents, while only eliciting mild nutritional ketosis, does not impair the acute or chronic skeletal muscle hypertrophic responses to resistance exercise. Copyright © 2016 the American Physiological Society.
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Prevention of disuse osteoporosis in rats by Cordyceps sinensis extract.
Qi, W; Yan, Y-B; Lei, W; Wu, Z-X; Zhang, Y; Liu, D; Shi, L; Cao, P-C; Liu, N
2012-09-01
Cordyceps sinensis has been known as a traditional medicine in China, and C. sinensis plus strontium could prevent osteoporosis in ovariectomized rats. The present study shows that daily oral administration of C. sinensis at higher doses in adult hind limb suspension rats can prevent disuse-induced bone loss and deterioration of trabecular microarchitecture. Cordyceps sinensis induces estradiol production and prevents osteoporosis in ovariectomized rats. This study was to examine whether C. sinensis can prevent disuse-induced osteoporosis. Rats were randomly divided into six groups, and five groups were treated with hind limb suspension (HLS). One HLS group received alendronate (2.0 mg/kg/day) orally, and to the three other HLS groups to each group, a different amount of C. sinensis (100, 300, and 500 mg/kg/day) was orally administered for 8 weeks before and after HLS. The remaining HLS group was set as a control without treatment. Each group consisted of 10 males and females. The body weights, biochemical parameters in serum and urine, bone mineral density (BMD), bone mineral content (BMC), mechanical testing, and bone microarchitecture were examined. Treatments with higher C. sinensis dosage (300 and 500 mg/kg/day) or alendronate had a positive effect on body weights, mechanical strength, BMD, and BMC compared to the other HLS groups. C. sinensis decreased markers of bone turnover dose dependently and increased the osteocalcin levels in HLS rats. The result of micro-CT analysis from the L4 vertebra showed that C. sinensis (500 mg/kg) significantly prevented the reduction of the bone volume fraction, connectivity density, trabeculae number, and thickness as well as improved the trabeculae separation and structure model index in HLS rats. The present study demonstrates that administration of C. sinensis at higher doses over an 8-week period can prevent the disuse osteoporosis in rats. It implies that C. sinensis might be an alternative therapy for prevention of disuse-induced osteoporosis also in humans.
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Directional asymmetry of pelvic vestiges in threespine stickleback.
Bell, Michael A; Khalef, Victoria; Travis, Matthew P
2007-03-15
Extensive reduction of the size and complexity of the pelvic skeleton (i.e., pelvic reduction) has evolved repeatedly in Gasterosteus aculeatus. Asymmetrical pelvic vestiges tend to be larger on the left side (i.e., left biased) in populations studied previously. Loss of Pitx1 expression is associated with pelvic reduction in G. aculeatus, and pelvic reduction maps to the Pitx1 locus. Pitx1 knockouts in mice have reduced hind limbs, but the left limb is larger. Thus left-biased directional asymmetry of stickleback pelvic vestiges may indicate the involvement of Pitx1 in pelvic reduction. We examined 6,356 specimens from 27 Cook Inlet populations of G. aculeatus with extensive pelvic reduction. Samples from 20 populations exhibit the left bias in asymmetrical pelvic vestiges expected if Pitx1 is involved, and three have a slight, non-significant left bias. However, samples from three populations have a significant right bias, and one large sample from another population has equal frequencies of specimens with larger vestiges on the left or right side. A sample of fossil threespine stickleback also has significantly left-biased pelvic vestiges. These results suggest that silencing of Pitx1 or the developmental pathway in which it functions in the pelvis is the usual cause of pelvic reduction in most Cook Inlet populations of G. aculeatu, and that it caused pelvic reduction at least 10 million years ago in a stickleback population. A different developmental genetic mechanism is implicated for three populations with right-biased pelvic vestiges and for the population without directional asymmetry. (c) 2006 Wiley-Liss, Inc.
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The salutary effect of dietary calcium on bone mass in a rat model of simulated weightlessness
NASA Technical Reports Server (NTRS)
Bikle, D. D.; Globus, R.; Halloran, B. P.; Morey-Holton, E.
1985-01-01
Whether supplementation of dietary calcium reduces the differences in bone mass of unweighed limbs and normally weighted limbs, and whether parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D) respond differently to dietary calcium in unweighted animals in comparison with pair-fed controls was studied. The hind limbs of rats were unweighted by a tail suspension method and diets containing 0.1% to 2.4% calcium. After 2 weeks serum calcium, phosphorus, PTH and 1,25(OH)2D intestinal calcium transport were determined and bone mass, ash weight, and calcium in the tibia, L-1 vertebra, and humerus were measured. No significant differences in body weights were observed among the various groups. Suspended rats maintained constant levels of serum calcium and phosphate over the wide range of dietary calcium. Serum PTH and 1,25(OH)2D and intestinal calcium transport fell as dietary calcium was increased. Bone calcium in the tibia and vertebra from suspended rats remained less than that from pair-fed control. It is suggested that although no striking difference between suspended and control animals was observed in response to dieteary calcium, increasing dietary calcium may reduce the negative impact of unloading on the calcium content of the unweighted bones. The salutary effect of high dietary calcium appears to be due to inhibition of bone resorption rather than to stimulation of bone formation.
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Rui, Jing; Runge, M Brett; Spinner, Robert J; Yaszemski, Michael J; Windebank, Anthony J; Wang, Huan
2014-10-01
Video-assisted gait kinetics analysis has been a sensitive method to assess rat sciatic nerve function after injury and repair. However, in conduit repair of sciatic nerve defects, previously reported kinematic measurements failed to be a sensitive indicator because of the inferior recovery and inevitable joint contracture. This study aimed to explore the role of physiotherapy in mitigating joint contracture and to seek motion analysis indices that can sensitively reflect motor function. Data were collected from 26 rats that underwent sciatic nerve transection and conduit repair. Regular postoperative physiotherapy was applied. Parameters regarding step length, phase duration, and ankle angle were acquired and analyzed from video recording of gait kinetics preoperatively and at regular postoperative intervals. Stride length ratio (step length of uninjured foot/step length of injured foot), percent swing of the normal paw (percentage of the total stride duration when the uninjured paw is in the air), propulsion angle (toe-off angle subtracted by midstance angle), and clearance angle (ankle angle change from toe off to midswing) decreased postoperatively comparing with baseline values. The gradual recovery of these measurements had a strong correlation with the post-nerve repair time course. Ankle joint contracture persisted despite rigorous physiotherapy. Parameters acquired from a 2-dimensional motion analysis system, that is, stride length ratio, percent swing of the normal paw, propulsion angle, and clearance angle, could sensitively reflect nerve function impairment and recovery in the rat sciatic nerve conduit repair model despite the existence of joint contractures.
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Cristofaro, Brunella; Shi, Yu; Faria, Marcella; Suchting, Steven; Leroyer, Aurelie S; Trindade, Alexandre; Duarte, Antonio; Zovein, Ann C; Iruela-Arispe, M Luisa; Nih, Lina R; Kubis, Nathalie; Henrion, Daniel; Loufrani, Laurent; Todiras, Mihail; Schleifenbaum, Johanna; Gollasch, Maik; Zhuang, Zhen W; Simons, Michael; Eichmann, Anne; le Noble, Ferdinand
2013-04-01
Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4(+/-) mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4(+/-) mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality.
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Cristofaro, Brunella; Shi, Yu; Faria, Marcella; Suchting, Steven; Leroyer, Aurelie S.; Trindade, Alexandre; Duarte, Antonio; Zovein, Ann C.; Iruela-Arispe, M. Luisa; Nih, Lina R.; Kubis, Nathalie; Henrion, Daniel; Loufrani, Laurent; Todiras, Mihail; Schleifenbaum, Johanna; Gollasch, Maik; Zhuang, Zhen W.; Simons, Michael; Eichmann, Anne; le Noble, Ferdinand
2013-01-01
Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4+/- mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4+/- mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality. PMID:23533173
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Murach, Kevin A; Confides, Amy L; Ho, Angel; Jackson, Janna R; Ghazala, Lina S; Peterson, Charlotte A; Dupont-Versteegden, Esther E
2017-10-01
Satellite cell depletion does not affect diaphragm adaptations to voluntary wheel running in young or aged mice. Satellite cell depletion early in life (4 months of age) has minimal effect on diaphragm phenotype by old age (24 months). Prolonged satellite cell depletion in the diaphragm does not result in excessive extracellular matrix accumulation, in contrast to what has been reported in hind limb muscles. Up-regulation of Pax3 mRNA+ cells after satellite cell depletion in young and aged mice suggests that Pax3+ cells may compensate for a loss of Pax7+ satellite cells in the diaphragm. Future investigations should focus on the role of Pax3+ cells in the diaphragm during adaptation to exercise and ageing. Satellite cell contribution to unstressed diaphragm is higher compared to hind limb muscles, which is probably attributable to constant activation of this muscle to drive ventilation. Whether satellite cell depletion negatively impacts diaphragm quantitative and qualitative characteristics under stressed conditions in young and aged mice is unknown. We therefore challenged the diaphragm with prolonged running activity in the presence and absence of Pax7+ satellite cells in young and aged mice using an inducible Pax7 CreER -R26R DTA model. Mice were vehicle (Veh, satellite cell-replete) or tamoxifen (Tam, satellite cell-depleted) treated at 4 months of age and were then allowed to run voluntarily at 6 months (young) and 22 months (aged). Age-matched, cage-dwelling, Veh- and Tam-treated mice without wheel access served as activity controls. Diaphragm muscles were analysed from young (8 months) and aged (24 months) mice. Satellite cell depletion did not alter diaphragm mean fibre cross-sectional area, fibre type distribution or extracellular matrix content in young or aged mice, regardless of running activity. Resting in vivo diaphragm function was also unaffected by satellite cell depletion. Myonuclear density was maintained in young satellite cell-depleted mice regardless of running, although it was modestly reduced in aged sedentary (-7%) and running (-19%) mice without satellite cells (P < 0.05). Using fluorescence in situ hybridization, we detected higher Pax3 mRNA+ cell density in both young and aged satellite cell-depleted diaphragm muscle (P < 0.05), which may compensate for the loss of Pax7+ satellite cells. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.
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Spontaneous diabetes mellitus in captive Mandrillus sphinx monkeys: a case report.
Pirarat, N; Kesdangsakolwut, S; Chotiapisitkul, S; Assarasakorn, S
2008-06-01
Case history The two obese mandrills (Mandrillus sphinx) showed clinical signs of depression, anorexia, hyperglycemia, hypertriglyceridemia, glucosuria, proteinuria and ketonuria. Septic bed sore wounds were noted on both fore and hind limbs. Results Histopathological study revealed severe islet amyloidosis in both mandrills. Immunohistochemical study using polyclonal anti-cat amylin antibody confirmed derivation of the islet amyloid from islet amyloid polypeptide (IAPP). Cardiomyopathy and myocardial fibrosis were also evident. Conclusions The present study documents diabetes mellitus in two obese mandrills. Diabetes in these animals had features very similar type 2 diabetes mellitus of humans, including the development of severe, IAPP-derived islet amyloidosis. The mandrill may, therefore, serve as an animal model of human type 2 diabetes mellitus.
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Quantifying the vascular response to ischemia with speckle variance optical coherence tomography
Poole, Kristin M.; McCormack, Devin R.; Patil, Chetan A.; Duvall, Craig L.; Skala, Melissa C.
2014-01-01
Longitudinal monitoring techniques for preclinical models of vascular remodeling are critical to the development of new therapies for pathological conditions such as ischemia and cancer. In models of skeletal muscle ischemia in particular, there is a lack of quantitative, non-invasive and long term assessment of vessel morphology. Here, we have applied speckle variance optical coherence tomography (OCT) methods to quantitatively assess vascular remodeling and growth in a mouse model of peripheral arterial disease. This approach was validated on two different mouse strains known to have disparate rates and abilities of recovering following induction of hind limb ischemia. These results establish the potential for speckle variance OCT as a tool for quantitative, preclinical screening of pro- and anti-angiogenic therapies. PMID:25574425
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Nelson, S.P.
1994-12-31
Hexsoamine synthetic pathway (HexNSP) controls the supply of essential substrates for glycoprotein synthesis. In vitro studies suggest that increased flux of glucose via the hexsoamine synthetic pathway may play a role in glucose induced insulin resistance of glucose transport. Glutamine: fructose-6-phosphate amindotransferase (GFAT) controls flux into the hexsoamine synthetic pathway; the major products are UDPN-acetylhexosamines (UDP.HexNac=UDP.GlcNAc= UDP.GalNac). I examined whether diabetes ({approximately} 7 days post intravenous streptozotocin, and genetically linked) affects the activity of glutamine: fructose-6-phosphate in rat and mouse skeletal muscle in vivo. Nucleotide linked HexNAc were analyzed by high pressure liquid chromatography(HPLC) in deproteinized hind limb muscle extracts.
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Flight of Sharovipteryx mirabilis: the world's first delta-winged glider.
Dyke, G J; Nudds, R L; Rayner, J M V
2006-07-01
The 225 million-year-old reptile Sharovipteryx mirabilis was the world's first delta-winged glider; this remarkable animal had a flight surface composed entirely of a hind-limb membrane. We use standard delta-wing aerodynamics to reconstruct the flight of S. mirabilis demonstrating that wing shape could have been controlled simply by protraction of the femora at the knees, and by variation in incidence of a small forelimb canard. Our method has allowed us to address the question of how identifying realistic glide performance can be used to set limits on aerodynamic design in this small animal. Our novel interpretation of the bizarre flight mode of S. mirabilis is the first based directly on interpretation of the fossil itself and the first grounded in aerodynamics.
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NASA Technical Reports Server (NTRS)
Lowry, Oliver H.; Krasnov, Igor; Kakueva, E. Ilyina; Nemeth, Patti M.; Mcdougal, David B., Jr.; Choksi, Rati; Carter, Joyce G.; Chi, Maggie M. Y.; Manchester, Jill K.; Pusateri, Mary Ellen
1990-01-01
The effects of microgravity and hind limb suspension on the enzyme patterns are assessed within a slow twitch muscle (soleus) and a fast twitch muscle (tibialis anterior). Studies were made on 95 soleus fibers and about 300 tibialis anterior (TA) fibers. Over 2200 individual enzyme measurements were made. Six key metabolic enzymes (hexokinase, pyruvate kinease, citrate kinase, beta-hydroxyacyl CoA dehydrogenase, glucose-6-P dehydrogenase, and aspartate aminotransferase) plus glutaminase and glutamate decarboxylase, as well as glutamate, aspartate, and GABA, were measured in 11 regions of the hippocampal formation of synchronous, flight, and tail suspension rats. Major differences were observed in the normal distribution of each enzyme and amine acid, but no substantive effects of either microgravity or tail suspension on these patterns were clearly demonstrated.
