Displaying publications 41 - 60 of 70 in total

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  1. Fulltext Multifaceted Characterization And In Vitro Assessment Of Polyurethane-Based Electrospun Fibrous Composite For Bone Tissue Engineering
    Jiang H, Mani MP, Jaganathan SK
    Int J Nanomedicine, 2019;14:8149-8159.
    PMID: 31632024 DOI: 10.2147/IJN.S214646
    Introduction: Recently several new approaches were emerging in bone tissue engineering to develop a substitute for remodelling the damaged tissue. In order to resemble the native extracellular matrix (ECM) of the human tissue, the bone scaffolds must possess necessary requirements like large surface area, interconnected pores and sufficient mechanical strength.

    Materials and methods: A novel bone scaffold has been developed using polyurethane (PE) added with wintergreen (WG) and titanium dioxide (TiO2). The developed nanocomposites were characterized through field emission scanning electron microscopy (FESEM), Fourier transform and infrared spectroscopy (FTIR), X-ray diffraction (XRD), contact angle measurement, thermogravimetric analysis (TGA), atomic force microscopy (AFM) and tensile testing. Furthermore, anticoagulant assays, cell viability analysis and calcium deposition were used to investigate the biological properties of the prepared hybrid nanocomposites.

    Results: FESEM depicted the reduced fibre diameter for the electrospun PE/WG and PE/WG/TiO2 than the pristine PE. The addition of WG and TiO2 resulted in the alteration in peak intensity of PE as revealed in the FTIR. Wettability measurements showed the PE/WG showed decreased wettability and the PE/WG/TiO2 exhibited improved wettability than the pristine PE. TGA measurements showed the improved thermal behaviour for the PE with the addition of WG and TiO2. Surface analysis indicated that the composite has a smoother surface rather than the pristine PE. Further, the incorporation of WG and TiO2 improved the anticoagulant nature of the pristine PE. In vitro cytotoxicity assay has been performed using fibroblast cells which revealed that the electrospun composites showed good cell attachment and proliferation after 5 days. Moreover, the bone apatite formation study revealed the enhanced deposition of calcium content in the fabricated composites than the pristine PE.

    Conclusion: Fabricated nanocomposites rendered improved physico-chemical properties, biocompatibility and calcium deposition which are conducive for bone tissue engineering.

