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Previous studies on anuran anomalies predominantly examine isolated cases or focus on external and skeletal features. Our study analyzes a comprehensive sample collected from 1991 to 2017, examining the muscle-tendon system in 24 anuran species across adult, juvenile, and metamorphic stages. This extensive sample size allows us to investigate consistent anomaly patterns across different developmental stages and anuran families, exploring potential common developmental or genetic factors. Our detailed anatomical examination, encompassing musculature, tendons, and skeletal structures, revealed that 21% of the specimens displayed anomalies, a noteworthy finding considering the extensive sample size and duration of the studied sample. Of these anomalies, 17% affected the locomotor system, predominantly in the upper limbs. Key anomalies included, forelimbs and hindlimbs brachydactyly, rotation in forelimbs, partial kyphotic lordosis, and scoliosis. Notably, the digit 4 in the forelimbs and digits 4 and 5 in the hindlimbs were particularly susceptible to teratogenic effects, indicating possible prolonged exposure during development. Our study also uncovered combinations of anomalies and identified a phenotype similar to Poland syndrome. The findings validate the "Logic of Monsters" (LoMo theory) by Alberch, although the name itself may not be deemed appropriate, showing that developmental disruptions in tetrapods are not random but follow distinct sequences and patterns. The name, while unfortunate, accurately reflects the unusual nature of these developmental anomalies. This contributes to the evolving "Evo-Devo-Path" framework, highlighting the study's importance in understanding developmental disruptions in tetrapods., (© 2024 American Association for Anatomy.)

Most published researches that describe an equine hoof form are based on lineal and angular measurements. Here we apply geometric morphometric methods to study symmetries between fore and hind pairs in a pure horse breed. For this purpose, we studied a sample of 27 right-left pairs of distal limbs (12 forelimb and 15 hindlimb pairs) from young Pyrenean Catalan Horses ("Cavall Pirinenc Català"), a meat local breed from Catalonia (Spain), managed under semi-extensive conditions at NE Pyrenees. The outline of the hoof was represented by a set of 2 landmarks and 88 semi-landmarks, which were studied by means of geometric morphometric methods. Surfaces were similar for all limbs but significant shape variations appeared in fluctuating asymmetry, with less contra-paired differences in hindlimbs than between forelimbs. The detected asymmetry of the solar surface in this study may provide, in our opinion, and indicator of mechanical, not environmental, stress, as hooves, acting as robust but malleable pieces, can change shape according to pressure forces. So, if the hoof surface in the Pyrenean Catalan Horse exhibits asymmetry, it may be just a mere plasticity due to pressure forces. This asymmetry would be expressed less markedly in the hind pair, which represents the "motor" part of the equine body and so, much linked to a perfect symmetrical functional oerforming. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Mesenchymal stem cell (MSC) transplantation has emerged as a very promising strategy for the treatments of peripheral artery disease (PAD). However, MSC-based therapies are limited by low cell retention and survival rate in the ischemic zone. Small molecular (SM) hydrogels have shown attractive abilities to enhance the therapeutic effects of human MSCs via promoting their proliferation or maintaining their differentiation potential. Here, we designed and synthesized a new bioactive and biocompatible hydrogel, Nap-GFFYK-Thiol, using disulfide bonds as cleavable linkers to control the molecular self-assembly and we hypothesized this hydrogel could enhance the retention and engraftment of human placenta-derived MSCs (hP-MSCs) in a mouse ischemic hindlimb model. In vitro results demonstrated that the Nap-GFFYK-Thiol hydrogel increased cell viability through paracrine effects. Moreover, it enhanced the proangiogenic and anti-apoptotic effects of hP-MSCs. In vivo , Nap-GFFYK-Thiol hydrogel improved the hP-MSC retention in the murine ischemic hindlimb model as visualized by bioluminescence imaging. Furthermore, cotransplantation of hP-MSCs with hydrogel improved blood perfusion, leading to superior limb salvage. These therapeutic effects may attribute to reduced inflammatory cell infiltration, enhanced angiogenesis as well as suppressed collagen deposition. In conclusion, the Nap-GFFYK-Thiol hydrogel fabricated using disulfide bonds as cleavable linkers serves as an artificial niche for promoting hP-MSC survival and proangiogenic factor secretion in PAD therapy and thereby provide an alternative strategy for PAD therapy. Statement of significance Although several phase I/II clinical trials of MSC-based treatments for critical limb ischemia (CLI) are ongoing, MSC-based therapies are still challenged by the low quality and quantity of cells in the ischemic zone, especially in cases of extensive or irreversible damage. Hydrogels have favorable biocompatibility and safety records in the medical field. In the current study, we engineered a new bioactive and biocompatible hydrogel, Nap-GFFYK-Thiol, using disulfide bonds as cleavable linkers to enhance the therapeutic efficacy of human placenta-derived MSCs (hP-MSCs) in mouse limb ischemia model. Notably, Nap-GFFYK-Thiol hydrogel acts as an artificial niche for promoting hP-MSC survival and proangiogenic factor secretion in PAD therapy, which further promoted the restoration of blood perfusion and regeneration of muscle cells. Considering the proangiogenic effect of Nap-GFFYK-Thiol on hP-MSCs, our results may provide a new strategy for the treatment of PAD. [ABSTRACT FROM AUTHOR]

Locomotor performance is a fundamental feature commonly related to many animals' fitness. In most cases, locomotor performance is closely related to morphology of the structures responsible for it, which is therefore under strong selective pressure. Hence, limb abnormality could hinder locomotion and, for that reason, be eradicated by selection, which could explain its overall low prevalence that makes proper research difficult. Here, we took advantage of the moderately high prevalence of hindlimb abnormality in a sample of Iberian spadefoot (Pelobates cultripes) metamorphs developed from tadpoles captured and transferred to the laboratory before selection could act against metamorph abnormality. We tested the hypothesis that limb abnormality impairs locomotor performance. Moreover, we measured several larval and metamorph morphometrics, and checked for differences between normal and abnormal- limbed individuals. We also assessed correlations between hindlimb ratio (hindlimb length/SVL) and jumping performance in normal and abnormal-limbed metamorphs. Larval traits measured could not predict hindlimb abnormality. In metamorphs, only hindlimb ratio differed between normal and abnormal-limbed individuals, being shorter in the latter. Abnormal-limbed metamorphs jumped considerably shorter distances than normal-limbed conspecifics. Therefore, selection against reduced locomotor performance could eliminate limb abnormality from populations. Hindlimb ratio was included in the model as a covariable, and thus controlled for. Consequently, other factors besides shorter hindlimbs, probably hindlimb abnormality itself, could play a role in worse jumping capability of abnormal-limbed individuals. Hindlimb ratio was positively related to jumping distance in both groups, although the relationship was weaker in abnormal-limbed metamorphs. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate skeletal pain associated with immobility-induced osteoporosis and to examine the inhibitory effect of bisphosphonate (BP) administration on pain in hindlimb-unloaded (HU) mice.Methods: The mechanism of osteoporotic pain in HU mice was evaluated through an examination of pain-related behavior, as well as immunohistochemical findings. In addition, the effects of alendronate (ALN), a potent osteoclast inhibitor, on these parameters were assessed.Results: HU mice with tail suspension developed bone loss and mechanical hyperalgesia in the hindlimbs. The HU mice showed an increase in the number of calcitonin gene-related peptide (CGRP)-immunoreactive neurons and in transient receptor potential channel vanilloid subfamily member 1 (TRPV1)-immunoreactive neurons in the dorsal root ganglions (DRGs) innervating the hindlimbs. Furthermore, administration of ALN prevented HU-induced bone loss, mechanical hyperalgesia, and upregulation of CGRP and TRPV1 expressions in DRG neurons of immobility-induced osteoporotic animal models.Conclusions: HU mice appear to be a useful model for immobility-induced osteoporotic pain and hindlimb-unloading-induced bone loss, as well as upregulation of CGRP and TRPV1 expressions in DRG neurons, and BP treatment prevented bone loss and mechanical hyperalgesia. The inhibitory effect of BP on osteoclast function might contribute to improving osteoporosis-related pain. [ABSTRACT FROM AUTHOR]

