Displaying publications 1 - 20 of 98 in total

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  1. Saif, A.M., Norazlina, M., Ima-Nirwana, S.
    Medicine & Health, 2016;11(2):278-288.
    MyJurnal
    Bone histomorphometric measurements are required to understand the efficacy
    of treatment on bone remodelling. Previous studies used the Weibel technique
    as a quantitative stereological method to determine bone cellular and dynamic
    changes. However, there was no description on how this technique was applied.
    This studyaimed to provide a full picture about the utilization of the Weibel
    technique to measure static and dynamic bone histomorphometric indices.
    Technical expertise, processing of bone samples, randomization of the trabecular
    sections and an adequate number of analysed images for each section are required to achieve reliable results with a low possibility of errors.
  2. Mohamad, N.V., Ima-Nirwana, S., Chin, K.Y.
    Medicine & Health, 2019;14(2):168-179.
    MyJurnal
    Androgen ablation therapy using gonadotropin-releasing hormone agonists is reported to be associated with metabolic abnormalities. Annatto tocotrienol (AnTT) is reported to reduce the expression of genes related to adipogenesis but the mechanism remains elusive. This study sought to determine the effects of annatto tocotrienol on body composition (lean and fat mass), serum adiponectin, leptin, and glucose levels in male rats treated with buserelin, a testosterone ablation agent. Three-month-old male Sprague Dawley rats (n=32) were randomly divided into four groups. The normal control (n=8) was given corn oil orally daily and normal saline subcutaneously daily. The remaining groups were injected with buserelin subcutaneously (75μg/kg/day). The buserelin group (n=8) was given corn oil orally, while the treatment groups were supplemented orally with AnTT at 60 or 100 mg/ kg (n = 8/group). After treatment of 12 weeks, rats were euthanized. Dual-energy x-ray absorptiometry was performed to determine the lean and fat mass of the rats. Blood was collected for the evaluation of adiponectin, leptin and glucose levels. After 12 weeks, the lean mass, fat mass, adiponectin and leptin levels for all groups increased significantly compared to their respective baseline levels irrespective of their treatment (P
  3. Ima Nirwana S, Fakhrurazi H
    Med J Malaysia, 2002 Jun;57(2):136-44.
    PMID: 24326643
    The aim of this study was to determine the effects of palm oil-derived vitamin E on glucocorticoid-induced osteoporosis. Three-month old male Wistar rats were adrenalectomised to remove circulating glucocorticoids. The animals were then administered with Dexamethasone 120 µg/kg body weight/day. Treatment with palm vitamin E 60 mg/kg body weight/day was given simultaneously. The results showed that palm vitamin E prevented the loss in regional and whole body bone mineral density seen in the Dexamethasone treated animals. Palm vitamin E improved femoral length and calcium content in the Dexamethasone treated animals. The results confirmed that palm oil-derived vitamin E was effective in preventing glucocorticoid-induced osteoporosis.
  4. Ima-Nirwana S, Suhaniza S
    J Med Food, 2004;7(1):45-51.
    PMID: 15117552
    Long-term glucocorticoid treatment is associated with severe side effects, such as obesity and osteoporosis. A palm oil-derived vitamin E mixture had been shown previously to be protective against osteoporosis in rats given 120 microg/kg dexamethasone daily for 12 weeks. In this study we determined the effects of two isomers of vitamin E (i.e., palm oil-derived gamma-tocotrienol and the commercially available alpha-tocopherol, 60 mg/kg of body weight/day) on body composition and bone calcium content in adrenalectomized rats replaced with two doses of dexamethasone, 120 microg/kg and 240 microg/kg daily. Treatment period was 8 weeks. gamma-Tocotrienol (60 mg/kg of body weight/day) was found to reduce body fat mass and increase the fourth lumbar vertebra bone calcium content in these rats, while alpha-tocopherol (60 mg/kg of body weight/day) was ineffective. Therefore, in conclusion, palm oil-derived gamma-tocotrienol has the potential to be utilized as a prophylactic agent in prevention of the side effects of long-term glucocorticoid use.
