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Albiglutide: Is a better hope against diabetes mellitus?

Sharma AK, Thanikachalam PV, Rajput SK

Biomed Pharmacother, 2016 Feb;77:120-8.
PMID: 26796275 DOI: 10.1016/j.biopha.2015.12.015

Type-2 diabetes mellitus (T2DM) is the chronic metabolic disorder which provokes several pitfall signalling. Though, a series of anti-diabetic drugs are available in the market but T2DM is still a huge burden on the developed and developing countries. Numerous studies and survey predict the associated baleful circumstances in near future due to incessant increase in this insidious disorder. The novelty of recent explored anti-diabetic drugs including glitazone, glitazaar and gliflozines seems to be vanished due to their associated toxic side effects. Brown and Dryburgh (1970) isolated an intestinal amino acid known as gastric inhibitory peptide (GIP) which had insulinotropic activity. Subsequently in 1985, another incretin glucagon likes peptide 1 (GLP-1) having potent insulinotropic properties was discovered by Schmidt and his co-workers. On the basis of results' obtained by Phase III Harmony program FDA approved (14 April, 2014) new GLP-1 agonist 'Albiglutide (ALB)', in addition to exiting components Exenatide (Eli Lilly, 2005) and Liraglutide (Novo Nordisk, 2010). ALB stimulates the release of protein kinase A (PKA) via different mechanisms which ultimately leads to increase in intracellular Ca(2+) levels. This increased intracellular Ca(2+) releases insulin vesicle from β-cells. In-addition, ALB being resistant to degradation by dipeptidyl peptidase-4 (DPP-4) and has longer half life. DPP-4 can significantly degrade the level of GLP-1 agonist by hydrolysis. In spite of potent anti-hypergycemic activity, ALB has pleiotropic action of improving cardiovascular physiology. In light of these viewpoints we reveal the individual pharmacological profile of ALB and the critical analyse about its future perspective in present review.

Matched MeSH terms: Calcium/metabolism
Fulltext Analysis of Comparative Sequence and Genomic Data to Verify Phylogenetic Relationship and Explore a New Subfamily of Bacterial Lipases

Masomian M, Rahman RN, Salleh AB, Basri M

PLoS One, 2016;11(3):e0149851.
PMID: 26934700 DOI: 10.1371/journal.pone.0149851

Thermostable and organic solvent-tolerant enzymes have significant potential in a wide range of synthetic reactions in industry due to their inherent stability at high temperatures and their ability to endure harsh organic solvents. In this study, a novel gene encoding a true lipase was isolated by construction of a genomic DNA library of thermophilic Aneurinibacillus thermoaerophilus strain HZ into Escherichia coli plasmid vector. Sequence analysis revealed that HZ lipase had 62% identity to putative lipase from Bacillus pseudomycoides. The closely characterized lipases to the HZ lipase gene are from thermostable Bacillus and Geobacillus lipases belonging to the subfamily I.5 with ≤ 57% identity. The amino acid sequence analysis of HZ lipase determined a conserved pentapeptide containing the active serine, GHSMG and a Ca(2+)-binding motif, GCYGSD in the enzyme. Protein structure modeling showed that HZ lipase consisted of an α/β hydrolase fold and a lid domain. Protein sequence alignment, conserved regions analysis, clustal distance matrix and amino acid composition illustrated differences between HZ lipase and other thermostable lipases. Phylogenetic analysis revealed that this lipase represented a new subfamily of family I of bacterial true lipases, classified as family I.9. The HZ lipase was expressed under promoter Plac using IPTG and was characterized. The recombinant enzyme showed optimal activity at 65 °C and retained ≥ 97% activity after incubation at 50 °C for 1h. The HZ lipase was stable in various polar and non-polar organic solvents.

Matched MeSH terms: Calcium/metabolism
Mechanism of the anticataract effect of liposomal MgT in galactose-fed rats

Iezhitsa I, Agarwal R, Saad SD, Zakaria FK, Agarwal P, Krasilnikova A, et al.

