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Fulltext Microwave-Assisted Brine Extraction for Enhancement of the Quantity and Quality of Lipid Production from Microalgae Nannochloropsis sp

Zghaibi N, Omar R, Kamal SMM, Biak DRA, Harun R

Molecules, 2019 Oct 04;24(19).
PMID: 31590304 DOI: 10.3390/molecules24193581

Toward attaining a sustainability and eco-friendly process, a green and low-cost solvent-brine (NaCl solution) is proposed, as microwave-assisted extraction (MAE) technique solvent to extract lipids from microalgae Nannochloropsis sp. The effect of NaCl concentration on the quantity and quality of the extracted lipid was assessed, while MAE parameters were optimized using response surface methodology (RSM). The content of fatty acid methyl esters (FAMEs) in the lipid was analyzed by using a gas chromatography-flame ionization detector (GC/FID). The highest lipid yield (16.1%) was obtained using 10% (w/v) brine at optimum extraction parameters of 5% (w/v) solid loading, 100 °C, and 30 min. The lipid extraction yield via optimized MAE-brine technique was thrice better than that Soxhlet extraction did and only 2% less than Bligh and Dyer (B&D) lipid extraction, which utilized harmful solvents. The proposed MAE-brine technique offered better quality lipids containing the highest amount of polyunsaturated fatty acids (PUFA) (44.5%) and omega-3 fatty acids (FAs) (43%). Hence, the MAE-brine solvent technique appears to be a promising extraction method for cheaper, greener, and faster extraction of a high-quality lipid for specialty food applications.
Fulltext Kinetics Study of Microwave-Assisted Brine Extraction of Lipid from the Microalgae Nannochloropsis sp

Zghaibi N, Omar R, Kamal SMM, Biak DRA, Harun R

Molecules, 2020 Feb 12;25(4).
PMID: 32059440 DOI: 10.3390/molecules25040784

The kinetics of lipid extraction utilizing microwave-assisted extraction (MAE) from Nannochloropsis sp. microalgae were studied using a low cost and green solvent, namely brine (NaCl) solution. The kinetic modelling of the lipid extraction was performed to evaluate the mechanism of the lipid mass transfer using different extraction models, including Fick's Law, First and Second-order Rate Law and the Patricelli mathematical model. The Patricelli mathematical model described the kinetics of lipid extraction well, with the highest average values of determination coefficient (R2 ≥ 0.952) and the lowest average values of mean relative percentage deviation (MRPD ≤ 8.666%). The lipid analysis indicated a positive influence of the microwave temperature and time on the quantity and quality of extracted lipids. SEM analysis of spent microalgae clearly shows an increase in the distorted cell with increase microwave temperature and time, which could be directly correlated to the mechanism of the MAE-brine technique.
Fulltext The assessment of risk factors for the Central/East African Genotype of chikungunya virus infections in the state of Kelantan: a case control study in Malaysia

Yusoff AF, Mustafa AN, Husaain HM, Hamzah WM, Yusof AM, Harun R, et al.

BMC Infect Dis, 2013 May 08;13:211.
PMID: 23656634 DOI: 10.1186/1471-2334-13-211

BACKGROUND: The aims of the study were to assess the risk factors in relation to cross border activities, exposure to mosquito bite and preventive measures taken.An outbreak of chikungunya virus (CHIKV) infection in Malaysia has been reported in Klang, Selangor (1998) and Bagan Panchor, Perak (2006). In 2009, CHIKV infection re-emerged in some states in Malaysia. It raises the possibilities that re-emergence is part of the epidemics in neighbouring countries or the disease is endemic in Malaysia. For this reason, A community-based case control study was carried out in the state of Kelantan.
METHODS: Prospective case finding was performed from June to December 2009. Those who presented with signs and symptoms of CHIKV infection were investigated. We designed a case control study to assess the risk factors. Assessment consisted of answering questions, undergoing a medical examination, and being tested for the presence of IgM antibodies to CHIKV. Descriptive epidemiological studies were conducted by reviewing both the national surveillance and laboratory data. Multivariable logistic regression analysis was performed to determine risk factors contributing to the illness. Cases were determined by positive to RT-PCR or serological for antibodies by IgM. CHIKV specificity was confirmed by DNA sequencing.
RESULTS: There were 129 suspected cases and 176 controls. Among suspected cases, 54.4% were diagnosed to have CHIKV infection. Among the controls, 30.1% were found to be positive to serology for antibodies [IgM, 14.2% and IgG, 15.9%]. For analytic study and based on laboratory case definition, 95 were considered as cases and 123 as controls. Those who were positive to IgG were excluded. CHIKV infection affected all ages and mostly between 50-59 years old. Staying together in the same house with infected patients and working as rubber tappers were at a higher risk of infection. The usage of Mosquito coil insecticide had shown to be a significant protective factor. Most cases were treated as outpatient, only 7.5% needed hospitalization. The CHIKV infection was attributable to central/east African genotype CHIKV.
CONCLUSIONS: In this study, cross border activity was not a significant risk factor although Thailand and Malaysia shared the same CHIKV genotype during the episode of infections.
Fulltext γ-Tocotrienol and 6-Gingerol in Combination Synergistically Induce Cytotoxicity and Apoptosis in HT-29 and SW837 Human Colorectal Cancer Cells