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Bipedal locomotion of bonnet macaques after spinal cord injury.
Babu, Rangasamy Suresh; Anand, P; Jeraud, Mathew; Periasamy, P; Namasivayam, A
2007-10-01
Experimental studies concerning the analysis of locomotor behavior in spinal cord injury research are widely performed in rodent models. The purpose of this study was to quantitatively evaluate the degree of functional recovery in reflex components and bipedal locomotor behavior of bonnet macaques (Macaca radiata) after spinal contusive injury. Six monkeys were tested for various reflex components (grasping, righting, hopping, extension withdrawal) and were trained preoperatively to walk in bipedal fashion on the simple and complex locomotor runways (narrow beam, grid, inclined plane, treadmill) of this investigation. The overall performance of the animals'motor behavior and the functional status of limb movements during bipedal locomotion were graded by the Combined Behavioral Score (CBS) system. Using the simple Allen weight-drop technique, a contusive injury was produced by dropping a 13-g weight from a height of 30 cm to the exposed spinal cord at the T12-L1 vertebral level of the trained monkeys. All the monkeys showed significant impairments in every reflex activity and in walking behavior during the early part of the postoperative period. In subsequent periods, the animals displayed mild alterations in certain reflex responses, such as grasping, extension withdrawal, and placing reflexes, which persisted through a 1-year follow-up. The contused animals traversed locomotor runways--narrow beam, incline plane, and grid runways--with more steps and few errors, as evaluated with the CBS system. Eventually, the behavioral performance of all spinal-contused monkeys recovered to near-preoperative level by the fifth postoperative month. The findings of this study reveal the recovery time course of various reflex components and bipedal locomotor behavior of spinal-contused macaques on runways for a postoperative period of up to 1 year. Our spinal cord research in primates is advantageous in understanding the characteristics of hind limb functions only, which possibly mimic the human motor behavior. This study may be also useful in detecting the beneficial effect of various donor tissue-neuroprotective drugs on the repair of impaired functions in a bipedal primate model of spinal injury.
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Terrestrial Microgravity Model and Threshold Gravity Simulation sing Magnetic Levitation
NASA Technical Reports Server (NTRS)
Ramachandran, N.
2005-01-01
What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for such a gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successiblly simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars.
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Ohwatashi, Akihiko; Ikeda, Satoshi; Harada, Katsuhiro; Kamikawa, Yurie; Yoshida, Akira
2013-01-01
Exercise has been considered to affect the functional recovery from central nervous damage. Neurotrophic factors have various effects on brain damage. However, the effects of exercise for expression of GDNF on functional recovery with brain damage are not well known. We investigated the difference in functional recovery between non-exercise and beam-walking exercise groups, and the expression of GDNF in both groups after photochemical infarction. Adult male Wistar rats (N = 64) were used. Animals were divided into two groups: non-exercise (N = 35), and beam-walking exercise (N = 29). All rats underwent surgical photochemical infarction. The rats of the beam-walking group were trained every day to walk on a narrow beam after a one-day recovery period and those of the non-exercise group were left to follow a natural course. Animals were evaluated for hind limb function every day using a beam-walking task with an elevated narrow beam. The number of GDNF-like immunoreactive cells in the temporal cortex surrounding the lesion was counted 1, 3, 5, and 7 days after the infarction. Functional recovery of the beam-walking exercise group was significantly earlier than that of the non-exercise group. At 3 days after infarction, the number of GDNF-positive cells in the temporal cortex surrounding the infarction was significantly increased in the beam-walking exercise group compared with that in the non-exercise group. In the exercise group, motor function was remarkably recovered with the increased expression of GDNF-like immunoreactive cells. Our results suggested that a rehabilitative approach increased the expression of GDNF and facilitated functional recovery from cerebral infarction.
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Sole vibration improves locomotion through the recovery of joint movements in a mouse cast model
Sakasaki, Juntaro; Kasae, Syota; Nishimura, Keisuke; Shin, Min-Chul; Yoshimura, Megumu
2017-01-01
We investigated the effects of a vibratory stimulus on the plantar surface of the hind limb for motor, sensory, and locomotive function using a mouse cast model. The right knee joint of C57BL/6 male mice (7 weeks, 20 g, n = 31) was flexed with aluminum splint and tape for 6 weeks. These mice were randomly divided into 2 groups (control group, n = 11 and vibration group, n = 12). The mice in the vibration group received vibration on the sole of the ankle for 15 minutes per day, 5 days per week. After the knee joint cast was removed, we measured the range of motion (ROM) of both knee and ankle joints and the sensory threshold of the sole. Further, both walking and swimming movements were analyzed with a digital video. The sole vibration did not affect the passive ROM of the knee joint and sensory threshold after cast removal. However, it increased the ankle dorsiflexion range and improved free walking, swimming, and active movement of the knee joint. In conclusion, we show that the vibration recovered both walking and swimming movements, which resulted from improvements in both the passive ankle dorsiflexion and active knee movement. PMID:29040289
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Physiological imaging of electrical trauma and therapeutic responses
NASA Astrophysics Data System (ADS)
Chen, Chin-Tu; Matthews, K.; Aarsvold, John N.; Mintzer, Robert A.; Yasillo, Nicholas J.; Hannig, Jurgen; Capelli-Schellpfefer, M.; Cooper, Malcolm; Lee, Raphael C.
2000-04-01
In victims of electrical trauma, electroporation of cell membrane, in which lipid bilayer is permeabilized by thermal and electrical forces, is thought to be a substantial cause of tissue damage. It has been suggested that certain mild surfactant in low concentration could induce sealing of permeabilized lipid bilayers, thus repairing cell membranes that had not been extensively damaged. With an animal model of electrically injured hind limb of rats, we have demonstrated and validated the use of radiotracer imaging technique to assess the physiology of the damaged tissues after electrical shock and of their repairs after applying surfactant as a therapeutic strategy. For example, using Tc-99m labeled pyrophosphate (PYP), which follows calcium in cellular function and is known to accumulate in damaged tissues, we have established a physiological imaging approach for assessment of the extent of tissue injury for diagnosis and surgical planning, as well as for evaluation of responses to therapy. With the use of a small, hand-held, miniature gamma camera, this physiological imaging method can be employed at patient's bedside and even in the field, for example, at accident site or during transfer for emergency care, rapid diagnosis, and prompt treatment in order to maximize the chance for tissue survival.
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A novel model to assess lamellar signaling relevant to preferential weight bearing in the horse.
Gardner, A K; van Eps, A W; Watts, M R; Burns, T A; Belknap, J K
2017-03-01
Supporting limb laminitis (SLL) is a devastating sequela to severe unilateral lameness in equine patients. The manifestation of SLL, which usually only affects one limb, is unpredictable and the etiology is unknown. A novel, non-painful preferential weight bearing model designed to mimic the effects of severe unilateral forelimb lameness was developed to assess lamellar signaling events in the supporting limb (SL). A custom v-shaped insert was attached to the shoe of one forelimb to prevent normal weight bearing and redistribute weight onto the SL. Testing of the insert using a custom scale platform built into the floor of stocks confirmed increased distribution of weight on the SL compared with the unloaded forelimb (UL) and the contralateral (CH) and ipsilateral (IH) hind limbs in six Standardbred horses. In a second part of the study, eight healthy Standardbred horses were fitted with the insert and tied with consistent monitoring and free access to hay and water for 48 h, after which the lamellae were harvested. Real-time qPCR was performed to assess lamellar mRNA concentrations of inflammatory genes and immunoblotting and immunofluorescence were performed to assess lamellar protein concentration and cellular localization of hypoxia-related proteins, respectively. Lamellar mRNA concentrations of inflammatory signaling proteins did not differ between SL and either CH or IH samples. HIF-1α concentrations were greater (P < 0.05) in the SL compared to the CH. This work establishes an experimental model to study preferential weight bearing and initial results suggest that lamellar hypoxia may occur in the SL. Copyright © 2017. Published by Elsevier Ltd.
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Revascularization and muscle adaptation to limb demand ischemia in diet-induced obese mice.
Albadawi, Hassan; Tzika, A Aria; Rask-Madsen, Christian; Crowley, Lindsey M; Koulopoulos, Michael W; Yoo, Hyung-Jin; Watkins, Michael T
2016-09-01
Obesity and type 2 diabetes are major risk factors for peripheral arterial disease in humans, which can result in lower limb demand ischemia and exercise intolerance. Exercise triggers skeletal muscle adaptation including increased vasculogenesis. The goal of this study was to determine whether demand ischemia modulates revascularization, fiber size, and signaling pathways in the ischemic hind limb muscles of mice with diet-induced obesity (DIO). DIO mice (n = 7) underwent unilateral femoral artery ligation and recovered for 2 wks followed by 4 wks with daily treadmill exercise to induce demand ischemia. A parallel sedentary ischemia (SI) group (n = 7) had femoral artery ligation without exercise. The contralateral limb muscles of SI served as control. Muscles were examined for capillary density, myofiber cross-sectional area, cytokine levels, and phosphorylation of STAT3 and ERK1/2. Exercise significantly enhanced capillary density (P < 0.01) and markedly lowered cross-sectional area (P < 0.001) in demand ischemia compared with SI. These findings coincided with a significant increase in granulocyte colony-stimulating factor (P < 0.001) and interleukin-7 (P < 0.01) levels. In addition, phosphorylation levels of STAT3 and ERK1/2 (P < 0.01) were increased, whereas UCP1 and monocyte chemoattractant protein-1 protein levels were lower (P < 0.05) without altering vascular endothelial growth factor and tumor necrosis factor alpha protein levels. Demand ischemia increased the PGC1α messenger RNA (P < 0.001) without augmenting PGC1α protein levels. Exercise-induced limb demand ischemia in the setting of DIO causes myofiber atrophy despite an increase in muscle capillary density. The combination of persistent increase in tumor necrosis factor alpha, lower vascular endothelial growth factor, and failure to increase PGC1α protein may reflect a deficient adaption to demand ischemia in DIO. Copyright © 2016 Elsevier Inc. All rights reserved.
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Pelvic girdle and fin of Tiktaalik roseae
Shubin, Neil H.; Daeschler, Edward B.; Jenkins, Farish A.
2014-01-01
A major challenge in understanding the origin of terrestrial vertebrates has been knowledge of the pelvis and hind appendage of their closest fish relatives. The pelvic girdle and appendage of tetrapods is dramatically larger and more robust than that of fish and contains a number of structures that provide greater musculoskeletal support for posture and locomotion. The discovery of pelvic material of the finned elpistostegalian, Tiktaalik roseae, bridges some of these differences. Multiple isolated pelves have been recovered, each of which has been prepared in three dimensions. Likewise, a complete pelvis and partial pelvic fin have been recovered in association with the type specimen. The pelves of Tiktaalik are paired and have broad iliac processes, flat and elongate pubes, and acetabulae that form a deep socket rimmed by a robust lip of bone. The pelvis is greatly enlarged relative to other finned tetrapodomorphs. Despite the enlargement and robusticity of the pelvis of Tiktaalik, it retains primitive features such as the lack of both an attachment for the sacral rib and an ischium. The pelvic fin of Tiktaalik (NUFV 108) is represented by fin rays and three endochondral elements: other elements are not preserved. The mosaic of primitive and derived features in Tiktaalik reveals that the enhancement of the pelvic appendage of tetrapods and, indeed, a trend toward hind limb-based propulsion have antecedents in the fins of their closest relatives. PMID:24449831
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Mees, Barend; Récalde, Alice; Loinard, Céline; Tempel, Dennie; Godinho, Marcia; Vilar, José; van Haperen, Rien; Lévy, Bernard; de Crom, Rini; Silvestre, Jean-Sébastien
2011-01-01
Bone marrow-derived mononuclear cells (BMMNCs) enhance postischemic neovascularization, and their therapeutic use is currently under clinical investigation. However, cardiovascular risk factors, including diabetes mellitus and hypercholesterolemia, lead to the abrogation of BMMNCs proangiogenic potential. NO has been shown to be critical for the proangiogenic function of BMMNCs, and increased endothelial NO synthase (eNOS) activity promotes vessel growth in ischemic conditions. We therefore hypothesized that eNOS overexpression could restore both the impaired neovascularization response and decreased proangiogenic function of BMMNCs in clinically relevant models of diabetes and hypercholesterolemia. Transgenic eNOS overexpression in diabetic, atherosclerotic, and wild-type mice induced a 1.5- to 2.3-fold increase in postischemic neovascularization compared with control. eNOS overexpression in diabetic or atherosclerotic BMMNCs restored their reduced proangiogenic potential in ischemic hind limb. This effect was associated with an increase in BMMNC ability to differentiate into cells with endothelial phenotype in vitro and in vivo and an increase in BMMNCs paracrine function, including vascular endothelial growth factor A release and NO-dependent vasodilation. Moreover, although wild-type BMMNCs treatment resulted in significant progression of atherosclerotic plaque in ischemic mice, eNOS transgenic atherosclerotic BMMNCs treatment even had antiatherogenic effects. Cell-based eNOS gene therapy has both proangiogenic and antiatherogenic effects and should be further investigated for the development of efficient therapeutic neovascularization designed to treat ischemic cardiovascular disease. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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Furuta, Sadayoshi; Watanabe, Lisa; Doi, Seira; Horiuchi, Hiroshi; Matsumoto, Kenjiro; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru
2012-02-01
Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz, which indicated that lumbar primary afferent Aδ sensitivity was enhanced in SDV rats. The whole-cell patch-clamp technique also revealed the hyper-excitability of acutely dissociated medium-sized lumbar dorsal root ganglion (DRG) neurons isolated from SDV rats. The contribution of changes in voltage-dependent potassium (Kv) channels was assessed, and transient A-type K(+) (I(A) ) current density was apparently decreased. Moreover, Kv4.3 immunoreactivity in medium-sized DRG neurons was significantly reduced in SDV rats compared to sham. These results indicate that SDV causes hyper-excitability of lumbar primary Aδ afferent neurons, which may be induced along with suppressing I(A) currents via the decreased expression of Kv4.3. Thus, peripheral Aδ neuroplasticity may contribute to the chronic lower limb pain caused by SDV. Copyright © 2011 Wiley Periodicals, Inc.