Mol Vis, 2016;22:734-47.
PMID: 27440992

PURPOSE: Increased lenticular oxidative stress and altered calcium/magnesium (Ca/Mg) homeostasis underlie cataractogenesis. We developed a liposomal formulation of magnesium taurate (MgT) and studied its effects on Ca/Mg homeostasis and lenticular oxidative and nitrosative stress in galactose-fed rats.
METHODS: The galactose-fed rats were topically treated with liposomal MgT (LMgT), liposomal taurine (LTau), or corresponding vehicles twice daily for 28 days with weekly anterior segment imaging. At the end of the experimental period, the lenses were removed and subjected to analysis for oxidative and nitrosative stress, Ca and Mg levels, ATP content, Ca(2+)-ATPase, Na(+),K(+)-ATPase, and calpain II activities.
RESULTS: The LTau and LMgT groups showed significantly lower opacity index values at all time points compared to the corresponding vehicle groups (p<0.001). However, the opacity index in the LMgT group was lower than that in the LTau group (p<0.05). Significantly reduced oxidative and nitrosative stress was observed in the LTau and LMgT groups. The lens Ca/Mg ratio in LMgT group was decreased by 1.15 times compared to that in the LVh group. Calpain II activity in the LMgT group was decreased by 13% compared to the LVh group. The ATP level and Na(+),K(+)-ATPase and Ca(2+)-ATPase activities were significantly increased in the LMgT group compared to the LVh group (p<0.05).
CONCLUSIONS: Topical liposomal MgT delays cataractogenesis in galactose-fed rats by maintaining the lens mineral homeostasis and reducing lenticular oxidative and nitrosative stress.

Matched MeSH terms: Calcium/metabolism
Calcium is required for ixotrophy of Aureispira sp. CCB-QB1

Furusawa G, Hartzell PL, Navaratnam V

Microbiology (Reading), 2015 Oct;161(10):1933-1941.
PMID: 26306656 DOI: 10.1099/mic.0.000158

Ixotrophy is a process that enables certain microbes to prey on other cells. The ability of cells to aggregate or adhere is thought to be a significant initial step in ixotrophy. The gliding, multicellular filamentous bacterium Aureispira sp. CCB-QB1 belongs to the family Saprospiraceae and preys on bacteria such as Vibrio sp. in seawater. Adhesion and cell aggregation were coincident with preying and were hypothesized to play an important role in the ixotrophy in this bacterium. To test this hypothesis, experiments to elucidate the mechanisms of aggregation or adhesion in this bacterium were performed. The ability of Aureispira QB1 to adhere and aggregate to prey bacterium, Vibrio sp., required divalent cations, especially calcium ions. In the presence of calcium, Aureispira QB1 cells captured 99 % of Vibrio sp. cells after 60 min of incubation. Toluidine blue O, which binds acidic polysaccharides, bound to Aureispira QB1 and inhibited adhesion of Aureispira QB1. These results suggest that acidic polysaccharides are needed for aggregation or adhesion of Aureispira and that calcium ions play a significant role in these phenomena.

Matched MeSH terms: Calcium/metabolism*
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*
Fulltext Mathematical modeling of subthreshold resonant properties in pyloric dilator neurons

Vazifehkhah Ghaffari B, Kouhnavard M, Aihara T, Kitajima T

Biomed Res Int, 2015;2015:135787.
PMID: 25960999 DOI: 10.1155/2015/135787

Various types of neurons exhibit subthreshold resonance oscillation (preferred frequency response) to fluctuating sinusoidal input currents. This phenomenon is well known to influence the synaptic plasticity and frequency of neural network oscillation. This study evaluates the resonant properties of pacemaker pyloric dilator (PD) neurons in the central pattern generator network through mathematical modeling. From the pharmacological point of view, calcium currents cannot be blocked in PD neurons without removing the calcium-dependent potassium current. Thus, the effects of calcium (I(Ca)) and calcium-dependent potassium (I(KCa)) currents on resonant properties remain unclear. By taking advantage of Hodgkin-Huxley-type model of neuron and its equivalent RLC circuit, we examine the effects of changing resting membrane potential and those ionic currents on the resonance. Results show that changing the resting membrane potential influences the amplitude and frequency of resonance so that the strength of resonance (Q-value) increases by both depolarization and hyperpolarization of the resting membrane potential. Moreover, hyperpolarization-activated inward current (I(h)) and I(Ca) (in association with I(KCa)) are dominant factors on resonant properties at hyperpolarized and depolarized potentials, respectively. Through mathematical analysis, results indicate that I h and I(KCa) affect the resonant properties of PD neurons. However, I(Ca) only has an amplifying effect on the resonance amplitude of these neurons.

