Displaying publications 41 - 60 of 75 in total

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  1. Fulltext Linkage and association studies in a Malaysian family with autosomal recessive non-syndromic hearing loss
    Farah WI, Aminuddin BS, Ruszymah BH
    Malays J Pathol, 2006 Jun;28(1):23-33.
    PMID: 17694956 MyJurnal
    Hearing loss is a common sensory deficit in humans. The hearing loss may be conductive, sensorineural, or mixed, syndromic or nonsyndromic, prelingual or postlingual. Due to the complexity of the hearing mechanism, it is not surprising that several hundred genes might be involved in causing hereditary hearing loss. There are at least 82 chromosomal loci that have been identified so far which are associated with the most common type of deafness--non-syndromic deafness. However, there are still many more which remained to be discovered. Here, we report the mapping of a locus for autosomal recessive, non-syndromic deafness in a family in Malaysia. The investigated family (AC) consists of three generations--parents who are deceased, nine affected and seven unaffected children and grandchildren. The deafness was deduced to be inherited in an autosomal recessive manner with 70% penetrance. Recombination frequencies were assumed to be equal for both males and females. Using two-point lod score analysis (MLINK), a maximum lod score of 2.48 at 0% recombinant (Z = 2.48, theta = 0%) was obtained for the interval D14S63-D14S74. The haplotype analysis defined a 14.38 centiMorgan critical region around marker D14S258 on chromosome 14q23.2-q24.3. There are 16 candidate genes identified with positive expression in human cochlear and each has great potential of being the deaf gene responsible in causing non-syndromic hereditary hearing loss in this particular family. Hopefully, by understanding the role of genetics in deafness, early interventional strategies can be undertaken to improve the life of the deaf community.
  2. Effects of glycyrrhizic acid and steroid treatment on corticotropin releasing factor and beta-endorphin containing neurons of the hypothalamus of the rat
    Ruszymah BH, Nabishah BM, Aminuddin S, Sarjit S, Khalid BA
    Malays J Pathol, 1999 Jun;21(1):51-8.
    PMID: 10879279
    Corticotrophin releasing factor (CRF) and beta-endorphin (beta EP) containing neurons are shown to be present in the hypothalamus and both neurons are found at the paraventricular nucleus (PVN). Steroid hormones have been found to alter the plasma level of these neurotransmitters. Glycyrrhizic acid (GCA) is the active component of liquorice. GCA inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase (11HSD) which is needed for the inactivation of the steroid pathway, so therefore would cause changes to these neurons. The aim of this study was to investigate the effects of GCA as well as deoxycorticosterone (DOC) and dexamethasone (DM) on the modulation of CRF and beta EP containing neuron at the PVN of the hypothalamus. Rats were given either DM, DOC or GCA and adrenalectomized (ADX) and given either DM or DOC. At the end of treatment rats were transfused transcardially before sacrifice and the brain were dissected for immunohistochemical analysis. We found that immunostaining of the CRF containing neurons demonstrate a reduction in the number of positive neurons in DM treated rats. DOC and GCA treated rats showed the same result as in DM rats but the reduction is less. ADX, DM, DOC and GCA treated rats did not show any changes in the number of beta EP containing neurons but naloxone increased the number of beta EP containing neurons markedly. In conclusion, GCA and DOC have similar effects on CRF and beta EP containing neurons at the PVN.
  3. Articular cartilage restoration in load-bearing osteochondral defects by implantation of autologous chondrocyte-fibrin constructs: an experimental study in sheep
    Munirah S, Samsudin OC, Chen HC, Salmah SH, Aminuddin BS, Ruszymah BH
    J Bone Joint Surg Br, 2007 Aug;89(8):1099-109.
    PMID: 17785753
    Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous 'chondrocyte-fibrin' construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis. All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O'Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage. Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI.
  4. Fulltext Basic fibroblast growth factor with human serum supplementation: enhancement of human chondrocyte proliferation and promotion of cartilage regeneration
    Chua KH, Aminuddin BS, Fuzina NH, Ruszymah BH
    Singapore Med J, 2007 Apr;48(4):324-32.
    PMID: 17384880
    The objectives of this study were to determine the optimum concentration of basic fibroblast growth factor (bFGF) in foetal bovine serum (FBS) or human serum (HS) supplemented medium for adult human nasal septum chondrocyte culture and to evaluate the potential of cartilage regeneration.
