-
Frontiers in Neuroscience 2024Medical imaging allows for the visualization of spinal cord compression sites; however, it is impossible to assess the impact of visible stenotic sites on neuronal...
UNLABELLED
Medical imaging allows for the visualization of spinal cord compression sites; however, it is impossible to assess the impact of visible stenotic sites on neuronal functioning, which is crucial information to formulate a correct prognosis and install targeted therapy. It is hypothesized that with the transcranial electrical stimulation (TES) technique, neurological impairment can be reliably diagnosed.
OBJECTIVE
To evaluate the ability of the TES technique to assess neuronal functional integrity in ataxic horses by recording TES-induced muscular evoked potentials (MEPs) in three different muscles and to structurally involve multiple ancillary diagnostic techniques, such as clinical neurological examination, plain radiography (RX) with ratio assessment, contrast myelography, and post-mortem gross and histopathological examination.
METHODS
Nine ataxic horses, showing combined fore and hindlimb ataxia (grades 2-4), were involved, together with 12 healthy horses. TES-induced MEPs were recorded bilaterally at the level of the trapezius (TR), the extensor carpi radialis (ECR), and tibialis cranialis (TC) muscles. Two Board-certified radiologists evaluated intra- and inter-sagittal diameter ratios on RX, reductions of dorsal contrast columns, and dural diameters (range skull-T1). Post-mortem gross pathological and segmental histopathological examination was also performed by a Board-certified pathologist.
RESULTS
TES-MEP latencies were significantly prolonged in both ECR and TC in all ataxic horses as opposed to the healthy horses. The TR showed a mixed pattern of normal and prolonged latency times. TES-MEP amplitudes were the least discriminative between healthy and ataxic horses. Youden's cutoff latencies for ataxic horses were 24.6 ms for the ECR and 45.5 ms for the TC (sensitivity and specificity of 100%). For healthy horses, maximum latency values were 22 and 37 ms, respectively. RX revealed spinal cord compression in 8 out of 9 involved ataxic horses with positive predictive values of 0-100%. All ataxic horses showed multi-segmental Wallerian degeneration. All pathological changes recorded in the white matter of the spinal cord were widely dispersed across all cervical segments, whereas gray matter damage was more localized at the specific segmental level.
CONCLUSION
TES-MEP latencies are highly sensitive to detect impairment of spinal cord motor functions for mild-to-severe ataxia (grades 2-4).
PubMed: 38665290
DOI: 10.3389/fnins.2024.1342803 -
The Journal of Endocrinology Jul 2011APPL1 is an adaptor protein that binds to both AKT and adiponectin receptors and is hypothesised to mediate the effects of adiponectin in activating downstream effectors...
APPL1 is an adaptor protein that binds to both AKT and adiponectin receptors and is hypothesised to mediate the effects of adiponectin in activating downstream effectors such as AMP-activated protein kinase (AMPK). We aimed to establish whether APPL1 plays a physiological role in mediating glycogen accumulation and insulin sensitivity in muscle and the signalling pathways involved. In vivo electrotransfer of cDNA- and shRNA-expressing constructs was used to over-express or silence APPL1 for 1 week in single tibialis cranialis muscles of rats. Resulting changes in glucose and lipid metabolism and signalling pathway activation were investigated under basal conditions and in high-fat diet (HFD)- or chow-fed rats under hyperinsulinaemic-euglycaemic clamp conditions. APPL1 over-expression (OE) caused an increase in glycogen storage and insulin-stimulated glycogen synthesis in muscle, accompanied by a modest increase in glucose uptake. Glycogen synthesis during the clamp was reduced by HFD but normalised by APPL1 OE. These effects are likely explained by APPL1 OE-induced increase in basal and insulin-stimulated phosphorylation of IRS1, AKT, GSK3β and TBC1D4. On the contrary, APPL1 OE, such as HFD, reduced AMPK and acetyl-CoA carboxylase phosphorylation and PPARγ coactivator-1α and uncoupling protein 3 expression. Furthermore, APPL1 silencing caused complementary changes in glycogen storage and phosphorylation of AMPK and PI3-kinase pathway intermediates. Thus, APPL1 may provide a means for crosstalk between adiponectin and insulin signalling pathways, mediating the insulin-sensitising effects of adiponectin on muscle glucose disposal. These effects do not appear to require AMPK. Activation of signalling mediated via APPL1 may be beneficial in overcoming muscle insulin resistance.
