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In vitro differences of hydroxyapatite from different resources in simulated body fluid

Hashim N, Sabudin S, Ibrahim S, Zin NM, Bakar SH, Fazan F

Med J Malaysia, 2004 May;59 Suppl B:103-4.
PMID: 15468839

Hydroxyapatite (HA; Ca10(PO4)6(OH)2), is one of the significant implant materials used in Orthopaedics and Dental applications. However, synthetically produced HA may not be stable under ionic environment, which it will unavoidably encounter during its applications. In this paper, the in vitro effects of three HA materials derived from different resources, i.e. commercial HA (HAC), synthesised HA from pure chemicals (HAS) and synthesised HA from kapur sireh; derived traditionally from natural limestone (HAK), were studied. The HA disc samples were prepared and immersed in simulated body fluid (SBF) for 31-day period. The evaluation conducted focuses on the changes of the pH and the Calcium ion (Ca-ion) and Phosphate ion (P-ion) concentrations in the SBF solution, as well as the XRD and SEM data representing the reactions on the HA materials. From the XRD, it was found that HAK has the smallest crystallite sizes, which in turn affect the pH of the SBF during immersion. The Ca and P-ion concentrations generally decrease over time at different rates for different HA. Upon 1-day immersion in SBF, apatite growth was observed onto all three surfaces, which became more pronounced after 3-day immersion. However, the appetites formed were observed to be different in shapes and sizes. The reasons for the difference in the apatite-crystals and their subsequent effects on cells are still being investigated.

Matched MeSH terms: Calcium/pharmacology*
Toluene promotes lid 2 interfacial activation of cold active solvent tolerant lipase from Pseudomonas fluorescens strain AMS8

Yaacob N, Mohamad Ali MS, Salleh AB, Rahman RNZRA, Leow ATC

J Mol Graph Model, 2016 07;68:224-235.
PMID: 27474867 DOI: 10.1016/j.jmgm.2016.07.003

The utilization of cold active lipases in organic solvents proves an excellent approach for chiral synthesis and modification of fats and oil due to the inherent flexibility of lipases under low water conditions. In order to verify whether this lipase can function as a valuable synthetic catalyst, the mechanism concerning activation of the lid and interacting solvent residues in the presence of organic solvent must be well understood. A new alkaline cold-adapted lipase, AMS8, from Pseudomonas fluorescens was studied for its structural adaptation and flexibility prior to its exposure to non-polar, polar aprotic and protic solvents. Solvents such as ethanol, toluene, DMSO and 2-propanol showed to have good interactions with active sites. Asparagine (Asn) and tyrosine (Tyr) were key residues attracted to solvents because they could form hydrogen bonds. Unlike in other solvents, Phe-18, Tyr-236 and Tyr-318 were predicted to have aromatic-aromatic side-chain interactions with toluene. Non-polar solvent also was found to possess highest energy binding compared to polar solvents. Due to this circumstance, the interaction of toluene and AMS8 lipase was primarily based on hydrophobicity and molecular recognition. The molecular dynamic simulation showed that lid 2 (residues 148-167) was very flexible in toluene and Ca(2+). As a result, lid 2 moves away from the catalytic areas, leaving an opening for better substrate accessibility which promotes protein activation. Only a single lid (lid 2) showed the movement following interactions with toluene, although AMS8 lipase displayed double lids. The secondary conformation of AMS8 lipase that was affected by toluene observed a reduction of helical strands and increased coil structure. Overall, this work shows that cold active lipase, AMS8 exhibits distinguish interfacial activation and stability in the presence of polar and non-polar solvents.

Matched MeSH terms: Calcium/pharmacology
Fulltext Effects of Calcium and Annatto Tocotrienol Supplementation on Bone Loss Induced by Pantoprazole in Male Rats

Chin KY, Thong BKS, Kamalulloh RF, Mohamad NV, Wong SK, Mohd Arlamsyah A, et al.

