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Ankle Joints (ankle + joint)
Selected AbstractsIn vivo inhibition of angiogenesis by interleukin-13 gene therapy in a rat model of rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 8 2007Christian S. Haas Objective Interleukin-13 (IL-13) is a pleiotropic cytokine that can affect vessel formation, an important component of the rheumatoid arthritis (RA) synovial tissue pannus. The purpose of this study was to use a gene therapy approach to investigate the role of IL-13 in angiogenesis in vivo, using a rat adjuvant-induced arthritis model of RA. Methods Ankle joints of female rats were injected preventatively with an adenovirus vector containing human IL-13 (AxCAIL-13), a control vector with no insert (AxCANI), or phosphate buffered saline (PBS). Joints were harvested at the peak of arthritis, and histologic and biochemical features were evaluated. Results AxCAIL-13,treated joint homogenates had lower hemoglobin levels, suggesting reduced joint vascularity, and both endothelial cell migration and tube formation were significantly inhibited (P < 0.05). Similarly, AxCAIL-13 inhibited capillary sprouting in the rat aortic ring assay and vessel growth in the Matrigel plug in vivo assay. IL-13 gene delivery resulted in up-regulation and association of phosphorylated ERK-1/2 and protein kinase C,/,II, suggesting a novel pathway in IL-13,mediated angiostasis. The angiostatic effect of AxCAIL-13 was associated with down-regulation of proangiogenic cytokines (IL-18, cytokine-induced neutrophil chemoattractant 1/CXCL1, lipopolysaccharide-induced CXC chemokine/CXCL5) and up-regulation of the angiogenesis inhibitor endostatin. The expression and activity of matrix metalloproteinases 2 and 9, which participate in angiogenesis, was impaired in response to IL-13 as compared with AxCANI and PBS treatment. Conclusion Our findings support a role for IL-13 as an in vivo antiangiogenic factor and provide a rationale for its use in RA to control pathologic neovascularization. [source] In vivo determination of muscle viscoelasticity in the human legACTA PHYSIOLOGICA, Issue 4 2001S. Fukashiro The purpose of this study was to examine the methodological validity of the free vibration technique for determining individual viscoelastic characteristics of the human triceps surae muscle-tendon complex (MTC) in vivo. Six subjects sat with first phalangeal joint of the forefoot on the edge of a force-plate. The special frame on the knee was loaded with weight (0,40 kg) for testing. Oscillations of the triceps surae MTC system were initiated with a hand-held hammer by tapping the weight. In order to keep the same posture, the output of the force plate was displayed on the oscilloscope and subjects were asked to maintain the beam on the oscilloscope at a particular location in relation to a reference line. The damped oscillations in conjunction with the equation of motion of a damped mass-spring model were used to calculate the viscosity of muscle (b) and the elasticity of muscle fibres and tendon (k) in each subject, considering moment arm of the ankle joint. With this arrangement, we have obtained high reproducibility in this method. The coefficient of variations (CVs) of b and k in five trials at each weight were quite small (range: 0.5,18.7% in b and 1.0,15.1% in k). There were no significant differences in viscoelastic coefficients between right and left legs. Therefore, it appears that free vibration technique, used here, is adequate in describing the viscoelastic characteristics of the triceps surae in vivo in humans. [source] Comparison of biomechanical gait parameters of young children with haemophilia and those of age-matched peersHAEMOPHILIA, Issue 2 2009D. STEPHENSEN Summary., Quality of life for children with haemophilia has improved since the introduction of prophylaxis. The frequency of joint haemorrhages has reduced, but the consequences of reduced bleeding on the biomechanical parameters of walking are not well understood. This study explored the differences in sagittal plane biomechanics of walking between a control group (Group 1) of normal age-matched children and children with haemophilia (Group 2) with a target ankle joint. A motion capture system and two force platforms were used to collect sagittal plane kinematic, kinetic and temporal,spatial data during walking of 14 age-matched normal children and 14 children with haemophilia aged 7,13 years. Group differences in maximum and minimum flexion/extension angles and moments of the hip, knee and ankle joints, ground reaction forces and temporal,spatial gait cycle parameters were analysed using one-way anova. Significant