    Matched MeSH terms: Calcium/metabolism
  2. Fulltext Rational mutagenesis of cyclodextrin glucanotransferase at the calcium binding regions for enhancement of thermostability
    Goh PH, Illias RM, Goh KM
    Int J Mol Sci, 2012;13(5):5307-23.
    PMID: 22754298 DOI: 10.3390/ijms13055307
    Studies related to the engineering of calcium binding sites of CGTase are limited. The calcium binding regions that are known for thermostability function were subjected to site-directed mutagenesis in this study. The starting gene-protein is a variant of CGTase Bacillus sp. G1, reported earlier and denoted as "parent CGTase" herein. Four CGTase variants (S182G, S182E, N132R and N28R) were constructed. The two variants with a mutation at residue 182, located adjacent to the Ca-I site and the active site cleft, possessed an enhanced thermostability characteristic. The activity half-life of variant S182G at 60 °C was increased to 94 min, while the parent CGTase was only 22 min. This improvement may be attributed to the formation of a shorter α-helix and the alleviation of unfavorable steric strains by glycine at the corresponding region. For the variant S182E, an extra ionic interaction at the A/B domain interface increased the half-life to 31 min, yet it reduced CGTase activity. The introduction of an ionic interaction at the Ca-I site via the mutation N132R disrupted CGTase catalytic activity. Conversely, the variant N28R, which has an additional ionic interaction at the Ca-II site, displayed increased cyclization activity. However, thermostability was not affected.
    Matched MeSH terms: Calcium/metabolism*
  3. Fulltext The Role of Calcium in Wound Healing
    Subramaniam T, Fauzi MB, Lokanathan Y, Law JX
    Int J Mol Sci, 2021 Jun 17;22(12).
    PMID: 34204292 DOI: 10.3390/ijms22126486
    Skin injury is quite common, and the wound healing is a complex process involving many types of cells, the extracellular matrix, and soluble mediators. Cell differentiation, migration, and proliferation are essential in restoring the integrity of the injured tissue. Despite the advances in science and technology, we have yet to find the ideal dressing that can support the healing of cutaneous wounds effectively, particularly for difficult-to-heal chronic wounds such as diabetic foot ulcers, bed sores, and venous ulcers. Hence, there is a need to identify and incorporate new ideas and methods to design a more effective dressing that not only can expedite wound healing but also can reduce scarring. Calcium has been identified to influence the wound healing process. This review explores the functions and roles of calcium in skin regeneration and reconstruction during would healing. Furthermore, this review also investigates the possibility of incorporating calcium into scaffolds and examines how it modulates cutaneous wound healing. In summary, the preliminary findings are promising. However, some challenges remain to be addressed before calcium can be used for cutaneous wound healing in clinical settings.
    Matched MeSH terms: Calcium/metabolism*
  4. Fulltext A comparative study on morphochemical properties and osteogenic cell differentiation within bone graft and coral graft culture systems
    Puvaneswary S, Balaji Raghavendran HR, Ibrahim NS, Murali MR, Merican AM, Kamarul T
    Int J Med Sci, 2013;10(12):1608-14.
    PMID: 24151432 DOI: 10.7150/ijms.6496
    The objective of this study was to compare the morphological and chemical composition of bone graft (BG) and coral graft (CG) as well as their osteogenic differentiation potential using rabbit mesenchymal stem cells (rMSCs) in vitro. SEM analysis of BG and CG revealed that the pores in these grafts were interconnected, and their micro-CT confirmed pore sizes in the range of 107-315 µm and 103-514 µm with a total porosity of 92% and 94%, respectively. EDS analysis indicated that the level of calcium in CG was relatively higher than that in BG. FTIR of BG and CG confirmed the presence of functional groups corresponding to carbonyl, aromatic, alkyl, and alkane groups. XRD results revealed that the phase content of the inorganic layer comprised highly crystalline form of calcium carbonate and carbon. Atomic force microscopy analysis showed CG had better surface roughness compared to BG. In addition, significantly higher levels of osteogenic differentiation markers, namely, alkaline phosphatase (ALP), Osteocalcin (OC) levels, and Osteonectin and Runx2, Integrin gene expression were detected in the CG cultures, when compared with those in the BG cultures. In conclusion, our results demonstrate that the osteogenic differentiation of rMSCs is relatively superior in coral graft than in bone graft culture system.
    Matched MeSH terms: Calcium/metabolism
  5. Vasorelaxant activities and the underlying pharmacological mechanisms of Gynura procumbens Merr. leaf extracts on rat thoracic aorta
    Iqbal Z, Bello I, Asmawi MZ, Al-Mansoub MA, Ahmad A, Jabeen Q, et al.
    Inflammopharmacology, 2019 Apr;27(2):421-431.
    PMID: 29185178 DOI: 10.1007/s10787-017-0422-4
