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1.
Malays J Pathol ; 45(3): 463-471, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38155387

ABSTRACT

INTRODUCTION: Chorioamnionitis is the inflammation of the placenta and is histologically defined as the presence of neutrophilic infiltration into the chorio-amnion membrane with and without involvement of the umbilical cord. Currently, the inflammatory mediators involved in the eliciting of inflammatory response is still largely under investigation. CD47 and CD36 are pro-inflammatory molecules that are still under investigation. The aim of this study was to determine the expressions of CD47 and CD36 in the placenta of mothers with chorioamnionitis. MATERIALS AND METHODS: This was a cross-sectional study, involving a total of 100 cases that comprised of acute subchorionitis (stage I, n=20), acute chorioamnionitis (stage II, n=20), acute necrotising chorioamnionitis (stage III, n=20) and non-chorioamnionitis placenta as control (n=40). All tissue blocks were retrieved from the archived pathology record over a period of 4 years. CD36 and CD47 immunohistochemistry were performed on all cases and their expression in various cell types on the placenta were analysed. RESULTS: CD36 was expressed only on the foetal vascular endothelial cells. Interestingly, CD47 showed positive staining on the neutrophils and its expression was significantly different between maternal inflammatory response stage II chorioamnionitis (n=13/20, p<0.001) with stage I and stage III chorioamnionitis. DISCUSSION: Our study showed CD47 was expressed in the neutrophils and it was associated with poorer perinatal outcomes and it may have a role in the pathogenesis of chorioamnionitis.


Subject(s)
Chorioamnionitis , Pregnancy , Female , Humans , Chorioamnionitis/metabolism , Chorioamnionitis/pathology , Endothelial Cells/metabolism , CD47 Antigen/metabolism , Cross-Sectional Studies , Placenta/metabolism , Placenta/pathology
3.
Malays J Pathol ; 44(2): 253-260, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36043588

ABSTRACT

INTRODUCTION: Qualitative Pandy test has long been used to indicate raised globulins in the cerebrospinal fluid (CSF). Despite its shortfalls and the availability of quantitative CSF protein assays, Pandy test continues to be performed in clinical laboratories across Malaysia. OBJECTIVES: (1) Compare diagnostic performance of Pandy test to CSF total protein and albumin; (2) Conduct literature review on clinical utility of Pandy test. MATERIALS AND METHODS: This is a retrospective, cross-sectional study involving 890 inpatients of all ages with CSF biochemistry analysed in Hospital Pulau Pinang over a period of 7 months. Patient demographics, clinical diagnosis and CSF total protein, albumin and Pandy results were collected and analysed using Mann-Whitney U test, Spearman rank-order correlation coefficient, Chi Square test and receiver operating characteristic (ROC) curve analysis. RESULTS: CSF total protein, CSF albumin, CSF protein-albumin difference and age showed significantly higher median values in patients with positive Pandy compared to negative Pandy. Significant associations were found between positive Pandy test with clinical diagnosis (Cramers V 0.443, p<0.01), sample haemolysis (Phi 0.326, p<0.01), CSF protein-albumin difference (Spearman 0.727, p<0.001), CSF total protein (Spearman 0.710, p<0.001) and CSF albumin (Spearman 0.662, p<0.01). All three quantified CSF parameters showed comparably good sensitivity and specificity in determining positive Pandy. DISCUSSION AND CONCLUSION: Good correlation with CSF proteins, analytical issues and reagent hazards indicate no added clinical value of Pandy test in the face of quantified CSF total protein and albumin. Abolishing the test saves resources, reduces occupational hazards and shortens turnaround time without compromising diagnosis.


Subject(s)
Albumins , Cross-Sectional Studies , Humans , Malaysia , Retrospective Studies , Sensitivity and Specificity
4.
Molecules ; 27(13)2022 Jun 23.
Article in English | MEDLINE | ID: mdl-35807287

ABSTRACT

The separation of benzene and cyclohexane is a challenging process in the petrochemical industry, mainly because of their close boiling points. Extractive separation of the benzene-cyclohexane mixture has been shown to be feasible, but it is important to find solvents with good extractive performance. In this work, 23 eutectic solvents (ESs) containing aromatic components were screened using the predictive COSMO-RS and their respective performance was compared with other solvents. The screening results were validated with experimental work in which the liquid-liquid equilibria of the three preselected ESs were studied with benzene and cyclohexane at 298.5 K and 101.325 kPa, with benzene concentrations in the feed ranging from 10 to 60 wt%. The performance of the ESs studied was compared with organic solvents, ionic liquids, and other ESs reported in the literature. This work demonstrates the potential for improved extractive separation of the benzene-cyclohexane mixture by using ESs with aromatic moieties.