  5. Elvy Suhana, M.R., Fairus, A., Norazlina, M., Mohamad Fairuz, Y., Ima Nirwana, S.
    Medicine & Health, 2018;13(1):175-197.
    MyJurnal
    Long term glucocorticoids administration induces oxidative stress which leads to alteration of bone structure and strength. Palm oil is rich in tocotrienol, an antioxidant. It can be used for the prevention of oxidative stress related diseases. The main objective of this study was to determine the mechanism of palm tocotrienol in maintaining the bone structure and strength in glucocorticoidinduced osteoporosis. Thirty two adult male Sprague-Dawley rats, aged 3 months, weighing 300-320 g rats were used in this study. Sixteen rats undergone adrenalectomy and were administered with 120µg/kg/day intramuscular injection of dexamethasone. Eight rats were supplemented with oral palm tocotrienol 60 mg/kg/day (Adrx+Dex+PTT) and the other eight rats were given oral vehicle palm olein 0.1 ml/kg/day (Adrx+Dex). Eight rats underwent sham procedure and were given vehicle palm olein 0.05 ml/kg/day by intramuscularly and oral 0.1 ml/kg/day (Sham). The rats were euthanized after two months of treatments. Eight rats were euthanized after acclimatic action without receiving any treatment (Baseline). The right femurs were used for bone biomechanical strength and histomorphometry analysis while the left for gene expression and oxidative stress enzymes activities. The results indicated that long-term glucocorticoid treatment significantly increased bone resorption marker, CTX (6060.7 ± 410 pg/ml) and decreased bone structure and strength. Osteoblast and osteoclast related genes expressions indicated an increase in bone turnover. Supplementation of palm tocotrienol had maintained serum resorption (2619.4 + 209 pg/ml) marker level and preserved bone structure and strength. Gene expression analysis showed decrease in bone resorption. The findings suggested that palm tocotrienol has potential benefits against glucocorticoid-induced osteoporosis by regulating osteoblast and osteoclast related gene expressions.
  6. Chin KY, Ima-Nirwana S
    Aging Male, 2015 Mar;18(1):60-6.
    PMID: 25166624 DOI: 10.3109/13685538.2014.954995
    This study aimed to determine the effects of orchidectomy and supraphysiological testosterone replacement on trabecular structure and gene expression in the bone.
  7. Chin KY, Ima-Nirwana S
    Clin Interv Aging, 2014;9:1247-59.
    PMID: 25120355 DOI: 10.2147/CIA.S67016
    BACKGROUND: Previous animal models have demonstrated that tocotrienol is a potential treatment for postmenopausal osteoporosis. This study evaluated the antiosteoporotic effects of annatto-derived tocotrienol (AnTT) using a testosterone-deficient osteoporotic rat model.
    METHODS: Forty rats were divided randomly into baseline, sham, orchidectomized, AnTT, and testosterone groups. The baseline group was euthanized without undergoing any surgical treatment or intervention. The remaining groups underwent orchidectomy, with the exception of the sham group. AnTT 60 mg/kg/day was given orally to the AnTT group, while the testosterone group received testosterone enanthate 7 mg/kg per week intramuscularly for 8 weeks. Structural changes in trabecular bone at the proximal tibia were examined using microcomputed tomography. Structural and dynamic changes at the distal femur were examined using histomorphometric methods. Serum osteocalcin and C-terminal of type 1 collagen crosslinks were measured. Bone-related gene expression in the distal femur was examined.
    RESULTS: There were significant degenerative changes in structural indices in the orchidectomized group (P<0.05), but no significant changes in dynamic indices, bone remodeling markers, or gene expression (P>0.05) when compared with the sham group. The AnTT group showed significant improvement in structural indices at the femur (P<0.05) and significantly increased expression of bone formation genes (P<0.05). Testosterone was more effective than AnTT in preventing degeneration of bone structural indices in the femur and tibia (P<0.05).