Yusof KM, Makpol S, Jamal R, Harun R, Mokhtar N, Ngah WZ

Molecules, 2015 Jun 03;20(6):10280-97.
PMID: 26046324 DOI: 10.3390/molecules200610280

Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect of γ-tocotrienol (γ-T3) and 6-gingerol (6G) in combination by evaluating apoptosis and active caspase-3 in HT-29 and SW837 colorectal cancer cells. MTS assays were performed to determine the anti-proliferative and cytotoxicity effect of γ-T3 (0-150 µg/mL) and 6G (0-300 µg/mL) on the cells. The half maximal inhibitory concentration (IC50) value of 6G+ γ-T3 for HT-29 was 105 + 67 µg/mL and for SW837 it was 70 + 20 µg/mL. Apoptosis, active caspase-3 and annexin V FITC assays were performed after 24 h of treatment using flow cytometry. These bioactives in combination showed synergistic effect on HT-29 (CI: 0.89 ± 0.02,) and SW837 (CI: 0.79 ± 0.10) apoptosis was increased by 21.2% in HT-29 and 55.4% in SW837 (p < 0.05) after 24 h treatment, while normal hepatic WRL-68 cells were unaffected. Increased apoptosis by the combined treatments was also observed morphologically, with effects like cell shrinkage and pyknosis. In conclusion, although further studies need to be done, γ-T3 and 6G when used in combination act synergistically increasing cytotoxicity and apoptosis in cancer cells.
Fulltext Screening of native microalgae species for carbon fixation at the vicinity of Malaysian coal-fired power plant

Yahya L, Harun R, Abdullah LC

Sci Rep, 2020 12 18;10(1):22355.
PMID: 33339883 DOI: 10.1038/s41598-020-79316-9

Global warming has become a serious issue nowadays as the trend of CO2 emission is increasing by years. In Malaysia, the electricity and energy sector contributed a significant amount to the nation's CO2 emission due to fossil fuel use. Many research works have been carried out to mitigate this issue, including carbon capture and utilization (CCUS) technology and biological carbon fixation by microalgae. This study makes a preliminary effort to screen native microalgae species in the Malaysian coal-fired power plant's surrounding towards carbon fixation ability. Three dominant species, including Nannochloropsis sp., Tetraselmis sp., and Isochrysis sp. were identified and tested in the laboratory under ambient and pure CO2 condition to assess their growth and CO2 fixation ability. The results indicate Isochrysis sp. as the superior carbon fixer against other species. In continuation, the optimization study using Response Surface Methodology (RSM) was carried out to optimize the operating conditions of Isochrysis sp. using a customized lab-scale photobioreactor under simulated flue gas exposure. This species was further acclimatized and tested under actual flue gas generated by the power plant. Isochrysis sp. had shown its capability as a carbon fixer with CO2 fixation rate of 0.35 gCO2/L day under actual coal-fired flue gas exposure after cycles of acclimatization phase. This work is the first to demonstrate indigenous microalgae species' ability as a carbon fixer under Malaysian coal-fired flue gas exposure. Thus, the findings shall be useful in exploring the microalgae potential as a biological agent for carbon emission mitigation from power plants more sustainably.
Fulltext Posterior intraorbital metallic foreign body: a case discussion