5.
Malays J Pathol ; 43(2): 281-290, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34448792

ABSTRACT

INTRODUCTION: Serum protein electrophoresis (SPE) is a well-established laboratory technique. However, reporting of results varies considerably between laboratories. The variation in reporting can cause confusion to the clinician with a potential of adversely impacting patient care. The purpose of the survey was to find out the variation in reporting and to prepare recommendations to the Malaysian laboratories based on the survey to reduce both the variation in reporting between laboratories and the risk of misinterpretation of reports. MATERIALS AND METHODS: To determine the extent of variation in reporting of protein electrophoresis results questionnaires were distributed to the pathologists of various laboratories in Malaysia regarding the method, quantification of paraprotein concentrations and immunoglobulin assays, and information regarding current laboratory electrophoresis practices. RESULTS: Variation was found in the following reporting practices: (a) screening protocol; (b) reporting of serum albumin; (c) numerical reporting of protein fractions and paraprotein; (d) co-migration of a paraprotein with a normal serum protein; (e) reporting of multiple paraprotein bands (f) appearance of small abnormal band and oligoclonal bands and (g) communication about of interferences. CONCLUSION: The pathologists of the country made recommendations on the reporting of protein electrophoresis. Harmonised reporting will reduce inconsistency, variation in reporting, improve the quality of the report and most importantly improve patient care.


Subject(s)
Electrophoresis , Blood Proteins , Humans , Malaysia , Paraproteins , Surveys and Questionnaires
6.
Malays Orthop J ; 15(2): 70-76, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34429825

ABSTRACT

INTRODUCTION: A dilemma arises when a bone graft or fracture fragment is accidentally dropped on the operation theatre floor and becomes contaminated. This study aimed to determine the efficacy of simple and readily available antiseptic solutions in disinfecting contaminated bones. MATERIAL AND METHODS: This experimental study involved 225 bone specimens prepared from discarded bone fragments during a series of 45 knee and hip arthroplasty surgeries. The bone fragments were cut into five identical cubes and were randomly assigned to either control (positive or negative), or experimental groups (0.5% chlorhexidine, 10% povidone-iodine or 70% alcohol). The control negative was to determine pre-contamination culture. All bone specimens, except the control negative group were uniformly contaminated by dropping on the operation theatre floor. Subsequently, the dropped bone specimens except for the control positive group, were disinfected by immersing in a respective antiseptic solution for 10 minutes, before transported to the microbiology laboratory for incubation. RESULTS: The incidence of a positive culture from a dropped bone fragment was 86.5%. From the 37 specimens sent for each group, the incidence of positive culture was 5.4% (2 specimens) after being disinfected using chlorhexidine, 67.6% (25 specimens) using povidone-iodine and 81.1% (30 specimens) using alcohol. Simple logistic regression analysis demonstrated that chlorhexidine was significantly effective in disinfecting contaminated bones (p-value <0.001, odd ratio 0.009). Povidone-iodine and alcohol were not statistically significant (p-value 0.059 and 0.53, respectively). Organisms identified were Bacillus species and coagulase negative Staphylococcus. No gram-negative bacteria were isolated. CONCLUSION: A total of 0.5% chlorhexidine is effective and superior in disinfecting contaminated bones.

7.
Malays J Pathol ; 43(1): 101-107, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33903313

ABSTRACT

INTRODUCTION: Haemolytic specimens are a frequent occurrence in clinical laboratories, and they interfere with the analysis of many tests. CASE REPORT: We describe here an unusual case of leptospirosis complicated by haemolytic anaemia in a 70-year-old man with established kidney failure. He presented with an abrupt onset of shortness of breath, flushing and erythematous rash after completing haemodialysis. The patient's biochemistry test samples were however rejected twice as they were grossly haemolysed. The integrated auto-verification alert system implemented in the hospital's laboratory information system alerted the staff of the possibility of in vivo haemolysis. DISCUSSION: The auto-verification alert system effectively distinguishes between in vitro and in vivo haemolysis and as such can be utilised as a diagnostic aid in patients with suspected intravascular haemolysis.


