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Rosario Hernandez - One of the best experts on this subject based on the ideXlab platform.
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poor regenerative outcome after skeletal Muscle Necrosis induced by bothrops asper venom alterations in microvasculature and nerves
PLOS ONE, 2011Co-Authors: Rosario Hernandez, Carmen Cabalceta, Patricia Saraviaotten, Alessandra Chaves, Jose Maria Gutierrez, Alexandra RucavadoAbstract:BACKGROUND: Viperid snakebite envenoming is characterized by prominent local tissue damage, including Muscle Necrosis. A frequent outcome of such local pathology is deficient skeletal Muscle regeneration, which causes Muscle dysfunction, Muscle loss and fibrosis, thus provoking permanent sequelae that greatly affect the quality of life of patients. The causes of such poor regenerative outcome of skeletal Muscle after viperid snakebites are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: A murine model of Muscle Necrosis and regeneration was adapted to study the effects of the venom and isolated toxins of Bothrops asper, the medically most important snake in Central America. Gastrocnemius Muscle was injected with either B. asper venom, a myotoxic phospholipase A(2) (Mtx), a hemorrhagic metalloproteinase (SVMP), or saline solution. At various time intervals, during one month, tissue samples were collected and analyzed by histology, and by immunocytochemical and immunohistochemical techniques aimed at detecting Muscle fibers, collagen, endothelial cells, myoblasts, myotubes, macrophages, TUNEL-positive nuclei, and axons. A successful regenerative response was observed in Muscle injected with Mtx, which induces myoNecrosis but does not affect the microvasculature. In contrast, poor regeneration, with fibrosis and atrophic fibers, occurred when Muscle was injected with venom or SVMP, both of which provoke Necrosis, microvascular damage leading to hemorrhage, and poor axonal regeneration. CONCLUSIONS/SIGNIFICANCE: The deficient skeletal Muscle regeneration after injection of B. asper venom is likely to depend on the widespread damage to the microvasculature, which affects the removal of necrotic debris by phagocytes, and the provision of nutrients and oxygen required for regeneration. In addition, deficient axonal regeneration is likely to contribute to the poor regenerative outcome in this model. Language: en
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poor regenerative outcome after skeletal Muscle Necrosis induced by bothrops asper venom alterations in microvasculature and nerves
PLOS ONE, 2011Co-Authors: Rosario Hernandez, Carmen Cabalceta, Patricia Saraviaotten, Alessandra Chaves, Jose Maria Gutierrez, Alexandra RucavadoAbstract:articulo (arbitrado) -- Universidad de Costa Rica, Instituto de Investigaciones Clodomiro Picado. 2011
Alexandra Rucavado - One of the best experts on this subject based on the ideXlab platform.
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poor regenerative outcome after skeletal Muscle Necrosis induced by bothrops asper venom alterations in microvasculature and nerves
PLOS ONE, 2011Co-Authors: Rosario Hernandez, Carmen Cabalceta, Patricia Saraviaotten, Alessandra Chaves, Jose Maria Gutierrez, Alexandra RucavadoAbstract:BACKGROUND: Viperid snakebite envenoming is characterized by prominent local tissue damage, including Muscle Necrosis. A frequent outcome of such local pathology is deficient skeletal Muscle regeneration, which causes Muscle dysfunction, Muscle loss and fibrosis, thus provoking permanent sequelae that greatly affect the quality of life of patients. The causes of such poor regenerative outcome of skeletal Muscle after viperid snakebites are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: A murine model of Muscle Necrosis and regeneration was adapted to study the effects of the venom and isolated toxins of Bothrops asper, the medically most important snake in Central America. Gastrocnemius Muscle was injected with either B. asper venom, a myotoxic phospholipase A(2) (Mtx), a hemorrhagic metalloproteinase (SVMP), or saline solution. At various time intervals, during one month, tissue samples were collected and analyzed by histology, and by immunocytochemical and immunohistochemical techniques aimed at detecting Muscle fibers, collagen, endothelial cells, myoblasts, myotubes, macrophages, TUNEL-positive nuclei, and axons. A successful regenerative response was observed in Muscle injected with Mtx, which induces myoNecrosis but does not affect the microvasculature. In contrast, poor regeneration, with fibrosis and atrophic fibers, occurred when Muscle was injected with venom or SVMP, both of which provoke Necrosis, microvascular damage leading to hemorrhage, and poor axonal regeneration. CONCLUSIONS/SIGNIFICANCE: The deficient skeletal Muscle regeneration after injection of B. asper venom is likely to depend on the widespread damage to the microvasculature, which affects the removal of necrotic debris by phagocytes, and the provision of nutrients and oxygen required for regeneration. In addition, deficient axonal regeneration is likely to contribute to the poor regenerative outcome in this model. Language: en
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poor regenerative outcome after skeletal Muscle Necrosis induced by bothrops asper venom alterations in microvasculature and nerves
PLOS ONE, 2011Co-Authors: Rosario Hernandez, Carmen Cabalceta, Patricia Saraviaotten, Alessandra Chaves, Jose Maria Gutierrez, Alexandra RucavadoAbstract:articulo (arbitrado) -- Universidad de Costa Rica, Instituto de Investigaciones Clodomiro Picado. 2011
Jose Maria Gutierrez - One of the best experts on this subject based on the ideXlab platform.