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2014-01-01
Locomotion over deformable substrates is a common occurrence in nature. Footprints represent sedimentary distortions that provide anatomical, functional, and behavioral insights into trackmaker biology. The interpretation of such evidence can be challenging, however, particularly for fossil tracks recovered at bedding planes below the originally exposed surface. Even in living animals, the complex dynamics that give rise to footprint morphology are obscured by both foot and sediment opacity, which conceals animal–substrate and substrate–substrate interactions. We used X-ray reconstruction of moving morphology (XROMM) to image and animate the hind limb skeleton of a chicken-like bird traversing a dry, granular material. Foot movement differed significantly from walking on solid ground; the longest toe penetrated to a depth of ∼5 cm, reaching an angle of 30° below horizontal before slipping backward on withdrawal. The 3D kinematic data were integrated into a validated substrate simulation using the discrete element method (DEM) to create a quantitative model of limb-induced substrate deformation. Simulation revealed that despite sediment collapse yielding poor quality tracks at the air–substrate interface, subsurface displacements maintain a high level of organization owing to grain–grain support. Splitting the substrate volume along “virtual bedding planes” exposed prints that more closely resembled the foot and could easily be mistaken for shallow tracks. DEM data elucidate how highly localized deformations associated with foot entry and exit generate specific features in the final tracks, a temporal sequence that we term “track ontogeny.” This combination of methodologies fosters a synthesis between the surface/layer-based perspective prevalent in paleontology and the particle/volume-based perspective essential for a mechanistic understanding of sediment redistribution during track formation. PMID:25489092
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Calpeptin is neuroprotective against acrylamide-induced neuropathy in rats.
Su, Benyu; Guan, Qiangdong; Wang, Miaomiao; Liu, Ning; Wei, Xiaomin; Wang, Shue; Yang, Xiwei; Jiang, Wenchong; Xu, Mengmeng; Yu, Sufang
2018-05-01
The aim of this study is to explore the potent neuroprotective effect of calpeptin (CP) on neuron damage induced by acrylamide (ACR) and its mechanism. Behavioural indicators such as hind limb splay, rota-rod performance, and gait analysis were assessed weekly to evaluate neurobehavioural changes after ACR and/or CP administration. The histopathological alterations and the changes of μ-calpain, m-calpain, microtubule-associated protein 2 (MAP2), and α-tubulin and β-tubulin protein levels in spinal cord were determined. Results showed that after administration of 30 mg/kg ACR, decreased body weight, attenuated neurobehavioural function, injury of motor neuron, increased protein levels of m-calpain and β-tubulin, suppressed MAP2 protein level, and no significant changes of μ-calpain and α-tubulin protein levels were observed compared with the control group rats. After administration of 200 μg/kg CP, partially restored body weight and neurobehavioural function, improvement of motor neuron injury, decreased protein levels of m- calpain and β-tubulin, and reversed effects of MAP2 protein level were observed compared with the ACR group rats. Our results suggested that CP alleviates neuropathy induced by ACR in rats. The calpain's overactivation causes the degrading of MAP2 and eventually leads to the destruction of microtubules (MTs), which may be one of the mechanisms of cytoskeletal damage induced by ACR. Copyright © 2018 Elsevier B.V. All rights reserved.
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Clayton, Hilary M.
2015-01-01
The study of animal movement commonly requires the segmentation of continuous data streams into individual strides. The use of forceplates and foot-mounted accelerometers readily allows the detection of the foot-on and foot-off events that define a stride. However, when relying on optical methods such as motion capture, there is lack of validated robust, universally applicable stride event detection methods. To date, no method has been validated for movement on a circle, while algorithms are commonly specific to front/hind limbs or gait. In this study, we aimed to develop and validate kinematic stride segmentation methods applicable to movement on straight line and circle at walk and trot, which exclusively rely on a single, dorsal hoof marker. The advantage of such marker placement is the robustness to marker loss and occlusion. Eight horses walked and trotted on a straight line and in a circle over an array of multiple forceplates. Kinetic events were detected based on the vertical force profile and used as the reference values. Kinematic events were detected based on displacement, velocity or acceleration signals of the dorsal hoof marker depending on the algorithm using (i) defined thresholds associated with derived movement signals and (ii) specific events in the derived movement signals. Method comparison was performed by calculating limits of agreement, accuracy, between-horse precision and within-horse precision based on differences between kinetic and kinematic event. In addition, we examined the effect of force thresholds ranging from 50 to 150 N on the timings of kinetic events. The two approaches resulted in very good and comparable performance: of the 3,074 processed footfall events, 95% of individual foot on and foot off events differed by no more than 26 ms from the kinetic event, with average accuracy between −11 and 10 ms and average within- and between horse precision ≤8 ms. While the event-based method may be less likely to suffer from scaling effects, on soft ground the threshold-based method may prove more valuable. While we found that use of velocity thresholds for foot on detection results in biased event estimates for the foot on the inside of the circle at trot, adjusting thresholds for this condition negated the effect. For the final four algorithms, we found no noteworthy bias between conditions or between front- and hind-foot timings. Different force thresholds in the range of 50 to 150 N had the greatest systematic effect on foot-off estimates in the hind limbs (up to on average 16 ms per condition), being greater than the effect on foot-on estimates or foot-off estimates in the forelimbs (up to on average ±7 ms per condition). PMID:26157641
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Laprais, Aurore F; Bizikova, Petra; Lashnits, Erin W; Tucker, Alison; Linder, Keith E
2017-10-01
In humans, scleromyxoedema is a chronic progressive skin condition traditionally characterized by deposits of mucin, increased number of fibroblasts and fibrosis in the skin, and by systemic disease. Thyroid disease is typically absent. A monoclonal gammopathy is usually present, as are other comorbidities. Descriptions of scleromyxoedema in the veterinary literature are limited to a single feline case. One dog, previously reported as having papular mucinosis, exhibited features that matched the more current diagnostic criteria of scleromyxoedema. To describe generalized papular mucinosis in a dog with systemic illness and to compare the signs with those of human lichen myxoedematosus conditions, specifically scleromyxoedema. A nine-year-old female, spayed English springer spaniel dog presented with generalized papules and nodules (0.5-5 cm) on the body and proximal fore and hind limbs, sparing the face and distal limbs distal to carpi/tarsi. Larger nodules were erythematous. Nodules occurred in proximal limb muscles. The dog had concurrent osteoarthritis of the elbows and coxofemoral joints, developed generalized weakness, declined in health and was euthanized. Thyroid disease was lacking and a monoclonal gammopathy was not present. Histopathological evaluation revealed the classic triad of mucin, fibroblast proliferation and fibrosis with very mild inflammation, as described for humans. We document scleromyxoedema in a dog with significant morbidity and features of the human disease. Recognizing the typical histopathology is important for identifying cases and to establish a diagnosis. Systemic evaluation is important to identify evidence of internal disease and associated comorbidities, which are common, variable, and impact classification and prognosis in humans. © 2017 ESVD and ACVD.
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Davis, Drew R; Geheber, Aaron D; Watters, Jessa L; Penrod, Michelle L; Feller, Kathryn D; Ashford, Alissa; Kouri, Josh; Nguyen, Daniel; Shauberger, Kathryn; Sheatsley, Kyra; Winfrey, Claire; Wong, Rachel; Sanguila, Marites B; Brown, Rafe M; Siler, Cameron D
2016-06-28
Studies of the diversity of Philippine amphibians and reptiles have resulted in the continued description of cryptic species. Species formerly thought to range across multiple recognized faunal regions are now considered to be assemblages of multiple unique species, each restricted to a single faunal region. This pattern continues to hold true when considering Philippine skinks of the genus Brachymeles. Recent studies have resulted in the description of numerous unique species with many exhibiting various degrees of digit loss or limb reduction, as well as suggesting that unique lineages are still present in the B. bonitae Complex. In this paper, we describe a new species of fossorial skink within this species complex from Tablas Island based on collections made nearly 50 years ago. Although no genetic data are available for the new species, examinations of morphological data (qualitative traits, meristic counts, and mensural measurements) support its distinction from all other members of the genus. Brachymeles dalawangdaliri sp. nov. is differentiated from other members of the genus based on a suite of unique phenotypic characteristics, including a small body size (SVL 66.0-80.9 mm), bidactyl fore-limbs, digitless, unidactyl, or bidactyl hind limbs, a high number of presacral vertebrae (49), the absence of auricular openings, and distinct dorsal head scale patterns. The description of the new species increases the diversity of endemic vertebrates recognized to occur in the Romblon Island Group in the central Philippines.
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Carter, Edward A.; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A.; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.
2014-01-01
Burn trauma to the extremities can produce marked systemic effects in mice1, 6, 7. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism (18FDG uptake) by brown adipose tissue (BAT) and NF-κB activity in a number of tissues including skeletal muscle. This study examined the effect of a single hindlimb burn in mice on 18FDG uptake by in vivo, NF-κB activity in vivo, and blood flow determined by laser Doppler techniques. Male mice NF-κB luciferase reporter mice (28 grams- 30 grams, male) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 ml, IP). The individual animals were placed in wire bottom cages with no food and free access to water. 24 hrs later, the animals were imaged with Laser Doppler for measurements of blood flow in the hind limb. The animals were then injected unanesthetized with 50 µCi of FDG or luciferin (1.0 mg), I.V. via tail vein. Five minutes after luciferin injection, NF-kB mice were studied by bioluminescence imaging with a CCD camera. One hour after 18FDG injection the animals were euthanized with carbon dioxide overdose and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than in the contralateral limb. Similarly luciferase activity and blood flow in the burned leg were lower than in the contralateral leg. 18FDG uptake by BAT and heart was increased, while brain was decreased. In conclusion, the present study suggests that burn injury to a single leg reduced 18FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression as compared to the contralateral leg and the uninjured skeletal muscle of the sham, but activated NF-κB expression in a number of other organs. These findings are consistent with the hypothesis that burn trauma to the extremities can produce marked systemic effects, including activation of NF-κB expression and activation of 18FDG uptake by BAT. PMID:25100541
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Mena, Hebe Agustina; Zubiry, Paula Romina; Dizier, Blandine; Schattner, Mirta; Boisson-Vidal, Catherine; Negrotto, Soledad
2018-05-02
We have previously demonstrated that acidic preconditioning of human endothelial colony-forming cells (ECFC) increased proliferation, migration, and tubulogenesis in vitro, and increased their regenerative potential in a murine model of hind limb ischemia without baseline disease. We now analyze whether this strategy is also effective under adverse conditions for vasculogenesis, such as the presence of ischemia-related toxic molecules or diabetes, one of the main target diseases for cell therapy due to their well-known healing impairments. Cord blood-derived CD34 + cells were seeded in endothelial growth culture medium (EGM2) and ECFC colonies were obtained after 14-21 days. ECFC were exposed at pH 6.6 (preconditioned) or pH 7.4 (nonpreconditioned) for 6 h, and then pH was restored at 7.4. A model of type 2 diabetes induced by a high-fat and high-sucrose diet was developed in nude mice and hind limb ischemia was induced in these animals by femoral artery ligation. A P value < 0.05 was considered statistically significant (by one-way analysis of variance). We found that acidic preconditioning increased ECFC adhesion and the release of pro-angiogenic molecules, and protected ECFC from the cytotoxic effects of monosodium urate crystals, histones, and tumor necrosis factor (TNF)α, which induced necrosis, pyroptosis, and apoptosis, respectively. Noncytotoxic concentrations of high glucose, TNFα, or their combination reduced ECFC proliferation, stromal cell-derived factor (SDF)1-driven migration, and tubule formation on a basement membrane matrix, whereas almost no inhibition was observed in preconditioned ECFC. In type 2 diabetic mice, intravenous administration of preconditioned ECFC significantly induced blood flow recovery at the ischemic limb as measured by Doppler, compared with the phosphate-buffered saline (PBS) and nonpreconditioned ECFC groups. Moreover, the histologic analysis of gastrocnemius muscles showed an increased vascular density and reduced signs of inflammation in the animals receiving preconditioned ECFC. Acidic preconditioning improved ECFC survival and angiogenic activity in the presence of proinflammatory and damage signals present in the ischemic milieu, even under high glucose conditions, and increased their therapeutic potential for postischemia tissue regeneration in a murine model of type 2 diabetes. Collectively, our data suggest that acidic preconditioning of ECFC is a simple and inexpensive strategy to improve the effectiveness of cell transplantation in diabetes, where tissue repair is highly compromised.
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Idiopathic acute onset myelopathy in cheetah (Acinonyx jubatus) cubs.
Walzer, Christian; Url, Angelika; Robert, Nadia; Kübber-Heiss, Anna; Nowotny, Norbert; Schmidt, Peter
2003-03-01
Numerous cases of ataxia, hind limb paresis, and paralysis have occurred in cheetah (Acinonyx jubatus) cubs over the past 10 yr within the European Endangered Species Program population, including 12 in mainland Europe, two in the British Isles, one in Namibia, and one in Dubai. The condition is the most important medical factor limiting European cheetah population growth. Eight cubs at the Salzburg Zoo, Austria, were affected. They demonstrated upper motor neuron lesions when alive and bilateral, symmetrical myelin degeneration of the spinal cord on necropsy. Ballooning of myelin sheaths surrounded mostly preserved axons, and no spheroids, characteristic of acute axonal degeneration, were found. Myelin loss markedly exceeded axonal degeneration. The syndrome's etiology is unclear, although viral, bacterial, parasitic, genetic, nutritional-metabolic, toxic, and physical causes have been considered.
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Ultrasound thermography: A new temperature reconstruction model and in vivo results
NASA Astrophysics Data System (ADS)
Bayat, Mahdi; Ballard, John R.; Ebbini, Emad S.
2017-03-01
The recursive echo strain filter (RESF) model is presented as a new echo shift-based ultrasound temperature estimation model. The model is shown to have an infinite impulse response (IIR) filter realization of a differentitor-integrator operator. This model is then used for tracking sub-therapeutic temperature changes due to high intensity focused ultrasound (HIFU) shots in the hind limb of the Copenhagen rats in vivo. In addition to the reconstruction filter, a motion compensation method is presented which takes advantage of the deformation field outside the region of interest to correct the motion errors during temperature tracking. The combination of the RESF model and motion compensation algorithm is shown to greatly enhance the accuracy of the in vivo temperature estimation using ultrasound echo shifts.
