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1.
Pharmacogenomics J ; 17(5): 461-470, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-27241059

RESUMO

Expanding the scope of pharmacogenomic research by including multiple global populations is integral to building robust evidence for its clinical translation. Deep whole-genome sequencing of diverse ethnic populations provides a unique opportunity to study rare and common pharmacogenomic markers that often vary in frequency across populations. In this study, we aim to build a diverse map of pharmacogenetic variants in South East Asian (SEA) Malay population using deep whole-genome sequences of 100 healthy SEA Malay individuals. We investigated the allelic diversity of potentially deleterious pharmacogenomic variants in SEA Malay population. Our analysis revealed 227 common and 466 rare potentially functional single nucleotide variants (SNVs) in 437 pharmacogenomic genes involved in drug metabolism, transport and target genes, including 74 novel variants. This study has created one of the most comprehensive maps of pharmacogenetic markers in any population from whole genomes and will hugely benefit pharmacogenomic investigations and drug dosage recommendations in SEA Malays.


Assuntos
Povo Asiático/genética , Epidemiologia Molecular/métodos , Farmacogenética/métodos , Variantes Farmacogenômicos , Bases de Dados Genéticas , Frequência do Gene , Genética Populacional , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Malásia , Anotação de Sequência Molecular
2.
BMC Complement Altern Med ; 16(1): 488, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27899097

RESUMO

BACKGROUND: Melastoma malabathricum L. (family Melastomaceae) has been traditionally used as remedies against various ailments including those related to pain. The methanol extract of M. malabathricum leaves has been proven to show antinociceptive activity. Thus, the present study aimed to determine the most effective fraction among the petroleum ether- (PEMM), ethyl acetate- (EAMM) and aqueous- (AQMM) fractions obtained through successive fractionation of crude, dried methanol extract of M. malabathricum (MEMM) and to elucidate the possible mechanisms of antinociception involved. METHODS: The effectiveness of fractions (100, 250 and 500 mg/kg; orally) were determine using the acetic acid-induced abdominal constriction test and the most effective extract was further subjected to the hot plate- or formalin-induced paw licking-test to establish its antinociceptive profile. Further elucidation of the role of opioid and vanilloid receptors, glutamatergic system, and nitric oxide/cyclic guanosine phosphate (NO/cGMP) pathway was also performed using the appropriate nociceptive models while the phytoconstituents analyses were performed using the phytochemical screening test and, HPLC-ESI and GCMS analyses. RESULTS: PEMM, EAMM and AQMM significantly (p < 0.05) attenuated acetic acid-induced nociception with the recorded EC50 of 119.5, 125.9 and 352.6 mg/kg. Based on the EC50 value, PEMM was further studied and also exerted significant (p < 0.05) antinociception against the hot plate- and formalin-induced paw licking-test. With regards to the mechanisms of antinociception,: i) PEMM significantly (p < 0.05) attenuated the nociceptive action in capsaicin- and glutamate-induced paw licking test.; ii) naloxone (5 mg/kg), a non-selective opioid antagonist, failed to significantly (p < 0.05) inhibit PEMM's antinociception iii) L-arginine (a nitric oxide precursor), but not NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase), methylene blue (MB; an inhibitor of cGMP), or their respective combination, significantly (p < 0.05) reversed the antinociception of PEMM. Phytochemical analyses revealed the presence of several antinociceptive-bearing bioactive compounds, such as triterpenes and volatile compounds like oleoamide and palmitic acid. The presence of low flavonoids, such as gallocatechin and epigallocatechin, saponins and tannins in PEMM might synergistically contribute to enhance the major compounds antinociceptive effect. CONCLUSION: PEMM exerted a non-opioid-mediated antinociceptive activity at the central and peripheral levels via the inhibition of vanilloid receptors and glutamatergic system, and the activation of NO-mediated/cGMP-independent pathway. Triterpenes, as well as volatile oleoamide and palmitic acid, might be responsible for the observed antinociceptive activity of PEMM.