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Why myotoxin-containing snake venoms possess powerful nucleotidases?
Biochemical and biophysical research communications, 2012Co-Authors: Paola Caccin, Bruno Lomonte, Jose Maria Gutierrez, Patrizia Pellegatti, Julián Fernández, Maria Vono, Mariana Cintra-francischinelli, Francesco Di Virgilio, Cesare MontecuccoAbstract:The venom of the snake Bothrops asper causes Muscle Necrosis, pain and inflammation. This venom contains myotoxins which cause an increase in intracellular Ca2+ concentration and release of K+ and ATP from myotubes. ATP is a key danger molecule that triggers a variety of reactions, including activation of the innate immune response. Here, using ATP-luciferase bioluminescence imaging technique, we show for the first time in vivo, that the purified myotoxins induce rapid release of ATP, whilst the complete venom of B. asper does at a very small extent. This apparent contradiction is explained by the finding that the venom contains powerful nucleotidases that in vivo convert ATP into ADP, AMP and Adenosine. These findings indicate that high concentrations of adenosine are generated by the double action of the venom and provide the experimental basis to the suggestion that in situ generated adenosine plays an important role in envenomation via its hypotensive, paralyzing and anti-coagulant activities.
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poor regenerative outcome after skeletal Muscle Necrosis induced by bothrops asper venom alterations in microvasculature and nerves
PLOS ONE, 2011Co-Authors: Rosario Hernandez, Carmen Cabalceta, Patricia Saraviaotten, Alessandra Chaves, Jose Maria Gutierrez, Alexandra RucavadoAbstract:BACKGROUND: Viperid snakebite envenoming is characterized by prominent local tissue damage, including Muscle Necrosis. A frequent outcome of such local pathology is deficient skeletal Muscle regeneration, which causes Muscle dysfunction, Muscle loss and fibrosis, thus provoking permanent sequelae that greatly affect the quality of life of patients. The causes of such poor regenerative outcome of skeletal Muscle after viperid snakebites are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: A murine model of Muscle Necrosis and regeneration was adapted to study the effects of the venom and isolated toxins of Bothrops asper, the medically most important snake in Central America. Gastrocnemius Muscle was injected with either B. asper venom, a myotoxic phospholipase A(2) (Mtx), a hemorrhagic metalloproteinase (SVMP), or saline solution. At various time intervals, during one month, tissue samples were collected and analyzed by histology, and by immunocytochemical and immunohistochemical techniques aimed at detecting Muscle fibers, collagen, endothelial cells, myoblasts, myotubes, macrophages, TUNEL-positive nuclei, and axons. A successful regenerative response was observed in Muscle injected with Mtx, which induces myoNecrosis but does not affect the microvasculature. In contrast, poor regeneration, with fibrosis and atrophic fibers, occurred when Muscle was injected with venom or SVMP, both of which provoke Necrosis, microvascular damage leading to hemorrhage, and poor axonal regeneration. CONCLUSIONS/SIGNIFICANCE: The deficient skeletal Muscle regeneration after injection of B. asper venom is likely to depend on the widespread damage to the microvasculature, which affects the removal of necrotic debris by phagocytes, and the provision of nutrients and oxygen required for regeneration. In addition, deficient axonal regeneration is likely to contribute to the poor regenerative outcome in this model. Language: en
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poor regenerative outcome after skeletal Muscle Necrosis induced by bothrops asper venom alterations in microvasculature and nerves
PLOS ONE, 2011Co-Authors: Rosario Hernandez, Carmen Cabalceta, Patricia Saraviaotten, Alessandra Chaves, Jose Maria Gutierrez, Alexandra RucavadoAbstract:articulo (arbitrado) -- Universidad de Costa Rica, Instituto de Investigaciones Clodomiro Picado. 2011
Miranda D Grounds - One of the best experts on this subject based on the ideXlab platform.