Topics: Adaptor Proteins, Signal Transducing; Animals; Carrier Proteins; Dietary Fats; GTPase-Activating Proteins; Gene Silencing; Glucose Clamp Technique; Glycogen; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Male; Muscle, Skeletal; Nerve Tissue Proteins; Phosphatidylinositol 3-Kinase; Phosphorylation; Proto-Oncogene Proteins c-akt; RNA, Small Interfering; Rats; Rats, Wistar; Signal Transduction
PubMed: 21543456
DOI: 10.1530/JOE-11-0039 -
American Journal of Physiology.... Apr 2014Insulin resistance (IR) in skeletal muscle is a prerequisite for type 2 diabetes and is often associated with obesity. IR also develops alongside muscle atrophy in older...
Insulin resistance (IR) in skeletal muscle is a prerequisite for type 2 diabetes and is often associated with obesity. IR also develops alongside muscle atrophy in older individuals in sarcopenic obesity. The molecular defects that underpin this syndrome are not well characterized, and there is no licensed treatment. Deletion of the transforming growth factor-β family member myostatin, or sequestration of the active peptide by overexpression of the myostatin propeptide/latency-associated peptide (ProMyo) results in both muscle hypertrophy and reduced obesity and IR. We aimed to establish whether local myostatin inhibition would have a paracrine/autocrine effect to enhance glucose disposal beyond that simply generated by increased muscle mass, and the mechanisms involved. We directly injected adeno-associated virus expressing ProMyo in right tibialis cranialis/extensor digitorum longus muscles of rats and saline in left muscles and compared the effects after 17 days. Both test muscles were increased in size (by 7 and 11%) and showed increased radiolabeled 2-deoxyglucose uptake (26 and 47%) and glycogen storage (28 and 41%) per unit mass during an intraperitoneal glucose tolerance test. This was likely mediated through increased membrane protein levels of GLUT1 (19% higher) and GLUT4 (63% higher). Interestingly, phosphorylation of phosphoinositol 3-kinase signaling intermediates and AMP-activated kinase was slightly decreased, possibly because of reduced expression of insulin-like growth factor-I in these muscles. Thus, myostatin inhibition has direct effects to enhance glucose disposal in muscle beyond that expected of hypertrophy alone, and this approach may offer potential for the therapy of IR syndromes.
Topics: Animals; Glucose; Glucose Transporter Type 4; HEK293 Cells; Humans; Hypertrophy; Insulin Resistance; Male; Muscle, Skeletal; Myostatin; Protein Precursors; Rats; Rats, Transgenic; Rats, Wistar; Tissue Distribution; Up-Regulation
PubMed: 24473441
DOI: 10.1152/ajpendo.00586.2013 -
Journal of Anatomy Dec 2006The functional anatomy of the pelvic limb of the ostrich (Struthio camelus) was investigated in order to assess musculoskeletal specialization related to locomotor...
The functional anatomy of the pelvic limb of the ostrich (Struthio camelus) was investigated in order to assess musculoskeletal specialization related to locomotor performance. The pelvic limbs of ten ostriches were dissected and detailed measurements of all muscle tendon units of the pelvic limb were made, including muscle mass, muscle length, fascicle length, pennation angle, tendon mass and tendon length. From these measurements other muscle properties such as muscle volume, physiological cross-sectional area (PCSA), tendon cross-sectional area, maximum isometric muscle force and tendon stress were derived, using standard relationships and published muscle data. Larger muscles tended to be located more proximally and had longer fascicle lengths and lower pennation angles. This led to an expected proximal to distal reduction in total muscle mass. An exception to this trend was the gastrocnemius muscle, which was found to have the largest volume and PCSA and also had the highest capacity for both force and power production. Generally high-power muscles were located more proximally in the limb, while some small distal muscles (tibialis cranialis and flexor perforatus digiti III), with short fibres, were found to have very high force generation capacities. The greatest proportion of pelvic muscle volume was for the hip extensors, while the highest capacity for force generation was observed in the extensors of the ankle, many of which were also in series with long tendons and thus were functionally suited to elastic energy storage.