    Previous studies have investigated the cardiovascular activity of Gynura procumbens Merr. single-solvent extracts. The objective of this study was to evaluate the in vitro vasorelaxant properties and the underlying pharmacological mechanisms of serial extracts and fractions of Gynura procumbens (GP). The leaves of GP were serially extracted with petroleum ether, chloroform, methanol and water using the maceration method. Suspended aortic ring preparations were pre-contracted with phenylephrine (PE 1 µM), followed by cumulative addition of GP extracts (0.25-3 mg/mL). The petroleum ether extract (GPPE) was the most potent among the four extracts. Pre-incubation of endothelium-intact aorta with atropine (1 µM), indomethacin (10 µM), methylene blue (10 µM), propranolol (1 µM) and potassium channel blockers such as TEA (1 µM), glibenclamide (10 µM), 4-aminopyridine (1 µM) and barium chloride (10 mM) had no effect on GPPE-induced vasorelaxation. The vasorelaxant effect of GPPE was partly diminished by pretreatment of aortic rings preparations with L-NAME (10 µM) and even more so in endothelium-denuded aortic rings, indicating a minimal involvement of endothelium-dependent pathway in GPPE-induced vasorelaxation. The calcium-induced vasocontractions were antagonized significantly and concentration-dependently by GPPE in calcium free and high potassium medium. These results illustrate that Ca2+ antagonizing actions of GPPE in rat isolated aorta are comparable to that of verapamil and may be mainly responsible for its vasodilation effect. The antioxidant activity of GPPE supports its vasorelaxant effect by attenuating the production of deleterious free radicals and reactive oxygen species in the vasculature.
    Matched MeSH terms: Calcium/metabolism
  6. A critical role of TRPM2 channel in Aβ42 -induced microglial activation and generation of tumor necrosis factor-α
    Alawieyah Syed Mortadza S, Sim JA, Neubrand VE, Jiang LH
    Glia, 2018 03;66(3):562-575.
    PMID: 29143372 DOI: 10.1002/glia.23265
    Amyloid β (Aβ)-induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin-related 2 (TRPM2) channel in Aβ-induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor-α (TNF-α), a key cytokine implicated in AD. Exposure to 10-300 nM Aβ42 induced concentration-dependent microglial activation and generation of TNF-α that were ablated by genetically deleting (TRPM2 knockout ;TRPM2-KO) or pharmacologically inhibiting the TRPM2 channel, revealing a critical role of this channel in Aβ42 -induced microglial activation and generation of TNF-α. Mechanistically, Aβ42 activated the TRPM2 channel via stimulating generation of reactive oxygen species (ROS) and activation of poly(ADPR) polymerase-1 (PARP-1). Aβ42 -induced generation of ROS and activation of PARP-1 and TRPM2 channel were suppressed by inhibiting protein kinase C (PKC) and NADPH oxidases (NOX). Aβ42 -induced activation of PARP-1 and TRPM2 channel was also reduced by inhibiting PYK2 and MEK/ERK. Aβ42 -induced activation of PARP-1 was attenuated by TRPM2-KO and moreover, the remaining PARP-1 activity was eliminated by inhibiting PKC and NOX, but not PYK2 and MEK/ERK. Collectively, our results suggest that PKC/NOX-mediated generation of ROS and subsequent activation of PARP-1 play a role in Aβ42 -induced TRPM2 channel activation and TRPM2-dependent activation of the PYK2/MEK/ERK signalling pathway acts as a positive feedback to further facilitate activation of PARP-1 and TRPM2 channel. These findings provide novel insights into the mechanisms underlying Aβ-induced AD-related neuroinflammation.
    Matched MeSH terms: Calcium/metabolism
  7. Antimicrobial activity of gallic acid against thermophilic Campylobacter is strain specific and associated with a loss of calcium ions
    Sarjit A, Wang Y, Dykes GA
    Food Microbiol, 2015 Apr;46:227-233.
    PMID: 25475290 DOI: 10.1016/j.fm.2014.08.002
    Gallic acid has been suggested as a potential antimicrobial for the control of Campylobacter but its effectiveness is poorly studied. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of gallic acid against Campylobacter jejuni (n = 8) and Campylobacter coli (n = 4) strains was determined. Gallic acid inhibited the growth of five C. jejuni strains and three C. coli strains (MIC: 15.63-250 μg mL(-1)). Gallic acid was only bactericidal to two C. coli strains (MBC: 125 and 62.5 μg mL(-1)). The mechanism of the bactericidal effect against these two strains (and selected non-susceptible controls) was investigated by determining decimal reduction times and by monitoring the loss of cellular content and calcium ions, and changes in cell morphology. Gallic acid did not result in a loss of cellular content or morphological changes in the susceptible strains as compared to the controls. Gallic acid resulted in a loss of calcium ions (0.58-1.53 μg mL(-1) and 0.54-1.17 μg mL(-1), respectively, over a 180 min period) from the susceptible strains but not the controls. Gallic acid is unlikely to be an effective antimicrobial against Campylobacter in a practical sense unless further interventions to ensure an effective bactericidal mode of action against all strains are developed.
    Matched MeSH terms: Calcium/metabolism*
  8. Effects of magnesium taurate on the onset and progression of galactose-induced experimental cataract: in vivo and in vitro evaluation
    Agarwal R, Iezhitsa I, Awaludin NA, Ahmad Fisol NF, Bakar NS, Agarwal P, et al.
    Exp Eye Res, 2013 May;110:35-43.
    PMID: 23428743 DOI: 10.1016/j.exer.2013.02.011