Vinodh VP, Sellamuthu P, Harun RH, Zenian MS

Med J Malaysia, 2014 Apr;69(2):89-91.
PMID: 25241819 MyJurnal

Intraorbital foreign body (IOFB) has been a rare phenomenon in the cases of gunshot wounds and always represents a dilemma in medical management. In Sabah, this scenario is becoming common as there is still certain population in the interiors who owns self made guns for hunting. They either present with self inflicted gunshot injuries or after being mistakenly shot while hunting. There are very few articles on this topic especially when it is located posteriorly in the orbit and occurs without visual impairment. This case reports the challenges faced in the management of the patient with a posteriorly located metallic IOFB. The appropriate management of the patient is discussed based on several international literatures. Author describes a 37 years old male farmer, who was referred from a nearby district hospital after he sustained gunshot injuries to his face and scalp. Urgent computed tomography (CT) scan showed that bullet pellets were at the left orbital floor, the left mandible and the left frontal bone. All bullet pellets were located extracranially only without intracranial involvement. Patient clinically does not have any neurologic deficit and without any visual impairment, thus he refused any surgical intervention. As there is no proper guideline in managing such cases, decision was made based on evidences from international literatures. It was concluded that metallic IOFB located in the posterior orbit may be conservatively managed with observation and regular follow-ups as they are well-tolerated and does not cause much impact on visual deterioration unless inflammation, infection, optic neuropathy or functional deficit occurs. This avoids unnecessary surgery and prevents risk of iatrogenic injury to the eye.
Fulltext Primary Central Nervous System Fibrosarcoma

Vinodh VP, Harun R, Sellamuthu P, Kandasamy R

J Neurosci Rural Pract, 2017 Aug;8(Suppl 1):S111-S113.
PMID: 28936084 DOI: 10.4103/jnrp.jnrp_165_17

We report a rare case of a young female with primary brain fibrosarcoma, and to the best of our knowledge, we believe that only <50 cases have been reported or described worldwide so far. Fibrosarcoma is a malignant neoplasm, in which histologically the predominant cells are fibroblasts that divide excessively without cellular control and they can invade local tissues or metastasize. Primary central nervous system fibrosarcomas are very aggressive neoplasms and generally have a poor prognosis. This tumor is either from sarcomatous transformation of a meningioma or arises de novo within the brain parenchyma. Our patient, a 48-year-old woman, who presented with progressive speech disorder over the period of 4 months, showed a left temporoparietal lesion with surrounding edema and local mass effect. Total surgical resection was achieved. Histopathology revealed classical fibrosarcoma features and secondary screening revealed no other distant lesion as diagnosis of primary brain fibrosarcoma was established. This case is deemed to be extremely rare because most reports claim that recurrence is within 6 months with poor prognosis; however, this patient is currently recurrence-free at 3 years. This would suggest of the possibility for a relook into this disease's course and recurrence rate when complete excision is achieved. Due to extreme rarity of these tumors, more comparative studies will be needed to improve the disease outcome.
Fulltext Subcritical Water Extraction of Chlorella pyrenoidosa: Optimization through Response Surface Methodology

Thiruvenkadam S, Izhar S, Hiroyuki Y, Harun R

Biomed Res Int, 2018;2018:1931634.
PMID: 30533428 DOI: 10.1155/2018/1931634

Subcritical water extraction (SCW) was used to extract oil from Chlorella pyrenoidosa. The operational factors such as reaction temperature, reaction time, and biomass loading influence the oil yield during the extraction process. In this study, response surface methodology was employed to identify the desired extraction conditions for maximum oil yield. Experiments were carried out in batch reactors as per central composite design with three independent factors including reaction temperature (170, 220, 270, 320, and 370°C), reaction time (1, 5, 10, 15, and 20 min), and biomass loading (1, 3, 5, 10, and 15%). A maximum oil yield of 12.89 wt.% was obtained at 320°C and 15 min, with 3% biomass loading. Sequential model tests showed the good fit of experimental data to the second-order quadratic model. This study opens the great potential of SCW to extract algal oil for use in algal biofuel production.
Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin

Teh LK, Langmia IM, Fazleen Haslinda MH, Ngow HA, Roziah MJ, Harun R, et al.

J Clin Pharm Ther, 2012 Apr;37(2):232-6.
PMID: 21507031 DOI: 10.1111/j.1365-2710.2011.01262.x

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.
Fulltext Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress

Soon BH, Abdul Murad NA, Then SM, Abu Bakar A, Fadzil F, Thanabalan J, et al.

