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Rat Muscle (rat + muscle)
Selected AbstractsThe Expression Profile of Myogenic Transcription Factors in Satellite Cells from Denervated Rat MuscleBRAIN PATHOLOGY, Issue 2 2002Annette Maier; The muscle-specific transcription factors of the MyoD family are altered after denervation. In order to determine whether this shift takes place in satellite cells (SC), we investigated the expression pattern of MyoD, myf5, myogenin, and MRF4 in SC. Hindlimb muscles of rats were denervated for 2 days to 4 weeks. SC were isolated, pooled and the transcription of all 4 factors was assessed by RT-PCR. Protein expression was assessed in histological sections of soleus and anterior tibial (TA) muscles; SC were identified by M-cadherin. Pooled SC from innervated muscles expressed myf5 mRNA, and very weakly MyoD and myogenin mRNA. MyoD and myogenin protein was found in only few SC. After denervation, pooled SC expressed myf5 mRNA, and very weakly myogenin and MRF4 mRNA. Myogenin protein was found in less than about 10% of the cells, whereas MRF4 protein was absent from SC. We conclude that the presence of myf5 and the absence of MyoD and MRF4 protein in SC after denervation indicated the quiescent state of the cell cycle. A subset of SC has additionally acquired myogenin. SC after denervation might be less easily recruited into the mitotic cycle than SC from normal muscle, rendering regeneration of denervated muscle less efficient than normal muscle. [source] No relationship between enzyme activity and structure of nucleotide binding site in sarcoplasmic reticulum Ca2+ -ATPase from short-term stimulated rat muscleACTA PHYSIOLOGICA, Issue 4 2009T. Mishima Abstract Aim:, We examined whether structural alterations to the adenine nucleotide binding site (ANBS) within sarcoplasmic (endo) reticulum Ca2+ -ATPase (SERCA) would account for contraction-induced changes in the catalytic activity of the enzyme as assessed in vitro. Methods:, Repetitive contractions were induced in rat gastrocnemius by electrical nerve stimulation. Measurements of sarcoplasmic reticulum properties were performed on control and stimulated muscles immediately after or at 30 min after the cessation of 5-min stimulation. In order to examine the properties at the ANBS, the binding capacity of SERCA to fluorescence isothiocyanate (FITC), a competitive inhibitor at the ANBS, was analysed in microsomes. Results:, Short-term electrical stimulation evoked a 23.9% and 32.6% decrease (P < 0.05) in SERCA activity and in the FITC binding capacity, respectively, in the superficial region of the muscle. Whereas SERCA activity reverted to normal levels during 30-min recovery, a restoration of the FITC binding capacity did not occur. Conclusion:, The discordant changes between the enzyme activity and the FITC binding suggest that, at least during recovery after exercise, changes in SERCA activity may not correlate closely with structural alterations to the ANBS within the enzyme. [source] Exercise is the primary factor associated with Hsp70 induction in muscle of treadmill running ratsACTA PHYSIOLOGICA, Issue 4 2006E. G. Noble Abstract Aim:, The cytoprotective, inducible stress protein, Hsp70, increases in muscles of rodents subjected to strenuous treadmill running. Most treadmill running protocols employ negative reinforcement to encourage animals to exercise. As these stimuli may themselves activate stress responses, the present investigation was conducted to determine their contribution to the exercise-induced expression of Hsp70. Methods:, Twenty-one male Sprague,Dawley rats were randomly divided into three equal groups including an exercise group (EX), which ran on a treadmill at 30 m min,1 for 60 min; a stimulation group (STIM), which was not allowed to run, but was stimulated with compressed air and mild electric shock concurrently with their exercising cohort; and a control group (CON), which was housed in the treadmill room during the exercise period. Animals were killed 24 h post-experiment and hearts (H), soleii (SOL) and white gastrocnemii (WG) were harvested and analysed for Hsp70 content (mean% ± SEM of standard). Results:, Significant increases in Hsp70 (as a % of standard) were noted in H and WG (H = 77.4 ± 8.5; WG = 93.9 ± 18.4) of EX but not in STIM (H = 32.5 ± 4.6; WG = 32.0 ± 3.4) or CON (H = 20.5 ± 3.7; WG = 32.4 ± 7.4). In SOL, Hsp70 expression in EX (126.7 ± 6.2) was different from STIM (98.3 ± 10.9) only. This occurred, despite the fact that all groups were exposed to a stressful environment and exhibited elevated (P < 0.001) temperatures (EX ,41.2 ± 0.1 °C > STIM ,40.5 ± 0.2 °C > CON ,39.0 ± 0.1 °C) indicative of a general