Fragility fractures are a well-known complication following oncologic radiotherapy, and it is suspected that radiation-induced embrittlement of bone within the treatment field may contribute to fracture risk. To explore this phenomenon, a mouse model (BALB/cJ) of fractionated, limited field, bilateral hindlimb irradiation (4x5 Gy) was used. The effects of radiation on femoral (cortical) bone fracture toughness, morphology, and biochemistry—including advanced glycation end products (AGEs)—were quantified and compared to Sham group samples prior to irradiation and at 0, 4, 8, and 12 weeks post-irradiation. Additionally, alterations to bone fracture toughness mediated directly by radiation (independent of cellular mechanisms) were determined using devitalized mouse cadaver femurs. Finally, the contribution of AGEs to reduced fracture toughness was examined by artificially ribosylating mouse femurs ex vivo. These data demonstrate that in vivo irradiation results in an immediate (-42% at 0 weeks, p < 0.001) and sustained (-28% at 12 weeks, p < 0.001) decrease in fracture toughness with small changes in morphology (-5% in cortical area at 12 weeks), and minimal changes in bone composition (tissue mineral density, mineral:matrix ratio, and AGE content). Irradiation of devitalized femurs also reduced fracture toughness (-29%, p < 0.001), but to a lesser extent than was seen in vivo. While artificial ribosylation decreased fracture toughness with time, the extent of glycation needed to induce this effect exceeded the AGE accumulation that occurred in vivo. Overall, hindlimb irradiation induced a substantial and sustained decrease in bone fracture toughness. Approximately half of this decrease in fracture toughness is due to direct radiation damage, independent of cellular remodeling. Collagen glycation in vivo was not substantially altered, suggesting other matrix changes may contribute to post-radiotherapy bone embrittlement. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that microgravity-induced arterial remodelling contributes to post-flight orthostatic intolerance and that multiple mechanisms are involved in arterial remodelling. However, the initial mechanism by which haemodynamic changes induce arterial remodelling is unknown. Focal adhesions (FAs) are dynamic protein complexes that have mechanotransduction properties. This study aimed to investigate the role of FAs in simulated-microgravity-induced basilar and femoral arterial remodelling. A 4-week hindlimb-unweighted (HU) rat model was used to simulate the effects of microgravity, and daily 1-hour intermittent artificial gravity (IAG) was used to prevent arterial remodelling. After 4-week HU, wall thickness, volume of smooth muscle cells (SMCs) and collagen content were increased in basilar artery but decreased in femoral artery (P < 0.05). Additionally, the expression of p-FAK Y397 and p-Src Y418 was increased and reduced in SMCs of basilar and femoral arteries, respectively, by HU (P < 0.05). The number of FAs was increased in basilar artery and reduced in femoral artery by HU (P < 0.05). Furthermore, daily 1-hour IAG prevented HU-induced differential structural adaptations and changes in FAs of basilar and femoral arteries. These results suggest that FAs may act as mechanosensors in arterial remodelling by initiating intracellular signal transduction in response to altered mechanical stress induced by microgravity. [ABSTRACT FROM AUTHOR]

ABSTRACT: Osteophytes are a typical radiographic finding during osteoarthritis (OA), but the mechanisms leading to their formation are not well known. Comparatively, fracture calluses have been studied extensively; therefore, drawing comparisons between osteophytes and fracture calluses may lead to a deeper understanding of osteophyte formation. In this study, we compared the time courses of osteophyte and fracture callus formation, and investigated mechanisms contributing to development of these structure. Additionally, we investigated the effect of mechanical unloading on the formation of both fracture calluses and osteophytes. Mice underwent either transverse femoral fracture or non‐invasive anterior cruciate ligament rupture. Fracture callus and osteophyte size and ossification were evaluated after 3, 5, 7, 14, 21, or 28 days. Additional mice were subjected to hindlimb unloading after injury for 3, 7, or 14 days. Protease activity and gene expression profiles after injury were evaluated after 3 or 7 days of normal ambulation or hindlimb unloading using in vivo fluorescence reflectance imaging (FRI) and quantitative PCR. We found that fracture callus and osteophyte growth achieved similar developmental milestones, but fracture calluses formed and ossified at earlier time points. Hindlimb unloading ultimately led to a threefold decrease in chondro/osteophyte area, and a twofold decrease in fracture callus area. Unloading was also associated with decreased inflammation and protease activity in injured limbs detected with FRI, particularly following ACL rupture. qPCR analysis revealed disparate cellular responses in fractured femurs and injured joints, suggesting that fracture calluses and osteophytes may form via different inflammatory, anabolic, and catabolic pathways. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:699–710, 2018. [ABSTRACT FROM AUTHOR]

Ultrasonographic examination of the femorotibial joint is now commonly performed for investigating hindlimb lamenesses. Different types of meniscal injuries have been described using this technique. In our practice, the cranial meniscotibial ligament of the medial meniscus (Cr MTL- MM) is the most frequently affected soft tissue structure of the stifle. This article describes the technique to image this ligament, normal images and the ultrasonographic manifestations of desmopathies and enthesopathies of the Cr MTL- MM. [ABSTRACT FROM AUTHOR]

Forelimbs (FLs) and hindlimbs (HLs) develop complex musculoskeletal structures that rely on the deployment of a conserved developmental program. Pitx1, a transcription factor gene with expression restricted to HL and absent from FL, plays an important role in generating HL features. The genomic mechanisms by which Pitx1 effects HL identity remain poorly understood. Here, we use expression profiling and analysis of direct Pitx1 targets to characterize the HL- and FL-restricted genetic programs in mouse and situate the Pitx1-dependent gene network within the context of limb-specific gene regulation. We show that Pitx1 is a crucial component of a narrow network of HL-restricted regulators, acting on a developmental program that is shared between FL and HL. Pitx1 targets sites that are in a similar chromatin state in FL and HL and controls expression of patterning genes as well as the chondrogenic program, consistent with impaired chondrogenesis in Pitx1-/- HL. These findings support a model in which multifactorial actions of a limited number of HL regulators redirect the generic limb development program in order to generate the unique structural features of the limb. [ABSTRACT FROM AUTHOR]

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

Jacob sheep (Ovis aries) are a pedigree breed known for their "polycerate" (multihorned) phenotype. We describe a four-horned Jacob lamb that exhibited progressive congenital hindlimb ataxia and paresis, and was euthanased four weeks post-partum. Necropsy and CT-scan revealed deformity and asymmetry of the occipital condyles, causing narrowing of the foramen magnum and spinal cord compression. Histopathology demonstrated Wallerian degeneration of the cervical spinal cord at the level of the foramen magnum. These findings are consistent with occipital condylar dysplasia. This condition has been infrequently reported in the literature as a suspected heritable disease of polycerate Jacob sheep in the USA, and is assumed to arise during selection for the polycerate trait. This is the first reported case in European-bred Jacob sheep. Occipital condylar dysplasia should be considered as a differential diagnosis in polycerate Jacob lambs showing ataxia. It is important to raise awareness of this disease due to its suspected heritability and link to the popular polycerate trait. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are a promising cell resource for the treatment of ischemic diseases, partially through paracrine effects. One of the major obstacles of MSC treatment is the poor survival rate and low efficiency of transplanted stem cells due to ischemic or inflammatory environments. Gremlin1 (GREM1), a regulator of growth, differentiation and development, has been identified as a novel proangiogenic factor. However, the role and mechanism of GREM1 in MSCs remains unclear. Therefore, we assessed the putative beneficial effects of GREM1 on MSC-based therapy for hindlimb ischemia. The lentiviral vector, EF1a-GREM1, was constructed using the Multisite Gateway System and used to transduce MSCs. In vitro studies demonstrated increased survival of GREM1-MSCs exposed to H2O2, which is consistent with the activation of caspase-3. Conditional medium from GREM1-MSCs (GREM1-MSC-CM) increased the anti-apoptotic effects of human umbilical vein endothelial cells (HUVECs), and this effect was attenuated by treatment with the PI3K/Akt pathway inhibitor LY294002. MSCs modified with GREM1 could significantly increase blood perfusion of the ischemic hindlimb in vivo in a mouse model, which was correlated to improved MSC survival. This study demonstrates that overexpression of GREM1 in MSCs have greater therapeutic effects against ischemia compared with wild-type MSCs by enhancing the survival of MSCs and ECs, which may provide new tools for studies investigating the treatment of ischemic diseases. J. Cell. Physiol. 232: 996-1007, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Single steps in different directions are often used for postural corrections. However, our knowledge about the neural mechanisms underlying their generation is scarce. This study was aimed to characterize the corrective steps generated in response to disturbances of the basic body configuration caused by forward, backward or outward displacement of the hindlimb, as well as to reveal location in the CNS of the corrective step generating mechanisms. Video recording of the motor response to translation of the supporting surface under the hindlimb along with contact forces and activity of back and limb muscles was performed in freely standing intact and in fixed postmammillary rabbits. In intact rabbits, displacement of the hindlimb in any direction caused a lateral trunk movement toward the contralateral hindlimb, and then a corrective step in the direction opposite to the initial displacement. The time difference between onsets of these two events varied considerably. The EMG pattern in the supporting hindlimb was similar for all directions of corrective steps. It caused the increase in the limb stiffness. EMG pattern in the stepping limb differed in steps with different directions. In postmammillary rabbits the corrective stepping movements, as well as EMG patterns in both stepping and standing hindlimbs were similar to those observed in intact rabbits. This study demonstrates that the corrective trunk and limb movements are generated by separate mechanisms activated by sensory signals from the deviated limb. The neuronal networks generating postural corrective steps reside in the brainstem, cerebellum, and spinal cord. [ABSTRACT FROM AUTHOR]