changes (P < 0.05) in kinematic and kinetic parameters but not temporal,spatial parameters were found in children with haemophilia; greater flexion angles and external moments of force at the knee, greater ankle plantarflexion external moments and lower hip flexion external moments. These results suggest that early biomechanical changes are present in young haemophilic children with a history of a target ankle joint and imply that lower limb joint function is more impaired than current clinical evaluations indicate. Protocols and quantitative data on the biomechanical gait pattern of children with haemophilia reported in this study provide a baseline to evaluate lower limb joint function and clinical progression. [source] Clinical and radiographic scores in haemophilic arthropathies: how well do these correlate to subjective pain status and daily activities?HAEMOPHILIA, Issue 6 2002T. Wallny Summary. Haemophilic patients who reached adulthood before the establishment of prophylactic treatment frequently show multiple and substantial arthropathies. The aim of this study was to determine to what extent haemophiliac's subjective impairment due to arthropathies correlates with objective clinical and radiographic parameters. By means of a questionnaire and a visual analogue scale, we consulted 79 haemophiliacs concerning their joint-pain status, how these were treated and to what extent their daily activities had been affected. Using a scoring system suggested by the Advisory Committee of the World Federation of Haemophilia, clinical evaluation was performed. Radiographs of 60 patients were assessed by means of the Petterson scale. The results were statistically compared. We found a significant correlation between pain intensity and clinical pathology as well as between pain intensity and radiographic joint damage for both knees and for the right ankle. The number of painful joints correlated well with the number of clinically/radiographically affected joints. The more pronounced the objective damage to joints, the more frequently patients claimed to have constant pain, depressive episodes and a dependency on pain-relieving medication. The more pronounced the objectively assessed damage to the knee and ankle joint, the higher the likelihood that the patient suffers from severe joint pain and reduction of activity. Treatment of painful symptoms from arthropathies is often insufficient. Scores and questionnaires may help to define the haemophiliacs pain status more clearly, thereby offering a possibility of assessment and long-term observation. [source] Alteration of proton diffusivity associated with passive muscle extension and contractionJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2008Masamitsu Hatakenaka MD Abstract Purpose To determine whether passive muscle extension and contraction affect the proton diffusivity of the muscle. Materials and Methods Five male subjects were examined. The fractional anisotropy (FA), and primary (,1), secondary (,2), and tertiary eigenvalues (,3) of the right tibialis anterior and medial gastrocnemius muscles were compared between conditions of passive plantar flexion and passive dorsiflexion of the ankle joint. Results In the tibialis anterior, FA, and ,1 at dorsiflexion decreased significantly (P < 0.01 and P < 0.01, respectively) compared to those at plantar flexion, but ,3 at dorsiflexion increased significantly (P = 0.02). In the gastrocnemius, FA and ,1 at dorsiflexion increased significantly (P < 0.01 and P < 0.01, respectively) compared to those at plantar flexion, but ,3 at dorsiflexion decreased significantly (P < 0.01). The ,2 value showed no significant change in either the tibialis anterior or medial gastrocnemius. Conclusion The results indicate that passive muscle extension and contraction associated with passive joint movement would affect the proton diffusivity of the muscle. This alteration of proton diffusivity is probably associated with microscopic structural changes of the muscle. J. Magn. Reson. Imaging 2008;27:932,937. © 2008 Wiley-Liss, Inc. [source] The effects of Masai Barefoot Technology, footwear on posture: an experimental designed studyPHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 4 2007Paul New Introduction.,This study was approved by the University of Southampton Ethics Committee. The aim of the study was to assess the anatomical changes to upright posture that occur in the sagittal plane as a result of wearing Masai Barefoot Technology (MBT) footwear during standing and walking. MBT claims that its innovative unstable shoes promote a more upright posture in which musculature is strengthened and joint wear reduced (Amann and Amann, 