stress response. Conclusions:, These data suggest that exercise per se, rather than environmental conditions or noxious stimuli, are responsible for the induction of Hsp70 in rat muscle during treadmill running. [source] Metabolic cost of lengthening, isometric and shortening contractions in maximally stimulated rat skeletal muscleACTA PHYSIOLOGICA, Issue 2 2004J. G. M. Beltman Abstract Aim:, The present study investigated the energy cost of lengthening, isometric and shortening contractions in rat muscle (n = 19). Methods:, With electrical stimulation the rat medial gastrocnemius muscle was maximally stimulated to perform 10 lengthening, isometric and shortening contractions (velocity 25 mm s,1) under experimental conditions (e.g. temperature, movement velocity) that resemble conditions in human movement. Results:, Mean ± SD force,time-integral of the first contraction was significantly different between the three protocols, 2.4 ± 0.2, 1.7 ± 0.2 and 1.0 ± 0.2 N s, respectively (P < 0.05). High-energy phosphate consumption was not significantly different between the three modes of exercise but a trend could be observed from lengthening (7.7 ± 2.7 ,mol , P muscle,1) to isometric (8.9 ± 2.2 ,mol , P muscle,1) to shortening contractions (10.4 ± 1.6 ,mol , P muscle,1). The ratio of high-energy phosphate consumption to force,time-integral was significantly lower for lengthening [0.3 ± 0.1 ,mol , P (N s),1] and isometric [0.6 ± 0.2 ,mol , P (N s),1] contractions compared with shortening [1.2 ± 0.2 ,mol , P (N s),1] contractions (P < 0.05). Conclusion:, The present results of maximally stimulated muscles are comparable with data in the literature for voluntary human exercise showing that the energy cost of force production during lengthening exercise is ,30% of that in shortening exercise. The present study suggests that this finding in humans probably does reflect intrinsic muscle properties rather than effects of differential recruitment and/or coactivation. [source] Expression of Na+/HCO3, co-transporter proteins (NBCs) in rat and human skeletal muscleACTA PHYSIOLOGICA, Issue 1 2004J. M. Kristensen Abstract Aim:, Sodium/bicarbonate co-transport (NBC) has been suggested to have a role in muscle pH regulation. We investigated the presence of NBC proteins in rat and human muscle samples and the fibre type distribution of the identified NBCs. Methods and results:, Western blotting of muscle homogenates and sarcolemmal membranes (sarcolemmal giant vesicles) were used to screen for the presence of NBCs. Immunohistochemistry was used for the subcellular localization. The functional test revealed that approximately half of the pH recovery in sarcolemmal vesicles produced from rat muscle is mediated by bicarbonate-dependent transport. This indicates that the NBCs are preserved in the vesicles. The western blotting experiments demonstrated the existence of at least two NBC proteins in skeletal muscle. One NBC protein (approximately 150 kDa) seems to be related to the kidney/pancreas/heart isoform NBC1, whereas the other protein (approximately 200 kDa) is related to the NBC4 isoform. The two NBC proteins represent the electrogenic isoforms named NBCe1 and NBCe2. Membrane fractionation and immunofluorescence techniques confirmed that the two NBCs are located in the sarcolemmal membrane as well as in some internal membranes, probably the T-tubules. The two NBCs localized in muscle have distinct fibre type distributions. Conclusions:, Skeletal muscle possesses two variants of the sodium/bicarbonate co-transporter (NBC) isoforms, which have been called NBCe1 and NBCe2. [source] Dynamics of skeletal muscle oxygenation during sequential bouts of moderate exerciseEXPERIMENTAL PHYSIOLOGY, Issue 3 2005Leonardo F. Ferreira In rat muscle, faster dynamics of microvascular PO2 (approximately blood flowto O2 uptakeratio) after prior contractions that did not alter blood [lactate] have been considered to be a consequence of fasterkinetics. However, in humans, prior exercise below the lactate threshold does not affect the pulmonarykinetics. To clarify this apparent discrepancy, we examined the effects of prior moderate exercise on the kinetics of muscle oxygenation (deoxyhaemoglobin, [HHb],) and pulmonaryin humans. Eight subjects performed two bouts (6 min each) of moderate-intensity cycling separated by 6 min of baseline pedalling. Muscle (vastus lateralis) oxygenation was evaluated by near-infrared spectroscopy andwas measured breath-by-breath. The time constant (,) of the primary component ofwas not significantly affected by prior exercise (21.5 ± 9.2 versus 25.6 ± 9.7 s; Bout 1 versus 2, P= 0.49). The time delay (TD) of [HHb] decreased (11.6 ± 2.6 versus 7.7 ± 1.5 s; Bout 1 versus 2, P < 0.05) and ,[HHb] increased (7.0 ± 3.5 versus 10.2 ± 4.6 s; Bout 1 versus 2, P < 0.05), while the mean response time (TD +,) did not change (18.6 ± 2.7 versus 17.9 ± 3.9 s) after prior moderate exercise. Thus, prior moderate exercise resulted in shorter onset and slower rate of increase in [HHb] during subsequent exercise. These data suggest that prior exercise altered the dynamic interaction betweenandfollowing the onset of exercise. [source] Differential Effects of Cold Exposure on Muscle Fibre Composition and Capillary Supply in Hibernator and Non-Hibernator RodentsEXPERIMENTAL PHYSIOLOGY, Issue 5 2001S. Egginton Changes in the composition of fibre types and the capillary supply of skeletal muscle (tibialis anterior) were quantified in rats and hamsters subjected to 8-10 weeks of cold exposure and reduced photoperiod (10 °C, 1 h light-23 h dark). Muscle mass decreased in both species (by 12% and 17%, respectively). Following acclimation to cold there were no specific changes in fibre cross-sectional area (FCSA) in rats, whereas in hamsters there was a substantial atrophy of Type II, but not Type I fibres. In rat muscle there was little difference between the two groups in average capillary to fibre ratio (C:F) (1.76 ± 0.15, normothermia, N; 1.69 ± 0.05, hypothermia, H) and average capillary density (CD) (188 ± 14 mm,2, N; 201 ± 12 mm -2, H). Similarly, the average C:F was unaltered in hamsters (2.75 ± 0.11, N; 2.72 ± 0.15, H), although the 30% smaller fibre size observed with hypothermia resulted in a corresponding increase in average CD, to 1539 ± 80 mm,2 (P < 0.01). However, there was a coordinated regional adaptation to cold exposure in hamsters resulting in capillary rarefaction in the glycolytic cortex and angiogenesis in the oxidative core. Following acclimation of rats to cold there was a reduction in the supply area of individual vessels (capillary domain), particularly in the cortex (9310, N; 8938 ,m2, H; P < 0.05). In contrast, hypothermic hamsters showed only a small decrease in mean domain area in the cortex (948 ,m2, N; 846 ,m2, H; n.s.) but a marked reduction in the core (871 ,m2, N; 604 ,m2, H; P < 0.01). Rats showed little or no change in local capillary supply (LCFR) to fast fibres on acclimation to cold, while in hamsters the LCFR of Type IIb fibres showed a decrease in the cortex (2.7, N; 2.3, H) and an increase in the core (3.0, N; 3.3, H) during acclimation to cold. These data suggest that during a simulated onset of winter rats maintain FCSA and capillary supply as part of an avoidance strategy, whereas hamsters increase muscle capillarity in part as a consequence of disuse atrophy. [source] Na,K-ATPase ,2 inhibition alters calcium responses in optic nerve astrocytesGLIA, Issue 3 2004April K. Hartford Abstract Experiments were conducted to test the effect of 1 ,M ouabain, an Na,K-ATPase inhibitor, on capacitative calcium entry (CCE) and calcium responses elicited by ATP in rat optic nerve astrocytes. In the rat, 1 ,M ouabain is sufficient to inhibit the ,2 Na,K-ATPase, but not the ,1. Immortalized astrocytes derived from Na,K-ATPase ,2 homozygous knockout (KO) mice and wild-type (WT) littermates were also used. Cytosolic calcium and sodium concentrations were measured using Fura-2 and SBFI, respectively. The magnitude of the increase in cytosolic calcium concentration during CCE was significantly greater in rat astrocytes exposed to 1 ,M ouabain. To measure calcium release from stores, cells were exposed to ATP in the absence of extracellular calcium. In astrocytes exposed to 1 ,M ouabain, a significantly greater calcium response to ATP was observed. 1 ,M ouabain was shown to inhibit ATP hydrolysis in membrane material containing Na,K-ATPase ,2 and ,1 isoforms (rat muscle) but not in membranes containing only Na,K-ATPase ,1 (rat kidney). In intact astrocytes, 1 ,M ouabain did not alter the cell-wide cytosolic sodium concentration. In mouse Na,K-ATPase ,2 KO astrocytes, the calcium increase during CCE was significantly higher than in WT cells, as was the magnitude of the calcium response to ATP. In KO astrocytes, but not WT, the cytosolic calcium increase during CCE was insensitive to 1 ,M ouabain. Taken together, the results suggest that selective inhibition of the Na,K-ATPase ,2 isoform has the potential to change calcium signaling and CCE. © 2003 Wiley-Liss, Inc. [source] Melatonin inhibits the expression of the inducible isoform of nitric oxide synthase and nuclear factor kappa B activation in rat skeletal muscleJOURNAL OF PINEAL RESEARCH, Issue 1 2006María Alonso Abstract:, This study investigated whether the induction of inducible nitric oxide synthase (iNOS) produced by