    CONCLUSION: AnTT supplementation improves bone health in testosterone-deficient rats by enhancing bone formation. Its potential should be evaluated further by varying the dosage and treatment duration.
    KEYWORDS: bone remodeling; osteoporosis; testosterone; tocotrienol
  8. Chin KY, Ima-Nirwana S
    Nutrients, 2014 Apr;6(4):1424-41.
    PMID: 24727433 DOI: 10.3390/nu6041424
    Recent studies have found conflicting evidence on the role of α-tocopherol (αTF) on bone health. This nonsystematic review aimed to summarize the current evidence on the effects of αTF on bone health from cell culture, animal, and human studies in order to clarify the role of αTF on bone health. Our review found that αTF exerted beneficial, harmful or null effects on bone formation cells. Animal studies generally showed positive effects of αTF supplementation on bone in various models of osteoporosis. However, high-dose αTF was possibly detrimental to bone in normal animals. Human studies mostly demonstrated a positive relationship between αTF, as assessed using high performance liquid chromatography and/or dietary questionnaire, and bone health, as assessed using bone mineral density and/or fracture incidence. Three possible reasons high dosage of αTF can be detrimental to bone include its interference with Vitamin K function on bone, the blocking of the entry of other Vitamin E isomers beneficial to bone, and the role of αTF as a prooxidant. However, these adverse effects have not been shown in human studies. In conclusion, αTF may have a dual role in bone health, whereby in the appropriate doses it is beneficial but in high doses it may be harmful to bone.
  9. Chin KY, Ima-Nirwana S
    Curr Drug Targets, 2013 Dec;14(14):1632-41.
    PMID: 24354587
    The Asian population whose soy intake is higher compared to Western populations shows a significantly lower incidence of osteoporotic fracture. Several meta-analyses have revealed that supplementation of soy isoflavones improve bone health status in women. This review examined the current evidence as to whether soy could exhibit similar bone protective effects on the male population. In vivo studies revealed that supplementation of soy protein or soy isoflavones improved bone health in both normal and osteoporotic male rodents. Cell culture studies showed that soy isoflavones influenced osteogenesis and osteoclastogenesis through mechanisms such as estrogen receptor binding activity, antiinflammatory activity and anti-parathyroid hormone activity. Soy isoflavones also affected calcium channel signaling and might exhibit direct effects on the osteoblastogenesis modulator, core binding factor 1. However, limited clinical trials involving soy intervention in males generally showed insignificant results. This could be attributed to the short duration of intervention, characteristics of the subjects or method of bone health assessment. More well-planned clinical trials are required to establish possible bone protective effects of soy in men.
  10. Chin KY, Ima-Nirwana S
    Int J Med Sci, 2013;10(12):1778-83.
    PMID: 24273451 DOI: 10.7150/ijms.6765
    Quantitative ultrasound (QUS) has emerged as a convenient and popular screening tool for osteoporosis. This review aimed to provide basic information on the principle of QUS measurement and discuss the properties of bone reflected by QUS indices. QUS employed high frequency sound waves generated by the device to determine bone health status in humans. In vitro studies showed that QUS indices were significantly associated with bone mineral density (BMD), bone microarchitecture and mechanical parameters. In humans, QUS indices were found to be associated with BMD as well. In addition, QUS could discriminate subjects with and without fracture history and predict risk for future fracture. In conclusion, QUS is able to reflect bone quality and should be used in the screening of osteoporosis, especially in developing countries where dual-X-ray absorptiometry devices are less accessible to the general population.