  5. Fulltext Shelf-life evaluation of bilayered human skin equivalent, MyDerm™
    Seet WT, Manira M, Maarof M, Khairul Anuar K, Chua KH, Ahmad Irfan AW, et al.
    PLoS One, 2012;7(8):e40978.
    PMID: 22927903 DOI: 10.1371/journal.pone.0040978
    Skin plays an important role in defense against infection and other harmful biological agents. Due to its fragile structure, skin can be easily damaged by heat, chemicals, traumatic injuries and diseases. An autologous bilayered human skin equivalent, MyDerm™, was engineered to provide a living skin substitute to treat critical skin loss. However, one of the disadvantages of living skin substitute is its short shelf-life, hence limiting its distribution worldwide. The aim of this study was to evaluate the shelf-life of MyDerm™ through assessment of cell morphology, cell viability, population doubling time and functional gene expression levels before transplantation. Skin samples were digested with 0.6% Collagenase Type I followed by epithelial cells dissociation with TrypLE Select. Dermal fibroblasts and keratinocytes were culture-expanded to obtain sufficient cells for MyDerm™ construction. MyDerm™ was constructed with plasma-fibrin as temporary biomaterial and evaluated at 0, 24, 48 and 72 hours after storage at 4°C for its shelf-life determination. The morphology of skin cells derived from MyDerm™ remained unchanged across storage times. Cells harvested from MyDerm™ after storage appeared in good viability (90.5%±2.7% to 94.9%±1.6%) and had short population doubling time (58.4±8.7 to 76.9±19 hours). The modest drop in cell viability and increased in population doubling time at longer storage duration did not demonstrate a significant difference. Gene expression for CK10, CK14 and COL III were also comparable between different storage times. In conclusion, MyDerm™ can be stored in basal medium at 4°C for at least 72 hours before transplantation without compromising its functionality.
  6. Fulltext Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration
    Leow SN, Luu CD, Hairul Nizam MH, Mok PL, Ruhaslizan R, Wong HS, et al.
    PLoS One, 2015;10(6):e0128973.
    PMID: 26107378 DOI: 10.1371/journal.pone.0128973
    To investigate the safety and efficacy of subretinal injection of human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats.
  7. A comparative study of skin cell activities in collagen and fibrin constructs
    Law JX, Musa F, Ruszymah BH, El Haj AJ, Yang Y
    Med Eng Phys, 2016 Sep;38(9):854-61.
    PMID: 27349492 DOI: 10.1016/j.medengphy.2016.05.017
    Collagen and fibrin are widely used in tissue engineering due to their excellent biocompatibility and bioactivities that support in vivo tissue formation. These two hydrogels naturally present in different wound healing stages with different regulatory effects on cells, and both of them are mechanically weak in the reconstructed hydrogels. We conducted a comparative study by the growth of rat dermal fibroblasts or dermal fibroblasts and epidermal keratinocytes together in collagen and fibrin constructs respectively with and without the reinforcement of electrospun poly(lactic acid) nanofiber mesh. Cell proliferation, gel contraction and elastic modulus of the constructs were measured on the same gels at multiple time points during the 22 day culturing period using multiple non-destructive techniques. The results demonstrated considerably different cellular activities within the two types of constructs. Co-culturing keratinocytes with fibroblasts in the collagen constructs reduced the fibroblast proliferation, collagen contraction and mechanical strength at late culture point regardless of the presence of nanofibers. Co-culturing keratinocytes with fibroblasts in the fibrin constructs promoted fibroblast proliferation but exerted no influence on fibrin contraction and mechanical strength. The presence of nanofibers in the collagen and fibrin constructs played a favorable role on the fibroblast proliferation when keratinocytes were absent. Thus, this study exhibited new evidence of the strong cross-talk between keratinocytes and fibroblasts, which can be used to control fibroblast proliferation and construct contraction. This cross-talk activity is extracellular matrix-dependent in terms of the fibrous network morphology, density and strength.
  8. Correlation of donor age and telomerase activity with in vitro cell growth and replicative potential for dermal fibroblasts and keratinocytes
    Ng MH, Aminuddin BS, Hamizah S, Lynette C, Mazlyzam AL, Ruszymah BH
    J Tissue Viability, 2009 Nov;18(4):109-16.