acute exercise in rat skeletal muscle could be prevented by melatonin and whether iNOS down-regulation was related to inhibition of nuclear factor kappaB (NF- ,B) activation. Male Wistar rats received melatonin i.p. at a dose of 1.0 mg/kg body weight 30 min before being exercised for 60 min on a treadmill at a speed of 25 m/min and a 10% slope. Exercise caused a significant induction of iNOS protein levels and a marked activation of NF- ,B that were significantly prevented in rats treated with melatonin. Exercise also resulted in increased I,B kinase, (IKK,) and phosphorylated I,B, protein levels, whereas I,B, content decreased. These effects were blocked by melatonin administration. The increase in the muscle concentration of thiobarbituric acid reactive substances and in the oxidized/reduced glutathione ratio induced by exercise was partially prevented by melatonin. Our data indicate that melatonin has potent protective effects against damage caused by acute exercise in rat muscle, preventing oxidative stress, NF- ,B activation and iNOS over-expression. These findings support the view that melatonin treatment, by abolishing the IKK/NF- ,B signal transduction pathway, might block the production of noxious mediators involved in the inflammatory process. [source] Inhibition of the initial wave of NF-,B activity in rat muscle reduces ischemia/reperfusion injuryMUSCLE AND NERVE, Issue 4 2001Sean T. Lille MD Abstract Nuclear factor kappaB (NF-,B) is thought to play an important role in the expression of genes expressed in response to ischemia/reperfusion (I/R) injury. In this report, the activation of NF-,B in rat skeletal muscle during reperfusion following a 4-h ischemic period was studied. NF-,B activation displayed a biphasic pattern, showing peak activities from 30 min to 3 h postperfusion and 6 h to 16 h postperfusion, with a decline to baseline binding activity levels between 3 h and 6 h. Inhibition of NF-,B activation was investigated using proline dithiocarbamate (Pro-DTC). NF-,B binding activity during reperfusion was significantly reduced by intravenous administration of Pro-DTC. Additionally, Pro-DTC resulted in decreased muscle edema and neutrophil activity, with an increased percentage of muscle survival compared with vehicle controls. These results demonstrate that NF-,B is activated during reperfusion in a biphasic manner and that the regulation of the initial phase of NF-,B activation affords physiological protection against a severe ischemic stress. Selective inhibition of NF-,B during early reperfusion may therefore be a therapeutic intervention for I/R injury. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 534,541, 2001 [source] Compartmental relaxation and diffusion tensor imaging measurements in vivo in ,-carrageenan-induced edema in rat skeletal muscle,NMR IN BIOMEDICINE, Issue 6 2008Reuben H. Fan Abstract Integrated diffusion tensor T2 measurements were made on normal and edematous rat muscle, and the data were fitted with one- and two-compartment models, respectively. Edematous muscle exhibited a short-lived component (T2,=,28,±,6,ms), with diffusion characteristics similar to that of normal muscle, and a long-lived component (T2,=,96,±,27,ms), with greater mean apparent diffusion coefficient (ADC) and lower fractional anisotropy (FA). With this two-component description of diffusion and relaxation, values of ADC and FA estimated with a conventional pulsed-gradient spin-echo sequence will depend on the echo time, relative fraction of short-lived and long-lived water signals, and the intrinsic ADC and FA values within the tissue. On the basis of the relative differences in water diffusion properties between long-lived and short-lived water signals, as well as the similarities between the short-lived component and normal tissue, it is postulated that these two signal components largely reflect intracellular and extracellular water. Copyright © 2007 John Wiley & Sons, Ltd. [source] Differential expression of skeletal muscle proteins in high-fat diet-fed rats in response to capsaicin feedingPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 15 2010Dong Hyun Kim Abstract In this study, the effects of capsaicin on expression of skeletal muscle proteins in Sprague,Dawley rats fed with a high-fat diet (HFD) were investigated. Rats were fed a HFD with or without capsaicin treatment for 8,wk. After HFD feeding, capsaicin-treated rats weighed an average of 8% less than those of the HFD control group. Gastrocnemius muscle tissue from lean and obese rats with or without capsaicin treatment was arrayed using 2-DE for detection of HFD-associated markers. Proteomic analysis using 2-DE demonstrated that 36 spots from a