Assuntos
Analgésicos/isolamento & purificação , Melastomataceae/química , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Alcanos , Analgésicos/farmacologia , Analgésicos/toxicidade , Animais , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Melastomataceae/toxicidade , Metanol , Camundongos , Camundongos Endogâmicos ICR , Dor/etiologia , Compostos Fitoquímicos , Extratos Vegetais/toxicidade , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Solventes , Canais de Cátion TRPV/antagonistas & inibidores
3.
Pharm Biol ; 52(12): 1598-623, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25068675

RESUMO

CONTEXT: Different parts of Muntingia calabura L. (Elaeocarpaceae), or "kerukup siam" in Malay, have been reported to possess medicinal value, supported by a number of scientific studies. OBJECTIVE: To gather all information related to the ethnomedicinal uses, phytochemical compositions, and pharmacological activities of M. calabura and present them as a comprehensive and systematic review article. MATERIALS AND METHODS: Literature has been retrieved from a number of databases (e.g., Pubmed, Science Direct, Springer Link, etc.). General web searches were also carried out using Google and Yahoo search engines by applying some related search terms (e.g., Muntingia calabura, phytochemical, pharmacological, extract, and traditional uses). The articles related to agriculture, ecology, and synthetic work and those using languages other than English or Malay have been excluded. The bibliographies of papers relating to the review subject were also searched for further relevant references. RESULTS AND DISCUSSION: The literature search conducted using the above-mentioned Internet search engines only lead to the identification of 36 journals published as early as 1987. From the articles reviewed, M. calabura possessed various pharmacological activities (e.g., cytotoxic, antinociceptive, antiulcer, anti-inflammatory), which supported the folklore claims and could be attributed to its phytoconstituents. CONCLUSION: Muntingia calabura possesses remarkable medicinal value, which warrants further and in-depth studies. Therefore, this review paper is presented to help guide researchers to plan their future studies related to this plant in the hope of isolating potential leads for future drug development.


Assuntos
Elaeocarpaceae/química , Medicina Tradicional , Extratos Vegetais/farmacologia , Animais , Humanos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
4.
Indian J Med Res ; 136(2): 249-59, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22960892

RESUMO

BACKGROUND & OBJECTIVES: Genetic polymorphisms of uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) have been associated with a wide variation of responses among patients prescribed with irinotecan. Lack of this enzyme is known to be associated with a high incidence of severe toxicity. The objective of this study was to investigate the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28), which are associated with reduced enzyme activity and increased irinotecan toxicity, in the three main ethnic groups in Malaysia (Malays, Chinese and Indians). METHODS: A total of 306 healthy unrelated volunteers were screened for UGT1A1*28, UGT1A1*6 and UGT1A1*27. Blood samples (5 ml) were obtained from each subject and DNA was extracted. PCR based methods were designed and validated for detection of UGT1A1*, UUGT1A1*27 and UUGT1A1*28. Direct DNA sequencing was performed to validate the results of randomly selected samples. RESULTS: Malays and Indian have two-fold higher frequency of homozygous of UGT1A1*28 (7TA/7TA) which was 8 and 8.8 per cent, respectively compared to the Chinese (4.9%). However, the distribution of UGT1A1*6 and UGT1A1*27 showed no significant differences among them. UGT1A1*27 which has not been detected in Caucasian and African American population, was found in the Malaysian Malays (3.33%) and Malaysian Chinese (2.0%). INTERPRETATION & CONCLUSIONS: There was interethnic variability in the frequency of UGT1A1*28 in the Malaysian population. Our results suggest that genotyping of UUGT1A1*6, UGT1A1*28 and UGT1A1*27 need to be performed before patients are prescribed with irinotecan due to their high prevalence of allelic variant which could lead to adverse drug reaction.


Assuntos
Biomarcadores Farmacológicos , Camptotecina/análogos & derivados , Etnicidade/genética , Glucuronosiltransferase/genética , Biomarcadores Farmacológicos/sangue , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Frequência do Gene , Genótipo , Glucuronosiltransferase/sangue , Humanos , Irinotecano , Malásia , Farmacogenética/métodos , Polimorfismo Genético , Análise de Sequência de DNA
5.
Artigo em Inglês | MEDLINE | ID: mdl-22611437

RESUMO

Muntingia calabura L. (family Elaeocarpaceae) has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC) and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test) and thermal (hot plate test) models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg) was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P < 0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), N(G)-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P < 0.05) change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