Drug Des Devel Ther, 2020;14:2561-2572.
PMID: 32753839 DOI: 10.2147/DDDT.S260565

Purpose: Prolonged use of proton pump inhibitors may cause bone loss, and limited therapeutic agents are available to prevent this skeletal side effect. The combination of annatto tocotrienol, a bone anabolic agent, with calcium presents a novel strategy to prevent bone loss caused by proton pump inhibitors. This study aims to compare the effects of calcium alone and in combination with annatto tocotrienol or vitamin D3 (Caltrate Plus) in preventing bone loss caused by pantoprazole.
Methods: Three-month-old Sprague Dawley male rats (n=30) were randomised into five groups (n=6/group). Bone loss was induced by pantoprazole (3 mg/kg p.o.) in four groups, and they were treated concurrently with either calcium carbonate (77 mg p.o.), calcium carbonate (77 mg p.o.) plus annatto tocotrienol (60 mg/kg p.o.) or Caltrate Plus (31 mg p.o.) for 60 days. The rats were euthanised at the end of the experiment, and their femurs were harvested for X-ray micro-computed tomography, bone cellular histomorphometry and bone mechanical strength analysis.
Results: Pantoprazole caused significant deterioration of trabecular bone microstructures but did not affect other skeletal indices. Calcium supplementation with or without annatto tocotrienol prevented the deterioration of trabecular microstructures at the femur but did not improve other skeletal indices. Annatto tocotrienol did not enhance the skeletal actions of calcium, whereas Caltrate Plus did not affect the bone health indices in these rats.
Conclusion: Calcium supplementation per se can prevent the deterioration of bone trabecular microstructures in rats receiving long-term treatment of pantoprazole.

Matched MeSH terms: Calcium/pharmacology*
Fulltext Studying neuroprotective effect of Atorvastatin as a small molecule drug on high glucose-induced neurotoxicity in undifferentiated PC12 cells: role of NADPH oxidase

Rayegan S, Dehpour AR, Sharifi AM

Metab Brain Dis, 2017 02;32(1):41-49.
PMID: 27476541 DOI: 10.1007/s11011-016-9883-1

Overproduction of reactive oxygen species (ROS) by NADPH oxidase (NOX) activation has been considered the essential mechanism induced by hyperglycemia in various tissues. However, there is no comprehensive study on the role of NOXs in high glucose (HG)-induced toxic effect in neural tissues. Recently, a therapeutic strategy in oxidative related pathologies has been introduced by blocking the undesirable actions of NOX enzymes by small molecules. The protective roles of Statins in ameliorating oxidative stress by NOX inhibition have been shown in some tissues except neural. We hypothesized then, that different NOXs may have role in HG-induced neural cell injury. Furthermore, we postulate that Atorvastatin as a small molecule may modulate this NOXs activity to protect neural cells. Undifferentiated PC12 cells were treated with HG (140 mM/24 h) in the presence and absence of Atorvastatin (1 μM/96 h). The cell viability was measured by MTT assay and the gene and protein expressions profile of NOX (1-4) were determined by RT-PCR and western blotting, respectively. Levels of ROS and malondialdehyde (MDA) were also evaluated. Gene and protein expression levels of NOX (1-4) and consequently ROS and MDA levels were elevated in HG-treated PC12 cells. Atorvastatin could significantly decrease HG-induced NOXs, ROS and MDA elevation and improve impaired cell viability. It can be concluded that HG could elevate NOXs activity, ROS and MDA levels in neural tissues and Atorvastatin as a small molecule NOX inhibitor drug may prevent and delay diabetic complications, particularly neuropathy.

Matched MeSH terms: Atorvastatin Calcium/pharmacology*
Fulltext Generic atorvastatin is as effective as the brand-name drug (LIPITOR®) in lowering cholesterol levels: a cross-sectional retrospective cohort study

Loch A, Bewersdorf JP, Kofink D, Ismail D, Abidin IZ, Veriah RS

BMC Res Notes, 2017 Jul 17;10(1):291.
PMID: 28716156 DOI: 10.1186/s13104-017-2617-6

BACKGROUND: In a world of ever increasing health care costs, generic drugs represent a major opportunity to ensure access to essential medicines for people who otherwise would be unable to afford them. However, some clinicians and patients are still questioning the safety and effectiveness of generic formulations compared to the proprietary drugs necessitating further systematic research analyzing the generic drugs' efficacy. Our objective was to compare the lipid lowering effects of generic and branded atorvastatin.
METHODS: This cross-sectional, retrospective cohort study was conducted at the University of Malaya Medical Centre from 1 May 2013 until 30 May 2013. We analyzed the lipid profiles (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides) of 629 patients before and at least 3 months after switching them from proprietary atorvastatin (Lipitor®) to generic atorvastatin (atorvastatin calcium from Ranbaxy Laboratories, Inc.). We also investigated if there was any difference in the effectiveness of both atorvastatin formulations in various ethnic groups.
RESULTS: 266 patients were included in this study. When comparing the median values we found no statistically significant differences (Wilcoxon signed-rank test; p calcium does not result in a less effective management of hyperlipidemia. Our findings lend support to the approach of lowering health care costs by switching patients from branded drugs to their less expensive generic analogues.