2004). This could be helpful in the management and prevention of conditions such as osteoarthritis and back pain. Method.,Twelve students (six male and six female), aged between 18 and 40 years, at the University of Southampton participated in the study. Participants attended one session at a biomechanics laboratory. The kinematics of posture while wearing MBT shoes during standing and gait were examined, using a two-dimensional motion analysis system, and compared to a control shoe. Statistical significance was tested by use of a paired t -test and a Wilcoxon signed-ranks test. Results.,Students standing in MBT footwear demonstrated a statistically significant increase in plantar flexion at the ankle joint (p = 0.025; mean flexion 3.02°; 95% confidence interval [95% CI] ,5.6 to ,0.4). Walking in MBT shoes showed a decrease in trunk flexion (p = 0.007; mean flexion 1.44°; 95% CI ,2.4 to ,0.4) and a reduction in anterior tilt of the pelvis (p = 0.003; mean tilt 3.20°; 95% CI ,5.06 to ,1.35) at heel strike. At toe-off a significant reduction in anterior pelvic tilt (p = 0.035; mean tilt 2.35°; 95% CI) was found in the MBT shoes. There was no significant difference found between the two shoe conditions at mid-stance, pelvic tilt (p = 0.53; mean tilt 1.83 degrees) trunk flexion (p = 0.05; mean flexion 0.95 deg). Conclusion.,MBT footwear changes certain characteristics of posture in quiet standing and walking. These findings could have positive implications for the management of conditions such as osteoarthritis and back pain; however, further research is needed. Copyright © 2007 John Wiley & Sons, Ltd. [source] Mechanical and neural stretch responses of the human soleus muscle at different walking speedsTHE JOURNAL OF PHYSIOLOGY, Issue 13 2009Neil J. Cronin During human walking, a sudden trip may elicit a Ia afferent fibre mediated short latency stretch reflex. The aim of this study was to investigate soleus (SOL) muscle mechanical behaviour in response to dorsiflexion perturbations, and to relate this behaviour to short latency stretch reflex responses. Twelve healthy subjects walked on a treadmill with the left leg attached to an actuator capable of rapidly dorsiflexing the ankle joint. Ultrasound was used to measure fascicle lengths in SOL during walking, and surface electromyography (EMG) was used to record muscle activation. Dorsiflexion perturbations of 6 deg were applied during mid-stance at walking speeds of 3, 4 and 5 km h,1. At each walking speed, perturbations were delivered at three different velocities (slow: ,170 deg s,1, mid: ,230 deg s,1, fast: ,280 deg s,1). At 5 km h,1, fascicle stretch amplitude was 34,40% smaller and fascicle stretch velocity 22,28% slower than at 3 km h,1 in response to a constant amplitude perturbation, whilst stretch reflex amplitudes were unchanged. Changes in fascicle stretch parameters can be attributed to an increase in muscle stiffness at faster walking speeds. As stretch velocity is a potent stimulus to muscle spindles, a decrease in the velocity of fascicle stretch at faster walking speeds would be expected to decrease spindle afferent feedback and thus stretch reflex amplitudes, which did not occur. It is therefore postulated that other mechanisms, such as altered fusimotor drive, reduced pre-synaptic inhibition and/or increased descending excitatory input, acted to maintain motoneurone output as walking speed increased, preventing a decrease in short latency reflex amplitudes. [source] Innervation of the Pelvic Limb of the Adult Ostrich (Struthio camelus)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2010T. El-Mahdy With 24 figures Summary The pelvic limb of the ostrich is innervated by the lumbar and sacral plexuses. The lumbar plexus gave rise to several nerves (N.s) including, N. coxalis cranialis, lateral and cranial femoral cutaneous N.s, N. femoralis, cranial, caudal and medial crural cutaneous N.s, and N. obturatorius. The remaining nerves emanated from the sacral plexus. The N. iliotibial, N. ischiofemoralis, N. iliofibularis, and N. coxae caudalis were distributed in the thigh, while the N. ischiadica, which terminated as the tibial and fibular N.s that innervated the leg and foot. The tibial N. gave rise to the parafibular N. then divided to form the Nn. suralis medialis and lateralis. The N. suralis medialis continued as the N. metatarsalis plantaris medialis. The parafibular N. continued as the N. plantaris lateralis, which terminated as the R. digitalis of the fourth digit. The fibular N. terminated as the superficial and deep fibular N.s. The superficial fibular N. continued as the N. metatarsalis dorsalis lateralis and divided into two digital N.s