    PMID: 19632116 DOI: 10.1016/j.jtv.2009.06.003
    Previous studies suggested telomerase activity as a determinant of cell replicative capacity by delaying cell senescence. This study aimed to evaluate the feasibility of adopting telomerase activity as a selection criterion for in vitro expanded skin cells before autologous transplantation. Fibroblasts and keratinoctyes were derived from the same consenting patients aged 9-69 years, and cultured separately in serum-supplemented and serum-free media, respectively. Telomerase activity of fresh and cultured cells were measured and correlated with cell growth rate, donor age and passage number. The results showed that telomerase activity and cell growth were independent of donor age for both cell types. Telomerase was expressed in freshly digested epidermis and dermis and continued expressing in vitro. Keratinocytes consistently showed 3-12 folds greater telomerase activity than fibroblast both in vivo and in vitro. Conversely, growth rate for fibroblast exceeded that of keratinocyte. Telomerase activity decreased markedly at Passage 6 for keratinocytes and ceased by Passage 3 for fibroblasts. The decrease or cessation of telomerase activity coincided with senescence for keratinocyte but not for fibroblast, implying a telomerase-regulated cell senescence for the former and hence a predictor of replicative capacity for this cell type. Relative telomerase activity for fibroblasts from the younger age group was significantly higher than that from the older age group; 69.7% higher for fresh isolates and 31.1% higher at P0 (p<0.05). No detectable telomerase activity was to be found at later subcultures for both age groups. Similarly for keratinocytes, telomerase activity in the younger age group was significantly higher (p<0.05) compared to that in the older age group; 507.7% at P0, 36.8% at P3 and the difference was no longer significant at P6. In conclusion, the study provided evidence that telomerase sustained the proliferation of keratinocytes but not fibroblasts. Telomerase activity is an important criterion for continued survival and replication of keratinocytes, hence its positive detection before transplantation is desirable. Inferring from our results, the use of keratinocytes from Passage 3 or lesser for construction of skin substitute or cell-based therapy is recommended owing to their sustained telomerase expression.
  9. Autologous versus pooled human serum for articular chondrocyte growth
    Munirah S, Ruszymah BH, Samsudin OC, Badrul AH, Azmi B, Aminuddin BS
    J Orthop Surg (Hong Kong), 2008 Aug;16(2):220-9.
    PMID: 18725677
    To evaluate the effect of autologous human serum (AHS) versus pooled human serum (PHS) versus foetal bovine serum (FBS) for growth of articular chondrocytes and formation of chondrocytefibrin constructs.
  10. Fulltext Congenital insensitivity to pain with anhydrosis in a Malaysian family: a genetic analysis
    Shalimar A, Sharaf I, Farah Wahida I, Ruszymah BH
    J Orthop Surg (Hong Kong), 2007 Dec;15(3):357-60.
    PMID: 18162686 DOI: 10.1177/230949900701500323
    A Malaysian family with congenital insensitivity to pain with anhydrosis was diagnosed based on clinical symptoms of chronic ulcers, joint deformities, malunited fractures, anhydrosis, and learning disabilities. We detected a compound heterozygous mutation in exon 16: V709L from the mother and G718S from the father. Two novel mutations were identified: at amino acid 709, a change of G to C at nucleotide 2209 (approximately 2209G to C) causing a valine to leucine substitution (V709L), and at amino acid 718, a change of G to A at nucleotide 2236 (approximately 2236G to A) causing a glycine to serine substitution (G718S). Polymorphisms identified were at nucleotides approximately 2113G to C and approximately 2176T to C.
  11. Aqueous extract of Centella asiatica promotes corneal epithelium wound healing in vitro
    Ruszymah BH, Chowdhury SR, Manan NA, Fong OS, Adenan MI, Saim AB
    J Ethnopharmacol, 2012 Mar 27;140(2):333-8.
    PMID: 22301444 DOI: 10.1016/j.jep.2012.01.023
    Centella asiatica is a traditional herbal medicine that has been shown to have pharmacological effect on skin wound healing, and could be potential therapeutic agent for corneal epithelial wound healing.
  12. Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone
    Ng AM, Tan KK, Phang MY, Aziyati O, Tan GH, Isa MR, et al.
    J Biomed Mater Res A, 2008 May;85(2):301-12.