Subject(s)
Anemia, Hemolytic , Hemolysis , Potassium/blood , Aged , Anemia, Hemolytic/diagnosis , Humans , Laboratories, Clinical , Male
8.
Malays J Pathol ; 42(3): 433-437, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33361725

ABSTRACT

INTRODUCTION: Salivary cortisol is used as an indicator of stress level and a recommended screening test for Cushing syndrome. The normal reference interval for salivary cortisol is dependent on the analytical methodology and the population studied and hence, establishment of a local population-based reference interval is recommended. MATERIALS AND METHODS: A total of 129 healthy blood donors and staffs of Penang General Hospital were recruited from June 2018-May 2019. Paired (morning and late-night) saliva samples were collected from individuals aged between 18 and 60 years old with no history of chronic medical illness. Salivary cortisol was assayed using electrochemiluminescence immunoassay technique. Non-parametric statistics were used for calculation of reference interval and 90% confidence intervals (90% CIs). RESULTS: The reference interval for morning and latenight salivary cortisol was 2.09 - 22.63 nmol/L and <12.00 nmol/L, respectively. CONCLUSION: The locally-derived adult reference intervals for morning and late-night salivary cortisol concentration was determined and varied with previous studies emphasising the need in establishing individual laboratory reference interval.


Subject(s)
Hydrocortisone/analysis , Saliva/chemistry , Adult , Cross-Sectional Studies , Female , Humans , Malaysia , Male , Middle Aged , Reference Values , Time Factors
9.
J Bone Metab ; 25(3): 165-173, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30237996

ABSTRACT

BACKGROUND: Many oral presentations of osteoporosis-a bone metabolic disease-were recorded. Thus, we aimed to assess panoramic radiomorphometric indices with bone mineral density (BMD) values among Saudi postmenopausal women and its importance in the prediction of osteoporosis. METHODS: A total of 431 Saudi women were enrolled in this study. Panoramic radiographs were obtained at the time of BMD measurement. Subjects were fatherly classified into; normal BMD, osteopenia, and osteoporosis groups. Serum follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E2), 25-hydroxy-vitamin D (25[OH]D) and intact-parathyroid hormone were measured. Moreover, serum creatinine, calcium, and phosphate, together with serum osteocalcin (s-OC), procollagen type I N-terminal propeptide (s-PINP) and cross-linked C-terminal telopeptide of type 1 collagen (s-CTX) were measured. Receiver-operator curve (ROC) curve analysis for use of mandibular cortical width (MCW), panoramic mandibular index (PMI), and maxillary-mandibular ratio (M/M ratio) to differentiate women with osteoporosis or osteopenia from normal subjects was calculated. Cut off values of 4.6 at T score <-1 and 4.1 at T score ≤-2.5 were used. RESULTS: Body mass index is significantly low in the osteoporotic group. There is no significant difference in serum levels of LH, E2, calcium, phosphate, and 25(OH)D between the studied groups. Moreover, s-OC, C-terminal propeptide of procollagen type I, s-PINP, s-CTX, and urinary-CTX are significantly higher in osteoporosis than normal and osteopenia groups. ROC curve analysis revealed that MCW and PMI showed significant data while M/M ratio is non-significant. CONCLUSIONS: It could be concluded that MCW as an important panoramic radiographic parameter can be used for prediction and diagnosis of osteoporosis in postmenopausal Saudi women with low BMD.

10.
J Bone Metab ; 25(2): 87-98, 2018 May.
Article in English | MEDLINE | ID: mdl-29900158

ABSTRACT

BACKGROUND: Higher sphingosine 1-phosphate (S1P) plasma levels are associated with decreased bone mineral density (BMD), and increased risk of prevalent vertebral fracture. So, we hypothesized that postmenopausal women with increased baseline plasma S1P levels have a greater risk for future incident fracture (osteoporosis-related fractures [ORFs]). METHODS: This study was conducted in a prospective longitudinal cohort of 707 women recruited in 2004 and followed up annually for a mean period of 5.2±1.3 years. They were postmenopausal (aged ≥50 years). The primary outcome measure was the time to the first confirmed ORF event using radiographs and/or a surgical report. RESULTS: The plasma S1P levels (µmol/L) were significantly higher in the women with incident fracture (7.23±0.79) than in those without ORFs (5.02±0.51; P<0.001). High S1P levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the hazard ratio (HR) was 6.12 (95% confidence interval [CI], 4.92-7.66) for each 1-standard deviation increase in plasma S1P levels. The women in the highest quartile of S1P levels had a significant increase in fracture risk (HR, 9.89; 95% CI, 2.83-34.44). Results were similar when we compared plasma S1P levels at the 1-year visit. CONCLUSIONS: The associations between plasma S1P levels and fracture risk were independent of BMD and other confounders. These findings demonstrate that high plasma S1P level at baseline and at years 1 to 5 is a strong and independent risk factor for future [ORFs] among postmenopausal women and could be a useful biomarker for fracture risk assessment in this population.