    Cataract, a leading cause of blindness, is characterized by lenticular opacities resulting from denaturation of lens proteins due to activation of calcium-dependent enzyme, calpain. Magnesium (Mg(2+)) plays an important role not only in maintaining a low lenticular calcium (Ca(2+)) and sodium concentration but also in preserving the lens redox status. Taurine has also been shown to reduce lenticular oxidative stress. Present study evaluated the anticataract effects of magnesium taurate in vivo and in vitro. Among the five groups of 9 Sprague Dawley rats each, two groups received 30% galactose diet with topical (GDMT) or oral treatment (GDMO) with magnesium taurate. Two groups received 30% galactose diet with topical (GDT) or oral vehicle (GDO). Remaining 1 group received normal diet (ND). Weekly slit lamp examination was done during 21 days experimental period and then all rats were sacrificed; Ca/Mg ratio and antioxidant parameters including reduced glutathione (GSH), catalase and superoxide dismutase (SOD) activities were measured in the isolated lenses using ELISA. In the in vitro study, 2 groups of 10 normal rat lenses were incubated in Dulbecco's Modified Eagle's Medium (DMEM) with galactose while 1 similar group was incubated in DMEM without galactose. In one of the groups, galactose containing medium was supplemented with magnesium taurate. After 48 h of incubation, lenses were photographed and Ca(2+)/Mg(2+) ratio and antioxidant parameters were measured as for in vivo study. The in vivo study, at the end of experimental period, demonstrated delay in the development of cataract with a mean opacity index of 0.53 ± 0.04 and 0.51 ± 0.03 in GDMO (p < 0.05 versus GDO) and GDMT (p < 0.01 versus GDT) respectively. Histopathological grading showed a lower mean value in treated groups, however, the differences from corresponding controls were not significant. Lenticular Ca(2+)/Mg(2+) ratio with a mean value of 1.20 ± 0.26 and 1.05 ± 0.26 in GDMO and GDMT was significantly lower than corresponding controls (p < 0.05) and in GDMT no significant difference was observed from ND. Lenticular GSH and catalase activities were significantly lower and SOD activity was significantly higher in all galactose fed groups. However, in GDMT, GSH and catalase were significantly higher than corresponding control with mean values of 0.96 ± 0.30 μmol/gm lens weight and 56.98 ± 9.86 μmol/g lens protein respectively (p < 0.05 for GSH and p < 0.01 for catalase). SOD activity with mean values of 13.05 ± 6.35 and 13.27 ± 7.61 units/mg lens protein in GDMO and GDMT respectively was significantly lower compared to corresponding controls (p < 0.05) signifying lesser upregulation of SOD due to lesser oxidative stress in treated groups. In the in vitro study, lenses incubated in magnesium taurate containing medium showed less opacity and a lower mean Ca(2+)/Mg(2+) ratio of 1.64 ± 0.03, which was not significantly different from lenses incubated in DMEM without galactose. Lens GSH and catalase activities were restored to normal in lenses incubated in magnesium taurate containing medium. Both in vivo and in vitro studies demonstrated that treatment with magnesium taurate delays the onset and progression of cataract in galactose fed rats by restoring the lens Ca(2+)/Mg(2+) ratio and lens redox status.
    Matched MeSH terms: Calcium/metabolism
  9. Palm vitamin E is comparable to alpha-tocopherol in maintaining bone mineral density in ovariectomised female rats
    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.
    Matched MeSH terms: Calcium/metabolism
  10. Underlying mechanism of vasorelaxant effect exerted by 3,5,7,2',4'-pentahydroxyflavone in rats aortic ring
    Tew WY, Tan CS, Asmawi MZ, Yam MF
    Eur J Pharmacol, 2020 Aug 05;880:173123.
    PMID: 32335091 DOI: 10.1016/j.ejphar.2020.173123
    Morin (3,5,7,2',4'-pentahydroxyflavone) is a yellow coloured natural flavonoid found in plants of the Moraceae family. This favonoid is easily sources from readily available fruits, vegetables and eve certain beverages. Among the sources that was identified, it is clear that morin is most abundantly found in almond, old fustic, Indian guava, and Osage orange. Multiple studies have suggested that morin has multiple therapeutic actions and possess potential to be a functional potent drug. Previous studies demonstrated that morin is capable of resolving deoxycorticosterone acetate-salt-induced hypertension and possess strong vasorelaxant properties. However, the exact mechanisms remains unknown. Therefore, this study is designed to investigate the in vitro mechanism of morin-induced vasorelaxant effects. The underlying mechanisms of morin's vasorelaxant activities were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats. Results from the study demonstrated morin causing vasodilatory reaction in phenylephrine and potassium chloride pre-contracted endothelium-intact aortic rings with the effect being significantly affected in endothelium-denuded aortic rings. Pre-incubation of the aortic rings with ODQ (selective cGMP-independent sGC inhibitor), indomethacin (nonselective COX inhibitor), L-NAME (endothelial nitric oxide inhibitor), propranolol (β2-adrenegic receptors blocker), and atropine (muscarinic receptors blocker) significantly reduced the vasorelaxant effect of morin. It was also found to be able to reduce the intracellular calcium level by blocking VOCC and calcium intake from the extracellular environment and the intracellular release of calcium from the sarcoplasmic reticulum. The present study showed that the vasorelaxant effect of morin potentially involves the NO/sGC, muscarinic receptors, β2-adrenegic receptors, and calcium channels.
    Matched MeSH terms: Calcium/metabolism
  11. Determinants of low bone mineral density in children with epilepsy
    Fong CY, Kong AN, Noordin M, Poh BK, Ong LC, Ng CC
    Eur. J. Paediatr. Neurol., 2018 Jan;22(1):155-163.
    PMID: 29122496 DOI: 10.1016/j.ejpn.2017.10.007
    INTRODUCTION: Children with epilepsy on long-term antiepileptic drugs (AEDs) are at risk of low bone mineral density (BMD). The aims of our study were to evaluate the prevalence and determinants of low BMD among Malaysian children with epilepsy.