    PMID: 17688285
    Biomaterial, an essential component of tissue engineering, serves as a scaffold for cell attachment, proliferation, and differentiation; provides the three dimensional (3D) structure and, in some applications, the mechanical strength required for the engineered tissue. Both synthetic and naturally occurring calcium phosphate based biomaterial have been used as bone fillers or bone extenders in orthopedic and reconstructive surgeries. This study aims to evaluate two popular calcium phosphate based biomaterial i.e., hydroxyapatite (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) granules as scaffold materials in bone tissue engineering. In our strategy for constructing tissue engineered bone, human osteoprogenitor cells derived from periosteum were incorporated with human plasma-derived fibrin and seeded onto HA or TCP/HA forming 3D tissue constructs and further maintained in osteogenic medium for 4 weeks to induce osteogenic differentiation. Constructs were subsequently implanted intramuscularly in nude mice for 8 weeks after which mice were euthanized and constructs harvested for evaluation. The differential cell response to the biomaterial (HA or TCP/HA) adopted as scaffold was illustrated by the histology of undecalcified constructs and evaluation using SEM and TEM. Both HA and TCP/HA constructs showed evidence of cell proliferation, calcium deposition, and collagen bundle formation albeit lesser in the former. Our findings demonstrated that TCP/HA is superior between the two in early bone formation and hence is the scaffold material of choice in bone tissue engineering.
  13. Surface modification of electrospun poly(methyl methacrylate) (PMMA) nanofibers for the development of in vitro respiratory epithelium model
    Rabiatul AR, Lokanathan Y, Rohaina CM, Chowdhury SR, Aminuddin BS, Ruszymah BH
    J Biomater Sci Polym Ed, 2015;26(17):1297-311.
    PMID: 26335265 DOI: 10.1080/09205063.2015.1088183
    Scaffold design is an important aspect of in vitro model development. In this study, nanoscaffold surface modification, namely UV radiation and genipin cross-linking to immobilize collagen on the surface of electrospun poly (methyl methacrylate) (PMMA) nanofiber sheet was investigated. Samples were divided into four groups; PMMA nanofibers (PMMA), collagen-coated PMMA nanofibers (PMMACOL), genipin cross-linked collagen-coated PMMA nanofibers (PMMAGEN), and UV-irradiated collagen-coated PMMA nanofibers (PMMAUV). 6 h of UV radiation significantly reduced the hydrophobicity of PMMA nanofibers from (131.88° ± 1.33°) to (110.04° ± 0.27°) (p 
  14. Stem cell genes are poorly expressed in chondrocytes from microtic cartilage
    Ishak MF, Chua KH, Asma A, Saim L, Aminuddin BS, Ruszymah BH, et al.
    Int J Pediatr Otorhinolaryngol, 2011 Jun;75(6):835-40.
    PMID: 21543123 DOI: 10.1016/j.ijporl.2011.03.021
    This study was aimed to see the difference between chondrocytes from normal cartilage compared to chondrocytes from microtic cartilage. Specific attentions were to characterize the growth of chondrocytes in terms of cell morphology, growth profile and RT-PCR analysis.
  15. Formation of tissue engineered composite construct of cartilage and skin using high density polyethylene as inner scaffold in the shape of human helix
    Ruszymah BH, Chua KH, Mazlyzam AL, Aminuddin BS
    Int J Pediatr Otorhinolaryngol, 2011 Jun;75(6):805-10.
    PMID: 21481479 DOI: 10.1016/j.ijporl.2011.03.012
    Formation of external ear via tissue engineering has created interest amongst surgeons as an alternative for ear reconstruction in congenital microtia.
  16. Pediatric auricular chondrocytes gene expression analysis in monolayer culture and engineered elastic cartilage
    Ruszymah BH, Lokman BS, Asma A, Munirah S, Chua K, Mazlyzam AL, et al.
    Int J Pediatr Otorhinolaryngol, 2007 Aug;71(8):1225-34.
    PMID: 17531328
    This study was aimed at regenerating autologous elastic cartilage for future use in pediatric ear reconstruction surgery. Specific attentions were to characterize pediatric auricular chondrocyte growth in a combination culture medium and to assess the possibility of elastic cartilage regeneration using human fibrin.
  17. Formation of in vivo tissue engineered human hyaline cartilage in the shape of a trachea with internal support
    Ruszymah BH, Chua K, Latif MA, Hussein FN, Saim AB
    Int J Pediatr Otorhinolaryngol, 2005 Nov;69(11):1489-95.
    PMID: 15941595
    Treatment and management of congenital as well as post-traumatic trachea stenosis remains a challenge in pediatric surgery. The aim of this study was to reconstruct a trachea with human nasal septum chondrocytes by using the combination of biodegradable hydrogel and non-biodegradable high-density polyethylene (HDP) as the internal predetermined shape scaffold.