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Aspergillus clavatus tremorgenic neurotoxicosis in cattle fed sprouted grains.
McKenzie, R A; Kelly, M A; Shivas, R G; Gibson, J A; Cook, P J; Widderick, K; Guilfoyle, A F
2004-10-01
Beef and dairy cattle from four different herds in southern and central Queensland fed hydroponically-produced sprouted barley or wheat grain heavily infested with Aspergillus clavatus developed posterior ataxia with knuckling of fetlocks, muscular tremors and recumbency, but maintained appetite. A few animals variously had reduced milk production, hyperaesthesia, drooling of saliva, hypermetria of hind limbs or muscle spasms. Degeneration of large neurones was seen in the brain stem and spinal cord grey matter. The syndrome was consistent with A clavatus tremorgenic mycotoxicosis of ruminants. The cases are the earliest known to be associated with this fungus in Australia. They highlight a potential hazard of hydroponic fodder production systems, which appear to favour A clavatus growth on sprouted grain, exacerbated in some cases by equipment malfunctions that increase operating temperatures.
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An unusual archosaurian from the marine Triassic of China
NASA Astrophysics Data System (ADS)
Li, Chun; Wu, Xiao-Chun; Cheng, Yen-Nien; Sato, Tamaki; Wang, Liting
2006-04-01
A new Triassic archosaurian from China shows a number of aquatic specializations, of which the most striking is the extreme lateral compression of the long tail. Others that may also reflect aquatic adaptations include platelike scapula and coracoid, elongate neck with extremely long and slender ribs, and reduction of osteoderms. In contrast, its pelvic girdle and hind limb have no aquatic modifications. Anatomic features, taphonomy, and local geological data suggest that it may have lived in a coastal-island environment. This lifestyle, convergent with some Jurassic marine crocodyliforms that lived at least 40 million years later and the saltwater species of extant Crocodylus, contradicts with the prevailing view that Triassic archosaurians were restricted to nonmarine ecosystems. Its mosaic anatomy represents a previously unknown ecomorph within primitive archosaurians.
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Chern, Jen-Suh; Kao, Chia-Chi; Lai, Po-Lian; Lung, Chi-Wen; Chen, Wen-Jer
2014-01-01
Center of pressure (CoP) progression during level walking in subjects with Adolescents Idiopathic Scoliosis (AIS) was measured. Participants were divided into three groups according to scoliosis severity. CoP progression among groups was compared quantitatively and qualitatively. The results showed that scoliosis severity affects CoP progression significantly in the hind-foot and forefoot areas. This result indicated that spine alignment might affect the control of heel, ankle and toe rockers in the ankle-foot complex. The effects of scoliosis severity is mainly on the CoP of right foot plantar surface, indicating asymmetrical influence of IS on bilateral lower limb coordination during walking. These results might contribute to musculoskeletal complains over the apparatus within trunk-foot in the later lives of this population.
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Shchelkunov, S N; Taranov, O S; Tregubchak, T V; Maksyutov, R A; Silkov, A N; Nesterov, A E; Sennikov, S V
2016-07-01
Wistar rats with collagen-induced arthritis were intramuscularly injected with the recombinant plasmid pcDNA/sTNF-BD encoding the sequence of the TNF-binding protein domain of variola virus CrmB protein (VARV sTNF-BD) or the pcDNA3.1 vector. Quantitative analysis showed that the histopathological changes in the hind-limb joints of rats were most severe in the animals injected with pcDNA3.1 and much less severe in the group of rats injected with pcDNA/sTNF-BD, which indicates that gene therapy of rheumatoid arthritis is promising in the case of local administration of plasmids governing the synthesis of VARV immunomodulatory proteins.
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Glucocorticoid sensitivity, disuse, and the regulation of muscle mass
NASA Technical Reports Server (NTRS)
Almon, R. R.; Dubois, D. C.
1983-01-01
A new noninvasive immobilization procedure to be used on rats has been developed to study immobilization-induced muscle hypersensitivity to normal glucocorticoid concentration, subsequent muscle atrophy, and atrophy recovery. The immobilization procedure involves encasing the hind limb in a light-weight plasticlike cast (10 percent the usual plaster weight), completely resistant to animal gnawing. The effects of right-angle immobilization of the ankle on the slow fiber soleus, and the fast fiber extensor digitorum longus, resemble the effects of weightlessness. The increased concentration of glucocorticoid receptor sites in immobilized and denervated muscle is discussed, along with the chronic loss of muscle mass that occurs in practically all dystrophies. It is concluded that lack of mechanical work in a zero gravity environment is a major cause of glucocorticoid hypersensitivity in the body's musculature.
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2D versus 3D in the kinematic analysis of the horse at the trot.
Miró, F; Santos, R; Garrido-Castro, J L; Galisteo, A M; Medina-Carnicer, R
2009-08-01
The handled trot of three Lusitano Purebred stallions was analyzed by using 2D and 3D kinematical analysis methods. Using the same capture and analysis system, 2D and 3D data of some linear (stride length, maximal height of the hoof trajectories) and angular (angular range of motion, inclination of bone segments) variables were obtained. A paired Student T-test was performed in order to detect statistically significant differences between data resulting from the two methodologies With respect to the angular variables, there were significant differences in scapula inclination, shoulder angle, cannon inclination and protraction-retraction angle in the forelimb variables, but none of them were statistically different in the hind limb. Differences between the two methods were found in most of the linear variables analyzed.
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Signaling in Human and Murine Lymphocytes in Microgravity: Parallels and Contrasts
NASA Technical Reports Server (NTRS)
Neal, Pellis; Alamelu, Sundaresan; Kulkarni, A. D.; Yamauchi, K.
2006-01-01
Immune function in space undergoes dramatic changes, some of which are detrimental to lymphocyte function. These changes may lead to significant immune suppression. Studies with human lymphocytes both in space flight and with ground-based models (NASA in vitro ground-based microgravity analog) indicate that T cell activation is inhibited in microgravity. Other lymphocyte functions, such as locomotion, are also inhibited. There is about an 80 percent homology in the immune response of mice to that of humans. A murine model was investigated because of its ability to parallel some microgravity using hind limb suspension. In in vivo antiorthostatically (AOS)-suspended mice, T cell activation is greatly suppressed, with the majority of activation related cytokines being inhibited. PHA activation in lymphocytes derived from AOS mice (in vivo ground-based microgravity analog) is also suppressed. Calcium ionophore studies in human lymphocytes exposed to modeled microgravity indicate that the calcium pathways are probably unaffected in microgravity. IP3 (inositol triphosphate) receptor expression in both human and mouse lymphocytes cultured in modeled microgravity indicate no suppression of calcium signaling. In the human system, microgravity seems to inhibit signaling cascades either at the level of, or up-stream of, Protein Kinase C (PKC). In particular, a membrane event, such as phospholipase C gamma 1 activity in human lymphocytes is affected, with its direct upstream effector, LAT, being deficiently expressed. In the mouse pathway, LAT is undiminished while another critical intermediate, SLP-76, is diminished significantly. This study identifies critical stages in the human and mouse immune systems and in lymphocytes as a function of microgravity.
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Lower Limb Function in Elderly Korean Adults Is Related to Cognitive Function.
Kim, A-Sol; Ko, Hae-Jin
2018-05-01
Patients with cognitive impairment have decreased lower limb function. Therefore, we aimed to investigate the relationship between lower limb function and cognitive disorders to determine whether lower limb function can be screened to identify cognitive decline. Using Korean National Health Insurance Service-National Sample Cohort database data, we assessed the cognitive and lower limb functioning of 66-year-olds who underwent national health screening between 2010 and 2014. Cognitive function was assessed via a questionnaire. Timed Up-and-Go (TUG) and one-leg-standing (OLS) tests were performed to evaluate lower limb function. Associations between cognitive and lower limb functions were analyzed, and optimal cut-off points for these tests to screen for cognitive decline, were determined. Cognitive function was significantly correlated with TUG interval ( r = 0.414, p < 0.001) and OLS duration ( r = −0.237, p < 0.001). Optimal cut-off points for screening cognitive disorders were >11 s and ≤12 s for TUG interval and OLS duration, respectively. Among 66-year-olds who underwent national health screening, a significant correlation between lower limb and cognitive function was demonstrated. The TUG and OLS tests are useful screening tools for cognitive disorders in elderly patients. A large-scale prospective cohort study should be conducted to investigate the causal relationship between cognitive and lower limb function.
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8. MAIN INLET FROM FILTER GALLERY AND CANAL INTO HINDS ...
8. MAIN INLET FROM FILTER GALLERY AND CANAL INTO HINDS PLANT. VIEW LOOKING DUE WEST OF HINDS COMPLEX IN BACKGROUND OF SAND FILTERS. - Hinds Pump Plant, East of Joshua Tree National Monument, 5 miles north of Route 10, Hayfield, Riverside County, CA
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Hayashi, Hiroyuki; Nakashima, Daiki; Matsuoka, Hiroka; Iwai, Midori; Nakamura, Shugo; Kubo, Ayumi; Tomiyama, Naoki
2017-11-06
Upper-limb function is important in patients with hip fracture so they can perform activities of daily living and participate in leisure activities. Upper-limb function of these patients, however, has not been thoroughly investigated. The aim of this study was to evaluate the upper-limb motor and sensory functions in patients with hip fracture by comparing these functions with those of community-dwelling older adults (control group). We compared the results of motor and sensory function tests of upper-limb function - range of motion, strength, sensibility, finger dexterity, comprehensive hand function - between patients with hip fracture (n= 32) and the control group (n= 32). Patients with hip fracture had significantly reduced grip strength, pinch strength, finger dexterity, and comprehensive hand function compared with the control group. Most upper-limb functions are impaired in the patients with hip fracture. Thus, upper-limb function of patients with hip fracture should be considered during treatment.
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[Range of Hip Joint Motion and Weight of Lower Limb Function under 3D Dynamic Marker].
Xia, Q; Zhang, M; Gao, D; Xia, W T
2017-12-01
To explore the range of reasonable weight coefficient of hip joint in lower limb function. When the hip joints of healthy volunteers under normal conditions or fixed at three different positions including functional, flexed and extension positions, the movements of lower limbs were recorded by LUKOtronic motion capture and analysis system. The degree of lower limb function loss was calculated using Fugl-Meyer lower limb function assessment form when the hip joints were fixed at the aforementioned positions. One-way analysis of variance and Tamhane's T2 method were used to proceed statistics analysis and calculate the range of reasonable weight coefficient of hip joint. There were significant differences between the degree of lower limb function loss when the hip joints fixed at flexed and extension positions and at functional position. While the differences between the degree of lower limb function loss when the hip joints fixed at flexed position and extension position had no statistical significance. In 95% confidence interval, the reasonable weight coefficient of hip joint in lower limb function was between 61.05% and 73.34%. Expect confirming the reasonable weight coefficient, the effects of functional and non-functional positions on the degree of lower limb function loss should also be considered for the assessment of hip joint function loss. Copyright© by the Editorial Department of Journal of Forensic Medicine
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Lagutina, Irina V.; Valentine, Virginia; Picchione, Fabrizio; Harwood, Frank; Valentine, Marcus B.; Villarejo-Balcells, Barbara; Carvajal, Jaime J.; Grosveld, Gerard C.
2015-01-01
Many recurrent chromosome translocations in cancer result in the generation of fusion genes that are directly implicated in the tumorigenic process. Precise modeling of the effects of cancer fusion genes in mice has been inaccurate, as constructs of fusion genes often completely or partially lack the correct regulatory sequences. The reciprocal t(2;13)(q36.1;q14.1) in human alveolar rhabdomyosarcoma (A-RMS) creates a pathognomonic PAX3-FOXO1 fusion gene. In vivo mimicking of this translocation in mice is complicated by the fact that Pax3 and Foxo1 are in opposite orientation on their respective chromosomes, precluding formation of a functional Pax3-Foxo1 fusion via a simple translocation. To circumvent this problem, we irreversibly inverted the orientation of a 4.9 Mb syntenic fragment on chromosome 3, encompassing Foxo1, by using Cre-mediated recombination of two pairs of unrelated oppositely oriented LoxP sites situated at the borders of the syntenic region. We tested if spatial proximity of the Pax3 and Foxo1 loci in myoblasts of mice homozygous for the inversion facilitated Pax3-Foxo1 fusion gene formation upon induction of targeted CRISPR-Cas9 nuclease-induced DNA double strand breaks in Pax3 and Foxo1. Fluorescent in situ hybridization indicated that fore limb myoblasts show a higher frequency of Pax3/Foxo1 co-localization than hind limb myoblasts. Indeed, more fusion genes were generated in fore limb myoblasts via a reciprocal t(1;3), which expressed correctly spliced Pax3-Foxo1 mRNA encoding Pax3-Foxo1 fusion protein. We conclude that locus proximity facilitates chromosome translocation upon induction of DNA double strand breaks. Given that the Pax3-Foxo1 fusion gene will contain all the regulatory sequences necessary for precise regulation of its expression, we propose that CRISPR-Cas9 provides a novel means to faithfully model human diseases caused by chromosome translocation in mice. PMID:25659124
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Role of Growth Hormone, Exercise and Serum Phosphorus in Unloaded Bone of Young Rats
NASA Technical Reports Server (NTRS)
Arnnaud, Sara B.; Harper, J. S.; Gosselink, K. L.; Navidi, M.; Fung, P.; Grindeland, R. E.; Wade, Charles E. (Technical Monitor)
1994-01-01
Growth hormone, known to be stimulated by exercise, is suppressed in rats after space flight and in a ground-based model in which the hind-limbs are unloaded (S). To determine the role of GH in the osteopenia of unloaded bones of S rats, young males were treated with GH combined with insulin-like growth factor-1 (IGF-1), a peptide that mediates the local actions of the hormone. 200 g rats, hypophysectomized (hypox) 17 d earlier, were treated with 1 mg/kg/d GH/IGF-1 (H) or saline (C) in 3 divided daily doses x10 d. Hind-limb bones were unloaded (S), ambulated (A) or exercised (X) by climbing a ladder while carrying a weight. Growth was monitored daily. Tibial growth plate (Tepi) was measured with a micrometer, and femoral (F) area, length, and mineral content (BMC) by DEXA. Parameters of calcium metabolism were measured by autoanalyzer and calciotropic hormones by radioimmunoassay. F bone density, g/square cm, (BMD) or BW were not affected by S in Hypox. However, FBMD was lower in S+H than A+H (p is less than 0.002) and H stimulated whole body growth in S (5.2 g/d) and SX (5.6 g/d) to a lesser extent than in A (6.6 g/d) (p is less than 0.05). Adjusted for BW, Tepi showed the greatest increase in S+H+X (64%), the next highest increase in S+H (50%) and no change in S+X. F area, length and BMC/100 g BW were lower in all H groups than respective C's. By multiple regression analysis, serum phosphorus (Pi) which correlated with Tepi (r = 0.88, p is less than 0.001) and was inversely related to FBMC (r = -0.68, p is less than 0.001) proved to be the most significant determinant of BMC. This illustrates the dependence of osteopenia in S on GH, the maximizing effect of X for epiphyseal growth and the major role of Pi metabolism on BMC in weight bearing bone during growth.