11.
Journal of Bone Metabolism ; : 165-173, 2018.
Article in English | WPRIM (Western Pacific) | ID: wpr-716569

ABSTRACT

BACKGROUND: Many oral presentations of osteoporosis-a bone metabolic disease-were recorded. Thus, we aimed to assess panoramic radiomorphometric indices with bone mineral density (BMD) values among Saudi postmenopausal women and its importance in the prediction of osteoporosis. METHODS: A total of 431 Saudi women were enrolled in this study. Panoramic radiographs were obtained at the time of BMD measurement. Subjects were fatherly classified into; normal BMD, osteopenia, and osteoporosis groups. Serum follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E2), 25-hydroxy-vitamin D (25[OH]D) and intact-parathyroid hormone were measured. Moreover, serum creatinine, calcium, and phosphate, together with serum osteocalcin (s-OC), procollagen type I N-terminal propeptide (s-PINP) and cross-linked C-terminal telopeptide of type 1 collagen (s-CTX) were measured. Receiver-operator curve (ROC) curve analysis for use of mandibular cortical width (MCW), panoramic mandibular index (PMI), and maxillary-mandibular ratio (M/M ratio) to differentiate women with osteoporosis or osteopenia from normal subjects was calculated. Cut off values of 4.6 at T score <−1 and 4.1 at T score ≤−2.5 were used. RESULTS: Body mass index is significantly low in the osteoporotic group. There is no significant difference in serum levels of LH, E2, calcium, phosphate, and 25(OH)D between the studied groups. Moreover, s-OC, C-terminal propeptide of procollagen type I, s-PINP, s-CTX, and urinary-CTX are significantly higher in osteoporosis than normal and osteopenia groups. ROC curve analysis revealed that MCW and PMI showed significant data while M/M ratio is non-significant. CONCLUSIONS: It could be concluded that MCW as an important panoramic radiographic parameter can be used for prediction and diagnosis of osteoporosis in postmenopausal Saudi women with low BMD.


Subject(s)
Female , Humans , Body Mass Index , Bone Density , Bone Diseases, Metabolic , Calcium , Collagen Type I , Creatinine , Diagnosis , Estradiol , Follicle Stimulating Hormone , Luteinizing Hormone , Osteocalcin , Osteoporosis , Postmenopause , Radiography, Panoramic , ROC Curve , Saudi Arabia
12.
Article in English | WPRIM (Western Pacific) | ID: wpr-714680

ABSTRACT

BACKGROUND: Higher sphingosine 1-phosphate (S1P) plasma levels are associated with decreased bone mineral density (BMD), and increased risk of prevalent vertebral fracture. So, we hypothesized that postmenopausal women with increased baseline plasma S1P levels have a greater risk for future incident fracture (osteoporosis-related fractures [ORFs]). METHODS: This study was conducted in a prospective longitudinal cohort of 707 women recruited in 2004 and followed up annually for a mean period of 5.2±1.3 years. They were postmenopausal (aged ≥50 years). The primary outcome measure was the time to the first confirmed ORF event using radiographs and/or a surgical report. RESULTS: The plasma S1P levels (µmol/L) were significantly higher in the women with incident fracture (7.23±0.79) than in those without ORFs (5.02±0.51; P < 0.001). High S1P levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the hazard ratio (HR) was 6.12 (95% confidence interval [CI], 4.92−7.66) for each 1-standard deviation increase in plasma S1P levels. The women in the highest quartile of S1P levels had a significant increase in fracture risk (HR, 9.89; 95% CI, 2.83−34.44). Results were similar when we compared plasma S1P levels at the 1-year visit. CONCLUSIONS: The associations between plasma S1P levels and fracture risk were independent of BMD and other confounders. These findings demonstrate that high plasma S1P level at baseline and at years 1 to 5 is a strong and independent risk factor for future [ORFs] among postmenopausal women and could be a useful biomarker for fracture risk assessment in this population.