6.
J Clin Pharm Ther ; 37(2): 237-41, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21545474

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA 94C>A) contribute to variable responses, including fatal adverse effects, among subjects treated with 6-mercaptopurine (6-MP). Our objectives were to investigate the distribution of specific TPMT and ITPA genotypes in healthy subjects and patients with acute lymphoblastic leukaemia (ALL) from the three main ethnic groups (Malays, Chinese and Indians) in Malaysia and the association of the polymorphisms with adverse effects of 6-MP. METHODS: Patients with ALL and healthy controls were recruited and genotyped for genetic variants of TPMT and ITPA 94C>A. The relationship between genotypes and clinical outcomes was investigated. RESULTS AND DISCUSSION: Acute lymphoblastic leukaemia patients with allele ITPA 94A were more likely to develop fever and liver toxicity with 6-MP. The prevalence of TPMT variants was low and this makes it unlikely that testing for them would be useful in our populations. Only patients heterozygous for TPMT*3C were detected. WHAT IS NEW AND CONCLUSION: Our results suggest that ITPA 94C>A testing, but not TPMT testing, may help in minimizing the adverse effects of 6-MP in Malaysian patients. However, whether this is true in clinical practice requires a larger study and formal randomized controlled evaluation.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Mercaptopurina/efeitos adversos , Metiltransferases/genética , Pirofosfatases/genética , Adolescente , Antimetabólitos Antineoplásicos/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Etnicidade/genética , Feminino , Genótipo , Humanos , Lactente , Malásia , Masculino , Mercaptopurina/uso terapêutico , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto Jovem , Inosina Trifosfatase
7.
J Clin Pharm Ther ; 37(2): 232-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21507031

RESUMO

WHAT IS KNOWN AND OBJECTIVES: Testing for cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles is recommended by the FDA for dosing of warfarin. However, dose prediction models derived from data obtained in one population may not be applicable to another. We therefore studied the impact of genetic polymorphisms of CYP2C9 and VKORC1 on warfarin dose requirement in Malaysia. METHODS: Patients who were attending clinics at our hospital and prescribed warfarin with stabilized INR levels of 2-4 were selected. DNA was extracted from blood samples and subsequently genotyped for CYP2C9*1, *2, *3, VKORC1 (G-1639A) and VKORC1 C1173T. Linear regression modelling using age, CYP2C9 and VKORC1 genotypes, sex, weight and height was undertaken to define a warfarin dosing algorithm. An initial model was developed using data from one cohort of patients and validated using data from a second cohort. RESULTS AND DISCUSSION: A model which included age and variants of CYP2C9 and VKORC1 account for about 37% of the variability in warfarin dose required to achieve INR of 2-4. Among the parameters evaluated, only VKORC1 (G-1639A) and (C1173T) alleles, and age correlated with warfarin dose at 6 month. The mean dose predicted using the algorithm derived from cohort 1 was lower than the actual dose for cohort 2 (3·30mg, SD 0·84 vs. 3·45mg, SD 1·42). There was no relationship between INR values and the dose taken by the patients. Race, sex, weight and height did not correlate with dose. WHAT IS NEW AND CONCLUSION: This study identifies factors which affect warfarin dosing in the Malaysia population. However, our best model does not account sufficiently for the variability in dose requirements for it to be used in dose prediction for the individual patient. Other important influential factors affecting warfarin dose requirement remain to be identified.


Assuntos
Anticoagulantes/administração & dosagem , Hidrocarboneto de Aril Hidroxilases/genética , Oxigenases de Função Mista/genética , Varfarina/administração & dosagem , Fatores Etários , Idoso , Algoritmos , Anticoagulantes/farmacocinética , Anticoagulantes/farmacologia , Estudos de Coortes , Citocromo P-450 CYP2C9 , Relação Dose-Resposta a Droga , Feminino , Genótipo , Humanos , Coeficiente Internacional Normatizado , Modelos Lineares , Malásia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Polimorfismo Genético , Vitamina K Epóxido Redutases , Varfarina/farmacocinética , Varfarina/farmacologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-21584247

RESUMO

Zingiber zerumbet Sm., locally known to the Malay as "Lempoyang," is a perennial herb found in many tropical countries, including Malaysia. The rhizomes of Z. zerumbet, particularly, have been regularly used as food flavouring and appetizer in various Malays' cuisines while the rhizomes extracts have been used in Malay traditional medicine to treat various types of ailments (e.g., inflammatory- and pain-mediated diseases, worm infestation and diarrhea). Research carried out using different in vitro and in vivo assays of biological evaluation support most of these claims. The active pharmacological component of Z. zerumbet rhizomes most widely studied is zerumbone. This paper presents the botany, traditional uses, chemistry, and pharmacology of this medicinal plant.