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The efficacy of intracoelomic fospropofol in red-eared sliders (Trachemys scripta elegans).
Schroeder, Carrie A; Johnson, Rebecca A
2013-12-01
Intravenous anesthetic delivery in reptiles can be challenging. Current injectable techniques have varied induction/recovery times and anesthetic quality. This study hypothesized that intracoelomic administration of a new anesthetic, fospropofol, in turtles would result in dose-dependent anesthesia and respiratory depression. A two-part prospective trial using adult red-eared slider turtles (Trachemys scripta elegans) weighing 764 +/- 17 g was conducted to determine an effective anesthetic dose and to evaluate the anesthetic quality, duration, and respiratory effects of an efficacious dose. In part 1, six turtles were randomly administered 25-mg/ kg (low-dose [LD]) and 50-mg/kg (high-dose [HD]) fospropofol in a crossover design. Respiratory rate, immobility, and muscle relaxation scores were evaluated for 180 min. In part 2, eight turtles were administered HD fospropofol. Immobility and muscle relaxation (front and hind limb) scores and time to endotracheal intubation/extubation were evaluated until scores returned to baseline. In part 1, the LD group had significantly lower immobility and muscle relaxation scores versus the HD group over time (both P < 0.05); scores were significantly elevated from baseline for 20-120 min and 15-180 min, respectively (all P < 0.05). Although not significantly different between groups (P > 0.05), respiratory rate was significantly decreased from baseline from 10 to 120 min (all P < 0.05). In part 2, HD fospropofol decreased respiratory rate from 21.5 +/- 2.9 breaths/min to 0.1 +/- 0.1 breaths/min, similar to the results in part 1. Maximal reductions in mobility and front and hind limb motor tone occurred at 39.0 +/- 4.1, 30.8 +/- 3.6, and 24.0 +/- 3.6 min, respectively. Intubation in 7/8 turtles occurred at 45.7 +/- 5.4 min and extubation at 147.0 +/- 23.2 min. However, 2/8 turtles showed prolonged anesthetic effects, requiring resuscitative efforts for recovery. Due to the unpredictable quality and duration of anesthesia with intracoelomic fospropofol, it should be used with caution for general anesthesia in red-eared sliders at the doses and administration route investigated.
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THE EFFICACY OF INTRACOELOMIC FOSPROPOFOL IN RED-EARED SLIDERS (TRACHEMYS SCRIPTA)
Schroeder, Carrie A.; Johnson, Rebecca A.
2015-01-01
Intravenous anesthetic delivery in reptiles can be challenging; current injectable techniques have varied induction/recovery times and anesthetic quality. This study hypothesized that intracoelomic administration of a new anesthetic, fospropofol, in turtles would result in dose-dependent anesthesia and respiratory depression. A two-part prospective trial using adult red-eared slider turtles (Trachemys scripta) weighing 764±17 g was conducted to 1) determine an effective anesthetic dose, and 2) evaluate the anesthetic quality, duration and respiratory effects of an efficacious dose. In Part 1, six turtles were randomly administered 25 mg kg−1 (low dose: LD) and 50 mg kg−1 (high dose: HD) fospropofol in a cross-over design. Respiratory rate, immobility and muscle relaxation scores were evaluated for 180 minutes. In Part 2, eight turtles were administered HD fospropofol. Immobility and muscle relaxation (front and hind limb) scores, and time to endotracheal intubation/extubation were evaluated until scores returned to baseline. In Part 1, the LD group had significantly lower immobility and muscle relaxation scores versus the HD group over time (both P<0.05); scores were significantly elevated from baseline for 20–120 minutes and 15–180 minutes, respectively (all P<0.05). Although not significantly different between groups (P>0.05), respiratory rate was significantly decreased from baseline from 10–120 minutes (all P<0.05). In Part 2, HD fospropofol decreased respiratory rate from 21.5±2.9 breaths min−1 to 0.1±0.1 breaths min−1, similar to the results in Part 1. Maximal reductions in immobility, front and hind limb motor tone occurred at 39.0±4.1, 30.8±3.6, and 24.0±3.6 minutes, respectively. Intubation in 7/8 turtles occurred at 45.7±5.4 min and extubation at 147.0±23.2 min. However, 2/8 turtles showed prolonged anesthetic effects, requiring resuscitative efforts for recovery. Due to the unpredictable quality and duration of anesthesia with intracoelomic fospropofol, it should be used with caution for general anesthesia in red-eared sliders at the doses and administration route investigated. PMID:24450053
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Ledford, Kelly J; Murphy, Nikki; Zeigler, Frank; Bartel, Ronnda L; Tubo, Ross
2015-03-13
Bone marrow derived cellular therapies are an emerging approach to promoting therapeutic angiogenesis in ischemic cardiovascular disease. However, the percentage of regenerative cells in bone marrow mononuclear cells (BMMNCs) is small, and large amounts of BMMNCs are required. Ixmyelocel-T, an expanded autologous multicellular therapy, is manufactured from a small sample of bone marrow aspirate. Ixmyelocel-T contains expanded populations of mesenchymal stromal cells (MSCs) and M2-like macrophages, as well as many of the CD45+ cells found in the bone marrow. It is hypothesized that this expanded multi-cellular therapy would induce angiogenesis and endothelial repair. A rat model of hind limb ischemia was used to determine the effects of ixmyelocel-T on blood flow recovery. To further determine the effects on endothelial cells, ixmyelocel-T was co-cultured with human umbilical vein endothelial cells (HUVEC) in non-contacting Transwell® inserts. Co-culture of HUVECs with ixmyelocel-T resulted secretion of a variety of pro-angiogenic factors. HUVECs stimulated by ixmyelocel-T exhibited enhanced migration, proliferation, and branch formation. Ixmyelocel-T co-culture also resulted in increased endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production. In tumor necrosis factor alpha (TNFα)-stimulated HUVECs, ixmyelocel-T co-culture decreased apoptosis and reactive oxygen species generation, increased super oxide dismutase activity, and decreased nuclear factor kappa B (NFκB) activation. Treatment with ixmyelocel-T in a rat model of hind limb ischemia resulted in significantly increased blood flow perfusion and capillary density, gene expression and plasma levels of the anti-inflammatory cytokine interleukin (IL)-10, plasma nitrates, plasma platelet-derived growth factor (PDGF)-BB, vascular endothelial growth factor (VEGF) expression, and significantly decreased plasma thiobarbituric acid reactive substances (TBARS). This work demonstrates that ixmyelocel-T interacts with endothelial cells in a paracrine manner, resulting in angiogenesis and endothelial protection. This data suggests that ixmyelocel-T could be useful for promoting of angiogenesis and tissue repair in ischemic cardiovascular diseases. In conclusion, ixmyelocel-T therapy may provide a new aspect of therapeutic angiogenesis in this patient population where expanded populations of regenerative cells might be required.
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Further characterisation of a rat model of varicella zoster virus (VZV)-associated pain
Hasnie, F. S.; Breuer, J.; Parker, S.; Wallace, V.; Blackbeard, J.; Lever, I.; Kinchington, P.R.; Dickenson, A. H.; Pheby, T.; Rice, A. S. C.
2007-01-01
Persistent herpes zoster-associated pain is a significant clinical problem and an area of largely unmet therapeutic need. Progress in elucidating the underlying pathophysiology of zoster-associated pain and related co-morbidity behaviour, in addition to appropriately targeted drug development has been hindered by the lack of an appropriate animal model. This study further characterises a recently developed rat model of zoster-associated hypersensitivity and investigates (a) response to different viral strains; (b) relationship between viral inoculum concentration (‘dose’) and mechanical hypersensitivity (‘response’); (c) attenuation of virus-associated mechanical hypersensitivity by clinically useful analgesic drugs; and (d) measurement of pain co-morbidity (anxiety-like behaviour) and pharmacological intervention in the open field paradigm (in parallel with models of traumatic peripheral nerve injury). VZV was propagated on fibroblast cells before subcutaneous injection into the glabrous footpad of the left hind limb of adult male Wistar rats. Control animals received injection of uninfected fibroblast cells. Hind-limb reflex withdrawal thresholds to mechanical, noxious thermal and cooling stimuli were recorded at specified intervals post-infection. Infection with all viral strains was associated with a dose-dependent mechanical hypersensitivity but not a thermal or cool hypersensitivity. Systemic treatment with intraperitoneal (i.p.) morphine (2.5mg/kg), amitriptyline (10mg/kg), gabapentin (30mg/kg), (S)-(+)-ibuprofen (20mg/kg) and the cannnabinoid WIN55,212-2 (2mg/kg) but not the antiviral, acyclovir (50mg/kg), was associated with a reversal of mechanical paw withdrawal thresholds. In the open field paradigm, virus-infected and nerve-injured animals demonstrated an anxiety-like pattern of ambulation (reduced entry into the central area of the open arena) which was positively correlated with mechanical hypersensitivity. This may reflect pain-related comorbidity. Further, anxiety-like behaviour was attenuated by acute i.p. administration of gabapentin (30mg/kg) in nerve-injured, but not virus-infected animals. This model will prove useful in elucidating the pathophysiology of zoster-associated pain and provide a tool for pre-clinical screening of analgesic drugs. PMID:17197105
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O’Mahoney, Thomas G.; Kitchener, Andrew C.; Manning, Phillip L.; Sellers, William I.
2016-01-01
The external appearance of the dodo (Raphus cucullatus, Linnaeus, 1758) has been a source of considerable intrigue, as contemporaneous accounts or depictions are rare. The body mass of the dodo has been particularly contentious, with the flightless pigeon alternatively reconstructed as slim or fat depending upon the skeletal metric used as the basis for mass prediction. Resolving this dichotomy and obtaining a reliable estimate for mass is essential before future analyses regarding dodo life history, physiology or biomechanics can be conducted. Previous mass estimates of the dodo have relied upon predictive equations based upon hind limb dimensions of extant pigeons. Yet the hind limb proportions of dodo have been found to differ considerably from those of their modern relatives, particularly with regards to midshaft diameter. Therefore, application of predictive equations to unusually robust fossil skeletal elements may bias mass estimates. We present a whole-body computed tomography (CT) -based mass estimation technique for application to the dodo. We generate 3D volumetric renders of the articulated skeletons of 20 species of extant pigeons, and wrap minimum-fit ‘convex hulls’ around their bony extremities. Convex hull volume is subsequently regressed against mass to generate predictive models based upon whole skeletons. Our best-performing predictive model is characterized by high correlation coefficients and low mean squared error (a = − 2.31, b = 0.90, r2 = 0.97, MSE = 0.0046). When applied to articulated composite skeletons of the dodo (National Museums Scotland, NMS.Z.1993.13; Natural History Museum, NHMUK A.9040 and S/1988.50.1), we estimate eviscerated body masses of 8–10.8 kg. When accounting for missing soft tissues, this may equate to live masses of 10.6–14.3 kg. Mass predictions presented here overlap at the lower end of those previously published, and support recent suggestions of a relatively slim dodo. CT-based reconstructions provide a means of objectively estimating mass and body segment properties of extinct species using whole articulated skeletons. PMID:26788418
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Terrestrial Microgravity Model and Threshold Gravity Simulation using Magnetic Levitation
NASA Technical Reports Server (NTRS)
Ramachandran, N.
2005-01-01
What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for such a gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successfully simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars. The paper will discuss experiments md modeling work to date in support of this project.
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Threshold Gravity Determination and Artificial Gravity Studies Using Magnetic Levitation
NASA Technical Reports Server (NTRS)
Ramachandran, N.; Leslie, F.
2005-01-01
What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required (magnitude and duration)? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for a variable gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successfully simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars.
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Stuart, Bryan L; Phimmachak, Somphouthone; Seateun, Sengvilay; Sheridan, Jennifer A
2013-12-03
The small rhacophorid frog Philautus abditus is geographically restricted to central Vietnam and adjacent Cambodia. Our fieldwork in northern Laos resulted in the discovery of a Philautus species that very closely resembles P. abditus, but is at least 330 km from the nearest known locality of that species. The Laos population differs from P. abditus in mitochondrial DNA and coloration, and is described here as a new species. Philautus nianeae sp. nov. is distinguished from its congeners by having the combination of a hidden tympanum; no nuptial pads; smooth skin; large black spots on the hidden surfaces of the hind limbs; light venter with dark spotting; and a bronze iris. A second species of Philautus from northern Laos, P. petilus, is transferred on the basis of morphology to the genus Theloderma.
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Myasthenia gravis in a polar bear (Ursus maritimus).
Kenny, David E; Baier, Jeffery; Knightly, Felicia; Steinheimer, Daniel; Getzy, David M; Shelton, G Diane
2004-09-01
A 14.6-yr-old, female, multiparous polar bear (Ursus maritimus) acutely developed an apparent hind limb weakness. Physical examination and diagnostic tests including a hemogram, serum biochemistry, electrolytes, radiographs, and myelogram did not provide a definitive diagnosis. No improvement in condition was noted during 4 days of supportive care, and the bear was euthanized. An ovoid mass was present in the anterior mediastinum, and a thymoma was confirmed histologically. Compared with control polar bears, elevated serum acetylcholine receptor (AChR) antibodies (0.13 +/- 0.06 nmol/L vs. 0.86 nmol/L) were detected by immunoprecipitation radioimmunoassay, which is consistent with myasthenia gravis (MG) in other species. Although the AChR antibody test has not been validated in the polar bear, we are confident in the postmortem diagnosis of MG, which is commonly associated with thymoma in other species.