Front Physiol, 2017;8:231.
PMID: 28484394 DOI: 10.3389/fphys.2017.00231

The role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations that could possibly affect the mitochondrial functions and also the oxidative stress status. Three different grades of human glioma cell lines and a normal human astrocyte cell line were cultured in-vitro and tested for oxidative stress biomarkers. Relative oxidative stress level, mitochondria activity, and mitochondrial mass were determined by live cell imaging with confocal laser scanning microscope using CM-H2DCFDA, MitoTracker Green, and MitoTracker Orange stains. The entire mitochondrial genome was sequenced using the AffymetrixGeneChip Human Mitochondrial Resequencing Array 2.0. The mitochondrial sequence variations were subjected to phylogenetic haplogroup assessment and pathogenicity of the mutations were predicted using pMUT and PolyPhen2. The Grade II astrocytoma cells showed increased oxidative stress wherea high level of 8-OHdG and oxidative stress indicator were observed. Simultaneously, Grade II and III glioma cells showed relatively poor mitochondria functions and increased number of mutations in the coding region of the mtDNA which could be due to high levels of oxidative stress in these cells. These non-synonymous mtDNA sequence variations were predicted to be pathogenic and could possibly lead to protein dysfunction, leading to oxidative phosphorylation (OXPHOS) impairment, mitochondria dysfunction and could create a vicious cycle of oxidative stress. The Grade IV cells had no missense mutation but preserved intact mitochondria and excellent antioxidant defense mechanisms thus ensuring better survival. In conclusion, Grade II and III glioma cells demonstrated coding region mtDNA mutations, leading to mitochondrial dysfunction and higher oxidative stress.
Hepatocyte nuclear factor 4 alpha P2 promoter variants associate with insulin resistance

Saif-Ali R, Harun R, Al-Jassabi S, Wan Ngah WZ

Acta Biochim. Pol., 2011;58(2):179-86.
PMID: 21633728

This study aimed to investigate the associations of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) and haplotype with insulin resistance and metabolic syndrome parameters. Nine SNPs spanning the HNF4 alpha P2 promoter (rs4810424, rs1884613 and rs1884614) and coding region (rs2144908, rs6031551, rs6031552, rs1885088, rs1028583 and rs3818247) were genotyped in 160 subjects without diabetes or metabolic syndrome. The HNF4 alpha P2 promoter SNPs rs4810424, rs1884613 and rs1884614 were associated with insulin resistance (p = 0.017; 0.037; 0.024) and body mass index (BMI) (p = 0.03; 0.035; 0.039). The intron 1D SNP rs2144908 was associated with high-density lipoprotein cholesterol (HDLc) (p = 0.020) and the intron 9 SNP rs3818247 showed association with systolic (p = 0.02) and diastolic (p = 0.034) blood pressure. HNF4 alpha common haplotype CCCGTC associated with higher insulin resistance (p = 0.022), fasting blood glucose (FBG) (p = 0.035) and lower HDLc (p = 0.001). In conclusion, subjects with HNF4 alpha P2 variants and haplotypes have been shown to have a higher insulin resistance and are therefore at a higher risk for developing type 2 diabetes mellitus.
Association of hepatocyte nuclear factor 4 alpha polymorphisms with type 2 diabetes with or without metabolic syndrome in Malaysia

Saif-Ali R, Harun R, Kamaruddin NA, Al-Jassabi S, Ngah WZ

Biochem Genet, 2012 Apr;50(3-4):298-308.
PMID: 21983932 DOI: 10.1007/s10528-011-9472-2

This study investigated the association of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) with type 2 diabetes with or without metabolic syndrome in Malaysia. Nine HNF4 alpha SNPs were genotyped in 390 type 2 diabetic subjects with metabolic syndrome, 135 type 2 diabetic subjects without metabolic syndrome, and 160 control subjects. The SNPs rs4810424, rs1884613, and rs2144908 were associated with protection against type 2 diabetes without metabolic syndrome (recessive P = 0.018, OR 0.32; P = 0.004, OR 0.25; P = 0.005, OR 0.24, respectively). The 6-SNP haplotype2 CCCGTC containing the risk genotype of these SNPs was associated with higher risk for type 2 diabetes with or without metabolic syndrome (P = 0.002, OR 2.2; P = 0.004, OR 3.1). These data suggest that HNF4 alpha SNPs and haplotypes contributed to increased type 2 diabetes risk in the Malaysian population.
Fulltext COSMO-RS Based Prediction for Alpha-Linolenic Acid (ALA) Extraction from Microalgae Biomass Using Room Temperature Ionic Liquids (RTILs)