total of approximately 600 matched spots showed significantly different expression; 27 spots were identified as gastrocnemius muscle proteins that had been altered in response to capsaicin feeding, and 6 spots could not be identified by mass fingerprinting. Expression of various muscle proteins was determined by immunoblot analysis for the determination of molecular mechanisms, whereby capsaicin caused inhibition of adipogenesis. Immunoblot analysis revealed increased uncoupling protein 3 (UCP3) protein expression in HFD-fed rats, whereas contents were reduced with capsaicin treatment. Compared with the HFD control group, capsaicin treatment increased phosphorylation of AMP-activated protein kinase (AMPIC) CP3 and acetyl-CoA carboxylase (ACC). To support this result, we also analyzed in vitro differential protein expression in L6 skeletal muscle cells. These data suggest that the AMPK-ACC-malonyl-CoA metabolic signaling pathway is one of the targets of capsaicin action. To the best of our knowledge, this is the first proteomic study to report on analysis of diet-induced alterations of protein expression that are essential for energy expenditure in rat muscle. [source] Intramuscular SP1017-formulated DNA electrotransfer enhances transgene expression and distributes hHGF to different rat tissuesTHE JOURNAL OF GENE MEDICINE, Issue 1 2004Marta Riera Abstract Background The systemic administration of a therapeutic protein is a common approach for the treatment of multiple disorders. Intramuscular (i.m.) injection of plasmids, followed by electroporation, has been shown to facilitate naked DNA gene transfer in skeletal muscle allowing proteins to be produced and secreted at therapeutically relevant levels. Methods Plasmid DNA, unformulated or formulated with the non-ionic carrier SP1017, was injected at the rat tibialis anterior muscle followed by the application of electric pulses. Follow-up of protein expression was measured. Results In our study we report that the non-ionic carrier SP1017 significantly increases transgene expression in rat muscle after the i.m. injection of a formulated-pCMV, plasmid followed by electroporation. Such increased expression was observed after delivering square-wave unipolar electric pulses at two different field strengths: low (110 V/cm) and high (175 V/cm). Moreover, elevated secreted placental alkaline phosphatase (SEAP) plasma levels were achieved with low-voltage (110 V/cm) electroporation. Our results also show that human hepatocyte growth factor (hHGF) can be produced from rat muscle and delivered to blood circulation at a biologically active level after a single i.m. injection of an SP1017-formulated plasmid (pCMV/hHGF) followed by electroporation. Tissue distribution studies mostly identified hHGF in the liver, but it was also found in the kidneys and lungs suggesting that here too the HGF could be of therapeutic benefit. Conclusions Our results indicate that SP1017 enhances the expression of electrotransferred genes. Such a delivery approach could prove an efficient method for the systemic production of therapeutic proteins. Copyright © 2003 John Wiley & Sons, Ltd. [source] Insulin and contraction increase nutritive blood flow in rat muscle in vivo determined by microdialysis of l -[14C]glucoseTHE JOURNAL OF PHYSIOLOGY, Issue 1 2007John M. B. Newman In the present study, a mathematical model using the microdialysis outflow: inflow (O/I) ratio of the novel analogue l -[14C]glucose has been developed which allows the calculation of the nutritive (and non-nutritive) flow in muscle as a proportion of total blood flow. Anaesthetized rats had microdialysis probes carrying l -[14C]glucose inserted through a calf muscle group (tibialis/plantaris/gastrocnemius). The nutritive fraction of total blood flow was determined under basal conditions and in response to contraction (electrical field stimulation), insulin (hyperinsulinaemic euglycaemic clamp with 10 mU min,1 kg,1 insulin) or saline control from limb blood flow and the microdialysis O/I ratio of l -[14C]glucose. Both contraction and insulin infusion decreased the O/I ratio of l -[14C]glucose and increased total limb blood flow. Calculations based on mathematical models using l -[14C]glucose O/I and limb blood flow revealed that during basal conditions, the nutritive fraction of total flow was 0.38 ± 0.06, indicating that basal flow was predominantly non-nutritive. Contraction and insulin increased the nutritive fraction to 0.82 ± 0.24 (P < 0.05) and 0.52 ± 0.12 (P < 0.05). Thus the increase in limb blood flow from insulin was fully accommodated by nutritive flow, while contraction increased nutritive flow at the expense of non-nutritive flow. This