Matched MeSH terms: Calcium/metabolism*
The effect of salinity on chlorophyll, proline and mineral nutrients in common weeds of coastal rice fields in Malaysia

Hakim MA, Juraimi AS, Hanafi MM, Ismail MR, Rafii MY, Aslani F, et al.

J Environ Biol, 2014 Sep;35(5):855-64.
PMID: 25204059

Six weed species (Leptochola chinensis, Echinochloa crus-galli, Echinochloa colona, Jussiaea linifolia, Oryza sativa (weedy rice) and Cyperus iria) were tested for their salt tolerant traits in terms of chlorophyll, proline and mineral nutrients accumulation against different salinity levels (0, 4, 8, 16, 24, 32, and 40 dS m(-1)). Chlorophyll a, b and total chlorophyll content, proline and mineral nutrients accumulation were determined. Salt stress showed prominent effect on all the parameters investigated and there were significant variations between the all weed species. Chlorophyll content, K+, Ca(2+) and Mg(2+) ions in both shoots and roots significantly decreased; while proline and Na+ accumulation significantly increased with increasing salinity up to 40 dS m(-1). In terms of overall performance, Cyperus iria and E. crus-galliwere relatively more tolerant; E. colona and J. linifolia were tolerant; L. chinensis and O. sativa L were salt sensitive, respectively.

Matched MeSH terms: Calcium/metabolism
Fulltext Genetical and comparative genomics of Brassica under altered Ca supply identifies Arabidopsis Ca-transporter orthologs

Graham NS, Hammond JP, Lysenko A, Mayes S, O Lochlainn S, Blasco B, et al.

Plant Cell, 2014 Jul;26(7):2818-30.
PMID: 25082855 DOI: 10.1105/tpc.114.128603

Although Ca transport in plants is highly complex, the overexpression of vacuolar Ca(2+) transporters in crops is a promising new technology to improve dietary Ca supplies through biofortification. Here, we sought to identify novel targets for increasing plant Ca accumulation using genetical and comparative genomics. Expression quantitative trait locus (eQTL) mapping to 1895 cis- and 8015 trans-loci were identified in shoots of an inbred mapping population of Brassica rapa (IMB211 × R500); 23 cis- and 948 trans-eQTLs responded specifically to altered Ca supply. eQTLs were screened for functional significance using a large database of shoot Ca concentration phenotypes of Arabidopsis thaliana. From 31 Arabidopsis gene identifiers tagged to robust shoot Ca concentration phenotypes, 21 mapped to 27 B. rapa eQTLs, including orthologs of the Ca(2+) transporters At-CAX1 and At-ACA8. Two of three independent missense mutants of BraA.cax1a, isolated previously by targeting induced local lesions in genomes, have allele-specific shoot Ca concentration phenotypes compared with their segregating wild types. BraA.CAX1a is a promising target for altering the Ca composition of Brassica, consistent with prior knowledge from Arabidopsis. We conclude that multiple-environment eQTL analysis of complex crop genomes combined with comparative genomics is a powerful technique for novel gene identification/prioritization.

Matched MeSH terms: Calcium/metabolism*
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
Fulltext Crystal structure and immunological properties of the first annexin from Schistosoma mansoni: insights into the structural integrity of the schistosomal tegument

Leow CY, Willis C, Osman A, Mason L, Simon A, Smith BJ, et al.