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identification of Muscle Necrosis in the mdx mouse model of duchenne muscular dystrophy using three dimensional optical coherence tomography
Journal of Biomedical Optics, 2011Co-Authors: Blake R Klyen, Miranda D Grounds, Thea Shavlakadze, Hannah G Radleycrabb, David D SampsonAbstract:Three-dimensional optical coherence tomography (3D-OCT) was used to image the structure and pathology of skeletal Muscle tissue from the treadmill-exercised mdx mouse model of human Duchenne muscular dystrophy. Optical coherence tomography (OCT) images of excised Muscle samples were compared with co-registered hematoxylin and eosin-stained and Evans blue dye fluorescence histology. We show, for the first time, structural 3D-OCT images of skeletal Muscle dystropathology well correlated with co-located histology. OCT could identify morphological features of interest and necrotic lesions within the Muscle tissue samples based on intrinsic optical contrast. These findings demonstrate the utility of 3D-OCT for the evaluation of small-animal skeletal Muscle morphology and pathology, particularly for studies of mouse models of muscular dystrophy.
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reduced Muscle Necrosis and long term benefits in dystrophic mdx mice after cv1q blockade of tnf treatment
Neuromuscular Disorders, 2008Co-Authors: Hannah G Radley, Marilyn Davies, Miranda D GroundsAbstract:Tumour Necrosis factor (TNF) is a potent inflammatory cytokine that appears to exacerbate damage of dystrophic Muscle in vivo. The monoclonal murine specific antibody cV1q that specifically neutralises murine TNF demonstrated significant anti-inflammatory effects in dystrophic mdx mice. cV1q administration protected dystrophic skeletal myofibres against Necrosis in both young and adult mdx mice and in adult mdx mice subjected to 48 h voluntary wheel exercise. Long-term studies (up to 90 days) in voluntarily exercised mdx mice showed beneficial effects of cV1q treatment with reduced histological evidence of myofibre damage and a striking decrease in serum creatine kinase levels. However, in the absence of exercise long-term cV1q treatment did not reduce Necrosis or background pathology in mdx mice. An additional measure of well-being in the cV1q treated mice was that they ran significantly more than control mdx mice.
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anti tnfα remicade therapy protects dystrophic skeletal Muscle from Necrosis
The FASEB Journal, 2004Co-Authors: Miranda D Grounds, Johanna TorrisiAbstract:Necrosis of skeletal Muscle fibers in the lethal childhood myopathy Duchenne muscular dystrophy (DMD) results from defects in the cell membrane-associated protein, dystrophin. This study tests the novel hypothesis that the initial sarcolemmal breakdown resulting from dystrophin deficiency is exacerbated by inflammatory cells and that cytokines, specifically tumor Necrosis factor-alpha (TNFalpha), contribute to Muscle Necrosis. To block in vivo TNFalpha bioactivity, young dystrophic mdx mice (a model for DMD) were injected weekly from 7 days of age with the anti-TNFalpha antibody Remicade before the onset of Muscle Necrosis and dystropathology that normally occurs at 21 days postnatally. The extent of inflammation, Muscle Necrosis, and myotube formation was measured by histological analysis from 18 to 28 days and Muscle damage was also visualized by penetration of Evans blue dye into myofibers. Data from Remicade-treated and control mdx mice were compared with mdx/TNFalpha-/- mice that lack TNFalpha. Pharmacological blockade of TNFalpha activity with Remicade clearly delayed and greatly reduced the breakdown of dystrophic Muscle, in marked contrast to the situation in mdx and mdx/TNFalpha-/- mice. Remicade had no adverse effect on new Muscle formation. Remicade is a highly specific anti-inflammatory intervention, and clinical application to muscular dystrophies is suggested by this marked protective effect against skeletal Muscle breakdown.