    METHOD: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in a tertiary hospital in Malaysia from 2014 to 2015. Detailed assessment of anthropometric measurements; environmental lifestyle risk factors; serum vitamin D, calcium and parathyroid hormone levels; genotyping of single nucleotide polymorphisms of genes in vitamin D and calcium metabolism; and lumbar spine BMD were obtained. Low BMD was defined as BMD Z-score ≤ -2.0 SD.

    RESULTS: Eighty-seven children with mean age of 11.9 years (56 males) participated in the study. The prevalence of low lumbar BMD was 21.8% (19 patients). Multivariate logistic regression analysis identified polytherapy >2 AEDs (OR: 7.86; 95% CI 1.03-59.96), small frame size with wrist breadth of <15th centile (OR 14.73; 95% CI 2.21-98.40), and body mass index Z-score 2 AEDs, underweight or with small frame size as they are at higher risk of having low BMD.

    Matched MeSH terms: Calcium/metabolism
  12. Crystal structure of a compact α-amylase from Geobacillus thermoleovorans
    Mok SC, Teh AH, Saito JA, Najimudin N, Alam M
    Enzyme Microb Technol, 2013 Jun 10;53(1):46-54.
    PMID: 23683704 DOI: 10.1016/j.enzmictec.2013.03.009
    A truncated form of an α-amylase, GTA, from thermophilic Geobacillus thermoleovorans CCB_US3_UF5 was biochemically and structurally characterized. The recombinant GTA, which lacked both the N- and C-terminal transmembrane regions, functioned optimally at 70°C and pH 6.0. While enzyme activity was not enhanced by the addition of CaCl2, GTA's thermostability was significantly improved in the presence of CaCl2. The structure, in complex with an acarbose-derived pseudo-hexasaccharide, consists of the typical three domains and binds one Ca(2+) ion. This Ca(2+) ion was strongly bound and not chelated by EDTA. A predicted second Ca(2+)-binding site, however, was disordered. With limited subsites, two novel substrate-binding residues, Y147 and Y182, may help increase substrate affinity. No distinct starch-binding domain is present, although two regions rich in aromatic residues have been observed. GTA, with a smaller domain B and several shorter loops compared to other α-amylases, has one of the most compact α-amylase folds that may contribute greatly to its tight Ca(2+) binding and thermostability.
    Matched MeSH terms: Calcium/metabolism
  13. Fulltext Calcium sensing receptor hyperactivation through viral envelop protein E of SARS CoV2: A novel target for cardio-renal damage in COVID-19 infection
    Singh Y, Ali H, Alharbi KS, Almalki WH, Kazmi I, Al-Abbasi FA, et al.
    Drug Dev Res, 2021 09;82(6):784-788.
    PMID: 33687087 DOI: 10.1002/ddr.21810
    Over the recent decades, a number of new pathogens have emerged within specific and diverse populations across the globe, namely, the Nipah virus, the Ebola virus, the Zika virus, and coronaviruses (CoVs) to name a few. Recently, a new form of coronavirus was identified in the city of Wuhan, China. Interestingly, the genomic architecture of the virus did not match with any of the existing genomic sequencing data of previously sequenced CoVs. This had led scientists to confirm the emergence of a new CoV strain. Originally, named as 2019-nCoV, the strain is now called as SARS-CoV-2. High serum levels of proinflammatory mediators, namely, interleukin-12 (IL-12), IL-1β, IL-6, interferon-gamma (IFNγ), chemoattractant protein-1, and IFN-inducible protein, have been repeatedly observed in subjects who were infected with this virus. In addition, the virus demonstrated strong coagulation activation properties, leading to further the understanding on the SARS-CoV2. To our understanding, these findings are unique to the published literature. Numerous studies have reported anomalies, namely, decline in the number of lymphocytes, platelets and albumins; and a rise in neutrophil count, aspartate transaminase, alanine aminotransaminase, lactate dehydrogenase, troponins, creatinine, complete bilirubin, D-dimers, and procalcitonin. Supplementation of calcium during the SARS CoV-2 associated hyperactive stage of calcium-sensing receptors (CaSR) may be harmful to the cardio-renal system. Thus, pharmacological inhibition of CaSR may prevent the increase in the levels of intracellular calcium, oxidative, inflammatory stress, and cardio-renal cellular apoptosis induced by high cytokines level in COVID-19 infection.
    Matched MeSH terms: Calcium/metabolism
  14. Fulltext Effect of tocotrienol from Bixa orellana (annatto) on bone microstructure, calcium content, and biomechanical strength in a model of male osteoporosis induced by buserelin
    Mohamad NV, Ima-Nirwana S, Chin KY
    Drug Des Devel Ther, 2018;12:555-564.
    PMID: 29588572 DOI: 10.2147/DDDT.S158410
    Background: Patients receiving androgen deprivation therapy experience secondary hypogonadism, associated bone loss, and increased fracture risk. It has been shown that tocotrienol from Bixa orellana (annatto) prevents skeletal microstructural changes in rats experiencing primary hypogonadism. However, its potential in preventing bone loss due to androgen deprivation therapy has not been tested. This study aimed to evaluate the skeletal protective effects of annatto tocotrienol using a buserelin-induced osteoporotic rat model.