Matched MeSH terms: Atorvastatin Calcium/pharmacology*
Divalent ion-induced aggregation of gold nanoparticles for voltammetry Immunosensing: comparison of transducer signals in an assay for the squamous cell carcinoma antigen

Letchumanan I, Gopinath SCB, Arshad MKM

Mikrochim Acta, 2020 01 14;187(2):128.
PMID: 31938893 DOI: 10.1007/s00604-020-4115-0

A method is described for the electrochemical determination of squamous cell carcinoma (SCC) antigen, and by testing the effect of 30 nm gold nanoparticles (GNPs). Three comparative studies were performed in the presence and absence of GNPs, and with agglomerated GNPs. The divalent ion Ca(II) was used to induce a strong agglomeration of GNPs, as confirmed by colorimetry and voltammetry. Herein, colorimetry was used to test the best amount of salt needed to aggregate the GNPs. Despite, voltammetry was used to determine the status of biomolecules on the sensor. The topography of the surface of ZnO-coated interdigitated electrodes was analyzed by using 3D-nano profilometry, scanning electron microscopy, atomic force microscopy and high-power microscopy. The interaction between SCC antigen and antibody trigger vibrations on the sensor and cause dipole moment, which was measured using a picoammeter with a linear sweep from 0 to 2 V at 0.01 V step voltage. The sensitivity level was 10 fM by 3σ calculation for the dispersed GNP-conjugated antigen. This indicates a 100-fold enhancement compared to the condition without GNP conjugation. However, the sensitivity level for agglomerated GNPs conjugated antibody was not significant with 100 fM sensitivity. Specificity was tested for other proteins in serum, namely blood clotting factor IX, C-reactive protein, and serum albumin. The SCC antigen was quantified in spiked serum and gave recoveries that ranged between 80 and 90%. Graphical abstractSchematic representation of SCC (squamous cell carcinoma) antigen determination using divalent ion induced agglomerated GNPs. Sensitivity increment depends on the occurrence of more SCC antigen and antibody binding event via GNPs integration. Notably, lower detection limit was achieved at femto molar with proper orientation of biological molecules.

Matched MeSH terms: Calcium/pharmacology
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/pharmacology
Zinc, magnesium, and calcium ion supplementation confers tolerance to acetic acid stress in industrial Saccharomyces cerevisiae utilizing xylose

Ismail KS, Sakamoto T, Hasunuma T, Zhao XQ, Kondo A

Biotechnol J, 2014 Dec;9(12):1519-25.
PMID: 24924214 DOI: 10.1002/biot.201300553

Lignocellulosic biomass is a potential substrate for ethanol production. However, pretreatment of lignocellulosic materials produces inhibitory compounds such as acetic acid, which negatively affect ethanol production by Saccharomyces cerevisiae. Supplementation of the medium with three metal ions (Zn(2+) , Mg(2+) , and Ca(2+) ) increased the tolerance of S. cerevisiae toward acetic acid compared to the absence of the ions. Ethanol production from xylose was most improved (by 34%) when the medium was supplemented with 2 mM Ca(2+) , followed by supplementation with 3.5 mM Mg(2+) (29% improvement), and 180 μM Zn(2+) (26% improvement). Higher ethanol production was linked to high cell viability in the presence of metal ions. Comparative transcriptomics between the supplemented cultures and the control suggested that improved cell viability resulted from the induction of genes controlling the cell wall and membrane. Only one gene, FIT2, was found to be up-regulated in common between the three metal ions. Also up-regulation of HXT1 and TKL1 might enhance xylose consumption in the presence of acetic acid. Thus, the addition of ionic nutrients is a simple and cost-effective method to improve the acetic acid tolerance of S. cerevisiae.

