Displaying publications 1 - 20 of 22 in total

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  1. Tan JY, Tan CY, Yahya MA, Shahrizaila N, Goh KJ
    Muscle Nerve, 2024 May;69(5):597-603.
    PMID: 38488306 DOI: 10.1002/mus.28081
    INTRODUCTION/AIMS: Muscle strength, functional status, and muscle enzymes are conventionally used to evaluate disease status in idiopathic inflammatory myopathies (IIM). This study aims to investigate the role of quantitative muscle ultrasound in evaluating disease status in IIM patients.

    METHODS: Patients with IIM, excluding inclusion body myositis, were recruited along with age- and sex-matched healthy controls (HC). All participants underwent muscle ultrasound and clinical assessments. Six limb muscles were unilaterally scanned using a standardized protocol, measuring muscle thickness (MT) and echo intensity (EI). Results were compared with HC, and correlations were made with outcome measures.

    RESULTS: Twenty IIM patients and 24 HC were recruited. The subtypes of IIM were dermatomyositis (6), necrotizing myositis (6), polymyositis (3), antisynthetase syndrome (3), and nonspecific myositis (2). Mean disease duration was 8.7 ± 6.9 years. There were no significant differences in demographics and anthropometrics between patients and controls. MT of rectus femoris in IIM patients was significantly lower than HC. Muscle EI of biceps brachii and vastus medialis in IIM patients were higher than HC. There were moderate correlations between MT of rectus femoris and modified Rankin Scale, Physician Global Activity Assessment, and Health Assessment Questionnaire, as well as between EI of biceps brachii and Manual Muscle Testing-8.

    DISCUSSION: Muscle ultrasound can detect proximal muscle atrophy and hyperechogenicity in patients with IIM. The findings correlate with clinical outcome measures, making it a potential tool for evaluating disease activity of patients with IIM in the late phase of the disease.

    Matched MeSH terms: Muscular Atrophy/pathology
  2. Tan CT
    J Neurol Neurosurg Psychiatry, 1985 Mar;48(3):285-6.
    PMID: 3981204
    Matched MeSH terms: Muscular Atrophy/diagnosis*
  3. Gandhi G, Abdullah S, Foead AI, Yeo WWY
    J Neurol Sci, 2021 08 15;427:117485.
    PMID: 34015517 DOI: 10.1016/j.jns.2021.117485
    Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by low levels of full-length survival motor neuron (SMN) protein due to the loss of the survival motor neuron 1 (SMN1) gene and inefficient splicing of the survival motor neuron 2 (SMN2) gene, which mostly affects alpha motor neurons of the lower spinal cord. Despite the U.S. Food and Drug Administration (FDA) approved SMN-dependent therapies including Nusinersen, Zolgensma® and Evrysdi™, SMA is still a devastating disease as these existing expensive drugs may not be sufficient and thus, remains a need for additional therapies. The involvement of microRNAs (miRNAs) in SMA is expanding because miRNAs are important mediators of gene expression as each miRNA could target a number of genes. Hence, miRNA-based therapy could be utilized in treating this genetic disorder. However, the delivery of miRNAs into the target cells remains an obstacle in SMA, as there is no effective delivery system to date. This review highlights the potential strategies for intracellular miRNA delivery into target cells and current challenges in miRNA delivery. Furthermore, we provide the future prospects of miRNA-based therapeutic strategies in SMA.
    Matched MeSH terms: Muscular Atrophy/pathology
  4. Leduc-Gaudet JP, Franco-Romero A, Cefis M, Moamer A, Broering FE, Milan G, et al.
    Nat Commun, 2023 Mar 02;14(1):1199.
    PMID: 36864049 DOI: 10.1038/s41467-023-36817-1
    Autophagy is a critical process in the regulation of muscle mass, function and integrity. The molecular mechanisms regulating autophagy are complex and still partly understood. Here, we identify and characterize a novel FoxO-dependent gene, d230025d16rik which we named Mytho (Macroautophagy and YouTH Optimizer), as a regulator of autophagy and skeletal muscle integrity in vivo. Mytho is significantly up-regulated in various mouse models of skeletal muscle atrophy. Short term depletion of MYTHO in mice attenuates muscle atrophy caused by fasting, denervation, cancer cachexia and sepsis. While MYTHO overexpression is sufficient to trigger muscle atrophy, MYTHO knockdown results in a progressive increase in muscle mass associated with a sustained activation of the mTORC1 signaling pathway. Prolonged MYTHO knockdown is associated with severe myopathic features, including impaired autophagy, muscle weakness, myofiber degeneration, and extensive ultrastructural defects, such as accumulation of autophagic vacuoles and tubular aggregates. Inhibition of the mTORC1 signaling pathway in mice using rapamycin treatment attenuates the myopathic phenotype triggered by MYTHO knockdown. Skeletal muscles from human patients diagnosed with myotonic dystrophy type 1 (DM1) display reduced Mytho expression, activation of the mTORC1 signaling pathway and impaired autophagy, raising the possibility that low Mytho expression might contribute to the progression of the disease. We conclude that MYTHO is a key regulator of muscle autophagy and integrity.
    Matched MeSH terms: Muscular Atrophy/genetics
  5. Khil EK, Choi JA, Hwang E, Sidek S, Choi I
    BMC Musculoskelet Disord, 2020 Jun 26;21(1):403.
    PMID: 32590960 DOI: 10.1186/s12891-020-03432-w
    BACKGROUND: To evaluate paraspinal back muscles of asymptomatic subjects using qualitative and quantitative analysis on CT and MRI and correlate the results with demographic data.