    Methods: Forty-six male Sprague Dawley rats aged 3 months were randomized into six groups. The baseline control (n=6) was sacrificed at the onset of the study. The normal control (n=8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n=8) received corn oil orally daily and subcutaneous buserelin injection (75 µg/kg) daily. The calcium control (n=8) was supplemented with 1% calcium in drinking water and daily subcutaneous buserelin injection (75 µg/kg). The remaining rats were given daily oral annatto tocotrienol at 60 mg/kg (n=8) or 100 mg/kg (n=8) plus daily subcutaneous buserelin injection (75 µg/kg) (n=8). At the end of the experiment, the rats were euthanized and their blood, tibia, and femur were harvested. Structural changes of the tibial trabecular and cortical bone were examined using X-ray micro-computed tomography. Femoral bone calcium content and biomechanical strength were also evaluated.

    Results: Annatto tocotrienol at 60 and 100 mg/kg significantly prevented the deterioration of trabecular bone and cortical thickness in buserelin-treated rats (P<0.05). Both doses of annatto tocotrienol also improved femoral biomechanical strength and bone calcium content in buserelin-treated rats (P<0.05). The effects of annatto tocotrienol were comparable to calcium supplementation.

    Conclusion: Annatto tocotrienol supplementation is effective in preventing degeneration of the bone induced by buserelin. Therefore, it is a potential antiosteoporotic agent for men receiving androgen deprivation therapy.