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Iwalewa, E O; Iwalewa, O J; Adeboye, J O
2003-06-01
The chloroform, methanolic and ether extracts of Vernonia cinerea (Asteraceae; Less) leaf (100, 200 and 400mg/kg intraperitoneally) were tested in: acetic acid-induced writhing in mice, carrageenin-induced oedema and brewer's yeast-induced pyrexia in rats to assess their analgesic, anti-inflammatory, antipyretic and behavioral activities, respectively. The changes in writhings and behavioural activities in mice, the pyrexia and paw volumes in rats were reduced significantly (P<0.05) compared to the control. There was an increase in pain threshold on the oedematous right hind limb paw of the rats. These results indicate that the extracts could possess analgesic, antipyretic and anti-inflammatory properties. All these effects and the changes in the behavioural activities could be suggested as contributory effects to the use of V. cinerea leaf in the treatment of malaria.
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Mechanisms and Treatments of Heterotopic Ossification Following Spinal Cord Injuries
2016-10-01
tissues from the completed etanercept and GW2580 experiments are being processed for immunohistology to stain for markers of M1 and M2...a defined area of the muscle. We observed that HO developed only if the mechanical damage was combined with injection of Gram ‐negative bacterial... staining on archival sections of mouse hind limb muscles generated prior to this award. As illustrated in Figure 4, we are able to successfully stain
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EMBRYOLOGY OF THE LITTLE AND BAGG X-RAYED MOUSE STOCK
DOE Office of Scientific and Technical Information (OSTI.GOV)
Carter, T.C.
1959-12-01
The morphology and development of the many defects in mice of the Little and Bagg x-rayed stock have been reinvestigated in an attempt to resolve the conflicts in the findings of earlier investigators. The observation that blebs occur on pseudencephalic embryos is incompatible with Bonnevie's hypothesis that they originate as cerebrospinal fluid in the myelencephalon; other observations support Plagens' hypothesis that the blebs originate as mesenchymal intercellular fluid. No unitary gene action was found. Four pedigrees of causes were constructed covering, respectively, defects of the central nervous system, bleb- induced lesions and defects of the body wall, morphological defects ofmore » the hind limbs, and defects of the urogenital system; there were cross-correlations between defects in the first three pedigrees, but the underlying mechanisms were not identified. (auth)« less
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Chordoma of the thoracic vertebrae in a Bengal tiger (Panthera tigris tigris)
KURAMOCHI, Mizuki; IZAWA, Takeshi; HORI, Mayuka; KUSUDA, Kayo; SHIMIZU, Junichiro; ISERI, Toshie; AKIYOSHI, Hideo; OHASHI, Fumihito; KUWAMURA, Mitsuru; YAMATE, Jyoji
2015-01-01
A 19-year-old female Bengal tiger (Panthera tigris tigris) was presented with hind limb weakness, ataxia and respiratory distress. Computed tomography revealed a mass between the left side of the T7 vertebra and the base of the left 7th rib. The tiger then died, and necropsy was performed. Grossly, the vertebral mass was 6 × 5.7 × 3 cm, and invaded the adjacent vertebral bone and compressed the T7 spinal cord. Histologically, the mass was composed of large, clear, vacuolated and polygonal cells with osteochondral matrix. Cellular and nuclear atypia were moderate. The vacuolated cells stained positively for cytokeratin and vimentin and negatively for S-100. Based on these findings, the present case was diagnosed as a vertebral chordoma; the first report in a tiger. PMID:25766770
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Sarcoptic mange in raccoons in Michigan.
Fitzgerald, Scott D; Cooley, Thomas M; Murphy, Alice; Cosgrove, Melinda K; King, Betty A
2004-04-01
Sarcoptic mange is a cause of pruritic skin disease in domestic dogs and a wide range of wildlife species. We describe sarcoptic mange in free-ranging raccoons (Procyon lotor). Three adult raccoons from upper Wayne County, Michigan (USA), were captured, killed, and submitted for diagnostic evaluation. The animals were intensely pruritic, and two had advanced alopecic and crusting lesions over their dorsum and hind limbs. Skin scrapings and skin biopsies revealed crusting and hyperkeratotic dermatitis with high numbers of Sarcoptes scabiei adults, larvae, nymphs, and eggs. These raccoons were not otherwise debilitated, with minimal internal parasites, good body condition, and no evidence of infectious bacterial or viral diseases. Because sarcoptic mange is highly contagious and affects many species, including humans, transiently, it is important that wildlife biologists and rehabilitators include sarcoptic mange in their differential list for raccoons exhibiting pruritus and alopecia.
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Adaptation of bone and tendon to prolonged hindlimb suspension in rats
NASA Technical Reports Server (NTRS)
Vailas, Arthur C.; Deluna, Diane M.; Lewis, Lisa L.; Curwin, Sandra L.; Roy, Roland R.
1988-01-01
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.
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Case series analysis of hindfoot injuries sustained by drivers in frontal motor vehicle crashes.
Ye, Xin; Funk, James; Forbes, Aaron; Hurwitz, Shepard; Shaw, Greg; Crandall, Jeff; Freeth, Rob; Michetti, Chris; Rudd, Rodney; Scarboro, Mark
2015-09-01
Improvements to vehicle frontal crashworthiness have led to reductions in toe pan and instrument panel intrusions as well as leg, foot, and ankle loadings in standardized crash tests. Current field data, however, suggests the proportion of foot and ankle injuries sustained by drivers in frontal crashes has not decreased over the past two decades. To explain the inconsistency between crash tests results and real world lower limb injury prevalence, this study investigated the injury causation scenario for the specific hind-foot injury patterns observed in frontal vehicle crashes. Thirty-four cases with leg, foot, and ankle injuries were selected from the Crash Injury Research and Engineering Network (CIREN) database. Talus fractures were present in 20 cases, representing the most frequent hind-foot skeletal injuries observed among the reviewed cases. While axial compression was the predominant loading mechanism causing 18 injuries, 11 injured ankles involved inversion or eversion motion, and 5 involved dorsiflexion as the injury mechanism. Injured ankles of drivers were more biased towards the right aspect with foot pedals contributing to injuries in 13 of the 34 cases. Combined, the results suggest that despite recent advancement of vehicle performance in crash tests, efforts to reduce axial forces sustained in lower extremity should be prioritized. The analysis of injury mechanisms in this study could aid in crash reconstructions and the development of safety systems for vehicles. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Ouweltjes, W; Gussekloo, S W S; Spoor, C W; van Leeuwen, J L
2016-02-01
Claw and locomotion problems are widespread in ungulates. Although it is presumed that mechanical overload is an important contributor to claw tissue damage and impaired locomotion, deformation and claw injury as a result of mechanical loading has been poorly quantified and, as a result, practical solutions to reduce such lesions have been established mostly through trial and error. In this study, an experimental technique was developed that allowed the measurement under controlled loading regimes of minute deformations in the lower limbs of dissected specimens from large ungulates. Roentgen stereophotogrammetric analysis (RSA) was applied to obtain 3D marker coordinates with an accuracy of up to 0.1 mm with optimal contrast and to determine changes in the spatial conformation. A force plate was used to record the applied forces in three dimensions. The results obtained for a test sample (cattle hind leg) under three loading conditions showed that small load-induced deformations and translations as well as small changes in centres of force application could be measured. Accuracy of the order of 0.2-0.3 mm was feasible under practical circumstances with suboptimal contrast. These quantifications of claw deformation during loading improve understanding of the spatial strain distribution as a result of external loading and the risks of tissue overload. The method promises to be useful in determining load-deformation relationships for a wide variety of specimens and circumstances. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Acute limb heating improves macro- and microvascular dilator function in the leg of aged humans.
Romero, Steven A; Gagnon, Daniel; Adams, Amy N; Cramer, Matthew N; Kouda, Ken; Crandall, Craig G
2017-01-01
Local heating of an extremity increases blood flow and vascular shear stress throughout the arterial tree. Local heating acutely improves macrovascular dilator function in the upper limbs of young healthy adults through a shear stress-dependent mechanism but has no such effect in the lower limbs of this age group. The effect of acute limb heating on dilator function within the atherosclerotic prone vasculature of the lower limbs of aged adults is unknown. Therefore, the purpose of this study was to test the hypothesis that acute lower limb heating improves macro- and microvascular dilator function within the leg vasculature of aged adults. Nine young and nine aged adults immersed their lower limbs at a depth of ~33 cm into a heated (~42°C) circulated water bath for 45 min. Before and 30 min after heating, macro (flow-mediated dilation)- and microvascular (reactive hyperemia) dilator functions were assessed in the lower limb, following 5 min of arterial occlusion, via Doppler ultrasound. Compared with preheat, macrovascular dilator function was unchanged following heating in young adults (P = 0.6) but was improved in aged adults (P = 0.04). Similarly, microvascular dilator function, as assessed by peak reactive hyperemia, was unchanged following heating in young adults (P = 0.1) but was improved in aged adults (P < 0.01). Taken together, these data suggest that acute lower limb heating improves both macro- and microvascular dilator function in an age dependent manner. We demonstrate that lower limb heating acutely improves macro- and microvascular dilator function within the atherosclerotic prone vasculature of the leg in aged adults. These findings provide evidence for a potential therapeutic use of chronic lower limb heating to improve vascular health in primary aging and various disease conditions. Copyright © 2017 the American Physiological Society.
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NASA Astrophysics Data System (ADS)
Oh, Seungyoung; Oh, Sehyeong; Choi, Haecheon; Lee, Boogeon; Park, Hyungmin; Kim, Sun-Tae
2015-11-01
The elytra are a pair of hardened wings that cover the abdomen of a beetle to protect beetle's hind wings. During the take-off, these elytra open and flap in phase with the hind wings. We investigate the effect of the elytra flapping on beetle's aerodynamic performance. Numerical simulations are performed at Re=10,000 (based on the wingtip mean velocity and mean chord length of the hind wing) using an immersed boundary method. The simulations are focused on a take-off, and the wing kinematics used is directly obtained from the experimental observations using high speed cameras. The simulation result shows three-dimensional vortical structures generated by the hind wing of the beetle and their interaction with the elytra. The presence of elytra has a negative effect on the lift generation by the hind wings, but the lift force on the elytra themselves is negligible. Further discussions on the elytra - hind wing interaction will be provided during the presentation. Supported by UD130070ID.
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Oh, Se-Il; Kim, Jin-Kyung; Park, So-Yeon
2015-12-01
[Purpose] This study aimed to examine the effects of visual field with prism glasses, and intensive upper limb functional training on reduction of hemineglect and improvement in upper limb function and activities of daily living in three stroke patients with hemineglect. [Subjects] This study included three stroke patients hospitalized in a sanatorium. [Methods] Intervention treatment involving prism glass use for 12 hours and 30 minutes and paretic side upper limb training was conducted 5 days a week for 15 weeks. Three upper limb training tasks (hitting a balloon, passing through a ring, and reading a newspaper) were performed for 10 minutes each session, for a total of 30 minutes. Line by Section, Motor-Free Visual Perception Test-3 (MVPT-3), Manual Function Test (MFT), Box & Block Test (BBT), and Assessment of Motor and Process Skills (AMPS) were conducted before and after intervention. [Results] Subjects' hemineglect decreased and upper limb function on the paretic side improved after intervention, which enhanced activities of daily living. [Conclusion] Prism glass use and paretic upper limb functional training effectively ameliorated stroke patients' hemineglect and improved upper limb function. Future research should focus on prism glasses that provide a wide visual field for use in patients with different conditions.
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Katayama, Masaaki
2016-11-01
To report appositional augmentation of Achilles tendon rupture in a toy breed dog with an intact flexor digitorum lateralis (FDL) muscle tendon. Clinical case report. Two-year-old spayed female Toy Poodle with Achilles tendon rupture. The Achilles tendon was accidentally ruptured by hair clippers during grooming. The dog demonstrated a plantigrade stance without digital flexion of the right hind limb. The ruptured gastrocnemius and superficial digital flexor tendons were sutured to their respective cut ends using a simple locking loop pattern under a surgical microscope. The repair site was appositionally augmented by the caudally retracted intact FDL. An aluminum splint was applied on the plantar aspect to immobilize the tarsal joint for the first 2 weeks, after which a soft bandage was applied for another 2 weeks. At the 7 month follow-up no lameness was detected during walking and no complications associated with decreased FDL function such as digital contracture were observed. The range of motion of the tarsal joint had improved and could be flexed to ∼60° and extended fully. Use of the FDL is feasible for augmenting Achilles tendon repair in toy breed dogs. © Copyright 2016 by The American College of Veterinary Surgeons.
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Díaz-Berenguer, Ester; Badiola, Ainara; Moreno-Azanza, Miguel; Canudo, José Ignacio
2018-03-23
Sirenians are the only extant herbivorous mammals fully adapted to an aquatic lifestyle. They originated in Africa during the Paleocene from an undetermined clade of afrotherian mammals, and by the end of the Eocene they were widely distributed across the tropical latitudes. Here we introduce Sobrarbesiren cardieli gen. et sp. nov. It is the first adequately-known quadrupedal sirenian from Eurasia and the oldest record of this clade from western Europe. Fossils have been recovered from the middle Lutetian (SBZ15) site of Castejón de Sobrarbe-41 (Huesca, Spain), and comprise many cranial and postcranial remains, including pelvic girdle and hind limb bones, from at least six sirenian individuals of different ontogenetic stages. Sobrarbesiren shows a suite of characters previously considered synapomorphies of different clades of derived sirenians, such as the presence of the processus retroversus of the squamosal and the pterygoid fossa, combined with ancestral characters such as the presence of an alisphenoid canal, a permanent P5, at least two sacral vertebrae, a primitive pelvis and functional femora and fibulae. Sobrarbesiren is recovered as the sister taxon of Dugongidae and represents a transitional stage of adaptation to aquatic life between the amphibious quadrupedal prorastomids and the aquatic quadrupedal protosirenids.