Key points Muscle atrophy is a debilitating condition that affects a high percentage of the population with a negative impact on quality of life., Dissecting the molecular level of the atrophy process, and the similarities/dissimilarities among different catabolic conditions, is a necessary step for designing specific countermeasures to attenuate/prevent muscle loss., The FoxO family transcription factors represent one of the most important regulators of atrophy programme stimulating the expression of many atrophy-related genes., The findings of the present study clearly indicate that the signalling network controlling the atrophy programme is specific for each catabolic condition., Abstract Muscle atrophy is a complex process that is in common with many different catabolic diseases including disuse/inactivity and ageing. The signalling pathways that control the atrophy programme in the different disuse/inactivity conditions have not yet been completely dissected. The inhibition of FoxO is considered to only partially spare muscle mass after denervation. The present study aimed: (i) to determine the involvement of FoxOs in hindlimb suspension disuse model; (ii) to define whether the molecular events of protein breakdown are shared among different unloaded muscles; and finally (iii) to compare the data obtained in this model with another model of inactivity such as denervation. Both wild-type and muscle-specific FoxO1,3,4 knockout (FoxO1,3,4−/−) mice were unloaded for 3 and 14 days and muscles were characterized by functional, morphological, biochemical and molecular assays. The data obtained show that FoxOs are required for muscle loss and force drop during unloading. Moreover, we found that FoxO-dependent atrogenes vary in different unloaded muscles and that they diverge from denervation. The findings of the present study clearly indicate that the signalling network that controls the atrophy programme is specific for each catabolic condition. [ABSTRACT FROM AUTHOR]

A hallmark of chronic inflammation is hypersensitivity to noxious and innocuous stimuli. This inflammatory pain hypersensitivity results partly from hyperexcitability of nociceptive dorsal root ganglion (DRG) neurons innervating inflamed tissue, although the underlying ionic mechanisms are not fully understood. However, we have previously shown that the nociceptor hyperexcitability is associated with increased expression of hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) protein and hyperpolarization-activated current ( I h ) in C-nociceptors. Here we used in vivo voltage-clamp and current-clamp recordings, in deeply anesthetized rats, to determine whether activation properties of I h in these C-nociceptors also change following persistent (not acute) hindlimb inflammation induced by complete Freund’s adjuvant (CFA). Recordings were made from lumbar (L4/L5) C-nociceptive DRG neurons. Behavioral sensory testing was performed 5–7 days after CFA treatment, and all the CFA-treated group showed significant behavioral signs of mechanical and heat hypersensitivity, but not spontaneous pain. Compared with control, C-nociceptors recorded 5–7 days after CFA showed: (a) a significant increase in the incidence of spontaneous activity (from ∼5% to 26%) albeit at low rate (0.14 ± 0.08 Hz (Mean ± SEM); range, 0.01–0.29 Hz), (b) a significant increase in the percentage of neurons expressing I h (from 35%, n = 43–84%, n = 50) based on the presence of voltage “sag” of >10%, and (c) a significant increase in the conductance (G h ) of the somatic channels conducting I h along with the corresponding I h, I h, activation rate, but not voltage dependence, in C-nociceptors. Given that activation of I h depolarizes the neuronal membrane toward the threshold of action potential generation, these changes in I h kinetics in CFA C-nociceptors may contribute to their hyperexcitability and thus to pain hypersensitivity associated with persistent inflammation. [ABSTRACT FROM AUTHOR]

The article presents case study of five year old Labrador retriever who was suffering from stifle disruption and was treated using a stifle stabilizing implant. Topics discussed includes stifle joint stabilization as a key concern for such surgeries, limb lameness experienced by the dog after slipping on ice, evaluation of other treatment options, acepromazine premedication given to dog, removal of damaged cranial during surgery, post operative icing process and complete recovery after surgery.

Objective: The aim of the present study was to determine whether low-level laser therapy (LLLT) at early stages postpartum could affect regeneration and degenerative processes in skeletal muscles of the dystrophic mdx mouse. Background data: LLLT has been found to modulate various biological processes. It was previously shown that LLLT can markedly promote the process of skeletal muscle regeneration and angiogenesis, as well as reduce apoptosis in skeletal muscle fibers in culture. Methods and results: Eight newborn mdx mice were used. Ga-Al-As diode laser (810 nm) was applied at a power density of10 mW/cm2 to the surface (area of 0.0255 cm2) of hindlimb muscle for 120 sec (fluence of 1.2 J/cm2) once a week for 4 consecutive weeks, commencing 1 week post-birth. The contralateral leg served as an untreated (sham) control. Mice were euthanized 2 days following the last laser application, and the muscles were processed for histology. Histological sections were scored for degenerative muscle foci. Statistical analysis revealed a score of 2.91±0.17 in the control, untreated group, which was significantly higher ( p<0.001) than the value in the laser-treated group (1.56±0.49), indicating less degenerative foci in the laser-treated muscles. Histology also indicated regeneration (numerous myotubes) in the laser-treated mice, and no regeneration in the non-laser-treated mice. Conclusions: The results indicate that LLLT applied to mdx mice during postnatal development may have a significant beneficial effect in the induction of regenerative capacity and reduction of degenerative muscle foci in these mice, with possible direct clinical relevance. [ABSTRACT FROM AUTHOR]