Topics: Animals; Biomechanical Phenomena; Female; Hindlimb; Locomotion; Male; Muscle Contraction; Muscle, Skeletal; Pelvis; Struthioniformes; Tendons
PubMed: 17118064
DOI: 10.1111/j.1469-7580.2006.00658.x -
Technology in Cancer Research &... Apr 2008Skeletal muscle is an attractive target tissue for delivery of therapeutic genes, since it is well vascularized, easily accessible, and has a high capacity for protein...
Skeletal muscle is an attractive target tissue for delivery of therapeutic genes, since it is well vascularized, easily accessible, and has a high capacity for protein synthesis. For efficient transfection in skeletal muscle, several protocols have been described, including delivery of low voltage electric pulses and a combination of high and low voltage electric pulses. The aim of this study was to determine the influence of different parameters of electrotransfection on short-term and long-term transfection efficiency in murine skeletal muscle, and to evaluate histological changes in the treated tissue. Different parameters of electric pulses, different time lags between plasmid DNA injection and application of electric pulses, and different doses of plasmid DNA were tested for electrotransfection of tibialis cranialis muscle of C57Bl/6 mice using DNA plasmid encoding green fluorescent protein (GFP). Transfection efficiency was assessed on frozen tissue sections one week after electrotransfection using a fluorescence microscope and also noninvasively, followed by an in vivo imaging system using a fluorescence stereo microscope over a period of several months. Histological changes in muscle were evaluated immediately or several months after electrotransfection by determining infiltration of inflammatory mononuclear cells and presence of necrotic muscle fibers. The most efficient electrotransfection into skeletal muscle of C57Bl/6 mice in our experiments was achieved when one high voltage (HV) and four low voltage (LV) electric pulses were applied 5 seconds after the injection of 30 microg of plasmid DNA. This protocol resulted in the highest short-term as well as long-term transfection. The fluorescence intensity of the transfected area declined after 2-3 weeks, but GFP fluorescence was still detectable 18 months after electrotransfection. Extensive inflammatory mononuclear cell infiltration was observed immediately after the electrotransfection procedure using the described parameters, but no necrosis or late tissue damage was observed. This study showed that electric pulse parameters, time lag between the injection of DNA and application of electric pulses, and dose of plasmid DNA affected the duration of transgene expression in murine skeletal muscle. Therefore, transgene expression in muscle can be controlled by appropriate selection of electrotransfection protocol.
Topics: Animals; Electric Stimulation; Electroporation; Female; Green Fluorescent Proteins; Inflammation; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Muscle, Skeletal; Plasmids; Transfection
PubMed: 18345697
DOI: 10.1177/153303460800700201 -
Biomedical Engineering Online Oct 2010Recent studies have shown the potential suitability of magnesium alloys as biodegradable implants. The aim of the present study was to compare the soft tissue... (Comparative Study)
Comparative Study
BACKGROUND
Recent studies have shown the potential suitability of magnesium alloys as biodegradable implants. The aim of the present study was to compare the soft tissue biocompatibility of MgCa0.8 and commonly used surgical steel in vivo.
METHODS
A biodegradable magnesium calcium alloy (MgCa0.8) and surgical steel (S316L), as a control, were investigated. Screws of identical geometrical conformation were implanted into the tibiae of 40 rabbits for a postoperative follow up of two, four, six and eight weeks. The tibialis cranialis muscle was in direct vicinity of the screw head and thus embedded in paraffin and histologically and immunohistochemically assessed. Haematoxylin and eosin staining was performed to identify macrophages, giant cells and heterophil granulocytes as well as the extent of tissue fibrosis and necrosis. Mouse anti-CD79α and rat anti-CD3 monoclonal primary antibodies were used for B- and T-lymphocyte detection. Evaluation of all sections was performed by applying a semi-quantitative score.
