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Khor B.-S.,Malaysian Institute of Pharmaceuticals and Nutraceuticals | Jamil M.F.,Malaysian Institute of Pharmaceuticals and Nutraceuticals | Adenan M.I.,Malaysian Institute of Pharmaceuticals and Nutraceuticals | Adenan M.I.,Malaysian Forest Research Institute | And 2 more authors.
PLoS ONE | Year: 2011

A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. © 2011 Khor et al. Source

Tan S.-H.,Universiti Sains Malaysia | Chung H.-H.,Universiti Sains Malaysia | Shu-Chien A.C.,Universiti Sains Malaysia | Shu-Chien A.C.,Malaysian Institute of Pharmaceuticals and Nutraceuticals
Biochemical and Biophysical Research Communications | Year: 2010

Despite the known importance of long-chained polyunsaturated fatty acids (LC-PUFA) during development, very little is known about their utilization and biosynthesis during embryogenesis. Combining the advantages of the existence of a complete range of enzymes required for LC-PUFA biosynthesis and the well established developmental biology tools in zebrafish, we examined the expression patterns of three LC-PUFA biosynthesis genes, Elovl2-like elongase (elovl2), Elovl5-like elongase (elovl5) and fatty acyl desaturase (fad) in different zebrafish developmental stages. The presence of all three genes in the brain as early as 24 hours post fertilization (hpf) implies LC-PUFA synthesis activity in the embryonic brain. This expression eventually subsides from 72 hpf onwards, coinciding with the initiation of elovl2 and fad expression in the liver and intestine, 2 organs known to be involved in adult fish LC-PUFA biosynthesis. Collectively, these patterns strongly suggest the necessity for localized production of LC-PUFA in the brain during in early stage embryos prior to the maturation of the liver and intestine. Interestingly, we also showed a specific expression of elovl5 in the proximal convoluted tubule (PCT) of the zebrafish pronephros, suggesting a possible new role for LC-PUFA in kidney development and function. © 2010 Elsevier Inc. All rights reserved. Source

Ramachandran H.,Universiti Sains Malaysia | Iqbal N.M.,Universiti Sains Malaysia | Sipaut C.S.,Universiti Malaysia Sabah | Abdullah A.A.-A.,Malaysian Institute of Pharmaceuticals and Nutraceuticals
Applied Biochemistry and Biotechnology | Year: 2011

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate) [P(3HB-co-3HV-co-4HB)] terpolymer was produced using Cupriavidus sp. USMAA2-4 via one-step cultivation process through combination of various carbon sources such as 1,4-butanediol or γ-butyrolactone with either 1-pentanol, valeric acid, or 1-propanol. Oleic acid was added to increase the biomass production. The composition of 3HV and 4HB monomers were greatly affected by the concentration of 1,4-butanediol and 1-pentanol. Terpolymers with 3HV and 4HB molar fractions ranging from 2 to 41 mol.% and 5 to 31 mol.%, respectively, were produced by varying the concentration of carbon precursors. The thermal and mechanical properties of the terpolymers containing different proportions of the constituent monomers were characterized using gel permeation chromatography (GPC), DSC, and tensile machine. GPC analysis showed that the molecular weights (M w) of the terpolymer produced were within the range of 346 to 1,710 kDa. The monomer compositions of 3HV and 4HB were also found to have great influences on the thermal and mechanical properties of the terpolymer P(3HB-co-3HV-co-4HB) produced. © 2011 Springer Science+Business Media, LLC. Source

Rennukka M.,Universiti Sains Malaysia | Amirul A.A.,Universiti Sains Malaysia | Amirul A.A.,Malaysian Institute of Pharmaceuticals and Nutraceuticals
Polymer Bulletin | Year: 2013

A new blend material was fabricated from poly(3-hydroxybutyrate-co- 4-hydroxybutyrate) [P(3HB-co-4HB)] and chitosan through simple solvent casting method. In this investigation, the impact of different contents of chitosan and molar fractions of 4HB monomer towards the hybrid films was determined. The hydrophobic nature of the P(3HB-co-4HB) copolymer was modified by blending with a hydrophilic polymer-chitosan. Thus, the water-absorption capacity and solubility of the blend films were increased proportionally with the increasing content of chitosan. Miscibility of the blend films between the pure components was detected through Fourier transform infrared analysis. The thermal property was altered in terms of melting temperature, whereas the thermal stability of the blend films was greatly increased. Moreover, the scanning electron microscope images indicated that the surface of the blend films was homogenous and porous. Impregnation of chitosan enabled the blend films to exhibit antimicrobial activity against both Gram-negative and Gram-positive bacteria. The blend films with 20 wt% of chitosan were more hydrophilic, porous, biocidal and they have a wider opportunity in various applications such as wound dressing and tissue engineering than the native P(3HB-co-4HB) copolymer. © Springer-Verlag Berlin Heidelberg 2013. Source

Ramachandran H.,Universiti Sains Malaysia | Amirul A.A.,Universiti Sains Malaysia | Amirul A.A.,Malaysian Institute of Pharmaceuticals and Nutraceuticals
Journal of Chemical Technology and Biotechnology | Year: 2013

Background: Development of bacterial strains that can utilize cheap and renewable carbon substrate will make the prices of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] competitive with synthetic plastics. Disposal of glycerine pitch, which is a scheduled waste from the oleochemicals industry, has raised awareness among communities as burning the waste literally means producing acrolein which is well known for its toxicity and adverse effects. Therefore, discovering potential application of glycerine pitch as carbon substrate is believed to overcome the waste management problem and reduce the P(3HB-co-4HB) production cost. Results: Cupriavidus sp. USMAHM13, a novel yellow-pigmented bacterium produced the highest 4HB composition (43 mol%) with cell dry weight and PHA content of 6.0 g L-1 and 49 wt%, respectively, through combination of glycerine pitch (5 g L-1) and 1,4-butanediol (5 g L-1) via one-stage cultivation. The yellow pigment extracts were analyzed using UV-VIS spectrophotometry and high performance liquid chromatography - mass spectrometry (HPLC-MS), which revealed that the yellow pigment might represent a new compound in the carotenoid group. Conclusion: Biosynthesis of P(3HB-co-4HB) by a novel yellow-pigmented Cupriavidus sp. using glycerine pitch together with 1,4-butanediol enhanced cost efficiency and sustainability in the production of P(3HB-co-4HB). © 2012 Society of Chemical Industry. Source

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