9.
Artigo em Inglês | MEDLINE | ID: mdl-21318140

RESUMO

The present study aims to determine the hepatoprotective effect of MARDI-produced virgin coconut oils, prepared by dried- or fermented-processed methods, using the paracetamol-induced liver damage in rats. Liver injury induced by 3 g/kg paracetamol increased the liver weight per 100 g bodyweight indicating liver damage. Histological observation also confirms liver damage indicated by the presence of inflammations and necrosis on the respective liver section. Interestingly, pretreatment of the rats with 10, but not 1 and 5, mL/kg of both VCOs significantly (P < .05) reduced the liver damage caused by the administration of paracetamol, which is further confirmed by the histological findings. In conclusion, VCO possessed hepatoprotective effect that requires further in-depth study.

10.
Med Princ Pract ; 20(3): 231-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21454992

RESUMO

OBJECTIVE: The present study was carried out to investigate the antinociceptive and anti-inflammatory activities of virgin coconut oil (VCO) produced by the Malaysian Agriculture Research and Development Institute (MARDI) using various in vivo models. MATERIALS AND METHODS: Two types of VCOs, produced via standard drying (VCOA) and fermentation (VCOB) processes were used in this study. Both VCOA and VCOB were serially diluted using 1% Tween 80 to concentrations (v/v) of 10, 50 and 100%. Antinociceptive and anti- inflammatory activities of both VCOs were examined using various in vivo model systems. The antinociceptive activity of the VCOs were compared to those of 1% Tween 80 (used as a negative control), morphine (5 mg/kg) and/or acetylsalicylic acid (100 mg/kg). RESULTS: Both VCOA and VCOB exhibited significant (p < 0.05) dose-dependent antinociceptive activity in the acetic acid-induced writhing test. Both VCOs also exerted significant (p < 0.05) antinociceptive activity in both phases of the formalin and hot-plate tests. Interestingly, the VCOs exhibited anti-inflammatory activity in an acute (carrageenan-induced paw edema test), but not in a chronic (cotton-pellet-induced granuloma test) model of inflammation. CONCLUSION: The MARDI-produced VCOs possessed antinociceptive and anti-inflammatory activities. Further studies are needed to confirm these observations.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Dor/tratamento farmacológico , Fitoterapia/métodos , Óleos de Plantas/farmacologia , Abdome/fisiologia , Animais , Óleo de Coco , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/prevenção & controle , Granuloma/prevenção & controle , Malásia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Contração Muscular/efeitos dos fármacos , Medição da Dor/métodos , Ratos , Ratos Sprague-Dawley
11.
J Clin Pharm Ther ; 35(6): 723-8, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21054465

RESUMO

WHAT IS KNOWN AND OBJECTIVE: CYP2C8 is involved in the cytochrome P450 (CYP) epoxygenase pathway. Arachidonic acid metabolites such as epoxyeicosatrienenoic acids and hydroxyeicosatetrenoic acids, produced may have a role in hypertension. We aimed to develop a medium through-put method for screening samples of known and new mutations of CYP2C8 using denaturing high performance liquid chromatography (DHPLC). METHODS: DNA samples from 200 subjects (hypertensive patients and healthy controls) were screened for SNPs in CYP2C8 using DHPLC. Genotypes and allelic frequencies of CYP2C8 between the healthy controls and patients with hypertension were compared. RESULTS AND DISCUSSIONS: Six variants were detected and two were new; T deletion at 5063 and substitution of C to T at 33468 in exon 8. Differences in variant frequencies were detected between the controls and hypertensive patients. The controls have significantly higher prevalence of C35322C compared to the patients. The functional significance of the SNP at 35322 requires further study. Having homozygous C35322C could be a protective factor for hypertension. WHAT IS NEW AND CONCLUSION: Denaturing high performance liquid chromatography is useful for population screening to identify new and existing SNPs. A higher frequency of the C35322T SNP was observed among hypertensive patients than control subjects. This potentially important observation requires confirmation and the clinical significance assessed.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Hipertensão/genética , Mutação , Polimorfismo de Nucleotídeo Único , Cromatografia Líquida de Alta Pressão/métodos , Citocromo P-450 CYP2C8 , Citocromo P-450 CYP2J2 , Sistema Enzimático do Citocromo P-450/metabolismo , Análise Mutacional de DNA , Frequência do Gene , Genótipo , Homozigoto , Humanos
13.
Genom Data ; 6: 128-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26697353

RESUMO

Acinetobacter baumannii is a Gram negative, strictly aerobic clinical pathogen causing mostly nosocomial infections globally. The DNA of an isolate from the blood of a local septicemic patient was sequenced using the Illumina GA IIx. The draft genome generated is 4,178,008 bp with a G + C content of 42%. From the annotation results, 47 resistance determinants including 16 multidrug resistance (MDR) genes were identified. The data may be accessed via the GenBank WGS master accession number APWV00000000.