Anamnesis: an adult horse that showed hind limb hyperflexion was examined. Clinical and laboratory findings: at locomotion examination bilateral hyperflexion was observed; the right hind limb was more severely affected than the left. Electromyographic and histopathological examination revealed neural denervation and muscular atrophy supporting the idiopathic stringhalt diagnosis. Treatment approach: a lateral digital extensor tenectomy and partial myectomy was practiced in both hind limbs, accompanied by medical treatment and implementation of a mild exercise plan. The effectiveness of surgery is still controversial in these cases; however, this patient evidenced slow improvement after surgery and exercise seemed to be instrumental in the recovery of his normal locomotion. Conclusion: to our knowledge, this is the first report of a clinical case compatible with idiopathic stringhalt in Colombian Creole horses, but further studies are necessary to clarify the etiology and pathogenesis of stringhalt in Colombia. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? We asked whether the combination of astaxanthin supplementation and intermittent loading would attenuate both the muscle atrophy and the capillary regression associated with chronic unloading., What is the main finding and its importance? Intermittent loading alone attenuated atrophy of the soleus, while astaxanthin treatment alone maintained the capillary network in the soleus. The combination of these two interventions ameliorated both the muscle atrophy and the capillary regression induced by chronic unloading., A chronic decrease in neuromuscular activity (activation and/or loading) results in muscle atrophy and capillary regression that are due, in part, to the overproduction of reactive oxygen species. We have reported that antioxidant treatment with astaxanthin attenuates the overexpression of reactive oxygen species in atrophied muscles that, in turn, ameliorates capillary regression in hindlimb-unloaded rats. Astaxanthin supplementation, however, had little effect on muscle mass and fibre cross-sectional area. In contrast, intermittent loading of the hindlimbs of hindlimb-unloaded rats ameliorates muscle atrophy. Therefore, we hypothesized that the combination of astaxanthin supplementation and intermittent loading would attenuate both muscle atrophy and capillary regression during hindlimb unloading. As expected, 2 weeks of hindlimb unloading resulted in atrophy, a decrease in capillary volume and a shift towards smaller-diameter capillaries in the soleus muscle. Intermittent loading alone (1 h of cage ambulation per day) attenuated atrophy of the soleus, while astaxanthin treatment alone maintained the capillary network to near control levels. The combination of intermittent loading and astaxanthin treatment, however, ameliorated atrophy of the soleus and maintained the capillary volume and luminal diameters and the superoxide dismutase-1 protein levels near control values. These results indicate that intermittent loading combined with astaxanthin supplementation could be an effective therapy for both the muscle atrophy and the capillary regression associated with a chronic decrease in neuromuscular activity. [ABSTRACT FROM AUTHOR]

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

Rostral segments of the spinal cord hindlimb enlargement are more important than caudal segments for generating locomotion and scratching rhythms in limbed vertebrates, but the adequacy of rostral segments has not been directly compared between locomotion and scratching. We separated caudal segments from immobilized low-spinal turtles by sequential spinal cord transections. After separation of the caudal four segments of the five-segment hindlimb enlargement, the remaining enlargement segment and five preenlargement segments still produced rhythms for forward swimming and both rostral and pocket scratching. The swimming rhythm frequency was usually maintained. Some animals continued to generate swimming and scratching rhythms even with no enlargement segments remaining, using only preenlargement segments. The preenlargement segments and rostral-most enlargement segment were also sufficient to maintain hip flexor (HF) motoneuron quiescence between HF bursts [which normally occurs during each hip extensor (HE) phase] during swimming. In contrast, the HFquiescent phase was increasingly absent (i.e., HE-phase deletions) during rostral and pocket scratching. Moreover, respiratory motoneurons that normally burst during HE bursts continued to burst during the HF quiescence of swimming even with the caudal segments separated. Thus the same segments are sufficient to generate the basic rhythms for both locomotion and scratching. These segments are also sufficient to produce a reliable HE phase during locomotion but not during rostral or pocket scratching. We hypothesize that the rostral HE-phase interneurons that rhythmically inhibit HF motoneurons and interneurons are sufficient to generate HF quiescence during HEbiased swimming but not during the more HF-biased rostral and pocket scratching. [ABSTRACT FROM AUTHOR]

Theuse of biomaterial carriers to improve the therapeutic efficacyof stem cells is known to augment cell delivery, retention, and viability.However, the way that carrier clearance kinetics boosts stem celldelivery and impacts stem cell function remains poorly characterized.In this study, we designed a platform to simultaneously quantify carrierclearance and stem cell retention to evaluate the impact of carrierclearance kinetics on stem cell retention. Additionally, a murinemodel of hindlimb ischemia was employed to investigate the effectsof various cell retention profiles on mitigating peripheral arterialdisease. To image the in vivo behaviors of material and cells, weused biotinylated hyaluronan with fluorescently labeled streptavidinand Discosomasp. Red (Ds-Red)-expressing human mesenchymalstem cells. We found that the retention of transplanted stem cellswas closely related to the remaining biomaterial. Furthermore, therapeuticeffectiveness was also affected by stem cell retention. These resultsdemonstrate that low-molecular-weight hyaluronan had a slow clearanceand high cell retention profile, improving the therapeutic efficacyof human stem cells. [ABSTRACT FROM AUTHOR]

The use of local flaps for the reconstruction of leg has lost their popularity with themore often performed flaps on the basis of perforators and microsurgical technique. Like the head and neck reconstruction, in the lower extremity there are limited units of tissue to base the flaps because of the lack of vascularity and arc of mobilization. The distally based sural flap represents an ideal flap for the reconstruction of heel, and with the inclusion of the sural nerve, we can neurotize the flap to give the stability of a weightbearing area and provide the necessary sensibility to avoid ulcerations of the reconstructed heel. We present a case of a 32-year-old woman with a traumatic loss of the tissue covering the heel, with a diagnosis of a pseudoepithelial hyperplasia treated in previous occasions with skin grafts that led to chronic ulcerations. A distally based sural flap was planned for a definitive coverage, planning a perineural neurorrhaphy, to the intermediate dorsal cutaneous branch of the superficial peroneal nerve to give sensibility to the flap. [ABSTRACT FROM AUTHOR]

Abstract: Botulinum neurotoxins (BoNT) are approved for a number of therapeutic indications, including blepharospasm, cervical dystonia and hyperhidrosis, and have also shown efficacy in a variety of pain disorders. The potency of any given BoNT preparation can be routinely assessed by using the Digit Abduction Score (DAS) assay, which measures the local muscle weakening efficacy of BoNT following injection into mouse hindlimb muscle. While most studies have employed mice to assess BoNT efficacy in the DAS, few have utilized rats. In this study, we applied the DAS assay to a rat model and compared the potency of IM-BOTOX® (onabotulinumtoxinA) injections between two separate hind limb muscles, gastrocnemius and tibialis anterior (TA). The results demonstrated that the DAS assay can be performed on rats with similar criteria and parameters as for mice. Moreover in the rat, BoNT can be injected into either the gastrocnemius or TA muscle to elicit similar DAS scoring responses. Interestingly, onabotulinumtoxinA potency in the rat DAS was ∼3-fold higher following TA injections than gastrocnemius injections. Additionally, our data showed that the durational kinetics of onabotulinumtoxinA in the rat DAS are approximately twice as long as in the mouse DAS. These results position the rat DAS as a more flexible model for examining the mechanisms of BoNT diffusion and muscle paralysis, while mouse DAS can be used for physiological screening of BoNT because of the potential for higher throughput. Overall, these data confirm the utility of the DAS assay for characterizing the physiological potency of BoNT and related compounds. [Copyright &y& Elsevier]

Highlights: [•] We studied a conditional transgenic mouse of spinocerebellar ataxia type 3 (SCA3Tg). [•] SCA3Tg mice exhibited striking hindlimb instability during quadrupedal standing. [•] We established the reaching task that required anticipatory postural adjustments (APAs). [•] Kinematic and electromyographic analyses in SCA3Tg mice showed APAs were impaired. [•] The cerebellum is critically involved in APAs to prevent any equilibrium disturbance. [ABSTRACT FROM AUTHOR]

Abstract: Remobilization of a previously immobilized rat right hindlimb in the ankle plantar-flexion-shortened position by free movement alone or associated with intermittent passive stretching was assessed by analysis of gait variables and dorsiflexion range of motion. The variables were related with the expression of extracellular matrix proteins and the addition of serial sarcomeres. Sixty-four female Wistar rats were divided into 8 groups: immobilized, free for 10 days, immobilized/stretched/free for 1, 3 or 10 days, immobilized/free for 1, 3 or 10 days. Gait variables, range of motion, serial sarcomeres number, localization and staining intensity of fibronectin, and expressions of types I and III collagen were analyzed. The hypokinesia changed the functional variables of gait, reduced the dorsiflexion range of motion (ROM), increased the number of fibers with intracellular fibronectin/total number of fibers (FIF/TNF), and decreased the expression of the type I collagen. After three days, morphological changes were exacerbated and the number of serial sarcomeres was increased in both groups, immobilized/stretched/free and immobilized/free. Functional impairment, ROM restriction and increased FIF/TNF were also observed. Despite the above described alterations, 10 days of stretching program increased the effectiveness of remobilization leading to recovery of the abnormalities observed in the muscle. [Copyright &y& Elsevier]