    Matched MeSH terms: Calcium/metabolism
  15. Vitamin D and Depression: The Evidence from an Indirect Clue to Treatment Strategy
    Wong SK, Chin KY, Ima-Nirwana S
    Curr Drug Targets, 2018;19(8):888-897.
    PMID: 28914205 DOI: 10.2174/1389450118666170913161030
    Depression is a common psychiatric disorder that decreases the quality of life and increases the mortality of patients. It incurs significant healthcare costs if left untreated. Even though intervention with antidepressants can reduce depressive symptoms, side effects are often an issue and relapse is very common. Vitamin D, commonly known as the sunshine vitamin, is an essential fat-soluble vitamin for the absorption of calcium to prevent rickets (children) and osteomalacia (adults). Evidence on a possible relationship between vitamin D deficiency and depression is growing. In this review, the authors summarized the evidence on the association between vitamin D status and depression in human observational studies, followed by clinical trials to evaluate the effects of vitamin D supplementation in treating depression. In conclusion, vitamin D deficiency may be associated with an increased risk or severity of depression. Supplementation of vitamin D may confer protection for depressed patients.
    Matched MeSH terms: Calcium/metabolism
  16. Fulltext Epac-induced ryanodine receptor type 2 activation inhibits sodium currents in atrial and ventricular murine cardiomyocytes
    Valli H, Ahmad S, Sriharan S, Dean LD, Grace AA, Jeevaratnam K, et al.
    Clin Exp Pharmacol Physiol, 2018 03;45(3):278-292.
    PMID: 29027245 DOI: 10.1111/1440-1681.12870
    Acute RyR2 activation by exchange protein directly activated by cAMP (Epac) reversibly perturbs myocyte Ca2+ homeostasis, slows myocardial action potential conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies, preserving in vivo extracellular and intracellular conditions, investigated Na+ current in intact cardiomyocytes in murine atrial and ventricular preparations following Epac activation. Depolarising steps to varying test voltages activated typical voltage-dependent Na+ currents. Plots of peak current against depolarisation from resting potential gave pretreatment maximum atrial and ventricular currents of -20.23 ± 1.48 (17) and -29.8 ± 2.4 (10) pA/μm2 (mean ± SEM [n]). Challenge by 8-CPT (1 μmol/L) reduced these currents to -11.21 ± 0.91 (12) (P  .05). Assessment of the inactivation that followed by applying subsequent steps to a fixed voltage 100 mV positive to resting potential gave concordant results. Half-maximal inactivation voltages and steepness factors, and time constants for Na+ current recovery from inactivation in double-pulse experiments, were similar through all the pharmacological conditions. Intracellular sharp microelectrode membrane potential recordings in intact Langendorff-perfused preparations demonstrated concordant variations in maximum rates of atrial and ventricular action potential upstroke, (dV/dt)max . We thus demonstrate an acute, reversible, Na+ channel inhibition offering a possible mechanism for previously reported pro-arrhythmic slowing of AP propagation following modifications of Ca2+ homeostasis, complementing earlier findings from chronic alterations in Ca2+ homeostasis in genetically-modified RyR2-P2328S hearts.
    Matched MeSH terms: Calcium/metabolism
  17. 'Targeting the feast of a sleeping beast': Nutrient and mineral dependencies of encysted Acanthamoeba castellanii
    Baig AM, Khan NA, Katyara P, Lalani S, Baig R, Nadeem M, et al.
    Chem Biol Drug Des, 2021 01;97(1):18-27.
    PMID: 32602961 DOI: 10.1111/cbdd.13755
    Acanthamoeba spp. cause a corneal infection, Acanthamoeba keratitis (AK), and a cerebral infection, granulomatous amoebic encephalitis (GAE). Though aggressive chemotherapy has been able to kill the active trophozoite form of Acanthamoeba, the encysted form of this parasite has remained problematic to resist physiological concentrations of drugs. The emergence of encysted amoeba into active trophozoite form poses a challenge to eradicate this parasite. Acanthamoeba trophozoites have active metabolic machinery that furnishes energy in the form of ATPs by subjecting carbohydrates and lipids to undergo pathways including glycolysis and beta-oxidation of free fatty acids, respectively. However, very little is known about the metabolic preferences and dependencies of an encysted trophozoite on minerals or potential nutrients that it consumes to live in an encysted state. Here, we investigate the metabolic and nutrient preferences of the encysted trophozoite of Acanthamoeba castellanii and the possibility to target them by drugs that act on calcium ion dependencies of the encysted amoeba. The experimental assays, immunostaining coupled with bioinformatics tools show that the encysted Acanthamoeba uses diverse nutrient pathways to obtain energy in the quiescent encysted state. These findings highlight potential pathways that can be targeted in eradicating amoebae cysts successfully.
    Matched MeSH terms: Calcium/metabolism
  18. Fulltext DJ-1 protects against cell death following acute cardiac ischemia-reperfusion injury