  11. Chin KY, Ima-Nirwana S
    PMID: 22919420 DOI: 10.1155/2012/747020
    Osteoporosis is a growing healthcare burden that affects the quality of life in the aging population. Vitamin E is a potential prophylactic agent that can impede the progression of osteoporosis. Various in vivo studies demonstrated the antiosteoporotic potential of vitamin E, but evidence on its molecular mechanism of action is limited. A few in vitro studies showed that various forms of vitamin E can affect the receptor activator of nuclear factor kappa-B ligand (RANKL) signaling and their molecular targets, thus preventing the formation of osteoclasts in the early stage of osteoclastogenesis. Various studies have also shown that the effects of the different isoforms of vitamin E differ. The effects of single isoforms and combinations of isoforms on bone metabolism are also different. Vitamin E may affect bone metabolism by disruption of free radical-mediated RANKL signaling, by its oestrogen-like effects, by its effects on the molecular mechanism of bone formation, by the anti-inflammatory effects of its long-chain metabolites on bone cells, and by the inhibition of 3-hydroxyl-3-methyglutaryl coenzyme A (HMG-CoA). In conclusion, the vitamin E isoforms have enormous potential to be used as prophylactic and therapeutic agents in preventing osteoporosis, but further studies should be conducted to elucidate their mechanisms of action.
  12. Chin KY, Ima-Nirwana S
    Int J Endocrinol, 2012;2012:208719.
    PMID: 23150727 DOI: 10.1155/2012/208719
    Male osteoporosis is a health problem which deserves more attention as nearly 30% of osteoporotic fractures happen in men aged 50 years and above. Although men do not experience an accelerated bone loss phase and testosterone deficiency is not a universal characteristic for aged men, osteoporosis due to age-related testosterone deficiency does have a negative impact on bone health status of men. Observations from epidemiological studies indicate that elderly men with higher testosterone can preserve their BMD better and thus are less prone to fracture. Observations on men with estrogen resistance or aromatase deficiency indicate that estrogen is equally important in the maintenance of bone health status. This had been validated in several epidemiological studies which found that the relationships between estrogen and bone health indices are significant and sometimes stronger than testosterone. Studies on the relationship between quantitative ultrasound and bone remodeling markers suggest that testosterone and estrogen may have differential effects on bone, but further evidence was needed. In conclusion, both testosterone and estrogen are important in the maintenance of bone health in men.
  13. Norazlina M, Chua CW, Ima-Nirwana S
    Med J Malaysia, 2004 Dec;59(5):623-30.
    PMID: 15889565
    Vitamin E deficiency has been found to impair bone calcification. This study was done to determine the effects of vitamin E deficiency and supplementation on parathyroid hormone, i.e. the hormone involved in bone regulation. Female Sprague-Dawley rats were divided into 4 groups: 1) normal rat chow (RC), 2) vitamin E deficiency (VED), vitamin E deficient rats supplemented with 3) 60 mg/kg alpha-tocotrienol (ATT) and 4) 60 mg/kg (alpha-tocopherol (ATF). Treatment was carried out for 3 months. Vitamin E deficiency caused hypocalcaemia during the first month of the treatment period, increased the parathyroid hormone level in the second month and decreased the bone calcium content in the 4th lumbar bone at the end of the treatment. Vitamin E supplementation (ATT and ATF) failed to improve these conditions. The bone formation marker, osteocalcin, and the bone resorption marker, deoxypyridinoline did not change throughout the study period. In conclusion vitamin E deficiency impaired bone calcium homeostasis with subsequent secondary hyperparathyroidism and vertebral bone loss. Replacing the vitamin E with pure ATF or pure ATT alone failed to correct the changes seen.
  14. Chin KY, Ima-Nirwana S
    Curr Drug Targets, 2018;19(5):439-450.
    PMID: 26343111 DOI: 10.2174/1389450116666150907100838
    BACKGROUND: Vitamin C, traditionally associated with scurvy, is an important nutrient for maintaining bone health. It is essential in the production of collagen in bone matrix. It also scavenges free radicals detrimental to bone health.

    OBJECTIVE: This review aims to assess the current evidence of the bone-sparing effects of vitamin C derived from cell, animal and human studies.