Matched MeSH terms: Calcium/pharmacology*
The effects of Cosmos caudatus (Ulam Raja) supplementation on bone biochemical parameters in ovariectomized rats

Mohamed N, Yin CM, Shuid AN, Muhammad N, Babji AS, Soelaiman IN

Pak J Pharm Sci, 2013 Sep;26(5):1027-31.
PMID: 24035963

Cosmos caudatus (ulam raja) contains high mineral content and possesses high antioxidant activity which may be beneficial in bone disorder such as postmenopausal osteoporosis. The effects of C. caudatus on bone metabolism biomarkers in ovariectomized rats were studied. 48 Sprague-Dawley rats aged three months were divided into 6 groups. One group of rats was sham-operated while the remaining rats were ovariectomized. The ovariectomized rats were further divided into 5 groups: the control, three groups force-fed with C. caudatus at the doses of 100mg/kg, 200mg/kg or 300mg/kg and another group supplemented with calcium 1% ad libitum. Treatments were given 6 days per week for a period of eight weeks. Blood samples were collected twice; before and after treatment. Parameters measured were bone resorbing cytokine; interleukin-1 and the bone biomarkers; osteocalcin and pyridinoline. Serum IL-1 and pyridinoline levels were significantly increased in ovariectomized rats. Supplementation of C. caudatus was able to prevent the increase of IL-1 and pyridinoline in ovariectomized rats. Besides that, C. caudatus showed the same effect as calcium 1% on biochemical parameters of bone metabolism in ovariectomized rats. In conclusion, Cosmos caudatus was as effective as calcium in preventing the increase in bone resorption in ovariectomized rats.

Matched MeSH terms: Calcium/pharmacology
Fulltext Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis

Adeyemi O, Alvarez-Laviada A, Schultz F, Ibrahim E, Trauner M, Williamson C, et al.

PLoS One, 2017;12(9):e0183167.
PMID: 28934223 DOI: 10.1371/journal.pone.0183167

BACKGROUND: Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated.
METHODS: High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes.
RESULTS: TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05) and slowed ventricular conduction velocity (CV) by 38.9±5.1% (P<0.05) exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T) blocker mibefradil 1μM (23.0±6.2%, P<0.05), but not with the L-type calcium current (ICa,L) blocker nifedipine 1μM (6.9±6.6%, NS). The sodium channel blocker lidocaine (30μM) reduced CV by 60.4±4.5% (P<0.05). UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (-10.2±1.5 versus -5.5±0.9 pA/pF, P<0.05) and neonatal rat ventricular myocytes (-22.3±1.1 versus -9.6±0.8 pA/pF, P<0.0001), whereas UDCA had limited efficacy on the ICa,L.
CONCLUSION: Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA.

Matched MeSH terms: Calcium/pharmacology
Fulltext Hepatoprotective Effects of a Novel Trihoney against Nonalcoholic Fatty Liver Disease: A Comparative Study with Atorvastatin

Alfarisi HAH, Ibrahim MB, Mohamed ZBH, Azahari N, Hamdan AHB, Che Mohamad CA

ScientificWorldJournal, 2020;2020:4503253.
PMID: 33132768 DOI: 10.1155/2020/4503253

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide with no curative therapy. The aim of this study was to investigate the hepatoprotective effects of a novel Trihoney against biochemical and histological manifestations of NAFLD in hypercholesterolemic rabbits. Methodology. Forty-eight male New Zealand white (NZW) rabbits were grouped into normal diet (C), normal diet with 0.6 g/kg/day of Trihoney (C + H), 1% cholesterol diet (HCD), 1% cholesterol diet with 0.3 g/kg/day of Trihoney (HCD + H1), 1% cholesterol diet with 0.6 g/kg/day of Trihoney (HCD + H2), and 1% cholesterol diet with 2 mg/kg/day of atorvastatin (HCD + At.). Animals were sacrificed after 12 weeks of treatment. Serum lipids and liver function test (LFT) were measured prior to and at the endpoint of the experiment for total cholesterol (TC), low-density lipoprotein (LDL-c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (T. Bil.). Liver was processed for histopathology study. Liver homogenate was analysed for oxidative stress parameters: superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Results. Lipid analysis approved the induction of hypercholesterolemia. A significant elevation (p < 0.01) of serum AST and ALT levels showed by the HCD group was compared to C and C + H groups. Trihoney exhibited a significant reduction (p < 0.001) of AST and ALT compared to the HCD group. Likewise, AST and ALT reduced significantly in the HCD + At. group (p < 0.001). Trihoney supplementation induced significant (p < 0.05) enhancement of SOD and GPx activities. Atorvastatin treatment was associated with significant (p < 0.05) reduction of SOD and GPx activities in the liver. Trihoney and atorvastatin showed marked (p < 0.001) reduction of hepatic lipid peroxidation. Trihoney showed histological protection against progression of NAFLD to nonalcoholic steatohepatitis (NASH). Atorvastatin exhibited no beneficial impact on hepatic architecture. Conclusion. Trihoney was able to maintain normal liver function and showed hepatoprotection against progression of NAFLD to NASH probably through hypocholesterolaemic and antioxidant functions.