novel method using microdialysis and the O/I ratio of l -[14C]glucose allows the determination of the nutritive fraction of total flow in muscle as well as the proportion of total flow that may be redistributed in response to contraction and insulin. [source] Real-time Polymerase Chain Reaction to Follow the Response of Muscle to TrainingARTIFICIAL ORGANS, Issue 8 2008Lauren M. Moore Abstract:, The adaptive response of muscle to changes in activity or loading can take many weeks. Changes in the levels of RNA within a muscle fiber can give an early indication of the nature of the response of that fiber to changes in activity or loading. We have designed a new primer set for quantitative polymerase chain reaction (PCR) that will allow us to follow these early transcriptional changes in rat muscle, and have shown that analysis can be performed by standard techniques on as little as 5 mg of muscle, an amount that can be obtained by needle biopsy. [source] Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathwayACTA PHYSIOLOGICA, Issue 4 2009C. Hourdé Abstract Aim:, We analysed the effect of physiological doses of androgens following orchidectomy on skeletal muscle and bone of male rats, as well as the relationships between muscle performance, hypertrophy and the Akt/mammalian target of rapamycin (mTOR) signalling pathway involved in the control of anabolic and catabolic muscle metabolism. Methods:, We studied the soleus muscle and tibia from intact rats (SHAM), orchidectomized rats treated for 3 months with vehicle (ORX), nandrolone decanoate (NAN) or dihydrotestosterone (DHT). Results:, Orchidectomy had very little effect on the soleus muscle. However, maximal force production by soleus muscle (+69%) and fatigue resistance (+35%) in NAN rats were both increased when compared with ORX rats. In contrast, DHT treatment did not improve muscle function. The relative number of muscle fibres expressing slow myosin heavy chain and citrate synthase activity were not different in NAN and ORX rats. Moreover, NAN and DHT treatments did not modify muscle weights and cross-sectional area of muscle fibres. Furthermore, phosphorylation levels of downstream targets of the Akt/mTOR signalling pathway, Akt, ribosomal protein S6 and eukaryotic initiation factor 4E-binding protein 1 were similar in muscles of NAN, DHT and ORX rats. In addition, trabecular tibia from NAN and DHT rats displayed higher bone mineral density and bone volume when compared with ORX rats. Only in NAN rats was this associated with increased bone resistance to fracture. Conclusion:, Physiological doses of androgens are beneficial to muscle performance in orchidectomized rats without relationship to muscle and fibre hypertrophy and activation of the Akt/mTOR signalling pathway. Taken together our data clearly indicate that the activity of androgens on muscle and bone could participate in the global improvement of musculoskeletal status in the context of androgen deprivation induced by ageing. [source] Adhesion molecule expression in experimental myositisMUSCLE AND NERVE, Issue 3 2002Tomoko Ito MD Abstract Experimental allergic myositis (EAM) in Lewis rats, induced with partially purified myosin, is regarded as a model of human polymyositis. To clarify the role of adhesion molecules in the pathogenesis of EAM in Lewis rats, we investigated intramysial expressions of the intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, and the serum level of soluble ICAM-1 in EAM rats. All the EAM rat muscles had scattered inflammatory foci, as well as cell infiltration and necrosis, by week 4 after the initial immunization (i.e., day 0 after the last immunization). As compared with the control muscles, ICAM-1 and VCAM-1 were strongly expressed immunohistochemically in the endothelium of vessels in the endomysium and perimysium, and to lesser extents in the inflammatory infiltrates and on the sarcolemma of nonnecrotic muscle fibers adjacent to the inflammatory infiltrates or invaded muscle fibers. ICAM-1 in the muscle extracts and sera from EAM rats increased on each test day, as compared with extracts from the normal controls. The values peaked on day 0 after the last immunization, then gradually decreased with time. ICAM-1 elevations in the muscle extracts were correlated with the percent of sections that had inflammatory lesions (P = 0.032) and the histological scores (P = 0.005) on day 0, whereas there was no significance on days 3 and 7. These findings suggest that the adhesion molecules ICAM-1 and VCAM-1 increase in the early stage of EAM, and function in the initiation of the inflammatory process of myositis. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000,000, 2002 [source] |