  18. Prevalence of otitis media with effusion amongst pre-school children in Malaysia
    Saim A, Saim L, Saim S, Ruszymah BH, Sani A
    Int J Pediatr Otorhinolaryngol, 1997 Jul 18;41(1):21-8.
    PMID: 9279632 DOI: 10.1016/s0165-5876(97)00049-9
    A cross-sectional screening test was done to determine the prevalence of otitis media with effusion amongst, preschool children in two district in Malaysia, namely Kuala Lumpur an urban district and Kuala Selangor a rural district. It involved 1097 preschool children aged between 5 and 6 years old. Presence of otitis media effusion (OME) is based on abnormal otoscopic finding, Type B tympanogram and absence of ipsilateral acoustical reflex. The overall prevalence rate of OME was 13.8%. The prevalence in Kuala Lumpur was 17.9%, while in Kuala Selangor it was 9.48%. Bottle feeding during infancy and high socioeconomic status of the parents was statistically associated with higher incidence of OME. Other factors such as race, premature delivery, passive smoking, allergy, asthma and family size, had no influence on the prevalence of otitis media with effusion.
  19. Tissue-engineered trachea: A review
    Law JX, Liau LL, Aminuddin BS, Ruszymah BH
    Int J Pediatr Otorhinolaryngol, 2016 Dec;91:55-63.
    PMID: 27863642 DOI: 10.1016/j.ijporl.2016.10.012
    Tracheal replacement is performed after resection of a portion of the trachea that was impossible to reconnect via direct anastomosis. A tissue-engineered trachea is one of the available options that offer many advantages compared to other types of graft. Fabrication of a functional tissue-engineered trachea for grafting is very challenging, as it is a complex organ with important components, including cartilage, epithelium and vasculature. A number of studies have been reported on the preparation of a graftable trachea. A laterally rigid but longitudinally flexible hollow cylindrical scaffold which supports cartilage and epithelial tissue formation is the key element. The scaffold can be prepared via decellularization of an allograft or fabricated using biodegradable or non-biodegradable biomaterials. Commonly, the scaffold is seeded with chondrocytes and epithelial cells at the outer and luminal surfaces, respectively, to hasten tissue formation and improve functionality. To date, several clinical trials of tracheal replacement with tissue-engineered trachea have been performed. This article reviews the formation of cartilage tissue, epithelium and neovascularization of tissue-engineered trachea, together with the obstacles, possible solutions and future. Furthermore, the role of the bioreactor for in vitro tracheal graft formation and recently reported clinical applications of tracheal graft were also discussed. Generally, although encouraging results have been achieved, however, some obstacles remain to be resolved before the tissue-engineered trachea can be widely used in clinical settings.
  20. Therapeutic potential of human umbilical cord-derived mesenchymal stem cells transplantation in rats with optic nerve injury
    Looi SY, Bastion MC, Leow SN, Luu CD, Hairul NMH, Ruhaslizan R, et al.
    Indian J Ophthalmol, 2022 Jan;70(1):201-209.
    PMID: 34937239 DOI: 10.4103/ijo.IJO_473_21
    Purpose: There are no effective treatments currently available for optic nerve transection injuries. Stem cell therapy represents a feasible future treatment option. This study investigated the therapeutic potential of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation in rats with optic nerve injury.

    Methods: Sprague-Dawley (SD) rats were divided into three groups: a no-treatment control group (n = 6), balanced salt solution (BSS) treatment group (n = 6), and hUC-MSCs treatment group (n = 6). Visual functions were assessed by flash visual evoked potential (fVEP) at baseline, Week 3, and Week 6 after optic nerve crush injury. Right eyes were enucleated after 6 weeks for histology.

    Results: The fVEP showed shortened latency delay and increased amplitude in the hUC-MSCs treated group compared with control and BSS groups. Higher cellular density was detected in the hUC-MSC treated group compared with the BSS and control groups. Co-localized expression of STEM 121 and anti-S100B antibody was observed in areas of higher nuclear density, both in the central and peripheral regions.

    Conclusion: Peribulbar transplantation of hUC-MSCs demonstrated cellular integration that can potentially preserve the optic nerve function with a significant shorter latency delay in fVEP and higher nuclear density on histology, and immunohistochemical studies observed cell migration particularly to the peripheral regions of the optic nerve.

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