Objective: The use of bone marrow cells (BMCs) in therapeutic angiogenesis has been studied extensively. However, the critical paracrine effects of this treatment are still unclear. Therefore, we studied autotransfusable cells that produce vascular endothelial growth factor (VEGF), especially VEGF-C. Methods: Male C57BL/6 mice with hind limb ischemia were administered intramuscular injections of phosphate-buffered saline as controls, or unsorted BMCs, sorted CD11b+, or CD11b? cells from BMCs, and recombinant VEGF-C. To evaluate the treatments, perfusion was measured by laser Doppler scanning performed on days 0, 1, 3, 7, 14, 21, and 28. A functional assay was performed in parallel, with mice traversing an enclosed walkway. Capillary density was determined by directly counting vessels stained positive with von Willebrand factor at individual time points. Lymphangiogenesis was assessed by LYVE-1 positive cells. Results: Postischemic recovery of hind limb perfusion significantly improved in BMC, CD11b+, and VEGF-C treatment groups compared with the control groups, as assessed by laser Doppler scanning. On early operative days 1 and 3, the blood flow recovery ratio was higher in the CD11b+-treated group compared with BMC and VEGF-C treatment groups. In the functional assay, the VEGF-C group dramatically recovered compared with the control group. The capillary/myofiber ratio in the thigh muscle and number of LYVE-1 positive cells was higher in the CD11b+ and VEGF-C groups than in controls. Furthermore, expression of VEGF-A, VEGF-C, and VEGF receptor messenger ribonucleic acid and protein was observed in CD11b+ cells. Conclusions: The VEGF-C derived from CD11b+ cells play a critical role in angiogenesis and lymphangiogenesis in a murine model of hind limb ischemia. Consequently, treatment with self-CD11b+ cells accelerated recovery from ischemia and may be a promising therapeutic strategy for peripheral arterial disease patients. [Copyright &y& Elsevier]

Objective: To identify differences in postexercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications. Methods: We enrolled healthy control subjects and three groups of patients with type 2 diabetes mellitus: without complications, with peripheral neuropathy, and with both peripheral neuropathy and peripheral arterial disease. We used magnetic resonance spectroscopic measurements to perform continuous measurements of phosphorous metabolites (PCr and inorganic phosphate [Pi]) during a 3-minute graded exercise at the level of the posterior calf muscles (gastrocnemius and soleus muscles). Micro- and macrovascular reactivity measurements also were performed. Results: The resting Pi/PCr ratio and PCr at baseline and the maximum reached during exercise were similar in all groups. The postexercise time required for recovery of Pi/PCr ratio and PCr levels to resting levels, an assessment of mitochondrial oxidative phosphorylation, was significantly higher in diabetic patients with neuropathy and those with both neuropathy and peripheral arterial disease (P < .01 for both measurements). These two groups also had higher levels of tumor necrosis factor-? (P < .01) and granulocyte colony-stimulating factor (P < .05). Multiple regression analysis showed that only granulocyte colony-stimulating factor, osteoprotegerin, and tumor necrosis factor-? were significant contributing factors in the variation of the Pi/PCr ratio recovery time. No associations were observed between micro- and macrovascular reactivity measurements and Pi/PCr ratio or PCr recovery time. Conclusions: Mitochondrial oxidative phosphorylation is impaired only in type 2 diabetes mellitus patients with neuropathy whether or not peripheral arterial disease is present and is associated with the increased proinflammatory state observed in these groups. [Copyright &y& Elsevier]

The article discusses the risk of inequality in height between claws within each hindlimb that could cause lameness in large dairy cattle herds in Canterbury, New Zealand. It examines the height differential between hind claws of the cows which blocked by age, breed and treatment. It cites the use of Dutch Method to prevent the differential in claw height.

Abstract: Mechanical loads play a pivotal role in the growth and maintenance of bone and joints. Although loading can activate anabolic genes and induce bone remodeling, damping is essential for preventing traumatic bone injury and fracture. In this study we investigated the damping capacity of bone, joint tissue, muscle, and skin using a mouse hindlimb model of enhanced loading in conjunction with finite element modeling to model bone curvature. Our hypothesis was that loads were primarily absorbed by the joints and muscle tissue, but that bone also contributed to damping through its compression and natural bending. To test this hypothesis, fresh mouse distal lower limb segments were cyclically loaded in axial compression in sequential bouts, with each subsequent bout having less surrounding tissue. A finite element model was generated to model effects of bone curvature in silico. Two damping-related parameters (phase shift angle and energy loss) were determined from the output of the loading experiments. Interestingly, the experimental results revealed that the knee joint contributed to the largest portion of the damping capacity of the limb, and bone itself accounted for approximately 38% of the total phase shift angle. Computational results showed that normal bone curvature enhanced the damping capacity of the bone by approximately 40%, and the damping effect grew at an accelerated pace as curvature was increased. Although structural curvature reduces critical loads for buckling in beam theory, evolution apparently favors maintaining curvature in the tibia. Histomorphometric analysis of the tibia revealed that in response to axial loading, bone formation was significantly enhanced in the regions that were predicted to receive a curvature-induced bending moment. These results suggest that in addition to bone''s compressive damping capacity, surrounding tissues, as well as naturally-occurring bone curvature, also contribute to mechanical damping, which may ultimately affect bone remodeling and bone quality. [Copyright &y& Elsevier]

Abstract: Bone fluid flow (BFF) has been demonstrated as a critical regulator in mechanotransductive signaling and bone adaptation. Intramedullary pressure (ImP) and matrix strain have been identified as potential generators to regulate BFF. To elevate in vivo oscillatory BFF using ImP, a dynamic hydraulic stimulation (DHS) approach was developed. The objective of this study was to evaluate the effects of DHS on mitigation of bone loss and structural alteration in a rat hindlimb suspension (HLS) functional disuse model. Sixty-one 5-month old female Sprague–Dawley rats were divided into five groups: 1) baseline control, 2) age-matched control, 3) HLS, 4) HLS+static loading, and 5) HLS+DHS. Hydraulic flow stimulation was carried out daily on a “10min on–5min off–10min on” loading regime, 5days/week, for a total of 4weeks in the tibial region. The metaphyseal trabecular regions of the proximal tibiae were analyzed using μCT and histomorphometry. Four weeks of HLS resulted in a significant loss of trabecular bone, leading to structural deterioration. HLS with static loading alone was not sufficient to attenuate the bone loss. Bone quantity and microarchitecture were significantly improved by applying DHS loading, resulting increase of 83% in bone volume fraction, 25% in trabecular number and mitigation of 26% in trabecular separation compared to HLS control. Histomorphometry analysis on trabecular mineralization coincided with the μCT analysis, in which DHS loading yielded increases of 34% in histomorphometric BV/TV, 121% in MS/BS, 190% in BFR/BS and 146% in BFR/BV, compared to the HLS control. Overall, the data demonstrated that dynamic hydraulic flow loading has potentials to provide regulatory signals for mitigating bone loss induced by functional disuse. This approach may provide a new alternative mechanical intervention for future clinical treatment for osteoporosis. [Copyright &y& Elsevier]

Abstract: Bone loss associated with microgravity unloading is well documented; however, the effects of spaceflight-relevant types and doses of radiation on the skeletal system are not well defined. In addition, the combined effect of unloading and radiation has not received much attention. In the present study, we investigated the effect of proton irradiation followed by mechanical unloading via hindlimb suspension (HLS) in mice. Sixteen-week-old female C57BL/6 mice were either exposed to 1Gy of protons or a sham irradiation procedure (n=30/group). One day later, half of the mice in each group were subjected to four weeks of HLS or normal loading conditions. Radiation treatment alone (IRR) resulted in approximately 20% loss of trabecular bone volume fraction (BV/TV) in the tibia and femur, with no effect in the cortical bone compartment. Conversely, unloading induced substantially greater loss of both trabecular bone (60–70% loss of BV/TV) and cortical bone (approximately 20% loss of cortical bone volume) in both the tibia and femur, with corresponding decreases in cortical bone strength. Histological analyses and serum chemistry data demonstrated increased levels of osteoclast-mediated bone resorption in unloaded mice, but not IRR. HLS+IRR mice generally experienced greater loss of trabecular bone volume fraction, connectivity density, and trabecular number than either unloading or irradiation alone. Although the duration of unloading may have masked certain effects, the skeletal response to irradiation and unloading appears to be additive for certain parameters. Appropriate modeling of the environmental challenges of long duration spaceflight will allow for a better understanding of the underlying mechanisms mediating spaceflight-associated bone loss and for the development of effective countermeasures. [Copyright &y& Elsevier]