    METHODS: Twenty-nine asymptomatic subjects were enrolled prospectively (age: mean 34.31, range 23-50; 14 men, 15 women) from August 2016 to April 2017. Qualitative analysis of muscles was done using Goutallier's system on CT and MRI. Quantitative analysis entailed cross sectional area (CSA) on CT and MRI, Hounsfield unit (HU) on CT, fat fraction using two-point Dixon technique on MRI. Three readers independently analyzed the images; intra- and inter-observer agreements were measured. Linear regression and Spearman's analyses were used for correlation with demographic data.

    RESULTS: CSA values were significantly higher in men (p 

    Matched MeSH terms: Muscular Atrophy/diagnosis*; Muscular Atrophy/pathology; Muscular Atrophy/physiopathology
  6. Sasongko, Teguh Haryo, Zilfalil Alwi
    MyJurnal
    Spinal muscular atrophy (SMA), a leading genetic cause of death in childhood, is caused by deletion of the SMN1 gene, located at chromosome 5q13. The molecular pathogenesis, which results in motor neuron degeneration within the anterior horn of spinal cord, is a focus of debate among scientists. The unique nature of the duplicative 5q chromosomal region provides considerable yet challenging opportunity for disease correction as well as complication in performing molecular diagnosis and understanding the molecular pathogenesis. This article reviewed recent findings in the molecular pathogenesis of SMA as well as the research advances in the molecular diagnosis and therapeutic approaches.
    Matched MeSH terms: Muscular Atrophy, Spinal
  7. Chong LC, Gandhi G, Lee JM, Yeo WWY, Choi SB
    Int J Mol Sci, 2021 Aug 20;22(16).
    PMID: 34445667 DOI: 10.3390/ijms22168962
    Spinal muscular atrophy (SMA), one of the leading inherited causes of child mortality, is a rare neuromuscular disease arising from loss-of-function mutations of the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. When lacking the SMN protein in neurons, patients suffer from muscle weakness and atrophy, and in the severe cases, respiratory failure and death. Several therapeutic approaches show promise with human testing and three medications have been approved by the U.S. Food and Drug Administration (FDA) to date. Despite the shown promise of these approved therapies, there are some crucial limitations, one of the most important being the cost. The FDA-approved drugs are high-priced and are shortlisted among the most expensive treatments in the world. The price is still far beyond affordable and may serve as a burden for patients. The blooming of the biomedical data and advancement of computational approaches have opened new possibilities for SMA therapeutic development. This article highlights the present status of computationally aided approaches, including in silico drug repurposing, network driven drug discovery as well as artificial intelligence (AI)-assisted drug discovery, and discusses the future prospects.
    Matched MeSH terms: Muscular Atrophy, Spinal/drug therapy*; Muscular Atrophy, Spinal/metabolism*; Muscular Atrophy, Spinal/physiopathology*
  8. Sasongko TH, Gunadi, Zilfalil BA, Zabidi-Hussin Z
    J. Neurogenet., 2011 Mar;25(1-2):15-6.
    PMID: 21338334 DOI: 10.3109/01677063.2011.559561
    The authors suggest a simplification for the current molecular genetic testing of spinal muscular atrophy (SMA). Deletion analysis of SMN1 exon 7 alone may be necessary and sufficient for the diagnosis of SMA. It is based on sole contribution of survival motor neuron 1 (SMN1) exon 7 to SMA pathogenesis.
    Matched MeSH terms: Muscular Atrophy, Spinal/diagnosis*; Muscular Atrophy, Spinal/genetics*
  9. Watihayati MS, Fatemeh H, Marini M, Atif AB, Zahiruddin WM, Sasongko TH, et al.
    Brain Dev, 2009 Jan;31(1):42-5.
    PMID: 18842367 DOI: 10.1016/j.braindev.2008.08.012
    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene. The SMN2 gene is highly homologous to SMN1 and has been reported to be correlated with severity of the disease. The clinical presentation of SMA varies from severe to mild, with three clinical subtypes (type I, type II, and type III) that are assigned according to age of onset and severity of the disease. Here, we aim to investigate the potential association between the number of copies of SMN2 and the deletion in the NAIP gene with the clinical severity of SMA in patients of Malaysian origin. Forty-two SMA patients (14 of type I, 20 type II, and 8 type III) carrying deletions of the SMN1 gene were enrolled in this study. SMN2 copy number was determined by fluorescence-based quantitative polymerase chain reaction assay. Twenty-nine percent of type I patients carried one copy of SMN2, while the remaining 71% carried two copies. Among the type II and type III SMA patients, 29% of cases carried two copies of the gene, while 71% carried three or four copies of SMN2. Deletion analysis of NAIP showed that 50% of type I SMA patients had a homozygous deletion of exon 5 of this gene and that only 10% of type II SMA cases carried a homozygous deletion, while all type III patients carried intact copies of the NAIP gene. We conclude that there exists a close relationship between SMN2 copy number and SMA disease severity, suggesting that the determination of SMN2 copy number may be a good predictor of SMA disease type. Furthermore, NAIP gene deletion was found to be associated with SMA severity. In conclusion, combining the analysis of deletion of NAIP with the assessment of SMN2 copy number increases the value of this tool in predicting the severity of SMA.
    Matched MeSH terms: Muscular Atrophy, Spinal/classification; Muscular Atrophy, Spinal/diagnosis; Muscular Atrophy, Spinal/genetics*
  10. Altan E, Nayman A, Yildirim A, Ozbaydar MU, Ciftci S, Karahan M
    Malays Orthop J, 2020 Jul;14(2):23-27.
    PMID: 32983374 DOI: 10.5704/MOJ.2007.007
    Introduction: Many factors could affect the supraspinatus (SSP) muscle after tendon rupture. We aimed to determine how infraspinatus and subscapularis tendon problems affect supraspinatus muscle atrophy associated with tears, in a retrospective cohort study conducted in a tertiary-level centre.