RESULTS
Clinically, both implant materials were tolerated well. Histology revealed that a layer of fibrous tissue had formed between implant and overlying muscle in MgCa0.8 and S316L, which was demarcated by a layer of synoviocyte-like cells at its interface to the implant. In MgCa0.8 implants cavities were detected within the fibrous tissue, which were surrounded by the same kind of cell type. The thickness of the fibrous layer and the amount of tissue necrosis and cellular infiltrations gradually decreased in S316L. In contrast, a decrease could only be noted in the first weeks of implantation in MgCa0.8, whereas parameters were increasing again at the end of the observation period. B-lymphocytes were found more often in MgCa0.8 indicating humoral immunity and the presence of soluble antigens. Conversely, S316L displayed a higher quantity of T-lymphocytes.
CONCLUSIONS
Moderate inflammation was detected in both implant materials and resolved to a minimum during the first weeks indicating comparable biocompatibility for MgCa0.8 and S316L. Thus, the application of MgCa0.8 as biodegradable implant material seems conceivable. Since the inflammatory parameters were re-increasing at the end of the observation period in MgCa0.8 it is important to observe the development of inflammation over a longer time period in addition to the present study.
Topics: Absorbable Implants; Alloys; Animals; Biocompatible Materials; Bone Screws; Calcium; Female; General Surgery; Inflammation; Magnesium; Materials Testing; Muscle, Skeletal; Rabbits; Radiography; Steel; Tibia
PubMed: 20974008
DOI: 10.1186/1475-925X-9-63 -
The Journal of Poultry Science Jan 2017A macroscopic examination of the huge leg of the Dong Tao breed from North Vietnam was conducted. Bone and muscular tendon morphometric data demonstrated that the Dong...
A macroscopic examination of the huge leg of the Dong Tao breed from North Vietnam was conducted. Bone and muscular tendon morphometric data demonstrated that the Dong Tao breed was equipped with the extraordinarily thick and large tarsometatarsal bone and distal parts of the related tibiotarsus regions. Morphological differences between dorsal and plantar sides were clearly observed. First, on the dorsal side, fleshy bundles were extended effectively using the enlarged dorsal surface of tarsometatarsal bone shown as Musuculus extensor digitorum brevis, M. extensor digiti I brevis and M. adductor digiti IV. The strong and fleshy extensor bellies of M. tibialis cranialis and M. extensor digitorum longus were enlarged in the crural region, functioning to dorsally pull the heavy tarsometatarsal region through the ankle joint. Second, on the plantar side, the flexor tendon groups around the ankle joint were wider and thicker than those of other ordinary breeds, possibly to stabilize the tarsometatarsal bone and to flex the phalange as observed in M. flexor perforatus digiti II, M. flexor perforans et perforatus digiti II, M. flexor perforatus digiti III, M. flexor perforans et perforatus digiti III, M. flexor perforatus digiti IV, and M. flexor perforans digitorum profundus. The mass of the huge tarsometatarsal region does not contribute to effective locomotion in the Dong Tao fowl in comparison with that associated with normal breeds. However, we suggest that these morphological changes in the musculoskeletal system may functionally compensate for the physical disadvantages of the large weight of the distal part of the hindlimb in the Dong Tao fowl.
PubMed: 32908409
DOI: 10.2141/jpsa.0160074 -
Journal of Veterinary Research Jun 2017The purpose of this study was to compare the effectiveness of four different suture techniques in the treatment of experimentally modelled tendon injuries with tissue...
INTRODUCTION
The purpose of this study was to compare the effectiveness of four different suture techniques in the treatment of experimentally modelled tendon injuries with tissue loss with autograft and grafting applications in rabbits.