14.
J Ethnopharmacol ; 166: 109-18, 2015 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-25792013

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Muntingia calabura L. has been used in Southeast Asia and tropical America as antipyretic, antiseptic, analgesic, antispasmodic and liver tonic. This study aims to determine the acute toxicity and the metabolic pathways involved in the hepatoprotective mechanism of M. calabura. MATERIALS AND METHODS: CCl4-induced hepatotoxic rat model was developed and a dose dependent effect of M. calabura was conducted. Body weight, food and water consumption were measured every day and rats were sacrificed to collect the serum samples at the end of the 10-days treatment. Liquid chromatography-mass spectrometry quadrapole time of flight (LC/MS-QTOF) combined with principal component analysis (PCA) were used to determine differentially expressed metabolites due to treatment with CCl4 and M. calabura extracts. Metabolomics Pathway Analysis (MetPA) was used for analysis and visualization of pathways involved. RESULTS: Body weight, food and water consumption were significantly decreased and histopathological study revealed steatosis in CCl4-induced rats. PCA score plots show distinct separation in the metabolite profiles of the normal group, CCl4-treated group and extract of M. calabura (MCME) pre-treated groups. Biomarkers network reconstruction using MetPA had identified 2 major pathways which were involved in the protective mechanism of MCME. These include the (i) biosynthesis of the primary bile acid, (ii) metabolism of arachidonic acid. CONCLUSION: This study has successfully isolated 2 major pathways involved in the hepatoprotecive effect of MCME against CCl4-induced liver injury using the LC/MS Q-TOF metabolomics approach. The involvement of archidonic acid and purine metabolism in hepatoprotection has not been reported previously and may provide new therapeutic targets and/or options for the treatment of liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Elaeocarpaceae/química , Redes e Vias Metabólicas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Tiliaceae/química , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Tetracloreto de Carbono/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Cromatografia Líquida/métodos , Masculino , Espectrometria de Massas/métodos , Metabolômica/métodos , Ratos , Ratos Sprague-Dawley
15.
Clin Chim Acta ; 336(1-2): 97-102, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14500040

RESUMO

BACKGROUND: Cytochrome P4502C9 (CYP2C9), a principle drug-metabolizing enzyme is polymorphic in humans and is responsible for important pharmacokinetic and pharmacodynamic variations of CYP2C9 substrates. We developed an allele-specific multiplex polymerase chain reaction (PCR) method for the detection of common CYP2C9 alleles. METHOD: Genomic DNA was extracted from blood obtained from 40 unrelated healthy Malaysian Indian volunteers. The DNA was subjected to a first PCR that was used to amplify both exons 3 and 7 simultaneously in one reaction tube and a second PCR that was used to detect the polymorphic sites of CYP2C9 alleles using allele-specific primers. Sequencing was performed to validate the test results. RESULTS: We were successful in amplifying the fragments of interest from the DNA samples. The method was also reproducible and specific. The amplified sequences showed 100% homology to CYP2C9 sequence. CONCLUSION: This is the first nested allele-specific multiplex PCR method reported to allow for the simultaneously detection of five CYP2C9 alleles.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Reação em Cadeia da Polimerase/métodos , Alelos , Citocromo P-450 CYP2C9 , DNA/sangue , Primers do DNA/genética , Eletroforese em Gel de Ágar , Genótipo , Humanos , Cloreto de Magnésio/química , Polimorfismo Genético/genética
16.
Clin Chim Acta ; 349(1-2): 191-8, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15469873

