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1.
Clin Exp Immunol ; 203(1): 3-12, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32939755

RESUMO

Variations in the immune response could explain resistance to hepatitis C virus (HCV) infection. Toll-like receptor gene (TLR)-3 is an innate detector of dsRNA viruses, and the TLR-9 gene recognizes bacterial and viral unmethylated cytosine-phosphate-guanosine (CpG) motifs. We previously reported that the TLR-3.rs3775290 CC genotype was associated with HCV chronicity and that the TLR-9 gene played no major role in this infection. This study identified the role of TLR-3.rs3775290 (c.1377C/T), TLR-9.rs5743836 (-1237T→C) and TLR-9.rs352140 (G2848A) gene polymorphisms in predicting the outcome of HCV-specific cell-mediated immunity (CMI) among Egyptian health-care workers (HCWs). We enrolled 265 HCWs in this study and divided them into four groups. Group 1: 140 seronegative-aviraemic HCWs; group 2: 20 seronegative-viraemic HCWs; group 3: 35 subjects with spontaneously resolved HCV infection; and group 4: 70 chronic HCV HCWs (patients). All subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for the TLR-3.rs3775290, TLR-9.rs5743836 and TLR-9.rs352140 single nucleotide polymorphisms (SNPs). We also quantified HCV-specific CMI in the four groups using an interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay in response to nine HCV genotype 4a, overlapping 15mer peptide pools covering the whole viral genome. No statistically significant difference was found between CMI-responding subjects with different HCV states and TLR-3.rs3775290 or TLR-9.rs352140 genotypes. However, there was a significant relationship between the outcome of the HCV-specific CMI and the TLR-9.rs5743836 genotype among the responding subjects (P = 0·005) and the chronic HCV patients (P = 0·044). In conclusion, TLR-9.rs5743836 SNP, but not TLR-3.rs3775290 or TLR-9.rs352140 genotypes, could predict the outcome of HCV-specific CMI responses among Egyptians infected with genotype-4.


Assuntos
Pessoal de Saúde , Hepacivirus , Hepatite C Crônica , Imunidade Celular , Polimorfismo de Nucleotídeo Único , Receptor 3 Toll-Like , Adulto , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C Crônica/genética , Hepatite C Crônica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/imunologia , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologia
2.
Artigo em Inglês | MEDLINE | ID: mdl-31885651

RESUMO

Methanol extract of Melastoma malabathricum (MEMM) has been traditionally used by the Malay to treat various ailments. In an attempt to develop the plant as an herbal product, MEMM was subjected to the subacute and subchronic toxicity and cytotoxicity studies. On the one hand, the subacute study was performed on three groups of male and three groups of female rats (n = 6), which were orally administered with 8% Tween 80 (vehicle control group) or MEMM (500 and 1000 mg/kg) daily for 28 days, respectively. On the other hand, the subchronic study was performed on four groups of rats (n = 6), which were orally administered with 8% Tween 80 (vehicle control group) or MEMM (50, 250, and 500 mg/kg) daily for 90 days, respectively. In the in vitro study, the cytotoxic effect of MEMM against the HT29 colon cancer cell line was assessed using the MTT assay. MEMM was also subjected to the UHPLC-ESI-HRMS analysis. The results demonstrated that MEMM administration did not cause any mortality, irregularity of behaviour, modification in body weight, as well as food and water intake following the subacute and subchronic oral treatment. There were no significant differences observed in haematological parameters between treatment and control groups in both studies, respectively. The in vitro study demonstrated that MEMM exerts a cytotoxic effect against the HT29 colon cancer cell line when observed under the inverted and phase-contrast microscope and confirmed by the acridine orange/propidium iodide (AOPI) staining. The UHPLC-ESI-HRMS analysis of MEMM demonstrated the occurrence of several compounds including quercetin, p-coumaric acid, procyanidin A, and epigallocatechin. In conclusion, M. malabathricum leaves are safe for oral consumption either at the subacute or subchronic levels and possess cytotoxic action against the HT29 colon cancer cells possibly due to the synergistic action of several flavonoid-based compounds.

3.
Trop Biomed ; 34(1): 84-88, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33592985

RESUMO

This study was carried out to investigate the Coagulase Negative Staphylococci (CoNS) nasal carriage and the presence of methicillin resistant Coagulase Negative Staphylococci (MR-CoNS) among health sciences students at Faculty of Medicine and Health Sciences, Universiti Putra Malaysia. A total of 120 isolates of CoNS (62.5%) was isolated from 192 student volunteers. The mecA gene was detected in 15 isolates of CoNS (12.5%). Eight out of the 15 isolates of mecA positive CoNS were resistant to cefoxitin in disc diffusion test whereas the remaining seven isolates of mecA positive CoNS were susceptible to cefoxitin. Analysis of questionnaires showed no significant association between CoNS nasal carriage and the socio-demographic and risk factors except for the genders and history of cold (P < 0.050). Generally, this finding showed a relatively low level of methicillin resistance among CoNS nasal carriage from student volunteers.