MATERIAL AND METHODS
The study was performed on 30 male mature (2-year-old) New Zealand rabbits with mean body weight of 3.1 kg, divided into three equal groups. A graft measuring 1 cm in length was collected from the of each rabbit under general anaesthesia. The graft collected from the right tendon was transplanted into the left tendon, and the graft from the left tendon was transplanted into the right tendon. In all groups, a simple interrupted suture was placed on the left tendon as control, a Bunnell-Mayer suture was placed on the right tendon in group I, a Locking-Loop suture in group II, and a Horizontal U suture in group III. Both hindlimbs were bandaged for four weeks. The tendons were assessed biomechanically and histopathologically.
RESULTS
According to the results of the tensile testing, the maximum durability of the techniques ranked as follows: Bunnell-Mayer, Horizontal U, Locking-Loop, and control groups.
CONCLUSION
The use of autografts was a good alternative for the treatment of tendon ruptures with tissue loss. Furthermore, even though there were no clinical or histopathological differences, the suture technique can be chosen based on the results of the tensile test.
PubMed: 29978078
DOI: 10.1515/jvetres-2017-0030 -
Journal of Anatomy Feb 2008The 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...
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.
Topics: Animals; Biomechanical Phenomena; Female; Hindlimb; Horses; Locomotion; Male; Muscle Contraction; Muscles; Statistics as Topic
PubMed: 18194205
DOI: 10.1111/j.1469-7580.2007.00848.x -
The Journal of Biological Chemistry Apr 2005Skeletal muscle is a major mass peripheral tissue that accounts for approximately 40% of total body weight and 50% of energy expenditure and is a primary site of glucose...
Skeletal muscle is a major mass peripheral tissue that accounts for approximately 40% of total body weight and 50% of energy expenditure and is a primary site of glucose disposal and fatty acid oxidation. Consequently, muscle has a significant role in insulin sensitivity, obesity, and the blood-lipid profile. Excessive caloric intake is sensed by the brain and induces beta-adrenergic receptor (beta-AR)-mediated adaptive thermogenesis. Beta-AR null mice develop severe obesity on a high fat diet. However, the target gene(s), target tissues(s), and molecular mechanism involved remain obscure. We observed that 30-60 min of beta-AR agonist (isoprenaline) treatment of C2C12 skeletal muscle cells strikingly activated (>100-fold) the expression of the mRNA encoding the nuclear hormone receptor, Nur77. In contrast, the expression of other nuclear receptors that regulate lipid and carbohydrate metabolism was not induced. Stable transfection of Nur77-specific small interfering RNAs (siNur77) into skeletal muscle cells repressed endogenous Nur77 mRNA expression. Moreover, we observed attenuation of gene and protein expression associated with the regulation of energy expenditure and lipid homeostasis, for example AMP-activated protein kinase gamma3, UCP3, CD36, adiponectin receptor 2, GLUT4, and caveolin-3. Attenuation of Nur77 expression resulted in decreased lipolysis. Finally, in concordance with the cell culture model, injection and electrotransfer of siNur77 into mouse tibialis cranialis muscle resulted in the repression of UCP3 mRNA expression. This study demonstrates regulatory cross-talk between the nuclear hormone receptor and beta-AR signaling pathways. Moreover, it suggests Nur77 modulates the expression of genes that are key regulators of skeletal muscle lipid and energy homeostasis. In conclusion, we speculate that Nur77 agonists would stimulate lipolysis and increase energy expenditure in skeletal muscle and suggest selective activators of Nur77 may have therapeutic utility in the treatment of obesity.
Topics: Animals; Blotting, Western; Carbohydrate Metabolism; Cell Line; Cell Nucleus; DNA Primers; DNA, Complementary; DNA-Binding Proteins; Electroporation; Gene Expression Regulation; Glucose; Hot Temperature; Lipid Metabolism; Mice; Models, Biological; Muscle, Skeletal; Nuclear Receptor Subfamily 4, Group A, Member 1; Plasmids; Protein Structure, Tertiary; RNA, Messenger; RNA, Small Interfering; Receptors, Adrenergic, beta; Receptors, Cytoplasmic and Nuclear; Receptors, G-Protein-Coupled; Receptors, Steroid; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Transcription Factors; Transfection
PubMed: 15640143
DOI: 10.1074/jbc.M409580200