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Interventional Medicine & Applied... Jun 2016The article is devoted to study the structural changes in the skeletal muscles caused by heavy metal salts. (Review)
Review
PURPOSE
The article is devoted to study the structural changes in the skeletal muscles caused by heavy metal salts.
MATERIALS AND METHODS
The study was conducted on 72 mature male rats. The experimental groups were given to drink water with combinations of heavy metal salts for one, two and three months. This type of water is typical for the water basins in the northern districts of the Sumy region. The study of morphological changes in the striated muscles was concluded using light and scanning electron microscopy.
RESULTS
The data analysis revealed that a prolonged duration of negative factor could intensify sclerotic and edematous processes. The structure of muscle fibers was destroyed, nuclei were deformed and placed irregularly, and many petechial hemorrhages occurred. Besides, cross-striation was irregular, I and A bands were deformed and destroyed, H band was hardly visualized. The inner mitochondrial membrane and cristae become deformed. The symplastic nuclei were placed irregularly within sarcoplasm. Besides, they were swollen. Against swollen and enlarged symplastic nuclei, pyknotic nuclei were also found. The structures of sarcoplasmic reticulum were mainly dilated with deformed and ruptured areas.
CONCLUSION
Our study approves that high concentrations of heavy metal salts have a destructive influence on the skeletal striated muscles.
PubMed: 28386464
DOI: 10.1556/1646.8.2016.2.7 -
Advances in Experimental Medicine and... 2013Cardiovascular disease is a leading cause of death worldwide, with ischemic heart disease alone accounting for >12% of all deaths, more than HIV/AIDS, tuberculosis,... (Review)
Review
Cardiovascular disease is a leading cause of death worldwide, with ischemic heart disease alone accounting for >12% of all deaths, more than HIV/AIDS, tuberculosis, lung, and breast cancer combined. Heart disease has been the leading cause of death in the United States for the past 85 years and is a major cause of disability and health-care expenditures. The cardiac conditions most likely to result in death include heart failure and arrhythmias, both a consequence of ischemic coronary disease and myocardial infarction, though chronic hypertension and valvular diseases are also important causes of heart failure. Sodium-calcium exchange (NCX) is the dominant calcium (Ca2+) efflux mechanism in cardiac cells. Using ventricular-specific NCX knockout mice, we have found that NCX is also an essential regulator of cardiac contractility independent of sarcoplasmic reticulum Ca2+ load. During the upstroke of the action potential, sodium (Na+) ions enter the diadic cleft space between the sarcolemma and the sarcoplasmic reticulum. The rise in cleft Na+, in conjunction with depolarization, causes NCX to transiently reverse. Ca2+ entry by this mechanism then "primes" the diadic cleft so that subsequent Ca2+ entry through Ca2+ channels can more efficiently trigger Ca2+ release from the sarcoplasmic reticulum. In NCX knockout mice, this mechanism is inoperative (Na+ current has no effect on the Ca2+ transient), and excitation-contraction coupling relies upon the elevated diadic cleft Ca2+ that arises from the slow extrusion of cytoplasmic Ca2+ by the ATP-dependent sarcolemmal Ca2+ pump. Thus, our data support the conclusion that NCX is an important regulator of cardiac contractility. These findings suggest that manipulation of NCX may be beneficial in the treatment of heart failure.
Topics: Animals; Calcium; Female; Heart Failure; Humans; Male; Mice; Mice, Knockout; Muscle Proteins; Myocardial Contraction; Myocardium; Sarcoplasmic Reticulum; Sodium-Calcium Exchanger
PubMed: 23224894
DOI: 10.1007/978-1-4614-4756-6_30 -
Muscle & Nerve Jul 2009The nucleic acid binding protein TDP-43 was recently identified in normal myonuclei and in the sarcoplasm of inclusion body myositis (IBM) muscle. Here we found TDP-43...
The nucleic acid binding protein TDP-43 was recently identified in normal myonuclei and in the sarcoplasm of inclusion body myositis (IBM) muscle. Here we found TDP-43 sarcoplasmic immunoreactivity in 23% of IBM myofibers, while other reported IBM biomarkers were less frequent, with rimmed vacuoles in 2.8%, fluorescent Congo red material in 0.57%, SMI-31 immunoreactivity in 0.83%, and focal R1282 beta-amyloid immunoreactivity in 0.00% of myofibers. The presence of as little as >1% of myofibers with nonnuclear sarcoplasmic TDP-43 was highly sensitive (91%) and specific (100%) to IBM among 50 inflammatory myopathy patient samples, although some patients with hereditary inclusion body myopathies and myofibrillar myopathy also had sarcoplasmic TDP-43. TDP-43 mutations were sought, and none were identified. TDP-43 could be one of many nucleic acid binding proteins that are abnormally present in IBM sarcoplasm. They could potentially interfere with the normal function of extranuclear RNAs that maintain myofiber protein production.