to the third and fourth digits. The deep fibular N. crossed the ankle joint and continued as the N. metatarsalis dorsalis medialis that continued as the R. digitalis of the third digit. In general, the innervation of the pelvic limb of the ostrich was similar to the pelvic limbs of several different species of domesticated birds, including the chicken. We discuss the few differences as well as appropriate sites to perform nerve blocks for the lateral and medial dorsal and the lateral plantar N.s. [source] Enhancement of the anti-inflammatory and anti-arthritic effects of theophylline by a low dose of a nitric oxide donor or non-specific nitric oxide synthase inhibitorBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2009Adel Gomaa Background and purpose:, Although there are many new specific phosphodiesterase inhibitors with anti-inflammatory activity, none have yet reached the market because of their low therapeutic efficacy. Our study was aimed to evaluate the anti-inflammatory and anti-arthritic effect of an established phosphodiesterase inhibitor, theophylline, and to investigate the effect of the nitric oxide (NO) donor, sodium nitroprusside (SNP) or NO synthase inhibitor, L-NG -monomethyl arginine (L-NMMA) on its actions. Experimental approach:, The effects of theophylline alone and combined with SNP or L-NMMA on the pathogenesis of adjuvant-induced arthritis in rats were evaluated. Key results:, Prophylactic or therapeutic doses of theophylline significantly ameliorated the pathogenesis of adjuvant arthritis in rats as evidenced by a significant decrease in the arthritis index, hind paws volume, ankle joint diameter, fever, body weight loss and hyperalgesia in a dose-dependent manner. Inflammatory cellular infiltrate in synovium of ankle joint and pannus formation were also markedly inhibited. Interleukin-10 (IL-10) levels were significantly increased in arthritic rats given theophylline alone or in combination with either SNP or L-NMMA. Co-administration of a low dose of SNP or L-NMMA enhanced significantly the anti-inflammatory and anti-arthritic effect of theophylline. In contrast, a high dose of SNP counteracted the anti-inflammatory and anti-arthritic effects of theophylline. Conclusions and Implication:, These findings confirm the anti-inflammatory and anti-arthritic activities of theophylline and suggest a new approach to enhance the anti-inflammatory and anti-arthritic effects of theophylline would be to administer it in combination with a low dose of a NO donor or a non-specific NO synthase inhibitor. [source] Relation between spasticity and strength in individuals with spastic diplegic cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 3 2002Sandy A Ross MHS PT PCS The relation between spasticity and strength in individuals with cerebral palsy (CP) has not been extensively researched. Knee and ankle spasticity and strength were quantified in a retrospective analysis of 60 individuals with spastic diplegic CP (mean age 12 years, range 3 to 38) and a group of 50 individuals without disabilities (WD group; mean age 12 years, range 4 to 36). Spasticity was measured using a KinCom dynamometer that stretched the passive knee flexors or ankle plantarflexors at different speeds and recorded the amount of resistive torques. For the strength tests, the participant performed a maximum contraction of the knee flexors/extensors and ankle plantarflexors/dorsiflexors throughout their range of motion at a speed of 10/s on the dynamometer. Pearson's correlation coefficient was used to determine if a relation existed between spasticity and strength within the same muscle group and in opposing muscle groups at the knee and ankle joints. A t-test was performed to determine if greater spasticity and less strength existed at the ankles compared with the knees in those with CP. Results show that there was no relation between spasticity and strength either within the same muscle group or at opposing muscle groups at the knee and ankle joints in persons with CP. Individuals with spastic diplegic CP were more involved (greater spasticity, less strength) distally at the ankles compared with the knees. The findings conflict with the literature, which contains several assumptions, one of which is that a spastic muscle is a strong muscle and that spasticity causes weakness in the opposing muscle group. We found no relation between spasticity and strength in individuals with CP. Our findings support the literature, which states that individuals with spastic diplegic CP are more involved distally compared with proximally in the lower extremities. [source] Comparison of biomechanical gait parameters of young children with