    RESULTS: Cell studies showed that vitamin C was able to induce osteoblast and osteoclast formation. However, high-dose vitamin C might increase oxidative stress and subsequently lead to cell death. Vitamin C-deficient animals showed impaired bone health due to increased osteoclast formation and decreased bone formation. Vitamin C supplementation was able to prevent bone loss in several animal models of bone loss. Human studies generally showed a positive relationship between vitamin C and bone health, indicated by bone mineral density, fracture probability and bone turnover markers. Some studies suggested that the relationship between vitamin C and bone health could be U-shaped, more prominent in certain subgroups and different between dietary and supplemental form. However, most of the studies were observational, thus could not confirm causality. One clinical trial was performed, but it was not a randomized controlled trial, thus confounding factors could not be excluded.

    CONCLUSION: vitamin C may exert beneficial effects on bone, but more rigorous studies and clinical trials should be performed to validate this claim.

  15. Chin KY, Ima-Nirwana S
    Drug Des Devel Ther, 2015;9:2049-61.
    PMID: 25897211 DOI: 10.2147/DDDT.S79660
    Osteoporosis causes significant health care and economic burden to society, leading to a relentless search for effective preventive agents. Tocotrienol, a member of the vitamin E family, has demonstrated promising potential as an osteoporosis-preventing agent. This review summarizes evidence on the effects of tocotrienol on bone in animal models. Techniques used to examine the effects of tocotrienol on bone in animals included bone histomorphometry, X-ray microtomography, dual-energy X-ray absorptiometry, bone turnover markers, bone calcium content, and biomechanical strength. Tocotrienol was shown to improve osteoblast number, bone formation, mineral deposition, and bone microarchitecture in osteopenic rats. It also decreased osteoclast number and bone erosion in the rats. Tocotrienol supplementation resulted in an improvement in bone mineral density, although biomechanical strength was not significantly altered in the rats. The beneficial effects of tocotrienol on bone can be attributed to its role as an antioxidant, anti-inflammatory agent, suppressor of the mevalonate pathway, and modulator of genes favorable to bone formation.
  16. Chin KY, Ima-Nirwana S
    Front Pharmacol, 2018;9:946.
    PMID: 30186176 DOI: 10.3389/fphar.2018.00946
    Osteoarthritis is a debilitating disease of the joint involving cartilage degeneration and chondrocytes apoptosis. Oxidative stress is one of the many proposed mechanisms underpinning joint degeneration in osteoarthritis. The current pharmacotherapies emphasize pain and symptomatic management of the patients but do not alter the biological processes underlying the cartilage degeneration. Vitamin E is a potential agent to prevent or treat osteoarthritis due to its antioxidant and anti-inflammatory effects. This review aims to summarize the current evidence on the relationship between vitamin E and osteoarthritis derived from preclinical and human studies. Cellular studies showed that vitamin E mitigated oxidative stress in cartilage explants or chondrocyte culture invoked by mechanical stress or free radicals. Animal studies suggested that vitamin E treatment prevented cartilage degeneration and improve oxidative status in animal models of osteoarthritis. Low circulating or synovial vitamin E was observed in human osteoarthritic patients compared to healthy controls. Observational studies also demonstrated that vitamin E was related to induction or progression of osteoarthritis in the general population. Vitamin E supplementation might improve the outcomes in patients with osteoarthritis, but negative results were also reported. Different isomers of vitamin E might possess distinct anti-osteoarthritic effects. As a conclusion, vitamin E may retard the progression of osteoarthritis by ameliorating oxidative stress and inflammation of the joint. Further studies are warranted to develop vitamin E as an anti-osteoarthritis agent to reduce the global burden of this disease.