Louis M Messina - One of the best experts on this subject based on the ideXlab platform.
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tetrahydrobiopterin l arginine and vitamin c act synergistically to decrease oxidant stress and increase nitric oxide that increases blood flow recovery after hindlimb ischemia in the rat
Molecular Medicine, 2012Co-Authors: Jinglian Yan, Guodong Tie, Louis M MessinaAbstract:Nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS) is a potent vasodilator and signaling molecule that plays essential roles in neovascularization. During limb ischemia, decreased NO bioavailability occurs secondary to increased oxidant stress, decreased L-arginine and tetrahydrobiopterin. This study tested the hypothesis that dietary cosupplementation with tetrahydrobiopterin (BH4), L-arginine and vitamin C acts synergistically to decrease oxidant stress, increase NO and thereby increase blood flow recovery after hindlimb ischemia. Rats were fed normal chow, chow supplemented with BH4 or L-arginine (alone or in combination) or chow supplemented with BH4 + L-arginine + vitamin C for 1 wk before induction of hindlimb ischemia. In the ischemic hindlimb, cosupplementation with BH4 + L-arginine resulted in greater eNOS and phospho-eNOS (P-eNOS) expression, Ca2+-dependent NOS activity and NO concentration in the ischemic calf region (gastrocnemius), as well as greater NO concentration in the region of collateral arteries (gracilis). Rats receiving cosupplementation of BH4 + L-arginine led to greater recovery of foot perfusion and greater collateral enlargement than did rats receiving either agent separately. The addition of vitamin C to the BH4 + L-arginine regimen further increased these dependent variables. In addition, rats given all three supplements showed significantly less Ca2+-independent activity, less nitrotyrosine accumulation, greater glutathione (GSH)-to-glutathione disulfide (GSSG) ratio and less gastrocnemius Muscle Necrosis, on both macroscopic and microscopic levels. In conclusion, cosupplementation with BH4 + L-arginine + vitamin C significantly increased blood flow recovery after hindlimb ischemia by reducing oxidant stress, increasing NO bioavailability, enlarging collateral arteries and reducing Muscle Necrosis. Oral cosupplementation of BH4, L-arginine and vitamin C holds promise as a biological therapy to induce collateral artery enlargement.
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the effect of gradual or acute arterial occlusion on skeletal Muscle blood flow arteriogenesis and inflammation in rat hindlimb ischemia
Journal of Vascular Surgery, 2005Co-Authors: Gale L Tang, David S Chang, Rajabrata Sarkar, Rong Wang, Louis M MessinaAbstract:Background Current experimental models of critical limb ischemia are based on acute ischemia rather than on chronic ischemia. Human peripheral vascular disease is largely a result of chromic ischemia. We hypothesized that a model of chronic hindlimb ischemia would develop more collateral arteries, more blood flow, and less Necrosis and inflammation than would acute hindlimb ischemia. We therefore developed a rat model of chronic hindlimb ischemia and compared the effects of chronic ischemia with those of acute ischemia on hindlimb skeletal Muscle. Methods Acute or chronic ischemia was induced in 36 male Sprague-Dawley rats. Chronic ischemia caused blood flow, as measured by laser Doppler scanning and confirmed by Muscle oxygen tension measurements, to gradually decrease over 1 to 2 weeks after operation. Results Histologic analysis showed chronic hindlimb ischemia better preserved Muscle mass and architecture and stimulated capillary angiogenesis, while lacking the Muscle Necrosis and inflammatory cell infiltrate seen after acute ischemia. Surprisingly, the chronic ischemia group recovered dermal blood flow more slowly and less completely than did the acute ischemia group, as measured by laser Doppler (0.66 ± 0.02 vs 0.76 ± 0.04, P P P P P Conclusions We describe here the first model of chronic hindlimb ischemia in the rat. Restoration of blood flow after induction of hindlimb ischemia is dependent on the rate of arterial occlusion. This difference in blood flow recovery correlates with distinct patterns of Muscle Necrosis, inflammatory cell infiltration, and cytokine induction in the ischemic Muscle. Differences between models of acute and chronic hindlimb ischemia may have important consequences for future studies of mechanisms regulating arteriogenesis and for therapeutic approaches aimed at promoting arteriogenesis in humans suffering from critical limb ischemia.