haemophilia and those of age-matched peersHAEMOPHILIA, Issue 2 2009D. STEPHENSEN Summary., Quality of life for children with haemophilia has improved since the introduction of prophylaxis. The frequency of joint haemorrhages has reduced, but the consequences of reduced bleeding on the biomechanical parameters of walking are not well understood. This study explored the differences in sagittal plane biomechanics of walking between a control group (Group 1) of normal age-matched children and children with haemophilia (Group 2) with a target ankle joint. A motion capture system and two force platforms were used to collect sagittal plane kinematic, kinetic and temporal,spatial data during walking of 14 age-matched normal children and 14 children with haemophilia aged 7,13 years. Group differences in maximum and minimum flexion/extension angles and moments of the hip, knee and ankle joints, ground reaction forces and temporal,spatial gait cycle parameters were analysed using one-way anova. Significant changes (P < 0.05) in kinematic and kinetic parameters but not temporal,spatial parameters were found in children with haemophilia; greater flexion angles and external moments of force at the knee, greater ankle plantarflexion external moments and lower hip flexion external moments. These results suggest that early biomechanical changes are present in young haemophilic children with a history of a target ankle joint and imply that lower limb joint function is more impaired than current clinical evaluations indicate. Protocols and quantitative data on the biomechanical gait pattern of children with haemophilia reported in this study provide a baseline to evaluate lower limb joint function and clinical progression. [source] Physical fitness in children with haemophilia and the effect of overweightHAEMOPHILIA, Issue 2 2009D. C. M. DOUMA-VAN RIET Summary., Although children with haemophilia are advised to participate in physical activities, their physical fitness has not been studied in a large group. In addition, children with haemophilia may be at increased risk for becoming overweight as a result of inactivity because of joint bleedings or because of overprotection. This study aimed to assess physical fitness (aerobic capacity), joint status, muscle strength, quality of life (QoL), self-reported motor competence and also prevalence of overweight and its association with physical parameters. Weight and height were measured. Skin folds were measured unilaterally at biceps, triceps, subscapular and supra-iliac sites. Aerobic capacity was determined on a cycle ergometer or with a 6-min walk test (6MWT). Muscle strength and active range of motion of elbows, knees and ankle joints were measured. Self-reported motor competence was measured with the ,Competentie BelevingsSchaal voor Kinderen'. Joint pain was scored on a Visual Analogue Scale. The Haemo-QoL Index was used to measure QoL. In 158 Dutch boys with haemophilia, with a mean age of 12.7 years (SD 2.9), normal aerobic capacity and muscle strength were found. Joint pain was reported by 16% of the participants. The prevalence of overweight (16%) was slightly increased when compared with healthy Dutch boys (13.5%). Being overweight had a negative association with the 6MWT and QoL. Dutch children with haemophilia have normal aerobic exercise capacity and muscle strength. The majority also has normal joint mobility. Prevalence of overweight is slightly increased. [source] Invasive aspergillosis with polyarthritisMYCOSES, Issue 11-12 2004S. F. Mekan Aspergillosis; Aspergillus fumigatus; invasive Infektion; polyarthritis Summary We report a case of septic arthritis of multiple joints in an 18-year-old male caused by Aspergillus fumigatus. His initial presentation was of low-grade fever followed by involvement of both knee and ankle joints. Later, there was also involvement of metacarpophalangeal joints. Diagnosis was based on biopsy and culture of the skin and joint lesions. The symptoms resolved readily under administration of itraconazole. We recommend that clinicians should be alerted of potential fungal etiology in cases of fever and chronic arthritis, which is unresponsive to conventional medical therapy. Zusammenfassung Es wird über einen Fall von Aspergillus fumigatus -bedingter septischer Arthritis mehrerer Gelenke bei einem 18-jährigen Mann berichtet. Die Anfangssymptomatik präsentierte sich als mäßiges Fieber gefolgt von Beschwerden in beiden Knie- und Fußgelenken. Später traten Beschwerden an den Mittelhandgelenken auf. Die Diagnose stützte sich auf Biopsie- und Kulturbefunde aus Haut- und Gelenkläsionen. Die Beschwerden heilten unter Itraconazol-Therapie rasch ab. Bei