4.
Tropical Biomedicine ; : 84-88, 2017.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-630970

RESUMO

This study was carried out to investigate the Coagulase Negative Staphylococci (CoNS) nasal carriage and the presence of methicillin resistant Coagulase Negative Staphylococci (MR-CoNS) among health sciences students at Faculty of Medicine and Health Sciences, Universiti Putra Malaysia. A total of 120 isolates of CoNS (62.5%) was isolated from 192 student volunteers. The mecA gene was detected in 15 isolates of CoNS (12.5%). Eight out of the 15 isolates of mecA positive CoNS were resistant to cefoxitin in disc diffusion test whereas the remaining seven isolates of mecA positive CoNS were susceptible to cefoxitin. Analysis of questionnaires showed no significant association between CoNS nasal carriage and the socio-demographic and risk factors except for the genders and history of cold (P < 0.050). Generally, this finding showed a relatively low level of methicillin resistance among CoNS nasal carriage from student volunteers.

5.
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
7.
Res Vet Sci ; 100: 226-31, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25818171

RESUMO

The anti-Trypanosoma evansi activity of Garcinia hombroniana (seashore mangosteen) leaves aqueous extract was tested on experimentally infected Sprague-Dawley rats. Treatment of infected rats with G. hombroniana extract resulted in a significantly extended post-infection longevity (p < 0.05), compared to the untreated control group. The possible mode of antitrypanosomal effect of the plant extract was also investigated on cultured T. evansi in HMI-9 medium with the addition of 25 µg/ml G. hombroniana aqueous extract. It was observed that the addition of G. hombroniana extract resulted in the inhibition of trypanosomal kinetoplast division, with no significant inhibitory effect on nuclear division. It is concluded from the current study that the aqueous extract of G. hombroniana has a potential antitrypanosomal activity through the inhibition of kinetoplast division, as one of the possible mechanisms of its antitrypanosomal effect. This plant could serve as a possible source of new antitrypanosomal compounds.


Assuntos
Garcinia/química , Extratos Vegetais/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos , Animais , Feminino , Masculino , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley
8.
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
9.
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
10.
Biomed Res Int ; 2014: 695678, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24868543

RESUMO

Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The present study is aimed at determining the hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using two models of liver injury in rats. Rats were divided into five groups (n=6) and received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM). The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total phenolic content were also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of hepatic structure was observed in group pretreated with N-acetylcysteine and MEMC. Hepatotoxic rats pretreated with NAC or MEMC exhibited significant decrease (P<0.05) in ALT and AST enzymes level. Moreover, the extract also exhibited good antioxidant activity. In conclusion, MEMC exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and, thus warrants further investigations.


Assuntos
Acetaminofen/toxicidade , Falência Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Sasa/química , Proteínas Quinases Ativadas por AMP/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Núcleo Celular/metabolismo , Dinoprostona/metabolismo , Regulação para Baixo , Humanos , Imuno-Histoquímica , Inflamação , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Falência Hepática/induzido quimicamente , Metanol , Camundongos , Microglia/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Folhas de Planta/química , Ratos , Fator de Necrose Tumoral alfa/metabolismo
11.
Trop Biomed ; 31(1): 89-96, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24862048

RESUMO

Trypanosoma evansi, the causative agent of "surra", infects many species of wild and domestic animals worldwide. In the current study, the aqueous and ethanolic extracts of six medicinal plants, namely, Aquilaria malaccensis, Derris elliptica, Garcinia hombroniana, Goniothalamus umbrosus, Nigella sativa, and Strobilanthes crispus were screened in vitro for activity against T. evansi. The cytotoxic activity of the extracts was evaluated on green monkey kidney (Vero) cells using MTT-cell proliferation assay. The median inhibitory concentrations (IC50) of the extracts ranged between 2.30 and 800.97 µg/ml and the median cytotoxic concentrations (CC50) ranged between 29.10 µg/ml and 14.53 mg/ml. The aqueous extract of G. hombroniana exhibited the highest selectivity index (SI) value of 616.36, followed by A. malaccensis aqueous extract (47.38). Phytochemical screening of the G. hombroniana aqueous extract revealed the presence of flavonoids, phenols, tannins, and saponins. It is demonstrated here that the aqueous extract of G. hombroniana has potential antitrypanosomal activity with a high SI, and may be considered as a potential source for the development of new antitrypanosomal compounds.


Assuntos
Flavonoides/farmacologia , Magnoliopsida/química , Extratos Vegetais/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos , Tripanossomíase/tratamento farmacológico , Acanthaceae/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Derris/química , Flavonoides/química , Flavonoides/isolamento & purificação , Garcinia/química , Goniothalamus/química , Concentração Inibidora 50 , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Plantas Medicinais , Sementes/química , Thymelaeaceae/química , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificação , Tripanossomíase/parasitologia , Células Vero
12.
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
13.
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.