    Dongworth RK, Mukherjee UA, Hall AR, Astin R, Ong SB, Yao Z, et al.
    Cell Death Dis, 2014 Feb 27;5:e1082.
    PMID: 24577080 DOI: 10.1038/cddis.2014.41
    Novel therapeutic targets are required to protect the heart against cell death from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia-reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in HL-1 cardiac cells conferred the following beneficial effects: reduced cell death following simulated IRI (30.4±4.7% with DJ-1 versus 52.9±4.7% in control; n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening (a critical mediator of cell death) (260±33 s with DJ-1 versus 121±12 s in control; n=6, P<0.05); and induction of mitochondrial elongation (81.3±2.5% with DJ-1 versus 62.0±2.8% in control; n=6 cells, P<0.05). These beneficial effects of DJ-1 were absent in cells expressing the non-functional DJ-1(L166P) and DJ-1(Cys106A) mutants. Adult mice devoid of DJ-1 (KO) were found to be more susceptible to cell death from in vivo IRI with larger myocardial infarct sizes (50.9±3.5% DJ-1 KO versus 41.1±2.5% in DJ-1 WT; n≥7, P<0.05) and resistant to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased mitochondrial fragmentation on electron microscopy, although there were no differences in calcium-induced MPTP opening, mitochondrial respiratory function or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart from acute IRI cell death by preventing mitochondrial dysfunction. We propose that DJ-1 may represent a novel therapeutic target for cardioprotection.
    Matched MeSH terms: Calcium/metabolism
  19. Differences in vitamin D status and calcium intake: possible explanations for the regional variations in the prevalence of hypercalcemia in tuberculosis
    Chan TY
    Calcif. Tissue Int., 1997 Jan;60(1):91-3.
    PMID: 9030487
    The prevalence of hypercalcemia in patients with untreated tuberculosis (TB) varies widely between countries. Since the vitamin D status and calcium intake are important determinants of hypercalcemia in TB, these two factors were compared among four populations (U.K., Hong Kong, Malaysia, Thailand) with a low prevalence (<3%) and two populations (Sweden, Australia) with a high prevalence (>25%). In the three Asian countries, the circulating vitamin D levels are abundant, but the calcium intakes are low. Subjects from the U.K. have the lowest circulating vitamin D level of all, although their calcium intake is high. In Sweden and Australia, both the circulating vitamin D levels and calcium intakes are high. Since serum 1,25(OH)2D concentration will only be raised if its substance for extrarenal conversion, 25(OH)D, is plentiful and the effect of a given serum 1,25 (OH)2D concentration on serum calcium is determined by the calcium intake, it is postulated that the regional variation in the prevalence of hypercalcemia in TB may be due to differences in the circulating vitamin D levels and calcium intakes in these populations.
    Matched MeSH terms: Calcium/metabolism*
  20. Fulltext Effect of flecainide derivatives on sarcoplasmic reticulum calcium release suggests a lack of direct action on the cardiac ryanodine receptor
    Bannister ML, Alvarez-Laviada A, Thomas NL, Mason SA, Coleman S, du Plessis CL, et al.
    Br J Pharmacol, 2016 08;173(15):2446-59.
    PMID: 27237957 DOI: 10.1111/bph.13521
    BACKGROUND AND PURPOSE: Flecainide is a use-dependent blocker of cardiac Na(+) channels. Mechanistic analysis of this block showed that the cationic form of flecainide enters the cytosolic vestibule of the open Na(+) channel. Flecainide is also effective in the treatment of catecholaminergic polymorphic ventricular tachycardia but, in this condition, its mechanism of action is contentious. We investigated how flecainide derivatives influence Ca(2) (+) -release from the sarcoplasmic reticulum through the ryanodine receptor channel (RyR2) and whether this correlates with their effectiveness as blockers of Na(+) and/or RyR2 channels.

    EXPERIMENTAL APPROACH: We compared the ability of fully charged (QX-FL) and neutral (NU-FL) derivatives of flecainide to block individual recombinant human RyR2 channels incorporated into planar phospholipid bilayers, and their effects on the properties of Ca(2) (+) sparks in intact adult rat cardiac myocytes.

    KEY RESULTS: Both QX-FL and NU-FL were partial blockers of the non-physiological cytosolic to luminal flux of cations through RyR2 channels but were significantly less effective than flecainide. None of the compounds influenced the physiologically relevant luminal to cytosol cation flux through RyR2 channels. Intracellular flecainide or QX-FL, but not NU-FL, reduced Ca(2) (+) spark frequency.

    CONCLUSIONS AND IMPLICATIONS: Given its inability to block physiologically relevant cation flux through RyR2 channels, and its lack of efficacy in blocking the cytosolic-to-luminal current, the effect of QX-FL on Ca(2) (+) sparks is likely, by analogy with flecainide, to result from Na(+) channel block. Our data reveal important differences in the interaction of flecainide with sites in the cytosolic vestibules of Na(+) and RyR2 channels.

    Matched MeSH terms: Calcium/metabolism*
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