Summary: Introduction: The scapular, parascapular and thoracodorsal artery perforator (TDAP) flaps represent fasciocutaneous flaps derived from the subscapular artery axis. These flaps can be harvested individually or combined as conjoint flaps, tailored to reconstruct a wide variety of defects in the extremities. Analysis and methods: All patients undergoing free-flap reconstruction at North Bristol trust with a fasciocutaneous flap of the subscapular axis from April 2006 until April 2010 were included. This cohort of 45 patients was retrospectively analysed. The Enneking score for return of limb function was used as an outcome measure after reconstruction. Donor-site morbidity analysis was carried out prospectively using Oxford Medical Research Council (MRC) score, Vancouver Scar Scale and disability of arm, shoulder and hand questionnaire (DASH) scores. Results: A total of 45 patients had extremity reconstruction using flaps of the subscapular artery axis following severe limb trauma, often comprising open tibial fractures. A total of 42 patients had lower limb injuries and three had upper limb injuries. All flaps survived. The mean Injury Severity Score (ISS) was 9.3, the mean Enneking score was 27 at 12 months mean follow-up. In the nine conjoint flaps, the mean area of tissue resurfaced was 257 cm2. Conclusions: In this case series of fasciocutaneous flaps of the subscapular artery axis, we establish that these flaps are robust and versatile. They replace ‘like-with-like’ and have good patient satisfaction. The donor site can be closed primarily, is discrete and has minimal donor morbidity. The conjoint flaps can be used for reconstruction of very large defects without the need to sacrifice functionally important muscle. [ABSTRACT FROM AUTHOR]

A case report of a male 6-day-old male layer chick featuring incomplete polymelia of the hind limbs and hindgut malformations is presented. The chick was submitted to computed tomography ( CT) examination and subsequent anatomical dissection. Apart from the two supernumerary hind limbs, the anatomical dissection revealed additional hindgut alterations: three uniform-sized caeca flanked the ileum, and the rectum branched into paired cloacae. The supernumerary hind limbs were localized caudal to the normal hind limbs in an inverted position and were attached to pelvic girdle elements and to a curtate pygostyle. They featured a prominent unpaired femur besides paired tibiotarsi, tarsometatarsi and species-specific phalanges of the toes. Additionally, two separate bones attached to the caudoventral aspect of the regular hip bones were developed. The supernumerary limbs were in part mobile and received nerve and vascular supply. Digital 3 D-reconstruction based on the CT datasets revealed the osseous components of the malformed body parts. The possible morphogenesis including an in-depth literature review and the clinical implications of the reported malformations are discussed. [ABSTRACT FROM AUTHOR]

Summary A foal with a cranio-dorsal coxofemoral luxation was treated with a prosthetic capsulorraphy technique after open reduction. After reluxation a femoral head ostectomy was performed for salvage purposes. The filly was discharged with minimal lameness and was using the limb properly after 51 days of hospitalisation. Four years later the filly is still doing well as a breeding mare, with an acceptable quality of life despite angular deformities in the contralateral limb. [ABSTRACT FROM AUTHOR]

Abstract: Optimization of implant osseointegration in patients with reduced bone healing potential is a challenge remaining in implant dentistry. Identification of the genes that are modulated during implant osseointegration in normal versus osteopenic bone is needed to successfully address these pertinent clinical needs. The present study aimed to assess the initial and early molecular events following titanium implant installation in normal and compromised bone in a rat tibia model. Peri-implant tissue from a well-defined tissue regeneration compartment was analyzed at 2 and 7 days post-surgery for the expression of select markers of inflammation, angiogenesis, bone resorption and bone formation. Impaired bone was induced by hindlimb unloading and validated using μCT. The essential step of angiogenesis preceding bone regeneration was evidenced for the peri-implant setting in healthy bone. Compromised bone significantly affected the angiogenesis-osteogenesis coupling in the initial phase (2 days post-surgery), with altered expressions of Vegfa and Epas1 coinciding with downregulated expressions of Col1a1, Bmp2, Bmp4, Alpl and Bglap. At 7 days post-implantation, differences between normal and compromised peri-implant bone were no longer observed. This in vivo molecular evidence of delayed implant osseointegration in compromised bone reassert modern strategies in implant development, such as surface modifications and bioengineered approaches, to improve implant osseointegration in compromised conditions. [Copyright &y& Elsevier]

The aim of this study was to characterize the orthopedic diseases of the hind limbs in dogs examined at the Veterinary Hospital of the School of Veterinary Medicine and Animal Science, Univ Estadual Paulista (UNESP) - Botucatu (São Paulo - Brasil), during a period of 7-years. A total of 889 dogs were evaluated: 31.9% had fractures of the long bones, 15.1% hip dysplasia, 13% medial patellar luxation, 11.7% cranial cruciate rupture, 11.5% multiple pelvic fractures, and 7.9% hip dislocation. The low-prevalence disorders (4.4%, n=39) were tibiotarsal and tarsometatarsal luxations, avascular necrosis of the femoral head, osteomyelitis and bone tumors, among others. Fractures of the tibia/fibula (14.5%) were more common than femoral fractures (14.2%), and males (54.2%) were more affected than females (45.8%). Considering the dogs with hip dysplasia, 67.9% were aged between 2 and 12 years, and the most common breed was the German shepherd (21.6%) followed by Rottweiler (17.2%) and Labrador (11.2%), while the mixed-breed dogs were 15.7% of total. Of the dogs with patellar luxation, 89.6% had medial luxation, and 36.2% were Poodle, 16.4% were mixed-breed and 12.9% were Pinscher. Cranial cruciate rupture was observed especially in Pit Bull (14.4%), Boxer (11.5%), Poodle (10.6%) and Rottweiler (10.6%) dogs, and mixed-breed dogs constituted 29.8% of the total. According to the age, 62.5% of them had less than 7 years. The most important cause for pelvic fractures was motor vehicle accidents (89.2%), being 52% of the dogs less than 3 years old and 45.1% of them were males. In 86.3% of the cases there were multiple fractures of the pelvis. Considering the dogs with hip dislocation, 57.1% of the cases were associated with motor vehicle accidents. The age ranged from 2 to 18 years, with high prevalence in mixed-breed dogs (44.3%), followed by Poodles (32.9%). In conclusion, the most often orthopedic diseases in decreasing order of occurrence were fractures of the long bones, automobile-induced; hip dysplasia, medial patellar luxation, cranial cruciate rupture, multiple pelvic fractures, and traumatic hip dislocation. [ABSTRACT FROM AUTHOR]

We examined the effects of hind limb unloading (HLU, 14 days) on constriction of carotid and iliac arterial beds in vivo in thiobutabarbital-anaesthetized rats and isolated carotid and iliac arteries in vitro. Both control and HLU rats had similar arterial pressure and carotid and iliac arterial flows. The HLU rats had increased carotid arterial but reduced iliac arterial constriction in response to methoxamine (α1-adrenoceptor agonist) in vivo. In contrast, constriction in response to methoxamine was reduced in the isolated carotid and unchanged in the iliac artery of HLU rats relative to control rats. Thus, HLU is associated with increased constriction of carotid arterial bed but reduced constriction of the isolated carotid artery, and reduced constriction of iliac arterial bed but unchanged constriction of the isolated iliac artery. These results show differential influence of HLU on constriction of cephalic and caudal arterial beds, and differential effect on constrictions of arterial beds relative to conduit arteries. [ABSTRACT FROM AUTHOR]