14.
Artigo em Inglês | MEDLINE | ID: mdl-23853662

RESUMO

In an attempt to further establish the pharmacological properties of Bauhinia purpurea (Fabaceae), hepatoprotective potential of methanol extract of B. purpurea leaves (MEBP) was investigated using the paracetamol- (PCM-) induced liver toxicity in rats. Five groups of rats (n = 6) were used and administered orally once daily with 10% DMSO (negative control), 200 mg/kg silymarin (positive control), or MEBP (50, 250, and 500 mg/kg) for 7 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay with the total phenolic content (TPC) also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of the normal hepatic structural was observed in group pretreated with silymarin and MEBP. Hepatotoxic rats pretreated with silymarin or MEBP exhibited significant decrease (P < 0.05) in ALT and AST enzyme level. Moreover, the extract also exhibited antioxidant activity and contained high TPC. In conclusion, MEBP exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and high phenolic content and thus warrants further investigation.

15.
Genome Announc ; 1(3)2013 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-23792750

RESUMO

Proteus mirabilis is one of the pathogenic agents that commonly causes urinary tract infections among elderly individuals and long-term catheterized patients. Here, we report a draft genome sequence of Proteus mirabilis strain PR03 (3,932,623 bp, with a G+C content of 38.6%) isolated from a local hospital in Malaysia.

16.
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
17.
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.

18.
Med Princ Pract ; 21(5): 501-3, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22517296

RESUMO

OBJECTIVE: To determine the potential antiulcer activity of methanol extract of Melastoma malabathricum leaves (MEMM) using various established rat models. MATERIALS AND METHODS: Ten groups of rats were used and orally administered 10% DMSO (negative control), 100 mg/kg ranitidine (positive control) or MEMM (50, 250 and 500 mg/kg) followed by gastric ulcer induction either using ethanol or indomethacin. The stomachs were collected and subjected to macroscopic and microscopic analyses. RESULTS: MEMM exhibited significant (p < 0.05) antiulcer activity in the ethanol, but not in the indomethacin-induced gastric ulcer model. The percentage of antiulcer activity for 50-500 mg/kg MEMM ranged between 3 and 75%, respectively. The gross observations were supported by histological findings. MEMM also aggravated the indomethacin-induced gastric ulcer, leading to an increase in ulcer area formation and ulcer score. CONCLUSION: The M. malabathricum leaves showed antiulcer activity, which could be attributed to their antioxidant and anti-inflammatory activities. This requires further in-depth studies.


Assuntos
Fármacos Gastrointestinais/farmacologia , Melastomataceae/química , Extratos Vegetais/farmacologia , Úlcera/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Fármacos Gastrointestinais/administração & dosagem , Indometacina/farmacologia , Masculino , Metanol/química , Extratos Vegetais/administração & dosagem , Folhas de Planta/química , Ranitidina/farmacologia , Ratos , Ratos Sprague-Dawley
19.
Med Princ Pract ; 21(5): 476-82, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22398984

RESUMO

OBJECTIVE: The aim of the present study was to determine the anti-ulcer activity of a methanol extract of Bauhinia purpurea leaf (MEBP). MATERIALS AND METHODS: MEBP was administered at doses of 100, 500 and 1,000 mg/kg and its effects on acute toxicity, absolute ethanol- and indomethacin-induced gastric ulceration, and pyloric ligation tests in rats were investigated. RESULTS: At a dose of 5,000 mg/kg, MEBP did not cause any signs of toxicity in rats when given orally. Oral administration of MEBP exerted anti-ulcer activity (p < 0.05) in all models tested. However, a dose-dependent protection was observed only in the indomethacin-induced gastric ulceration model. Histological studies supported the observed anti-ulcer activity of MEBP. In the pyloric ligation assay, MEBP significantly increased gastric wall mucus secretion (p < 0.05), but did not affect the acidity of the gastric contents. CONCLUSION: MEBP exhibited anti-ulcer activity, which could be due to the presence of flavonoids, saponins or other polyphenols, thereby validating the traditional use of B. purpurea in the treatment of ulcers.


Assuntos
Bauhinia , Fármacos Gastrointestinais/farmacologia , Extratos Vegetais/farmacologia , Úlcera/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Indometacina/farmacologia , Masculino , Metanol/química , Omeprazol/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Folhas de Planta , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente
20.
Artigo em Inglês | MEDLINE | ID: mdl-22242040

RESUMO

Melastoma malabathricum L. (Melastomataceae) is one of the 22 species found in the Southeast Asian region, including Malaysia. Considered as native to tropical and temperate Asia and the Pacific Islands, this commonly found small shrub has gained herbal status in the Malay folklore belief as well as the Indian, Chinese, and Indonesian folk medicines. Ethnopharmacologically, the leaves, shoots, barks, seeds, and roots of M. malabathricum have been used to treat diarrhoea, dysentery, hemorrhoids, cuts and wounds, toothache, and stomachache. Scientific findings also revealed the wide pharmacological actions of various parts of M. malabthricum, such as antinociceptive, anti-inflammatory, wound healing, antidiarrheal, cytotoxic, and antioxidant activities. Various types of phytochemical constituents have also been isolated and identifed from different parts of M. malabathricum. Thus, the aim of the present review is to present comprehensive information on ethnomedicinal uses, phytochemical constituents, and pharmacological activities of M. malabathricum.

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