    Material and Methods: Fifty-eight patients with a full-thickness SSP tendon tear who fulfilled the inclusion criteria were enrolled in the study. They were evaluated for tear retraction, fatty degeneration, and other rotator cuff tendon pathologies. Supraspinatus muscle was assessed using the Goutallier classification, and its average area was also measured. Accompanying lesions of the subscapularis and infraspinatus tendons and degree of supraspinatus muscle atrophy were evaluated using magnetic resonance imaging.

    Results: Our results showed that supraspinatus tendon tears ranged between 3mm and 41mm, and the estimated average cross-sectional area of the SSP muscle was 247.6mm2. Any degree of infraspinatus tendon pathology, ranging from tendinosis to full-thickness tears, was significantly correlated with the SSP muscle area (P < 0.05). The subscapularis tendon pathologies did not show a similar correlation. The interobserver and intraobserver reliabilities of the measurements were graded as excellent.

    Conclusion: Impairment of any of the rotator cuff muscles may affect the other muscles inversely. Our study showed that all infraspinatus tendon pathologies and partial subscapularis tears affect and alter the SSP muscle belly. We suggest early intervention for supraspinatus tears to avoid further fatty degeneration, as muscle atrophy and fatty degeneration progress in combination with the accompanying lesions.

    Matched MeSH terms: Muscular Atrophy
  11. Fatemeh, H., Watihayati, M.S., Marini, M., NurShafawati, A.R., Atif, A.B., Zabidi-Hussin, Z.A.M.H., et al.
    MyJurnal
    Spinal Muscular Atrophy (SMA) is a heredity neuromuscular disorder and is one of the most common genetic causes of childhood fatality. SMA is classified into three groups based on age of onset and achieved motor milestone. Survival Motor Neuron (SMN) gene has been identified as the responsible gene for SMA. From August 2003 until Feb 2007 we have received 93 samples for SMN1 gene deletion analysis from various hospitals in Malaysia. All the patients except for 3 patients were Malaysian (71 Malays, 5 Indians, 9 Chinese and 5 patients are mixed ethnicity). DNA were extracted from blood samples using DNA extraction kit and subjected to SMN/ gene deletion analysis by PCR-RE. Forty nine out of 93 samples (20 type I, 21 type II, and 8 type III) were found to have homozygous deletion of at least exon 7 of the SMN1 gene. Twelve patients (7 type I, 4 type II, 1 type III) showed the presence of the SMN1 gene and the rest were excluded as they did not fulfill the criteria of International SMA Consortium. Deletion analysis of exon 7 of the SMN gene can be an alternative to the existing diagnostic modalities of SMA.
    Matched MeSH terms: Muscular Atrophy, Spinal
  12. Zilfalil BA, Zabidi-Hussin AMH, Watihayati MS, Rozainah MY, Naing L, Sutomo R, et al.
    Med J Malaysia, 2004 Oct;59(4):512-4.
    PMID: 15779584 MyJurnal
    In Malaysia, Spinal Muscular Atrophy (SMA) is diagnosed based on clinical observation with or without muscle biopsy. Molecular analyses of the SMA-related genes have not been available so far. In this preliminary study, we searched for homozygous deletion of Survival Motor Neuron (SMN1) and Neuronal Apoptosis Inhibitory Protein (NAIP) genes in Malay patients with SMA and found homozygous deletion of SMN1 exon 7 and 8 in all the patients while homozygous deletion of NAIP exon 5 was detected in only our type 1 patients but not in the type 3 patient. To the best of our knowledge, these are the first SMA cases diagnosed at the molecular level in Malaysia.
    Matched MeSH terms: Muscular Atrophy, Spinal/genetics*
  13. Harahap NI, Takeuchi A, Yusoff S, Tominaga K, Okinaga T, Kitai Y, et al.
    Brain Dev, 2015 Aug;37(7):669-76.
    PMID: 25459970 DOI: 10.1016/j.braindev.2014.10.006