Subject(s)
Animals , Female , Humans , Bone Density , Cohort Studies , Ecthyma, Contagious , Open Reading Frames , Osteoporosis , Osteoporotic Fractures , Outcome Assessment, Health Care , Plasma , Prospective Studies , Risk Assessment , Risk Factors , Sphingosine
13.
Reprod Biol ; 17(2): 133-143, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28431992

ABSTRACT

To study the genomics/genetic factors associated with recurrent spontaneous abortion (RSA), as ∼50% of RSA are unexplained. However, chromosome abnormalities have been reported to play major role in RSA. We performed whole genome array-CGH based genomic analysis of forty four Saudi RSA patients to identify potential molecular and chromosomal abnormalities. We identified a total of 845 alterations, usually not detected by classic cytogenetic methods, in different genomic regions using a cut off value of -0.25 and 0.25 for structural loss and gain, whereas -1.0 and 0.58 were used for single copy number deletion and duplication respectively. We identified frequent (present at least in 10% of patients) alterations including three macro-alteration at 8p23.1, 10q11.21-q11.22 and 15q11.2 as well as large numbers of micro-deletions/amplifications with affected genes including 22q11.23 (GSTT1), 3p22.2 (CTDSPL), 6p21.32 (HLA), and 8p22 (MSR1). Pathway analysis of genes located in detected CNVs regions revealed the allograft rejection signaling, IL-4 signaling, and autoimmune thyroid disease signaling as the most significant canonical pathways associated with RSA. Whole genome array CGH technique can be used to identify potential genes, biofunctions and chromosomal abnormalities associated with RSA which is supported by our findings of a number of novel CNVs/genes (22q11.23/GSTT1, 3p22.2/CTDSPL, 6p21.32/HLA, 8p22/MSR1, and 14q32.33/AKT1) and pathways in patients affected with RSA. To improve diagnosis and treatment of RSA, a comprehensive procedure is needed for identification and validation of causative genes.


Subject(s)
Abortion, Habitual/genetics , Genomics/methods , Abortion, Habitual/epidemiology , Chromosome Aberrations , Chromosome Deletion , Chromosomes, Human , Comparative Genomic Hybridization , Cytogenetic Analysis , DNA Copy Number Variations , Female , Fetus , Genome-Wide Association Study , Humans , Male , Pregnancy , Saudi Arabia/epidemiology
14.
Bioinorg Chem Appl ; 2017: 7914714, 2017.
Article in English | MEDLINE | ID: mdl-28420949

ABSTRACT

This study aims to produce optimized biochar from oil palm empty fruit bunches (OPEFB), as a green, low cost adsorbent for uptake of zinc from aqueous solution. The impact of pyrolysis conditions, namely, highest treatment temperature (HTT), heating rate (HR), and residence time (RT) on biochar yield and adsorption capacity towards zinc, was investigated. Mathematical modeling and optimization of independent variables were performed employing response surface methodology (RSM). HTT was found to be the most influential variable, followed by residence time and heating rate. Based on the central composite design (CCD), two quadratic models were developed to correlate three independent variables to responses. The optimum production condition for OPEFB biochar was found as follows: HTT of 615°C, HR of 8°C/min, and RT of 128 minutes. The optimum biochar showed 15.18 mg/g adsorption capacity for zinc and 25.49% of yield which was in agreement with the predicted values, satisfactory. Results of the characterization of optimum product illustrated well-developed BET surface area and porous structure in optimum product which favored its sorptive ability.

15.
BMC Genomics ; 18(1): 258, 2017 03 24.
Article in English | MEDLINE | ID: mdl-28340555

ABSTRACT

BACKGROUND: The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. RESULTS: The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency. On average, 57 million reads (short reads or short mRNA sequences < ~200 bases) were sequenced, 52 million reads were mapped, and 24,616 known transcripts were quantified according to the bovine reference genome. A comparison of the high- and low-RFI groups revealed 70 and 19 significantly DEGs in Holstein and Jersey cows, respectively. The interaction analysis (high vs. low RFI x control vs. high concentrate diet) showed no interaction effects in the Holstein cows, while two genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. CONCLUSION: We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP's and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins.