Topics: Amyloid beta-Peptides; Congo Red; DNA-Binding Proteins; Humans; Indoles; Muscle Fibers, Skeletal; Myositis, Inclusion Body; Neurofilament Proteins; Oligonucleotide Array Sequence Analysis; Sarcoplasmic Reticulum
PubMed: 19533646
DOI: 10.1002/mus.21386 -
The Journal of Physiology Jul 2006
Topics: Action Potentials; Animals; Calcium; Cell Membrane; Female; Heart Failure; Intracellular Membranes; Mice; Mice, Inbred C57BL; Myocardial Contraction; Myocytes, Cardiac; Sarcoplasmic Reticulum; Signal Transduction
PubMed: 16728445
DOI: 10.1113/jphysiol.2006.113803 -
The Journal of Physiology Mar 2022
Topics: Calcium; Myocytes, Cardiac; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 35001395
DOI: 10.1113/JP282659 -
Kardiochirurgia I Torakochirurgia... Jul 2019Cardiocyte myofibrillolysis and interstitial fibrosis belong to histopathological changes in cardiomyopathies, leading to heart failure.
INTRODUCTION
Cardiocyte myofibrillolysis and interstitial fibrosis belong to histopathological changes in cardiomyopathies, leading to heart failure.
AIM
To evaluate these changes in apical resection during left ventricular assist device (LVAD) implantation.
MATERIAL AND METHODS
The studied group consisted of 40 patients with cardiomyopathy, and apical samples excised during left ventricular assist device implantation were studied (CM/VAD group, mean: 48.1 ±10 y/o). A control group consisted of 6 apical samples from healthy heart graft donors (mean: 29 ±2.3 years old). Area fraction (AF) was calculated for: fibrosis, cardiocytes with myofibrillolysis (MFL), non-myofibrillolytic cardiocytes (non-MFL).
RESULTS
Single lymphocytes were seen in 18 (45%) cases in the CM/VAD group. Cardiomyopathy grade evaluated semiquantitatively in CM/VAD was: slight (25% of a group), moderate (35.5%), advanced (35.5%). CM/VAD cases showed nearly ten times higher fibrosis than the control group. The MFL cells occupied nearly a five times larger area in CM/VAD than in the control group, whereas non-MFL cells were found in the control group, as a predominant pattern. The linear regression calculated between fibrosis AF and types of cardiocytes indicated the depletion of cardiomyocytes with fibrosis increase. The control group presented insignificant dependency between fibrosis and MFL cells, suggesting the lack of replacement fibrosis. Significant negative dependence between fibrosis and non-MFL cardiocytes suggested remodeling in controls. Correlation analysis showed a strong relation between depletion of normal cardiocytes and progression of fibrosis.
CONCLUSIONS
Progression of cardiomyopathy and fibrosis depends on the loss of cardiocytes rather than degeneration of these cells.
PubMed: 31410091
DOI: 10.5114/kitp.2019.86356 -
Applied Immunohistochemistry &... Oct 2017Succinate dehydrogenase (SDH) is a key mitochondrial enzyme complex composed of 4 subunits. SDH histochemistry is routinely utilized in the assessment of muscle biopsies...
Succinate dehydrogenase (SDH) is a key mitochondrial enzyme complex composed of 4 subunits. SDH histochemistry is routinely utilized in the assessment of muscle biopsies to reveal underlying pathology such as subsarcolemmal mitochondrial aggregates. In this study, we evaluated the utility of succinate dehydrogenase B (SDHB) immunohistochemistry (IHC) in 27 muscle biopsies, including 13 mitochondrial myopathies (MMs), 9 inflammatory myopathies, and 5 controls. SDHB IHC was performed on formalin-fixed, paraffin-embedded tissue sections with a mouse monoclonal antibody (Abcam 21A11AE7) in parallel with histochemical SDH stains on a fresh-frozen tissue. In all muscle biopsies, SDHB IHC exhibited granular immunoreactivity and highlighted the dark type 1 and lighter type 2 staining pattern observed by histochemistry. In all cases of MM, SDHB IHC showed subsarcolemmal granular aggregates involving the entire periphery of the fibers that were more distinct than those seen by SDH histochemistry. In 3 extraocular muscle biopsies, SDHB immunoreactive speckles of various sizes were distributed throughout the entire sarcoplasm that were more prominent than those seen on SDH histochemistry. Subsarcolemmal and cytoplasmic granular aggregates seen on SDHB IHC correlated with mitochondrial pathology on electron microscopy. In cases of inflammatory myopathy, there was diffuse sarcoplasmic SDHB immunoreactivity in degenerating fibers, but no evidence of subsarcolemmal aggregates. This study demonstrates that SDHB IHC is highly sensitive and specific in the identification of MM. The automation, reproducibility, and cost efficiency of SDHB IHC offer advantages over the labor-intensive histochemical method requiring frozen sections. As this technique is performed on formalin-fixed, paraffin-embedded tissues, it can be easily applied for retrospective studies.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Male; Middle Aged; Muscle, Skeletal; Succinate Dehydrogenase; Young Adult
PubMed: 27556822
DOI: 10.1097/PAI.0000000000000432 -
Mediators of Inflammation 2023Skeletal muscle of patients with sporadic inclusion body myositis (sIBM) presents with inflammation, including upregulation of inflammatory cytokines such as interferon...