Abstract: Background: Subtalar arthrodesis (SA) is the preferred treatment for painful isolated subtalar disease. Although results are generally favourable, analysis of current operative techniques will help optimizing this treatment. The aim was to give an overview of SA-techniques and their pitfalls. Possible solutions were identified. Materials and methods: A literature search was performed for papers that presented SA operative techniques. The general technique was divided into phases: surgical approach, cartilage removal, bone graft selection, hindfoot deformity correction and fixation. Results: The published series were invariably retrospective reviews of small heterogenous groups of different hindfoot pathologies. The weighted outcome rate for SA was 85% (68–100%) performed in 766 feet and for SA requiring correction of malalignment 65% (36–96%) in 1001 feet. Non-union (weighted percentage 12%), malalignment (18%), and screw removal (17%) were the prevailing late complications. Pitfalls: The following pitfalls were identified: 1) early complications related to the incisions made in open approaches, 2) insufficient cartilage removal, improper bone graft selection and fixation techniques, all possibly leading to non-union, 3) morbidity caused by bone graft harvesting and secondary screw removal, 4) under- or overcorrection of the hindfoot possibly due to improper intraoperative verification and 5) inadequate assessment of bony fusion. Solutions: The review provides solutions to possibly overcome some pitfalls: 1) if applicable use an arthroscopic approach in combination with distraction devices and new burrs, 2) if possible use local bone graft or allografts, 3) use two screws for fixation to prevent rotational micromotion, and 4) improve assessment of operative outcome by application of appropriate assessment of bony fusion and alignment. Conclusion: The review provides practical suggestions to optimize SA-techniques. [Copyright &y& Elsevier]

Abstract: Despite cross-slope surfaces being a regular feature of our environment, little is known about segmental adaptations required to maintain both balance and forward locomotion. The purpose of this study was to determine kinematic adaptations of the foot segments in relation to transverse (cross-sloped) walking surfaces. Ten young adult males walked barefoot along an inclinable walkway (level, 0° and cross-slope, 10°). Kinematic adaptations of hindfoot with respect to tibia (HF/TB), forefoot with respect to hindfoot (FF/HF), and hallux with respect to forefoot (HX/FF) in level walking (LW), inclined walking up-slope (IWU), i.e., the foot at the higher elevation, and inclined walking down-slope (IWD), i.e., the foot at the lower elevation, were measured. Multivariate analysis of variance (MANOVA) for repeated measures was used to analyze the data. In the sagittal plane, the relative FF/HF and HX/FF plantar/dorsiflexion angles differed across conditions (p =0.024 and p =0.026, respectively). More importantly, numerous frontal plane alterations occurred. For the HF/TB angle, inversion of IWU and eversion of IWD was seen at heel-strike (p <0.001). This pattern reversed with IWU showing eversion and IWD inversion in early stance (p =0.024). For the FF/HF angle, significant differences were observed in mid-stance with IWD revealing inversion while IWU was everted (p <0.004). At toe-off, the pattern switched to eversion of IWD and inversion of IWU (p =0.032). The information obtained from this study enhances our understanding of the kinematics of the human foot in stance during level and cross-slope walking. [Copyright &y& Elsevier]

Abstract: Our recent studies have indicated that acetylcholine (ACh) protects cardiomyocytes from prolonged hypoxia through activation of the PI3K/Akt/HIF-1α/VEGF pathway and that cardiomyocyte-derived VEGF promotes angiogenesis in a paracrine fashion. These results suggest that a cholinergic system plays a role in modulating angiogenesis. Therefore, we assessed the hypothesis that the cholinergic modulator donepezil, an acetylcholinesterase inhibitor utilized in Alzheimer''s disease, exhibits beneficial effects, especially on the acceleration of angiogenesis. We evaluated the effects of donepezil on angiogenic properties in vitro and in vivo, using an ischemic hindlimb model of α7 nicotinic receptor-deleted mice (α7 KO) and wild-type mice (WT). Donepezil activated angiogenic signals, i.e., HIF-1α and VEGF expression, and accelerated tube formation in human umbilical vein endothelial cells (HUVECs). ACh and nicotine upregulated signal transduction with acceleration of tube formation, suggesting that donepezil promotes a common angiogenesis pathway. Moreover, donepezil-treated WT exhibited rich capillaries with enhanced VEGF and PCNA endothelial expression, recovery from impaired tissue perfusion, prevention of ischemia-induced muscular atrophy with sustained surface skin temperature in the limb, and inhibition of apoptosis independent of the α7 receptor. Donepezil exerted comparably more effects in α7 KO in terms of angiogenesis, tissue perfusion, biochemical markers, and surface skin temperature. Donepezil concomitantly elevated VEGF expression in intracardiac endothelial cells of WT and α7 KO and further increased choline acetyltransferase (ChAT) protein expression, which is critical for ACh synthesis in endothelial cells. The present study concludes that donepezil can act as a therapeutic tool to accelerate angiogenesis in cardiovascular disease patients. [Copyright &y& Elsevier]

Trauma is one of the main causes of upper- and lower-limb defects. Limb injuries frequently result in complex defects, hence reconstruction can be demanding. The basic principles of trauma management and methods of reconstruction are analyzed. Then, the evolution of free tissue transfer is reviewed with particular attention to the use of anterolateral thigh flap in reconstruction of upper- and lower-limb trauma cases. The anterolateral thigh flap is the workhorse flap in our department due to its versatility in the reconstruction of complex defects. Finally, the concept of free-style perforator flaps is presented. Microsurgery has supplied the armamentarium of the plastic surgeon with a very powerful tool. Essentially, microsurgery may almost always provide a solution in cases of complex defects that cannot be covered with the simpler options of the reconstructive ladder. The recently acquired perforator flap concept will gradually become the most popular method of microsurgical reconstruction, as it minimizes donor-site morbidity and replaces "like tissue with like tissue." [ABSTRACT FROM AUTHOR]

Peripheral neuropathy is a broad category of disorders with a diverse etiology, grouped together by their common pathogenic effect on the peripheral nervous system (PNS). Because of the heterogeneity observed to be responsible for these disorders, a forward genetics method of gene discovery was used to identify additional affected pathways. In this report, we describe the mutant mouse line 20884, generated by N-ethyl-N-nitrosourea mutagenesis, which is characterized by adult-onset transitory hindlimb paralysis. Linkage mapping revealed that two point mutations are responsible for the phenotype: a partial loss-of-function mutation in the gene for phosphatidate phosphatase Lpin1 and a truncation mutation in the gene that encodes the neuronal cell adhesion molecule NrCAM. To investigate how the 20884 Lpin1 and Nrcam mutations interact to produce the paralysis phenotype, the double mutant and both single mutants were analyzed by quantitative behavioral, histological, and electrophysiological means. The Lpin120884 mutant and the double mutant are characterized by similar levels of demyelination and aberrant myelin structures. Nevertheless, the double mutant exhibits more severe electrophysiological abnormalities than the Lpin120884 mutant. The Nrcam20884 mutant is characterized by normal sciatic nerve morphology and a mild electrophysiological defect. Comparison of the double mutant phenotype with the two single mutants does not point to an additive relationship between the two defects; rather, the Lpin120884 and Nrcam20884 defects appear to act synergistically to produce the 20884 phenotype. It is proposed that the absence of NrCAM in a demyelinating environment has a deleterious effect, possibly by impairing the process of remyelination. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Bone marrow cell therapy contributes to collateral formation through the secretion of angiogenic factors by progenitor cells and muscle cells per se, thereby presenting a novel option for patients with critical limb ischemia. However, some cases are refractory to this therapy due to graft failure. Therefore, we used genetic modification of mesenchymal stem cells (MSCs) to overexpress a vasoregulatory protein, prostacyclin (PGI2), to examine whether it could enhance engraftment and neovascularization in hindlimb ischemia. Methods and results: We engineered the overexpression of PGI2 synthase (PGIS) within MSCs, which resulted in higher expression levels of phosphorylated Akt and Bcl-2 than in control. Under hypoxic conditions, the overexpression of PGIS led to upregulated expression of cyclooxigenase-2 and peroxisome proliferator-activated receptor δ, following a 40% increased rate of proliferation in MSCs. We then produced unilateral hindlimb ischemia in C57BL6/J mice, which were injected either with MSCs transfected with GFP, with MSCs overexpressing PGIS, or with vehicle. Laser Doppler analyses demonstrated that the administration of MSCs effectively recovered blood perfusion, and that the peak blood flow was reached within 7 days of surgery in mice with MSCs overexpressing PGIS, which was earlier than that in mice with MSCs transfected with GFP. This beneficial effect was correlated to enhanced collateral formation and muscle bundle proliferation. Conclusion: Sustained release of PGI2 enhanced the proangiogenic function of MSCs and subsequent muscle cell regrowth in the ischemic tissue suggesting potential therapeutic benefits of cell-based gene therapy for critical limb ischemia. [Copyright &y& Elsevier]