    More than 90% of spinal muscular atrophy (SMA) patients show homozygous deletion of SMN1 (survival motor neuron 1). They retain SMN2, a highly homologous gene to SMN1, which may partially compensate for deletion of SMN1. Although the promoter sequences of these two genes are almost identical, a GCC insertion polymorphism has been identified at c.-320_-321 in the SMN1 promoter. We have also found this insertion polymorphism in an SMN2 promoter in an SMA patient (Patient A) who has SMA type 2/3.
    Matched MeSH terms: Muscular Atrophy, Spinal/diagnosis*; Muscular Atrophy, Spinal/genetics*
  14. Sasongko TH, Gunadi, Yusoff S, Atif AB, Fatemeh H, Rani A, et al.
    Brain Dev, 2010 May;32(5):385-9.
    PMID: 19664890 DOI: 10.1016/j.braindev.2009.06.008
    The majority of spinal muscular atrophy (SMA) patients showed homozygous deletion or other mutations of SMN1. However, the genetic etiology of a significant number of SMA patients has not been clarified. Recently, mutation in the gene underlying cat SMA, limb expression 1 (LIX1), has been reported. Similarity in clinical and pathological features of cat and human SMA may give an insight into possible similarity of the genetic etiology.
    Matched MeSH terms: Muscular Atrophy, Spinal/ethnology; Muscular Atrophy, Spinal/genetics*
  15. Marini M, Sasongko TH, Watihayati MS, Atif AB, Hayati F, Gunadi, et al.
    Indian J Med Res, 2012;135:31-5.
    PMID: 22382180
    Genetic diagnosis of spinal muscular atrophy (SMA) is complicated by the presence of SMN2 gene as majority of SMA patients show absence or deletion of SMN1 gene. PCR may amplify both the genes non selectively in presence of high amount of DNA. We evaluated whether allele-specific PCR for diagnostic screening of SMA is reliable in the presence of high amount of genomic DNA, which is commonly used when performing diagnostic screening using restriction enzymes.
    Matched MeSH terms: Muscular Atrophy, Spinal/diagnosis*; Muscular Atrophy, Spinal/pathology
  16. Mohseni J, Zabidi-Hussin ZA, Sasongko TH
    Genet Mol Biol, 2013 Sep;36(3):299-307.
    PMID: 24130434 DOI: 10.1590/S1415-47572013000300001
    Histone acetylation plays an important role in regulation of transcription in eukaryotic cells by promoting a more relaxed chromatin structure necessary for transcriptional activation. Histone deacetylases (HDACs) remove acetyl groups and suppress gene expression. HDAC inhibitors (HDACIs) are a group of small molecules that promote gene transcription by chromatin remodeling and have been extensively studied as potential drugs for treating of spinal muscular atrophy. Various drugs in this class have been studied with regard to their efficacy in increasing the expression of survival of motor neuron (SMN) protein. In this review, we discuss the current literature on this topic and summarize the findings of the main studies in this field.
    Matched MeSH terms: Muscular Atrophy, Spinal
  17. Wong SK, Ima-Nirwana S, Chin KY
    Exp Ther Med, 2020 Oct;20(4):2941-2952.
    PMID: 32855659 DOI: 10.3892/etm.2020.9075
    Sarcopenia refers to the involuntary and generalized deterioration of skeletal muscle mass and strength, which may lead to falls, frailty, physical disability, loss of independence, morbidity and mortality. The majority of molecular and cellular changes involved in the degeneration of muscle tissues are mediated by oxidative stress. Therefore, astaxanthin may act as a potential adjunct therapy for sarcopenia owing to its antioxidant activity. The present review examines the effects of astaxanthin on the promotion of skeletal muscle performance and prevention of muscle atrophy and the potential mechanisms underlying these effects. The available evidence till date was retrieved from PubMed and Medline electronic databases. The present review reported