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Bartley, Jenna M; Pan, Sarah J; Keilich, Spencer R; Hopkins, Jacob W; Al-Naggar, Iman M; Kuchel, George A; Haynes, Laura
2016-04-01
Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized that upon challenge with influenza, aging would be associated with functional impairments, as well as upregulation of skeletal muscle inflammatory and atrophy genes. Infected young and aged mice demonstrated decreased mobility and altered gait kinetics. These declines were more prominent in hind limbs and in aged mice. Skeletal muscle expression of genes involved in inflammation, as well as muscle atrophy and proteolysis, increased during influenza infection with an elevated and prolonged peak in aged mice. Infection also decreased expression of positive regulators of muscle mass and myogenesis components to a greater degree in aged mice. Gene expression correlated to influenza-induced body mass loss, although evidence did not support direct muscle infection. Overall, influenza leads to mobility impairments with induction of inflammatory and muscle degradation genes and downregulation of positive regulators of muscle. These effects are augmented and prolonged with aging, providing a molecular link between influenza infection, decreased resilience and increased risk of disability in the elderly.
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Lee, Jun Hee; Yoon, Yeo Min; Lee, Sang Hun
2017-06-21
Mesenchymal stem cells (MSC) are ideal materials for stem cell-based therapy. As MSCs reside in hypoxic microenvironments (low oxygen tension of 1% to 7%), several studies have focused on the beneficial effects of hypoxic preconditioning on MSC survival; however, the mechanisms underlying such effects remain unclear. This study aimed to uncover the potential mechanism involving 78-kDa glucose-regulated protein (GRP78) to explain the enhanced MSC bioactivity and survival in hindlimb ischemia. Under hypoxia (2% O₂), the expression of GRP78 was significantly increased via hypoxia-inducible factor (HIF)-1α. Hypoxia-induced GRP78 promoted the proliferation and migration potential of MSCs through the HIF-1α-GRP78-Akt signal axis. In a murine hind-limb ischemia model, hypoxic preconditioning enhanced the survival and proliferation of transplanted MSCs through suppression of the cell death signal pathway and augmentation of angiogenic cytokine secretion. These effects were regulated by GRP78. Our findings indicate that hypoxic preconditioning promotes survival, proliferation, and angiogenic cytokine secretion of MSCs via the HIF-1α-GRP78-Akt signal pathway, suggesting that hypoxia-preconditioned MSCs might provide a therapeutic strategy for MSC-based therapies and that GRP78 represents a potential target for the development of functional MSCs.
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Blocki, Anna; Wang, Yingting; Koch, Maria; Goralczyk, Anna; Beyer, Sebastian; Agarwal, Nikita; Lee, Michelle; Moonshi, Shehzahdi; Dewavrin, Jean-Yves; Peh, Priscilla; Schwarz, Herbert; Bhakoo, Kishore; Raghunath, Michael
2015-03-01
Autologous cells hold great potential for personalized cell therapy, reducing immunological and risk of infections. However, low cell counts at harvest with subsequently long expansion times with associated cell function loss currently impede the advancement of autologous cell therapy approaches. Here, we aimed to source clinically relevant numbers of proangiogenic cells from an easy accessible cell source, namely peripheral blood. Using macromolecular crowding (MMC) as a biotechnological platform, we derived a novel cell type from peripheral blood that is generated within 5 days in large numbers (10-40 million cells per 100 ml of blood). This blood-derived angiogenic cell (BDAC) type is of monocytic origin, but exhibits pericyte markers PDGFR-β and NG2 and demonstrates strong angiogenic activity, hitherto ascribed only to MSC-like pericytes. Our findings suggest that BDACs represent an alternative pericyte-like cell population of hematopoietic origin that is involved in promoting early stages of microvasculature formation. As a proof of principle of BDAC efficacy in an ischemic disease model, BDAC injection rescued affected tissues in a murine hind limb ischemia model by accelerating and enhancing revascularization. Derived from a renewable tissue that is easy to collect, BDACs overcome current short-comings of autologous cell therapy, in particular for tissue repair strategies.
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Blocki, Anna; Wang, Yingting; Koch, Maria; Goralczyk, Anna; Beyer, Sebastian; Agarwal, Nikita; Lee, Michelle; Moonshi, Shehzahdi; Dewavrin, Jean-Yves; Peh, Priscilla; Schwarz, Herbert; Bhakoo, Kishore; Raghunath, Michael
2015-01-01
Autologous cells hold great potential for personalized cell therapy, reducing immunological and risk of infections. However, low cell counts at harvest with subsequently long expansion times with associated cell function loss currently impede the advancement of autologous cell therapy approaches. Here, we aimed to source clinically relevant numbers of proangiogenic cells from an easy accessible cell source, namely peripheral blood. Using macromolecular crowding (MMC) as a biotechnological platform, we derived a novel cell type from peripheral blood that is generated within 5 days in large numbers (10–40 million cells per 100 ml of blood). This blood-derived angiogenic cell (BDAC) type is of monocytic origin, but exhibits pericyte markers PDGFR-β and NG2 and demonstrates strong angiogenic activity, hitherto ascribed only to MSC-like pericytes. Our findings suggest that BDACs represent an alternative pericyte-like cell population of hematopoietic origin that is involved in promoting early stages of microvasculature formation. As a proof of principle of BDAC efficacy in an ischemic disease model, BDAC injection rescued affected tissues in a murine hind limb ischemia model by accelerating and enhancing revascularization. Derived from a renewable tissue that is easy to collect, BDACs overcome current short-comings of autologous cell therapy, in particular for tissue repair strategies. PMID:25582709
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Bartley, Jenna M.; Pan, Sarah J.; Keilich, Spencer R.; Hopkins, Jacob W.; Al-Naggar, Iman M.; Kuchel, George A.; Haynes, Laura
2016-01-01
Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized that upon challenge with influenza, aging would be associated with functional impairments, as well as upregulation of skeletal muscle inflammatory and atrophy genes. Infected young and aged mice demonstrated decreased mobility and altered gait kinetics. These declines were more prominent in hind limbs and in aged mice. Skeletal muscle expression of genes involved in inflammation, as well as muscle atrophy and proteolysis, increased during influenza infection with an elevated and prolonged peak in aged mice. Infection also decreased expression of positive regulators of muscle mass and myogenesis components to a greater degree in aged mice. Gene expression correlated to influenza-induced body mass loss, although evidence did not support direct muscle infection. Overall, influenza leads to mobility impairments with induction of inflammatory and muscle degradation genes and downregulation of positive regulators of muscle. These effects are augmented and prolonged with aging, providing a molecular link between influenza infection, decreased resilience and increased risk of disability in the elderly. PMID:26856410
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Histone Deacetylase 3 Is Necessary for Proper Brain Development*
Norwood, Jordan; Franklin, Jade M.; Sharma, Dharmendra; D'Mello, Santosh R.
2014-01-01
The functional role of histone deacetylase 3 (HDAC3) in the developing brain has yet to be elucidated. We show that mice lacking HDAC3 in neurons and glia of the central nervous system, Nes-Cre/HDAC3 conditional KO mice, show major abnormalities in the cytoarchitecture of the neocortex and cerebellum and die within 24 h of birth. Later-born neurons do not localize properly in the cortex. A similar mislocalization is observed with cerebellar Purkinje neurons. Although the proportion of astrocytes is higher than normal, the numbers of oligodendrocytes are reduced. In contrast, conditional knockout of HDAC3 in neurons of the forebrain and certain other brain regions, using Thy1-Cre and calcium/calmodulin dependent protein kinase II α-Cre for ablation, produces no overt abnormalities in the organization of cells within the cortex or of cerebellar Purkinje neurons at birth. However, both lines of conditional knockout mice suffer from progressive hind limb paralysis and ataxia and die around 6 weeks after birth. The mice display an increase in overall numbers of cells, higher numbers of astrocytes, and Purkinje neuron degeneration. Taken together, our results demonstrate that HDAC3 plays an essential role in regulating brain development, with effects on both neurons and glia in different brain regions. PMID:25339172
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Komatsu, Toshiaki; Takenami, Tamie; Nara, Yoshihiro; Yagishita, Saburo; Kurashige, Chie; Okamoto, Hirotsugu; Yago, Kazuo
2013-01-01
Epinephrine can potentially worsen the neurotoxic effects of local anesthetics when used for spinal or epidural anesthesia. The vasoconstrictive property of epinephrine reduces dural blood flow, which in turn reduces the clearance of local anesthetics from the subarachnoid space. This study examined the histological and neurofunctional effects of intrathecally administered lidocaine combined with epinephrine in rats. Sixty-two rats were divided into 9 treatment groups: 5% or 7.5% lidocaine in 10% glucose solution with or without 0.1 or 0.5 mg/mL epinephrine, or epinephrine alone at 0.1 or 0.5 mg/mL in 10% glucose, or 10% glucose alone. Hind-limb motor function was evaluated immediately after drug injection by walking behavior. Sensory function was assessed by the response to radiant heat stimulation at just before and 1 week after the injection. Seven days after the injection, L3 spinal cord with anterior and posterior roots, the dorsal ganglion, and cauda equina were harvested and examined histologically. Histological lesions were limited to the posterior root just at entry into the spinal cord in rats injected with 7.5% lidocaine, with and without epinephrine. No histological abnormalities were noted in other areas or other groups. There was no significant change in sensory threshold in all groups. Significantly, prolongation of gait recovery time was noted in 5% and 7.5% lidocaine with epinephrine groups compared with 5% or 7.5% lidocaine alone. Intrathecal epinephrine prolonged the action of intrathecal lidocaine but did not worsen lidocaine-induced histological damage and functional impairment.
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Extracorporeal shock wave therapy does not improve hypertensive nephropathy.
Caron, Jonathan; Michel, Pierre-Antoine; Dussaule, Jean-Claude; Chatziantoniou, Christos; Ronco, Pierre; Boffa, Jean-Jacques
2016-06-01
Low-energy extracorporeal shock wave therapy (SWT) has been shown to improve myocardial dysfunction, hind limb ischemia, erectile function, and to facilitate cell therapy and healing process. These therapeutic effects were mainly due to promoting angiogenesis. Since chronic kidney diseases are characterized by renal fibrosis and capillaries rarefaction, they may benefit from a proangiogenic treatment. The objective of our study was to determine whether SWT could ameliorate renal repair and favor angiogenesis in L-NAME-induced hypertensive nephropathy in rats. SWT was started when proteinuria exceeded 1 g/mmol of creatinine and 1 week after L-NAME removal. SWT consisted of implying 0.09 mJ/mm(2) (400 shots), 3 times per week. After 4 weeks of SWT, blood pressure, renal function and urinary protein excretion did not differ between treated (LN + SWT) and untreated rats (LN). Histological lesions including glomerulosclerosis and arteriolosclerosis scores, tubular dilatation and interstitial fibrosis were similar in both groups. In addition, peritubular capillaries and eNOS, VEGF, VEGF-R, SDF-1 gene expressions did not increase in SWT-treated compared to untreated animals. No procedural complications or adverse effects were observed in control (C + SWT) and hypertensive rats (LN + SWT). These results suggest that extracorporeal kidney shock wave therapy does not induce angiogenesis and does not improve renal function and structure, at least in the model of hypertensive nephropathy although the treatment is well tolerated. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers
Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew
2015-01-01
Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996
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Nerve regeneration in nerve grafts conditioned by vibration exposure.
Bergman, S; Widerberg, A; Danielsen, N; Lundborg, G; Dahlin, L B
1995-01-01
Regeneration distances were studied in nerves from vibration-exposed limbs. One hind limb of anaesthetized rats was attached to a vibration exciter and exposed to vibration (80 Hz/32 m/s2) for 5 h/day for 2 or 5 days. Seven days after the latest vibration period a 10-mm long nerve graft was taken from the vibrated sciatic nerve and sutured into a corresponding defect in the con-tralateral sciatic nerve and vice versa, thereby creating two different models within the same animal: (i) regeneration from a freshly transected unvibrated nerve into a vibrated graft and (ii) regeneration from a vibrated nerve into a fresh nerve graft (vibrated recipient side). Four, 6 or 8 days postoperatively (p.o.) the distances achieved by the regenerating axons were determined using the pinch reflex test. Two days of vibration did not influence the regeneration, but 5 days of vibration reduced the initial delay period and a slight reduction of regeneration rate was observed. After 5 days of vibration an increased regeneration distance was observed in both models at day 4 p.o. and at day 6 p.o. in vibrated grafts. This study demonstrates that vibration can condition peripheral nerves and this may be caused by local changes in the peripheral nerve trunk and in the neuron itself.
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The first well-preserved coelophysoid theropod dinosaur from Asia.
You, Hai-Lu; Azuma, Yoichi; Wang, Tao; Wang, Ya-Ming; Dong, Zhi-Ming
2014-10-16
Coelophysoid dinosaurs represent the earliest major radiation of neotheropods. These small-to-medium-sized agile bipeds lived throughout much of Pangaea during the Late Triassic-arly Jurassic. Previously reported coelophysoid material from Asia (excluding the Gondwanan territory of India) is limited to two specimens that comprise only limb fragments. This paper describes a new genus and species of coelophysoid, Panguraptor lufengensis, from the Lower Jurassic Lufeng Formation of Yunnan Province, China. The new taxon is represented by a well-preserved skeleton, including the skull and lower jaw, the presacral vertebral column and partial ribs, the right scapula, a partial forelimb, part of the pelvic girdle, and an almost complete hind limb. It is distinguished from other coelophysoid theropods by the unique combination of the following three character states: 1) diagonal (rostrodorsal-caudoventral) ridge on lateral surface of maxilla, within antorbital fossa, 2) elliptical, laterally facing fenestra caudodorsal to aforementioned diagonal ridge, and 3) hooked craniomedial corner of distal tarsal IV. Cladistic analysis recovers Panguraptor lufengensis deeply nested within Coelophysoidea as a member of Coelophysidae, and it is more closely related to Coelophysis than to "Syntarsus". Panguraptor represents the first well-preserved coelophysoid theropod dinosaur from Asia, and provides fresh evidence supporting the hypothesis that terrestrial tetrapods tended to be distributed pan-continentally during the Early Jurassic.