Matched MeSH terms: Atorvastatin Calcium/pharmacology
Protective effects of atorvastatin on high glucose-induced oxidative stress and mitochondrial apoptotic signaling pathways in cultured chondrocytes

Hosseinzadeh A, Bahrampour Juybari K, Kamarul T, Sharifi AM

J Physiol Biochem, 2019 Jun;75(2):153-162.
PMID: 30796627 DOI: 10.1007/s13105-019-00666-8

The high glucose concentration is able to disturb chondrocyte homeostasis and contribute to OA pathogenesis. This study was designed to investigate the protective effects of atorvastatin (ATO) on high glucose (HG)-mediated oxidative stress and mitochondrial apoptosis in C28I2 human chondrocytes. The protective effect of ATO (0.01 and 0.1 μM) on HG (75 mM)-induced oxidative stress and apoptosis was evaluated in C28I2 cells. The effects of ATO on HG-induced intracellular ROS production and lipid peroxidation were detected and the protein expression levels of Bax, Bcl-2, caspase-3, total and phosphorylated JNK and P38 MAPKs were analyzed by Western blotting. The mRNA expression levels of antioxidant enzymes including heme oxygenase-1, NAD(P)H quinine oxidoreductase, glutathione S-transferase-P1, catalase, superoxide dismutase-1, glutathione peroxidase-1, -3, -4 were evaluated by reverse transcription-polymerase chain reaction. Pretreatment with ATO remarkably increased the gene expression levels of antioxidant enzymes and reduced HG-induced elevation of ROS, lipid peroxidation, Bax/Bcl-2 ratio, caspase-3 activation, and JNK and P38 phosphorylation. Atorvastatin could considerably reduce HG-induced oxidative stress and mitochondrial apoptosis through increasing the expression of antioxidant enzymes. Atorvastatin may be considered as a promising agent to prevent high glucose-induced cartilage degradation in OA patients.

Matched MeSH terms: Atorvastatin Calcium/pharmacology*
Fulltext Gynura procumbens ethanol extract improves vascular dysfunction by suppressing inflammation in postmenopausal rats fed a high-fat diet

Ahmad Nazri KA, Haji Mohd Saad Q, Mohd Fauzi N, Buang F, Jantan I, Jubri Z

Pharm Biol, 2021 Dec;59(1):1203-1215.
PMID: 34493166 DOI: 10.1080/13880209.2021.1970199

CONTEXT: Gynura procumbens (Lour.) Merr. (Asteraceae) has been reported to have various pharmacological activities including anti-inflammatory effects.
OBJECTIVE: This study sought to determine whether Gynura procumbens (GP) could improve vascular reactivity by suppressing inflammation in postmenopausal rats fed with five-times heated palm oil (5HPO) diet.
MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were randomly divided into sham [non-ovariectomized; grouped as control, GP extracts (250 and 500 mg/kg), atorvastatin (ATV, 10 mg/kg)] and postmenopausal (PM) groups [ovariectomized rats fed with 5HPO; grouped as PM, GP extracts (250 and 500 mg/kg) and ATV (10 mg/kg)]. Each group (n = 6) was either supplemented with GP extract or ATV orally once daily for 6 months.
RESULTS: In comparison with the untreated PM group, 250 and 500 mg/kg GP supplementation to PM groups reduced the systolic blood pressure (103 ± 2.7, 86 ± 2.4 vs. 156 ± 7.83 mmHg, p

Matched MeSH terms: Atorvastatin Calcium/pharmacology

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