Skeletal muscle of patients with sporadic inclusion body myositis (sIBM) presents with inflammation, including upregulation of inflammatory cytokines such as interferon (IFN). Non-inflammatory features are also observed, like the sarcoplasmic accumulation of proteins including TDP-43 and p62. This study aimed to investigate the effect of IFN and interleukin 1- (IL-1) on TDP-43 and p62 aggregation in vitro. Primary human myotubes were treated with IL-1 (20 ng/mL) and IFN (750 ng/mL) separately or combined for 48 hr. Sarcoplasmic TDP-43 aggregates and p62 puncta were assessed using image analysis for size, frequency, and colocalization with each other. Total protein expression of TDP-43, p62 and LC3 was assessed using western blotting. The subcellular localization of TDP-43 was also analyzed using image analysis. Combined IL-1 and IFN treatment increased puncta size of p62 compared to control (0.49 ± 0.13 m versus 0.28 ± 0.06 m), without affecting puncta frequency or p62 expression but with an increased LC3II/LC3I ratio, suggesting autophagic alterations. IL-1 or IFN did not alter p62 puncta size or frequency, suggesting a combined insult of multiple inflammatory mediators is necessary to cause p62 alterations. IL-1 increased p62 protein expression in an autophagy-independent manner. None of the cytokine treatments affected TDP-43 protein expression, size, or frequency of TDP-43 aggregates or localization, suggesting IL-1 and IFN may influence TDP-43 processing in human skeletal muscle cells. TDP-43 was localized to the sarcoplasm under control conditions, suggesting this may not be a pathological feature. Overall, sIBM-like TDP-43/p62 features were not triggered by IL-1 and/or IFN.
Topics: Humans; Cytokines; Interferon-gamma; Muscle Fibers, Skeletal; Muscle, Skeletal; DNA-Binding Proteins
PubMed: 37731843
DOI: 10.1155/2023/9018470 -
The American Journal of Pathology Dec 2009Limb-girdle muscular dystrophy 2B, Miyoshi myopathy, and distal myopathy of anterior tibialis are severely debilitating muscular dystrophies caused by genetically...
Limb-girdle muscular dystrophy 2B, Miyoshi myopathy, and distal myopathy of anterior tibialis are severely debilitating muscular dystrophies caused by genetically determined dysferlin deficiency. In these muscular dystrophies, it is the repair, not the structure, of the plasma membrane that is impaired. Though much is known about the effects of dysferlin deficiency in skeletal muscle, little is known about the role of dysferlin in maintenance of cardiomyocytes. Recent evidence suggests that dysferlin deficiency affects cardiac muscle, leading to cardiomyopathy when stressed. However, neither the morphological location of dysferlin in the cardiomyocyte nor the progression of the disease with age are known. In this study, we examined a mouse model of dysferlinopathy using light and electron microscopy as well as echocardiography and conscious electrocardiography. We determined that dysferlin is normally localized to the intercalated disk and sarcoplasm of the cardiomyocytes. In the absence of dysferlin, cardiomyocyte membrane damage occurs and is localized to the intercalated disk and sarcoplasm. This damage results in transient functional deficits at 10 months of age, but, unlike in skeletal muscle, the cell injury is sublethal and causes only mild cardiomyopathy even at advanced ages.
Topics: Animals; Cardiomyopathies; Disease Models, Animal; Dysferlin; Image Processing, Computer-Assisted; Immunohistochemistry; Membrane Proteins; Mice; Microscopy, Electron, Transmission; Muscle Proteins; Muscular Dystrophies, Limb-Girdle; Myocardium
PubMed: 19875504
DOI: 10.2353/ajpath.2009.080930 -
The FEBS Journal Sep 2011Studies of ion pumps, such as ATP synthetase and Ca(2+)-ATPase, have a long history. The crystal structures of several kinds of ion pump have been resolved, and provide...
Studies of ion pumps, such as ATP synthetase and Ca(2+)-ATPase, have a long history. The crystal structures of several kinds of ion pump have been resolved, and provide static pictures of mechanisms of ion transport. In this study, using fast-scanning atomic force microscopy, we have visualized conformational changes in the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) in real time at the single-molecule level. The analyses of individual SERCA molecules in the presence of both ATP and free Ca(2+) revealed up-down structural changes corresponding to the Albers-Post scheme. This fluctuation was strongly affected by the ATP and Ca(2+) concentrations, and was prevented by an inhibitor, thapsigargin. Interestingly, at a physiological ATP concentrations, the up-down motion disappeared completely. These results indicate that SERCA does not transit through the shortest structure, and has a catalytic pathway different from the ordinary Albers-Post scheme under physiological conditions.
Topics: Adenosine Triphosphate; Animals; Biocatalysis; Calcium; Deoxycholic Acid; Enzyme Inhibitors; Enzymes, Immobilized; Imaging, Three-Dimensional; Kinetics; Microscopy, Atomic Force; Microscopy, Video; Muscle Proteins; Osmolar Concentration; Protein Conformation; Rabbits; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Single-Cell Analysis; Surface-Active Agents; Thapsigargin
PubMed: 21707923
DOI: 10.1111/j.1742-4658.2011.08222.x