fieberhafter chronicher Arthritis sollte deshalb stets eine Pilziätiologie erwogen werden, wenn das Krankheitsbild nicht auf eine konventionelle Therapie anspricht. [source] The Hindlimb Muscles of Rhea americana (Aves, Palaeognathae, Rheidae)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2010M. B. J. Picasso With 13 figures Summary The Greater Rhea is the largest cursorial Ratitae bird native to South America. Due to its increasing importance in farming and therefore in the sustainable use of this species, a comprehensive knowledge of their anatomy is essential. The goal of this study was to provide an anatomical description of the hindlimb muscles of Rhea americana. Six adult birds of both sexes were macroscopically studied analysing the origin and insertion of thigh and shank muscles. The thigh showed the highest number of muscles, whereas the shank showed the lowest number; this feature minimizes inertia and allows achieving high stride frequencies. The muscles of the shank showed long tendons of insertion that reduce the energetic cost during running. The major muscles responsible for extension of the hip and the ankle joints were massive and robust indicating their importance for cursorial locomotion. The pelvic limb muscles of Rhea americana resemble those of other cursorial Ratitae and their features are consistent with specialization for high-speed locomotion. [source] The Arterial Supply of the Pelvic Limb of the Adult Ostrich (Struthio camelus)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 4 2010S. M. El-Nahla With 25 figures Summary Blood to the pelvic limb of the ostrich is provided by the external iliac and ischiatic arteries that arise from the descending aorta. The external iliac artery (a.) gave rise to the pubic a. that supplied the obturator muscles and continued as the femoral a. The femoral a. gave off three branches: (1) cranial coxal a. to muscles above the pre-acetabular ilium; (2) cranial femoral a. to muscles cranial to the femur, the gastrocnemius muscle, hip and stifle joints and (3) medial femoral a. to muscles caudal and medial to the femur. The ischiatic a. gave rise to the caudal coxal a. that supplied muscles caudal to the femur, muscular branches to the iliotibialis lateralis muscle and to the deep femoral a. that supplied the iliofibularis muscle, cutanea femoralis caudalis and lateralis aa., and branches to the flexors of the leg and knee joint, then terminated as the sural and popliteal arteries. The sural a. supplied most of the flexors of the foot. The popliteal a. supplied the knee joint and flexors of the leg, and then terminated as the cranial and caudal tibial arteries. The caudal tibial a. supplied flexors of the foot. The cranial tibial a. provided four branches to the knee and ankle joints and to the leg. The cranial tibial a. continued into the foot as the common dorsal metatarsal a., which gave off seven different branches to the ankle and foot. With few exceptions, the arteries of the ostrich pelvic limb are similar to those of domestic fowl. [source] A20 suppresses inflammatory responses and bone destruction in human fibroblast-like synoviocytes and in mice with collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 8 2010Young-Sool Hah Objective Nuclear factor-,B (NF-,B) has been implicated as a therapeutic target for the treatment of rheumatoid arthritis (RA). The purpose of this study was to determine whether A20, a universal inhibitor of NF-,B, might have antiarthritic effects. Methods An adenovirus containing A20 complementary DNA (AdA20) was used to deliver A20 to human rheumatoid fibroblast-like synoviocytes (FLS) in vitro as well as to mice with collagen-induced arthritis (CIA) in vivo via intraarticular injection into the ankle joints bilaterally. Results In vitro experiments demonstrated that AdA20 suppressed NF-,B activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor , in FLS. Mice with CIA that were treated with AdA20 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiologic and histopathologic findings, and inflammatory cytokine levels, than did control virus,injected mice. The protective effects of AdA20 were mediated by the inhibition of the NF-,B signaling pathway. The severity of arthritis was also significantly decreased in the untreated front paws, indicating a beneficial systemic effect of local suppression of NF-,B. Surprisingly, mice treated with AdA20 after the onset of CIA had significantly decreased arthritis severity from the onset of clinical signs to the end of the study. Conclusion These results suggest that using A20 to block the NF-,B pathway in rheumatoid joints reduces both the inflammatory response and