Subject(s)
Animal Feed , Animal Nutritional Physiological Phenomena , Gene Expression Profiling , Gene Expression Regulation , Signal Transduction , Transcriptome , Animals , Breeding , Cattle , Chromosome Mapping , Cluster Analysis , Gene Regulatory Networks , Genes, Regulator , High-Throughput Nucleotide Sequencing , Liver/metabolism
16.
Sci Rep ; 7: 40010, 2017 01 12.
Article in English | MEDLINE | ID: mdl-28079120

ABSTRACT

The development of microstructure during melting, reactive wetting and solidification of solder pastes on Cu-plated printed circuit boards has been studied by synchrotron radiography. Using Sn-3.0Ag-0.5Cu/Cu and Sn-0.7Cu/Cu as examples, we show that the interfacial Cu6Sn5 layer is present within 0.05 s of wetting, and explore the kinetics of flux void formation at the interface between the liquid and the Cu6Sn5 layer. Quantification of the nucleation locations and anisotropic growth kinetics of primary Cu6Sn5 crystals reveals a competition between the nucleation of Cu6Sn5 in the liquid versus growth of Cu6Sn5 from the existing Cu6Sn5 layer. Direct imaging confirms that the ß-Sn nucleates at/near the Cu6Sn5 layer in Sn-3.0Ag-0.5Cu/Cu joints.

17.
J Control Release ; 248: 117-124, 2017 02 28.
Article in English | MEDLINE | ID: mdl-28077264

ABSTRACT

Lycopene is a natural anti-oxidant that has attracted much attention due to its varied applications such as protection against loss of bone mass, chronic diseases, skin cancer, prostate cancer, and cardiovascular disease. However, high instability and extremely low oral bioavailability limit its further clinical development. We selected a green tea catechin derivative, oligomerized (-)-epigallocatechin-3-O-gallate (OEGCG) as a carrier for oral lycopene delivery. Lycopene-loaded OEGCG nanoparticles (NPs) were prepared by a nano-precipitation method, followed by coating with chitosan to form a shell. This method not only can easily control the size of the NP to be around 200nm to improve its bioavailability, but also can effectively protect the lycopene against degradation due to EGCG's anti-oxidant property. OEGCG was carefully characterized with nuclear magnetic resonance spectroscopy and mass spectrometry. Lycopene-loaded polylactic-co-glycolic acid (PLGA) NPs were prepared by the same method. Chitosan-coated OEGCG/lycopene NPs had a diameter of 152±32nm and a ζ-potential of 58.3±4.2mv as characterized with transmission electron microscopy and dynamic light scattering. The loading capacity of lycopene was 9% and encapsulation efficiency was 89%. FT-IR spectral analysis revealed electrostatic interaction between OEGCG and chitosan. Freeze drying of the NPs was also evaluated as a means to improve shelf life. Dynamic light scattering data showed that no aggregation occurred, and the size of the NP increased 1.2 times (Sf/Si ratio) in the presence of 10% sucrose after freeze drying. The in vitro release study showed slow release of lycopene in simulated gastric fluid at acidic pH and faster release in simulated intestinal fluid. In an in vivo study in mice, lycopene pharmacokinetic parameters were improved by lycopene/OEGCG/chitosan NPs, but not improved by lycopene/PLGA/chitosan NPs. The self-assembled nanostructure of OEGCG combined with lycopene may be a promising application in oral drug delivery in various indications.


Subject(s)
Antioxidants/administration & dosage , Carotenoids/administration & dosage , Catechin/analogs & derivatives , Drug Carriers/chemistry , Nanoparticles/chemistry , Tea/chemistry , Administration, Oral , Animals , Antioxidants/pharmacokinetics , Biological Availability , Carotenoids/pharmacokinetics , Catechin/chemistry , Lycopene , Male , Mice, Inbred C57BL , Nanoparticles/ultrastructure
18.
Pharmacogenomics J ; 17(5): 461-470, 2017 10.
Article in English | MEDLINE | ID: mdl-27241059

ABSTRACT

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.


Subject(s)
Asian People/genetics , Molecular Epidemiology/methods , Pharmacogenetics/methods , Pharmacogenomic Variants , Databases, Genetic , Gene Frequency , Genetics, Population , Genome, Human , Genome-Wide Association Study , Humans , Malaysia , Molecular Sequence Annotation
19.
BMC Complement Altern Med ; 16(1): 488, 2016 Nov 29.
Article in English | MEDLINE | ID: mdl-27899097

ABSTRACT

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.


Subject(s)
Analgesics/isolation & purification , Melastomataceae/chemistry , Pain/drug therapy , Plant Extracts/pharmacology , Alkanes , Analgesics/pharmacology , Analgesics/toxicity , Animals , Chromatography, High Pressure Liquid , Disease Models, Animal , Gas Chromatography-Mass Spectrometry , Male , Melastomataceae/toxicity , Methanol , Mice , Mice, Inbred ICR , Pain/etiology , Phytochemicals , Plant Extracts/toxicity , Plant Leaves/chemistry , Rats , Rats, Sprague-Dawley , Solvents , TRPV Cation Channels/antagonists & inhibitors
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