AbstractThe Basso, Beattie, Bresnahan (BBB) locomotor rating scale has proven a reliable tool to evaluate impairments of hindlimb locomotor skills after thoracic spinal cord injury (SCI). With the increasing use of cervical SCI rat models, there is a critical need to develop scoring scales designed to more precisely examine alteration and recovery of forelimb functions. The main goal of the present study was to elaborate and evaluate a new rating scale for open-field testing of the fore- and hindlimb locomotor functions after cervical SCI. We also assessed the effectiveness of this rating scale for discriminating the functional consequences of dorsolateral (Hdl group), lateral (Hl group), or complete C4 unilateral hemisections (Hc group). Our findings show that the new rating scale can be considered as a sensitive and reliable descriptor of the postoperative time course of deficits affecting differentially the fore- and hindlimb sensorimotor functions following injuries of various severities. This new method provides reproducible data and can be used reliably by non-expert examiners. The proposed rating scale appears to be a useful tool for the assessment of various treatments designed to promote functional recovery after SCI. See online Supplementary Material (scoring spreadsheet and videotape recordings) at www.liebertonline.com. [ABSTRACT FROM AUTHOR]

Background: Contrast arteriography (CA) has been the traditional method of evaluation of patients with suspected aortoiliac occlusive disease (AIOD). Recently, less invasive methods, such as Doppler ultrasonography, have been used for the same purpose. Objective: The present study prospectively compares Doppler ultrasonography with CA and direct arterial manometry (DAM) in the preoperative evaluation of patients with suspected AIOD. Methods:Atotal of 125 patients admitted for treatment of arterial occlusive disease of the lower extremities underwent Doppler ultrasonography and CA, comparatively evaluating 552 aortic, common iliac e external iliac segments. The lesions found were classified into five categories: 1) normal and mild stenosis (0-19%); 2) moderate stenosis (20-49%); 3) significant stenosis (50-79%); 4) critical stenosis (80-99%); and 5) total occlusion. DAM was used in 19 segments of 15 patients to classify borderline lesions. Validity indexes (sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy) were calculated to distinguish hemodynamically significant from non-significant stenosis and to discriminate critical stenosis from total occlusions. The gold standard was CA, supplemented by DAM. Correlation coefficients (kappa statistics) between arteriography and Doppler ultrasonography were also calculated for the whole sample of aortoiliac segments. Results: Clinically relevant lesions (stenoses between 50-99% and total occlusions) were observed on Doppler ultrasonography in 163 segments (29.5%) and on CA in 158 segments (28.6%). Doppler ultrasonography showed high validity indexes to distinguish hemodynamically significant from non-significant lesions (overall accuracy = 92%; kappa = 0.81) and an overall accuracy of 86% (kappa = 0.73) to distinguish critical stenosis from total occlusion. Optimal correlation coefficients between the results of Doppler ultrasonography and CA were observed for all aortoiliac segments. Conclusion: Doppler ultrasonography has high validity indexes and optimal correlation coefficients with CA in the evaluation of patients with suspected AIOD. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of the present study was to establish a rat bipedal walking model to examine the effects of bipedal walking on the central nervous system by training rats to perform bipedal walking over a period of 3 months. The characteristics of bipedal walking were investigated using kinematic and electromyographic methods in established bipedal walking models. Stable bipedal walking was achieved in rats by training them to stand with an upright posture and to walk with the hindlimbs using bipedal-walking training equipment to obtain a water reward. A stable head position in the rat bipedal walking model was attained primarily by closing the swing-phase period with a large angular change in the hip, knee, and ankle joints. The EMG burst pattern of the knee extensor (m. rectus femoris) and the erector muscle of the spine (m. longissimus) during bipedal walking was similar to that during quadrupedal walking in rats. We established two bipedal walking models using normal and forelimb-amputated rats. Comparative studies of these two bipedal walking models are expected to provide the information about the influence of forelimb movements on neuronal control of bipedal walking. [Copyright &y& Elsevier]

Background: There is a lot of controversy in the recent literature with regard to the optimal treatment of anterior cruciate ligament (ACL) injuries during growth. latrogenic growth disturbance due to physeal damage is a potential complication, forcing many orthopaedic surgeons to treat these injuries conservatively. Hypothesis: It is possible to perform a fully transphyseal AOL reconstruction in an ovine model with wide-open physes without creating growth disturbances. Study Design: Descriptive laboratory study. Materials and Methods: Four-month-old skeletally immature sheep underwent a transphyseal AOL reconstruction of the right knee. The surgical technique followed the criteria known to be essential to avoid growth disturbances in humans; the tibial tuberosity was spared to prevent a genu recurvatum, thermal damage to the growth plates was avoided, the physes were perforated with a smalldiameter drill in the center of the growth plate, a soft tissue graft was used, graft fixation was achieved far away from the growth plates, the perforated growth plates were filled by the soft tissue graft, and the graft was moderately pretensioned before fixation. The left knee served as a control. A computer-assisted evaluation of long radiographs (frontal and sagittal plane) of the exarticulated hindlimbs was performed to exactly evaluate the limb alignment, joint orientation, and leg length. The animals were sacrificed in groups of 6 after 3, 6, 12, and 24 weeks. Results: No angular deformities or leg-length discrepancies occurred after this transphyseal AOL reconstruction procedure throughout the remaining growth. Conclusion: This large-animal study supports the clinical observation that it is possible to perform an AOL reconstruction without creating growth disturbances as long as a number of key principles are followed. Clinical Relevance: Previous animal studies argued against AOL reconstruction in skeletally immature patients. This largeanimal study provides support for early operative treatment of AOL ruptures even in young patients with open physes. [ABSTRACT FROM AUTHOR]

Background: Most current animal models of hindlimb ischemia use acute arterial occlusion that does not accurately reflect the pathogenesis of gradual arterial occlusion in humans. We, therefore, developed the first mouse model of gradual arterial occlusion and tested the hypothesis that the mechanisms regulating blood flow recovery are critically dependent on the rate of arterial occlusion. Methods: Gradual arterial occlusion was induced by placing ameroid constrictors on the proximal and distal left femoral artery, and ligating the femoral arterial branches (n = 36). Acute arterial occlusion was accomplished by excising the left femoral artery (n = 36). The blood flow recovery was studied by laser Doppler imaging. Differential gene expression between these two models was assessed by quantitative real-time polymerase chain reactions (PCR). Inflammatory and progenitor cells recruitment were determined by immunohistochemistry. Results: We found that hypoxia-related genes increased significantly in the calf, but not in the thigh, after gradual and acute femoral arterial occlusion (P < .05). Shear-stress dependent genes and inflammatory genes were upregulated immediately in the thigh only after acute femoral arterial occlusion (P < .05). These differences in gene expression were consistent with increased SDF-1α expression, recruitment of macrophages and hemangiocytes, and higher blood flow recovery after acute arterial occlusion than after gradual arterial occlusion (P < .05). Conclusion: This is the first study to show the mechanisms that regulate blood flow recovery are critically dependent on the rate of arterial occlusion. This novel model of gradual arterial occlusion may more closely resemble the human diseases, and may provide more accurate mechanistic insights for creating novel molecular therapies. [Copyright &y& Elsevier]