the tissue destruction. The development of an immunoregulatory strategy based on A20 may therefore have therapeutic potential in the treatment of RA. [source] Indocyanine green,enhanced imaging of antigen-induced arthritis with an integrated optical imaging/radiography system,ARTHRITIS & RHEUMATISM, Issue 8 2010Reinhard Meier Objective To evaluate a combined indocyanine green,enhanced optical imaging/radiography system for the detection of arthritic joints in a rat model of antigen-induced arthritis. Methods Arthritis of the knee and ankle joints was induced in 6 Harlan rats, using peptidoglycan,polysaccharide polymers. Three rats served as untreated controls. Optical imaging of the knee and ankle joints was done with an integrated optical imaging/radiography system before and up to 24 hours following intravenous injection of 10 mg/kg indocyanine green. The fluorescence signal intensities of arthritic and normal joints were compared for significant differences, using generalized estimating equation models. Specimens of knee and ankle joints were further processed and evaluated by histology. Results Immediately after administration, indocyanine green provided a significant increase in the fluorescence signal of arthritic joints compared with baseline values (P < 0.05). The fluorescence signal of arthritic joints was significantly higher compared with that of nonarthritic control joints at 1,720 minutes after intravenous injection (P < 0.05). Fusion of indocyanine green,enhanced optical imaging and radiography allowed for anatomic coregistration of the inflamed tissue with the associated joint. Hematoxylin and eosin staining confirmed marked synovial inflammation of arthritic joints and the absence of inflammation in control joints. Conclusion Indocyanine green,enhanced optical imaging is a clinically applicable tool for detection of arthritic tissue. Using relatively high doses of indocyanine green, long-term enhanced fluorescence of arthritic joints can be achieved. This may facilitate simultaneous evaluations of multiple joints in a clinical setting. Fusion of indocyanine green,enhanced optical imaging scans with radiography increases anatomic resolution. [source] Genetic deficiency of Syk protects mice from autoantibody-induced arthritisARTHRITIS & RHEUMATISM, Issue 7 2010Zoltán Jakus Objective The Syk tyrosine kinase plays an important role in diverse functions in hematopoietic lineage cells. Although previous in vitro and pharmacologic analyses suggested Syk to be a possible player in the development of autoimmune arthritis, no in vivo genetic studies addressing that issue have yet been reported. The aim of the present study was to test whether genetic deficiency of Syk affects autoantibody-induced experimental arthritis in the K/BxN serum,transfer model. Methods Syk,/, bone marrow chimeras carrying a Syk-deficient hematopoietic system were generated by transplanting Syk,/, fetal liver cells into lethally irradiated wild-type recipients. After complete repopulation of the hematopoietic compartment, autoantibody-mediated arthritis was induced by injection of arthritogenic K/BxN serum. Arthritis development was monitored by macroscopic and microscopic observation of the ankle joints, micro,computed tomography of bone morphology, as well as a joint function assay. Results Genetic deficiency of Syk in the hematopoietic compartment completely blocked the development of all macroscopic and microscopic signs of arthritis. The Syk,/, mutation also prevented the appearance of periarticular bone erosions. Finally, Syk,/, bone marrow chimeras were completely protected from arthritis-induced loss of articular function. Conclusion Our results indicate that Syk is critically involved in the development of all clinically relevant aspects of autoantibody-mediated K/BxN serum,transfer arthritis in experimental mice. These results provide the first in vivo genetic evidence of the role of Syk in the development of autoimmune arthritis. [source] Attenuation of pain and inflammation in adjuvant-induced arthritis by the proteasome inhibitor MG132ARTHRITIS & RHEUMATISM, Issue 7 2010Aisha S. Ahmed Objective In rheumatoid arthritis (RA), pain and joint destruction are initiated and propagated by the production of proinflammatory mediators. Synthesis of these mediators is regulated by the transcription factor NF-,B, which is controlled by the ubiquitin proteasome system (UPS). The present study explored the effects of the proteasome inhibitor MG132 on inflammation, pain, joint destruction, and expression of sensory neuropeptides as markers of neuronal response in a rat model of arthritis. Methods Arthritis was induced in rats by injection