FEBS J, 2014 Feb;281(4):1209-25.
PMID: 24428567 DOI: 10.1111/febs.12700

Schistosomiasis is a major parasitic disease of humans, second only to malaria in its global impact. The disease is caused by digenean trematodes that infest the vasculature of their human hosts. These flukes are limited externally by a body wall composed of a syncytial epithelium, the apical surface membrane of which is a parasitism-adapted dual membrane complex. Annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the first structural and immunobiochemical characterization of an annexin from Schistosoma mansoni. The crystal structure of annexin B22 confirms the presence of the previously predicted α-helical segment in the II/III linker and reveals a covalently linked head-to-head dimer. From the calcium-bound crystal structure of this protein, canonical type II, type III and B site positions are occupied, and a novel binding site has been identified. The dimer arrangement observed in the crystal structure suggests the presence of two prominent features, a potential non-canonical membrane binding site and a potential binding groove opposite to the former. Results from transcriptional profiling during development show that annexin B22 expression is correlated with life stages of the parasite that possess the syncytial tegument layer, and ultrastructural localization by immuno-electron microscopy confirms the occurrence of annexins in the tegument of S. mansoni. Data from membrane binding and aggregation assays indicate the presence of differential molecular mechanisms and support the hypothesis of annexin B22 providing structural integrity in the tegument.

Matched MeSH terms: Calcium/metabolism
A review of oxalate poisoning in domestic animals: tolerance and performance aspects

Rahman MM, Abdullah RB, Wan Khadijah WE

J Anim Physiol Anim Nutr (Berl), 2013 Aug;97(4):605-14.
PMID: 22548678 DOI: 10.1111/j.1439-0396.2012.01309.x

Published data on oxalate poisoning in domestic animals are reviewed, with a focus on tolerance and performance. Oxalic acid is one of a number of anti-nutrients found in forage. It can bind with dietary calcium (Ca) or magnesium (Mg) to form insoluble Ca or Mg oxalate, which then may lead to low serum Ca or Mg levels as well as to renal failure because of precipitation of these salts in the kidneys. Dietary oxalate plays an important role in the formation of Ca oxalate, and a high dietary intake of Ca may decrease oxalate absorption and its subsequent urinary excretion. Oxalate-rich plants can be supplemented with other plants as forage for domestic animals, which may help to reduce the overall intake of oxalate-rich plants. Non-ruminants appear to be more sensitive to oxalate than ruminants because in the latter, rumen bacteria help to degrade oxalate. If ruminants are slowly exposed to a diet high in oxalate, the population of oxalate-degrading bacteria in the rumen increases sufficiently to prevent oxalate poisoning. However, if large quantities of oxalate-rich plants are eaten, the rumen is overwhelmed and unable to metabolize the oxalate and oxalate-poisoning results. Based on published data, we consider that <2.0% soluble oxalate would be an appropriate level to avoid oxalate poisoning in ruminants, although blood Ca level may decrease. In the case of non-ruminants, <0.5% soluble oxalate may be acceptable. However, these proposed safe levels of soluble oxalate should be regarded as preliminary. Further studies, especially long-term studies, are needed to validate and improve the recommended safe levels in animals. This review will encourage further research on the relationships between dietary oxalate, other dietary factors and renal failure in domestic animals.

Matched MeSH terms: Calcium/metabolism
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
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
Catechin-rich oil palm leaf extract enhances bone calcium content of estrogen-deficient rats

Bakhsh A, Mustapha NM, Mohamed S

Nutrition, 2013 Apr;29(4):667-72.
PMID: 23290096 DOI: 10.1016/j.nut.2012.09.005

Postmenopausal estrogen deficiency often causes bone density loss and osteoporosis. This study evaluated the effects of an oral administration of oil palm leaf extract (OPL) on bone calcium content and structure, bone density, ash weights, and serum total alkaline phosphatase (T-ALP) of estrogen-deficient ovariectomized (OVX) rats.

Matched MeSH terms: Calcium/metabolism
Fulltext In-VITRo effect of Ficus deltoidea on the contraction of isolated rat's uteri is mediated via multiple receptors binding and is dependent on extracellular calcium

Salleh N, Ahmad VN

BMC Complement Altern Med, 2013;13:359.
PMID: 24330515 DOI: 10.1186/1472-6882-13-359

Ficus deltoidea, is a perennial herb that is used to assist labor, firm the uterus post-delivery and to prevent postpartum bleeding. In view of its claimed uterotonic action, the mechanisms underlying plant's effect on uterine contraction were investigated.