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Lin, Zhi-Hang; Wang, Si-Yuan; Chen, Li-Li; Zhuang, Jia-Yuan; Ke, Qing-Feng; Xiao, Dan-Rui; Lin, Wen-Ping
2017-01-01
The spinal cord injury (SCI) is a detrimental neurological disease involving the primary mechanical injury and secondary inflammatory damage. Curtailing the detrimental neuroinflammation would be beneficial for spinal cord function recovery. Microglia reside in the spinal cord and actively participate in the onset, progression and perhaps resolution of post-SCI neuroinflammation. In the current study, we tested the effects of methylene blue on microglia both in vitro and in a rat SCI model. We found that methylene blue inhibited the protein levels of IL-1β and IL-18 rather than their mRNA levels in activated microglia. Further investigation indicated that methylene blue deceased the activation of NLRP3 inflammasome and NLRC4 inflammasome in microglia in vitro . Moreover, in the rat SCI model, the similar effect of methylene blue on post-SCI microglia was also observed, except that the activation of NLRC4 inflammasome was not seen. The inhibition of microglia NLRP3 inflammasome was associated with down-regulation of intracellular reactive oxygen species (ROS). The administration of methylene blue mitigated the overall post-SCI neuroinflammation, demonstrated by decreased pro-inflammatory cytokine production and leukocyte infiltrates. Consequently, the neuronal apoptosis was partially inhibited and the hind limb locomotor function was ameliorated by methylene blue treatment. Our research highlights the role of methylene blue in inhibiting post-SCI neuroinflammation, and suggests that methylene blue might be used for SCI therapy.
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Lin, Zhi-Hang; Wang, Si-Yuan; Chen, Li-Li; Zhuang, Jia-Yuan; Ke, Qing-Feng; Xiao, Dan-Rui; Lin, Wen-Ping
2017-01-01
The spinal cord injury (SCI) is a detrimental neurological disease involving the primary mechanical injury and secondary inflammatory damage. Curtailing the detrimental neuroinflammation would be beneficial for spinal cord function recovery. Microglia reside in the spinal cord and actively participate in the onset, progression and perhaps resolution of post-SCI neuroinflammation. In the current study, we tested the effects of methylene blue on microglia both in vitro and in a rat SCI model. We found that methylene blue inhibited the protein levels of IL-1β and IL-18 rather than their mRNA levels in activated microglia. Further investigation indicated that methylene blue deceased the activation of NLRP3 inflammasome and NLRC4 inflammasome in microglia in vitro. Moreover, in the rat SCI model, the similar effect of methylene blue on post-SCI microglia was also observed, except that the activation of NLRC4 inflammasome was not seen. The inhibition of microglia NLRP3 inflammasome was associated with down-regulation of intracellular reactive oxygen species (ROS). The administration of methylene blue mitigated the overall post-SCI neuroinflammation, demonstrated by decreased pro-inflammatory cytokine production and leukocyte infiltrates. Consequently, the neuronal apoptosis was partially inhibited and the hind limb locomotor function was ameliorated by methylene blue treatment. Our research highlights the role of methylene blue in inhibiting post-SCI neuroinflammation, and suggests that methylene blue might be used for SCI therapy. PMID:29311826
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Wang, Qian; Zeng, Hansong; Best, Thomas M.; Haas, Caroline; Heffner, Ned T.; Agarwal, Sudha; Zhao, Yi
2013-01-01
Massage therapy has a long history and has been widely believed effective in restoring tissue function, relieving pain and stress, and promoting overall well-being. However, the application of massage-like actions and the efficacy of massage are largely based on anecdotal experiences that are difficult to define and measure. This leads to a somewhat limited evidence-based interface of massage therapy with modern medicine. In this study, we introduce a mechatronic device that delivers highly reproducible massage-like mechanical loads to the hind limbs of small animals (rats and rabbits), where various massage-like actions are quantified by the loading parameters (magnitude, frequency and duration) of the compressive and transverse forces on the subject tissues. The effect of massage is measured by the difference in passive viscoelastic properties of the subject tissues before and after mechanical loading, both obtained by the same device. Results show that this device is useful in identifying the loading parameters that are most conducive to a change in tissue mechanical properties, and can determine the range of loading parameters that result in sustained changes in tissue mechanical properties and function. This device presents the first step in our effort for quantifying the application of massage-like actions used clinically and measurement of their efficacy that can readily be combined with various quantitative measures (e.g., active mechanical properties and physiological assays) for determining the therapeutic and mechanistic effects of massage therapies. PMID:23943071
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Limb Bone Structural Proportions and Locomotor Behavior in A.L. 288-1 ("Lucy").
Ruff, Christopher B; Burgess, M Loring; Ketcham, Richard A; Kappelman, John
2016-01-01
While there is broad agreement that early hominins practiced some form of terrestrial bipedality, there is also evidence that arboreal behavior remained a part of the locomotor repertoire in some taxa, and that bipedal locomotion may not have been identical to that of modern humans. It has been difficult to evaluate such evidence, however, because of the possibility that early hominins retained primitive traits (such as relatively long upper limbs) of little contemporaneous adaptive significance. Here we examine bone structural properties of the femur and humerus in the Australopithecus afarensis A.L. 288-1 ("Lucy", 3.2 Myr) that are known to be developmentally plastic, and compare them with other early hominins, modern humans, and modern chimpanzees. Cross-sectional images were obtained from micro-CT scans of the original specimens and used to derive section properties of the diaphyses, as well as superior and inferior cortical thicknesses of the femoral neck. A.L. 288-1 shows femoral/humeral diaphyseal strength proportions that are intermediate between those of modern humans and chimpanzees, indicating more mechanical loading of the forelimb than in modern humans, and by implication, a significant arboreal locomotor component. Several features of the proximal femur in A.L. 288-1 and other australopiths, including relative femoral head size, distribution of cortical bone in the femoral neck, and cross-sectional shape of the proximal shaft, support the inference of a bipedal gait pattern that differed slightly from that of modern humans, involving more lateral deviation of the body center of mass over the support limb, which would have entailed increased cost of terrestrial locomotion. There is also evidence consistent with increased muscular strength among australopiths in both the forelimb and hind limb, possibly reflecting metabolic trade-offs between muscle and brain development during hominin evolution. Together these findings imply significant differences in both locomotor behavior and ecology between australopiths and later Homo.
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Dash, Biraja C; Thomas, Dilip; Monaghan, Michael; Carroll, Oliver; Chen, Xizhe; Woodhouse, Kimberly; O'Brien, Timothy; Pandit, Abhay
2015-10-01
Critical limb ischemia is a major clinical problem. Despite rigorous treatment regimes, there has been only modest success in reducing the rate of amputations in affected patients. Reduced level of blood flow and enhanced inflammation are the two major pathophysiological changes that occur in the ischemic tissue. The objective of this study was to develop a controlled dual gene delivery system capable of delivering therapeutic plasmid eNOS and IL-10 in a temporal manner. In order to deliver multiple therapeutic genes, an elastin-like polypeptide (ELP) based injectable system was designed. The injectable system was comprised of hollow spheres and an in situ-forming gel scaffold of elastin-like polypeptide capable of carrying gene complexes, with an extended manner release profile. In addition, the ELP based injectable system was used to deliver human eNOS and IL-10 therapeutic genes in vivo. A subcutaneous dose response study showed enhanced blood vessel density in the treatment groups of eNOS (20 μg) and IL-10 (10 μg)/eNOS (20 μg) and reduced inflammation with IL-10 (10 μg) alone. Next, we carried out a hind-limb ischemia model comparing the efficacy of the following interventions; Saline; IL-10, eNOS and IL-10/eNOS. The selected dose of eNOS, exhibited enhanced angiogenesis. IL-10 treatment groups showed reduction in the level of inflammatory cells. Furthermore, we demonstrated that eNOS up-regulated major proangiogenic growth factors such as vascular endothelial growth factors, platelet derived growth factor B, and fibroblast growth factor 1, which may explain the mechanism of this approach. These factors help in formation of a stable vascular network. Thus, ELP injectable system mediating non-viral delivery of human IL10-eNOS is a promising therapy towards treating limb ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Limb Bone Structural Proportions and Locomotor Behavior in A.L. 288-1 ("Lucy")
Ruff, Christopher B.; Burgess, M. Loring; Ketcham, Richard A.; Kappelman, John
2016-01-01
While there is broad agreement that early hominins practiced some form of terrestrial bipedality, there is also evidence that arboreal behavior remained a part of the locomotor repertoire in some taxa, and that bipedal locomotion may not have been identical to that of modern humans. It has been difficult to evaluate such evidence, however, because of the possibility that early hominins retained primitive traits (such as relatively long upper limbs) of little contemporaneous adaptive significance. Here we examine bone structural properties of the femur and humerus in the Australopithecus afarensis A.L. 288–1 ("Lucy", 3.2 Myr) that are known to be developmentally plastic, and compare them with other early hominins, modern humans, and modern chimpanzees. Cross-sectional images were obtained from micro-CT scans of the original specimens and used to derive section properties of the diaphyses, as well as superior and inferior cortical thicknesses of the femoral neck. A.L. 288–1 shows femoral/humeral diaphyseal strength proportions that are intermediate between those of modern humans and chimpanzees, indicating more mechanical loading of the forelimb than in modern humans, and by implication, a significant arboreal locomotor component. Several features of the proximal femur in A.L. 288–1 and other australopiths, including relative femoral head size, distribution of cortical bone in the femoral neck, and cross-sectional shape of the proximal shaft, support the inference of a bipedal gait pattern that differed slightly from that of modern humans, involving more lateral deviation of the body center of mass over the support limb, which would have entailed increased cost of terrestrial locomotion. There is also evidence consistent with increased muscular strength among australopiths in both the forelimb and hind limb, possibly reflecting metabolic trade-offs between muscle and brain development during hominin evolution. Together these findings imply significant differences in both locomotor behavior and ecology between australopiths and later Homo. PMID:27902687
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Soy undecapeptide induces Drosophila hind leg grooming via dopamine receptor.
Karim, M Rezaul; Yanagawa, Aya; Ohinata, Kousaku
2018-05-15
β-Conglycinin α subunit (323-333) [βCGα(323-333)] is an exogenous neuromodulating undecapeptide found from enzymatic digest of β-conglycinin, a soy major storage protein by mice behavior tests. We investigated effect of βCGα(323-333) on Drosophila behavior. Oral administration of βCGα(323-333) in Drosophila increased hind leg grooming, which may act through specific sets of neurons. It was reported that dopamine receptor (DopR) meditates hind leg grooming, and we tested involvement of DopR in βCGα(323-333)-induced hind leg grooming by using DopR knockout flies. In the wild type but not in the DopR-knockout flies, βCGα(323-333) increased hind leg grooming. These results suggest that βCGα(323-333) induces hind leg grooming via activating the DopR. This is the first report showing that exogenously administered peptide changes fly behaviors. Copyright © 2018 Elsevier Inc. All rights reserved.
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Nation, Kelsey M; De Felice, Milena; Hernandez, Pablo I; Dodick, David W; Neugebauer, Volker; Navratilova, Edita; Porreca, Frank
2018-05-01
The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.
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Nemeth, Richard S.
2006-01-01
Many species of groupers form spawning aggregations, dramatic events where 100s to 1000s of individuals gather annually at specific locations for reproduction. Spawning aggregations are often targeted by local fishermen, making them extremely vulnerable to over fishing. The Red Hind Bank Marine Conservation District located in St. Thomas, United States Virgin Islands, was closed seasonally in 1990 and closed permanently in 1999 to protect an important red hind Epinephelus guttatus spawning site. This study provides some of the first information on the population response of a spawning aggregation located within a marine protected area. Tag-and-release fishing and fish transects were used to evaluate population characteristics and habitat utilization patterns of a red hind spawning aggregation between 1999 and 2004. Compared with studies conducted before the permanent closure, the average size of red hind increased mostly during the seasonal closure period (10 cm over 12 yr), but the maximum total length of male red hind increased by nearly 7 cm following permanent closure. Average density and biomass of spawning red hind increased by over 60% following permanent closure whereas maximum spawning density more than doubled. Information from tag returns indicated that red hind departed the protected area following spawning and migrated 6 to 33 km to a ca. 500 km2 area. Protection of the spawning aggregation site may have also contributed to an overall increase in the size of red hind caught in the commercial fishery, thus increasing the value of the grouper fishery for local fishermen. PMID:16612415
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
Once installed, the 'HindCast Player' HyperCard stack displays the spill trajectory of the EXXON Valdez oil spill in the Prince William Sound in March of 1989. The product, 'Exxon Valdez Hind Cast' contains one compressed file and one documentation file. The file containing the documentation is named 'Read.me', and the compressed file is named Exxon HindCasts'. The compressed folder contains a moov file called 'EXXON Valdez', a HyperCard Stack called, 'HindCast Player v/2', and Apples QuickTime(TM) extension file.
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Survival after anaphylaxis induced by a bumblebee sting in a dog.
Thomas, Emily; Mandell, Deborah C; Waddell, Lori S
2013-01-01
A 3.5 yr old castrated male miniature schnauzer was referred with a history of collapse after a bee sting to the left hind limb. At the time of presentation, 14 hr after the sting, the dog was hypotensive, comatose, seizuring, and had a brief period of cardiac arrest. Over the following 48 hr, the dog developed azotemia, severely elevated liver enzyme levels, hypertension, hematochezia, hematemesis, and disseminated intravascular coagulation (DIC). The dog's neurologic status improved slowly, but significant behavioral abnormalities remained. The dog was discharged after 7 days with ongoing polyuria, polydipsia, and behavioral changes. The polydipsia and polyuria resolved within a few days, but the behavioral changes continued for 6 wk. Reports of anaphylaxis from any cause are sparse in the veterinary literature. This is the first report of suspected anaphylaxis following a bee sting. There are no previous reports of behavioral changes after physical recovery from anaphylaxis.
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Physiological comparison of rat muscle in body suspension and weightlessness
NASA Technical Reports Server (NTRS)
Musacchia, X. J.; Steffen, J. M.; Fell, R. D.; Dombrovski, J.
1987-01-01
Hind limb unloading is achieved with whole body suspension (WBS) and with tail suspension (TS). Comparable levels of muscle mass loss and decreases in protein levels result during one to three weeks of exposure to microgravity (microG), WBS, and TS. Losses are most apparent in soleus (S), intermediate in gastrocnemius (G) and least in extensor digigorum longus (EDL). Comparison of S and EDL type I and II fiber changes (numbers and area) after seven days of microG flight and WBS showed, in S, an increase in Type I and Type II fiber density and a decrease in area. Except for a decrease in Type I fiber density in EDL, all other parameters remained comparable. The general conclusions were that the S under microG and WBS responds in a similar manner. The EDL, for the most part, shows little change under both conditions.