of heat-killed Mycobacterium butyricum. Arthritis severity was scored, and nociception was evaluated by mechanical pressure applied to the hind paw. Joint destruction was assessed by radiologic and histologic analyses. NF-,B DNA-binding activity was analyzed by electromobility shift assay, and changes in the expression of the p50 NF-,B subunit and the proinflammatory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) were detected by immunohistochemistry. Results Arthritic rats treated with MG132 demonstrated a marked reduction in inflammation, pain, and joint destruction. The elevated DNA-binding activity of the NF-,B/p50 homodimer and p50, as well as the neuronal expression of SP and CGRP, observed in the ankle joints of arthritic rats were normalized after treatment with MG132. Conclusion In arthritic rats, inhibition of proteasome reduced the severity of arthritis and reversed the pain behavior associated with joint inflammation. These effects may be mediated through the inhibition of NF-,B activation and may possibly involve the peripheral nervous system. New generations of nontoxic proteasome inhibitors may represent a novel pharmacotherapy for RA. [source] Amelioration of experimental arthritis by a telomerase-dependent conditionally replicating adenovirus that targets synovial fibroblastsARTHRITIS & RHEUMATISM, Issue 11 2009Shih-Yao Chen Objective Synovial fibroblasts (SFs) play a pivotal role in the pathogenesis of rheumatoid arthritis (RA). It has been documented that the phenotype of rheumatoid synovium is similar, in many respects, to that of an aggressive tumor. In this study, a novel, genetically engineered adenovirus was designed to lyse SFs that exhibit high telomerase activity and p53 mutations, and its effects as a novel therapeutic strategy were assessed in an experimental arthritis model. Methods An E1B,55-kd,deleted adenovirus driven by the human telomerase reverse transcriptase promoter was constructed (designated Ad.GS1). Cytolysis of SFs and productive replication of Ad.GS1 in the SFs of rats with collagen-induced arthritis (CIA), as well as the SFs of patients with RA (RASFs), were assessed in vitro and in vivo. Treatment responses, as well as the presence of disease-related cytokines and enzymes in the ankle joints, were determined in the murine model. Results Ad.GS1 replicated in and induced cytolysis of human RASFs and SFs from arthritic rats, but spared normal fibroblasts. Bioluminescence imaging in vivo also demonstrated replication of Ad.GS1 in arthritic rat joints, but not in normal rat joints. Intraarticular administration of Ad.GS1 significantly reduced the ankle circumference, articular index scores, radiographic scores, and histologic scores and decreased the production of interleukin-1,, matrix metalloproteinase 9, and prolyl 4-hydroxylase in rats with CIA compared with their control counterparts. Conclusion This study is the first to demonstrate the amelioration of arthritic symptoms by a novel, telomerase-dependent adenovirus in the rat CIA model, an experimental model that resembles human RA. In addition, the results suggest that because of its ability to induce cytolysis of SFs, this virus may be further explored as a therapeutic agent in patients with RA. [source] Botulinumtoxin A treatment in toddlers with cerebral palsyACTA PAEDIATRICA, Issue 8 2010K Tedroff Abstract Aims:, In this study the aim was to evaluate the effect of botulinum toxin A (BoNT-A) treatment on muscle tone, contracture development and gait pattern in young children with cerebral palsy (CP). Method:, Fifteen children with spastic CP (mean age = 16 months) were included in a randomized control study. All received a daily stretching programme and children in the BoNT-A group additionally received two injections, 6 months apart in the gastrocnemius muscle. Outcomes were assessed at baseline, and after 1 and 3.5 years. A 3D gait-analysis was performed at 5 years of age. Results:, Plantarflexor muscle tone in the BoNT-A group was significantly reduced after 3.5 years, while the muscle tone at the ankle and knee in the control group remained unchanged. The change-score in knee-flexion muscle tone between the groups was significantly different after 3.5 years. The knee joint ROM was significantly increased at 1 year in the BoNT-A group but reduced at the knee and ankle joints in the control group after 3.5 years. No group differences were found for gait analysis, GMFM-66 or PEDI. Conclusion:, Early treatment of BoNT-A in children with spastic CP may decrease muscle tone and decelerate contracture development after 3.5 years. The effect on gait development remains inconclusive. [source] | |||||||||||||