Matched MeSH terms: Calcium/metabolism*
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
Fulltext Hypotensive effect of Gentiana floribunda is mediated through Ca++ antagonism pathway

Khan AU, Mustafa MR, Khan AU, Murugan DD

BMC Complement Altern Med, 2012;12:121.
PMID: 22883710 DOI: 10.1186/1472-6882-12-121

Gentiana floribunda was investigated for the possible hypotensive and vasodilator activities in an attempt to rationalize its traditional use in hypertension.

Matched MeSH terms: Calcium/metabolism*
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*
The anti-osteoporotic effect of Eurycoma Longifolia in aged orchidectomised rat model

Shuid AN, Abu Bakar MF, Abdul Shukor TA, Muhammad N, Mohamed N, Soelaiman IN

Aging Male, 2011 Sep;14(3):150-4.
PMID: 20874437 DOI: 10.3109/13685538.2010.511327

Osteoporosis in elderly men is becoming an important health issue with the aging society. Elderly men with androgen deficiency are exposed to osteoporosis and can be treated with testosterone replacement. In this study, Eurycoma longifolia (EL), a plant with androgenic effects, was supplemented to an androgen-deficient osteoporotic aged rat as alternative to testosterone. Aged 12 months old Sprague-Dawley rats were divided into groups of normal control (NC), sham-operated (SO), orchidectomised-control (OrxC), orchidectomised and supplemented with EL (Orx + El) and orchidectomised and given testosterone (Orx + T). After 6 weeks of treatment, serum osteocalcin, serum terminal C-telopeptide Type 1 collagen (CTX) and the fourth lumbar bone calcium were measured. There were no significant differences in the osteocalcin levels before and after treatment in all the groups. The CTX levels were also similar for all the groups before treatment. However, after treatment, orchidectomy had caused significant elevation of CTX compared to normal control rats. Testosterone replacements in orchidectomised rats were able to prevent the rise of CTX. Orchidectomy had also reduced the bone calcium level compared to normal control rats. Both testosterone replacement and EL supplementation to orchidectomised rats were able to maintain the bone calcium level, with the former showing better effects. As a conclusion, EL prevented bone calcium loss in orchidectomised rats and therefore has the potential to be used as an alternative treatment for androgen deficient osteoporosis.

Matched MeSH terms: Calcium/metabolism*
The effects of Labisia pumila var. alata on bone markers and bone calcium in a rat model of post-menopausal osteoporosis

Shuid AN, Ping LL, Muhammad N, Mohamed N, Soelaiman IN

J Ethnopharmacol, 2011 Jan 27;133(2):538-42.
PMID: 20971181 DOI: 10.1016/j.jep.2010.10.033

AIM OF THE STUDY: Postmenopausal osteoporosis is mainly treated with estrogen replacement therapy (ERT). However, ERT causes side effects, mainly breast cancer, uterine cancer and thromboembolic problems. Labisia pumila var. arata (LPva), a herb with phytoestrogenic effects has the potential to be used as an alternative agent to ERT. This study was conducted to determine the effects of LPva on bone biochemical markers and bone calcium content in ovariectomised rats.
MATERIALS AND METHODS: Thirty two Wistar rats were divided into 4 groups, with 8 rats in each group. The first group was sham operated (Sham), the second group was ovariectomised (OVX), the third (LPva) and fourth group (ERT) were also ovariectomised and given LPva 17.5 mg/kg and Premarin(®) 64.5 μg/kg, respectively. Blood samples were taken before and after treatment to measure osteocalcin and C-terminal telopeptide of type 1 collagen levels using ELISA while the fifth lumbar bone samples were taken to measure bone calcium content using the Atomic Absorption Spectrophotometer (AAS).
RESULTS: The osteocalcin levels were significantly higher in both the LPva and ERT groups compared to the OVX group. The CTX levels were significantly lower in both the LPva and ERT groups compared to the OVX group. However, only the ERT group had significantly higher bone calcium level compared to the OVX group.
CONCLUSION: The supplementation of 17.5 mg/kg of LPva to ovariectomised rats for 8 weeks was able to prevent the changes in bone biochemical markers but failed to prevent the bone calcium loss induced by ovariectomy.

Matched MeSH terms: Calcium/metabolism

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