  17. Chin KY, Ima-Nirwana S
    PMID: 27472350 DOI: 10.3390/ijerph13080755
    Skeletal degeneration due to aging, also known as osteoporosis, is a major health problem worldwide. Certain dietary components confer protection to our skeletal system against osteoporosis. Consumption of olives, olive oil and olive polyphenols has been shown to improve bone health. This review aims to summarize the current evidence from cellular, animal and human studies on the skeletal protective effects of olives, olive oil and olive polyphenols. Animal studies showed that supplementation of olives, olive oil or olive polyphenols could improve skeletal health assessed via bone mineral density, bone biomechanical strength and bone turnover markers in ovariectomized rats, especially those with inflammation. The beneficial effects of olive oil and olive polyphenols could be attributed to their ability to reduce oxidative stress and inflammation. However, variations in the bone protective, antioxidant and anti-inflammatory effects between studies were noted. Cellular studies demonstrated that olive polyphenols enhanced proliferation of pre-osteoblasts, differentiation of osteoblasts and decreased the formation of osteoclast-like cells. However, the exact molecular pathways for its bone health promoting effects are yet to be clearly elucidated. Human studies revealed that daily consumption of olive oil could prevent the decline in bone mineral density and improve bone turnover markers. As a conclusion, olives, olive oil and its polyphenols are potential dietary interventions to prevent osteoporosis among the elderly.
  18. Chin KY, Ima-Nirwana S
    Int J Endocrinol Metab, 2017 Jan;15(1):e43053.
    PMID: 28835763 DOI: 10.5812/ijem.43053
    BACKGROUND: Testosterone deficiency is linked to low-grade inflammation in humans, but this condition is not replicated in an animal study. The current study aims at determining the effects of testosterone deficiency and its replacement on the circulating inflammatory cytokine level in orchidectomized male rats.

    METHODS: Three-month-old Sprague-Dawley male rats (n = 18) were randomized equally into 3 groups. Bilateral orchidectomy was performed on 2 groups. The sham group was subjected to similar surgical stress, but their testes were retained. One of the orchidectomized groups received intramuscular injection of 7 mg/kg testosterone enanthate suspended in peanut oil weekly and the other 2 groups received equivolume of peanut oil injection. After 8 weeks, the rats were sacrificed and their blood was collected for the analysis of the levels of inflammatory cytokines and testosterone.

    RESULTS: Testosterone level was significantly lower in the untreated orchidectomized group compared to the sham group. Testosterone replacement significantly increased the level of testosterone in the orchidectomized rats compared to the sham and untreated orchidectomized rats. Interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNFα) showed an increasing trend in orchidectomized rats, albeit not statistically significant. Interleukin-6 (IL-6) level increased significantly in the orchidectomized group compared to the sham group. Testosterone replacement at the supraphysiological dose did not alter the level of inflammatory cytokines significantly in orchidectomized rats.

    CONCLUSIONS: Testosterone deficiency can elicit a state of low-grade inflammation, shown by an increase in interleukin-6 level, but exogenous supraphysiological testosterone replacement does not suppress the inflammation.

  19. Shuid AN, Ima Nirwana S, Das S
    Curr Drug Targets, 2013 Dec;14(14):1631.
    PMID: 24383964
  20. Norazlina M, Ima-Nirwana S, Gapor MT, Khalid BA
    Exp. Clin. Endocrinol. Diabetes, 2000;108(4):305-10.
    PMID: 10961363
    Vitamin E has been shown to affect bone metabolism. In this study we determined the effects of palm vitamin E and alpha-tocopherol on bone metabolism. Sprague-Dawley female rats fed with normal rat chow were divided into 4 groups and supplemented with either palm vitamin E 30 mg/kg rat weight, palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight. One group was not supplemented. Half of these rats were ovariectomised before supplementation was given for 10 months. As expected, bone mineral density of the ovariectomised rats fed on normal rat chow diet was lower compared to the intact rats. However, these changes were not seen in the supplemented group of rats. Both intact and ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight had a lower bone calcium content in both femoral and vertebral bones whilst rats fed palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight were able to maintain bone calcium content. Alkaline phosphatase activity was elevated in ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight and alpha-tocopherol 30 mg/kg rat weight compared to the intact rats. Alpha-tocopherol also reduced the activity of tartrate-resistant acid phosphatase post-ovariectomy. These findings indicate that both palm vitamin E and alpha-tocopherol maintained bone mineral density in ovariectomised rats but caused conflicting effects on bone calcium content. Further study is needed in order to determine the mechanisms involved.
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