RESUMO

BACKGROUND: Cytochrome P450 (CYP) 2C8 is a principle enzyme responsible for the metabolism of many clinically important drugs as well as endogenous compounds such as arachidonic acid. The enzyme is genetically polymorphic but a simple method is not available to study its genetic polymorphism. We developed and optimized a variant-specific PCR techniques to detect CYP2C8*2, CYP2C8*3 and CYP2C8*4. METHOD: Genomic DNA was extracted from blood using standard extraction methods. A two-step PCR method was developed to detect simultaneously three CYP2C8 variants. In the first PCR (PCR1), specific regions from exons 3, 5 and 8 of the CYP2C8 gene were amplified. The products were used as templates in parallel alleles-specific PCR (PCR2). This method was tested against DNA samples obtained from 57 healthy Malaysian volunteers. RESULT: The bands of interest were successfully amplified. This method showed specific and reproducible results when tested on healthy volunteers. DNA sequencing further confirmed genotype results obtained from current method. CONCLUSION: We have successfully developed and optimized a multiplex PCR method suitable for use in population studies of CYP2C8 polymorphism.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Alelos , Hidrocarboneto de Aril Hidroxilases/análise , Citocromo P-450 CYP2C8 , Primers do DNA , Éxons , Frequência do Gene , Variação Genética , Genótipo , Humanos , Malásia/epidemiologia , Polimorfismo Genético , Reprodutibilidade dos Testes
17.
Gene ; 548(2): 263-9, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25042454

RESUMO

This is the first documentation of the complete mitochondrial genome sequence of the Malaysian Mahseer, Tor tambroides. The 16,690 bp mitogenome with GenBank accession number JX444718 contains 13 protein genes, 22 tRNAs, two rRNAs, and a noncoding control region (D-loop) as is typical of most vertebrates. The phylogenomic reconstruction of this newly generated data with 21 Cypriniformes GenBank accession ID concurs with the recognized status of T. tambroides within the subfamily Cyprininae. This is in agreement with previous hypotheses based on morphological and partial mitochondrial analyses.


Assuntos
Cyprinidae/genética , Genoma Mitocondrial , Mitocôndrias/genética , RNA/genética , Animais , Cipriniformes/genética , Evolução Molecular , Genes Mitocondriais , Filogenia , RNA Mitocondrial , RNA Ribossômico/genética , RNA de Transferência/genética
18.
Clin Biochem ; 47(6): 427-31, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24582698

RESUMO

BACKGROUND: Acute lymphoblastic leukaemia (ALL) has posed challenges to the clinician due to variable patients' responses and late diagnosis. With the advance in metabolomics, early detection and personalised treatment are possible. METHODS: Metabolomic profile of 21 ALL patients treated with 6-mercaptopurine and 10 healthy volunteers were analysed using liquid chromatography/mass spectrometry quadrupole-time of flight (LC/MS Q-TOF). Principal components analysis (PCA), recursive analysis, clustering and pathway analysis were performed using MassHunter Qualitative and Mass Profiler Professional (MPP) software. RESULTS: Several metabolites were found to be expressed differently in patients treated with 6-mercaptopurine. Interestingly, 13 metabolites were significantly differently expressed [p-value <0.01 (unpaired t-test) and 2-fold change] in 19% of the patients who had relapses in their treatment. Down-regulated metabolites in relapsed patients were 1-tetrahexanoyl-2-(8-[3]-ladderane-octanyl)-sn-GPEtn, GPEtn (18:1(9Z)/0:0), GPCho(O-6:0/O-6:0), GPCho(O-2:0/O-1:0), methyl 8-[2-(2-formyl-vinyl)-3-hydroxy-5-oxo-cyclopentyl]-octanoate and plasma free amino acids (PFAA). Characterizing the subjects according to their ITPA 94C>A genotypes reveal differential expression of metabolites. CONCLUSIONS: Our research contributes to identification of metabolites that could be used to monitor disease progress of patients and allow targeted therapy for ALL at different stages, especially in preventing complication of relapse.


Assuntos
Mercaptopurina/uso terapêutico , Metaboloma , Metabolômica/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Adolescente , Aminoácidos/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Análise de Componente Principal
19.
Genome Announc ; 1(3)2013 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-23766409

RESUMO

Streptococcus agalactiae (group B streptococcus [GBS]) is a Gram-positive bacterium that was first recognized as a causative agent of bovine mastitis. S. agalactiae has subsequently emerged as a significant cause of human diseases. Here, we report the draft genome sequence of S. agalactiae PR06, which was isolated from a septicemic patient in a local hospital in Malaysia.

20.
Genome Announc ; 1(4)2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23950113

RESUMO

Klebsiella pneumoniae PR04 was isolated from a patient hospitalized in Malaysia. The draft genome sequence of K. pneumoniae PR04 shows differences compared to the reference sequences of K. pneumoniae strains MGH 78578 and NTUH-K2044 in terms of their genomic structures.

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