the beneficial effects of astaxanthin in preventing muscle degeneration in various animal models of sarcopenia. In humans, the effects of astaxanthin in combination with other antioxidants on muscle health are mixed, wherein positive and negligible effects were reported. Mechanistic studies revealed that astaxanthin promotes muscle health by reducing oxidative stress, myoblast apoptosis and proteolytic pathways while promoting mitochondria regeneration and formation of blood vessels. Thus, astaxanthin is a potential therapeutic agent for sarcopenia but its effects in humans require further validation.
    Matched MeSH terms: Muscular Atrophy
  18. Mohseni J, Al-Najjar BO, Wahab HA, Zabidi-Hussin ZA, Sasongko TH
    J Hum Genet, 2016 Sep;61(9):823-30.
    PMID: 27251006 DOI: 10.1038/jhg.2016.61
    Several histone deacetylase inhibitors (HDACis) are known to increase Survival Motor Neuron 2 (SMN2) expression for the therapy of spinal muscular atrophy (SMA). We aimed to compare the effects of suberoylanilide hydroxamic acid (SAHA) and Dacinostat, a novel HDACi, on SMN2 expression and to elucidate their acetylation effects on the methylation of the SMN2. Cell-based assays using type I and type II SMA fibroblasts examined changes in transcript expressions, methylation levels and protein expressions. In silico methods analyzed the intermolecular interactions between each compound and HDAC2/HDAC7. SMN2 mRNA transcript levels and SMN protein levels showed notable increases in both cell types, except for Dacinostat exposure on type II cells. However, combined compound exposures showed less pronounced increase in SMN2 transcript and SMN protein level. Acetylation effects of SAHA and Dacinostat promoted demethylation of the SMN2 promoter. The in silico analyses revealed identical binding sites for both compounds in HDACs, which could explain the limited effects of the combined exposure. With the exception on the effect of Dacinostat in Type II cells, we have shown that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene.
    Matched MeSH terms: Muscular Atrophy, Spinal/drug therapy; Muscular Atrophy, Spinal/genetics*
  19. Watihayati MS, M S W, Zabidi AM, A M H ZH, Tang TH, T H T, et al.
    Kobe J Med Sci, 2007;53(4):171-5.
    PMID: 17932457
    Spinal Muscular Atrophy (SMA) is an autosomal recessive disease, which is characterized by degeneration of the anterior horn cells of the spinal cord. SMA is classified into 3 clinical subtypes, type I (severe), type II (intermediate), and type III (mild). Two genes, SMN1 and NAIP, have been identified as SMA-related genes. The SMN1 gene is now recognized as a responsible gene for the disease because it is deleted or mutated in most SMA patients. However, the role of the NAIP gene in SMA has not been fully clarified. To clarify the contribution of NAIP to the disease severity of SMA, we studied the relationship between NAIP-deletion and clinical phenotype in Malaysian patients. A total of 39 patients lacking SMN1 (12 type I, 19 type II, and 8 type III patients) were enrolled into this study. Seven out of 12 patients with type I SMA (approximately 60%) showed NAIP deletion. On the contrary, only 2 out of 20 type II patients and none of type III patients showed NAIP deletion. There was a statistically significant difference in NAIP-deletion frequency among the clinical subtypes (Fisher's exact probability test, p value = 0.014). In conclusion, according to our data that NAIP deletion was more frequent in type I SMA than in type II-III SMA, the NAIP gene may be a modifying factor for disease severity of SMA.
    Matched MeSH terms: Muscular Atrophy, Spinal/genetics*
  20. Tay CH, Jek WT
    Med J Malaya, 1972 Jun;26(4):272-7.
    PMID: 5069417
    Matched MeSH terms: Muscular Atrophy
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