Rezaei Motlagh S, Harun R, Awang Biak DR, Hussain SA, Omar R, Elgharbawy AA

Mar Drugs, 2020 Feb 12;18(2).
PMID: 32059424 DOI: 10.3390/md18020108

One of the essential fatty acids with therapeutic impacts on human health is known to be omega-3 polyunsaturated fatty acids (PUFA). More lately, ionic liquids (ILs) have received significant attention among scientists in overcoming the disadvantages of traditional solvents in biomass lipid extraction. However, the large pool of cations and anions possibly accessible will lead to a growing number of innovatively synthesized ILs. Nevertheless, the exhaustive measurement of all these systems is economically impractical. The conductive screening model for real solvents (COSMO-RS) is considered a precious approach with the availability of a few models to predict the characteristics of ILs. This work introduces the estimate of capacity values at infinite dilution for a range of ILs using COSMO-RS software as part of solid-liquid extraction. This favorable outcome presented that the capacity values of the IL molecules are extremely dependent on both anions and cations. Among the 352 combinations of cation/anion tested, short alkyl chain cations coupled with inorganic anions were found to be most efficient and therefore superior in the extraction method. Sulphate-, chloride-, and bromide-based ILs were found to have higher extraction capacities in contrast with the remainders, while propanoate revealed an extraordinary capacity when combined with ethyl-based cations. Eventually, the predicted results from COSMO-RS were validated through the experimentally calculated extraction yield of alpha-linolenic acid (ALA) compound from Nannochloropsis sp. microalgae. Three selected ILs namely [EMIM][Cl], [TMAm][Cl], and [EMPyrro][Br] were selected from COSMO-RS for empirical extraction purpose and the validation results pinpointed the good prediction capability of COSMO-RS.
Fulltext Patient-specific frontal titanium mesh fabrication using a moulding technique

Rengarajoo J, Harun RH, Royan SJ, Kohir S, Mamat MR

Ann R Coll Surg Engl, 2022 Jul;104(7):556.
PMID: 35174718 DOI: 10.1308/rcsann.2021.0299
Fulltext NFIX as a Master Regulator for Lung Cancer Progression

Rahman NIA, Abdul Murad NA, Mollah MM, Jamal R, Harun R

Front Pharmacol, 2017;8:540.
PMID: 28871224 DOI: 10.3389/fphar.2017.00540

About 40% of lung cancer cases globally are diagnosed at the advanced stage. Lung cancer has a high mortality and overall survival in stage I disease is only 70%. This study was aimed at finding a candidate of transcription regulator that initiates the mechanism for metastasis by integrating computational and functional studies. The genes involved in lung cancer were retrieved using in silico software. 10 kb promoter sequences upstream were scanned for the master regulator. Transient transfection of shRNA NFIXs were conducted against A549 and NCI-H1299 cell lines. qRT-PCR and functional assays for cell proliferation, migration and invasion were carried out to validate the involvement of NFIX in metastasis. Genome-wide gene expression microarray using a HumanHT-12v4.0 Expression BeadChip Kit was performed to identify differentially expressed genes and construct a new regulatory network. The in silico analysis identified NFIX as a master regulator and is strongly associated with 17 genes involved in the migration and invasion pathways including IL6ST, TIMP1 and ITGB1. Silencing of NFIX showed reduced expression of IL6ST, TIMP1 and ITGB1 as well as the cellular proliferation, migration and invasion processes. The data was integrated with the in silico analyses to find the differentially expressed genes. Microarray analysis showed that 18 genes were expressed differentially in both cell lines after statistical analyses integration between t-test, LIMMA and ANOVA with Benjamini-Hochberg adjustment at p-value < 0.05. A transcriptional regulatory network was created using all 18 genes, the existing regulated genes including the new genes PTCH1, NFAT5 and GGCX that were found highly associated with NFIX, the master regulator of metastasis. This study suggests that NFIX is a promising target for therapeutic intervention that is expected to inhibit metastatic recurrence and improve survival rate.
Fulltext Tocotrienol-rich fraction, [6]-gingerol and epigallocatechin gallate inhibit proliferation and induce apoptosis of glioma cancer cells

Rahman AA, Makpol S, Jamal R, Harun R, Mokhtar N, Ngah WZ

Molecules, 2014 Sep 12;19(9):14528-41.
PMID: 25221872 DOI: 10.3390/molecules190914528

Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles.
Fulltext Smartphones in remote medicine and daily neurosurgery: The Sabah update

Perumall VV, Sellamuthu P, Harun R, Zenian MS

Asian J Neurosurg, 2015 Jan-Mar;10(1):1-4.
PMID: 25767567 DOI: 10.4103/1793-5482.151500

Healthcare costs continue to rise every day as the demand outgrows the supply of surgeons. The application of telephone consultation for immediate management is needed as most neurosurgeons are technology orientated. This enables a specialist at a remote mobile site to receive the necessary information and reduce transmission time, from the second the patient is seen till the management is obtained.
Fulltext Alveolar soft part sarcoma with brain metastases

Perumall VV, Harun R, Sellamuthu P, Shah MSM

Asian J Neurosurg, 2017 4 18;12(1):112-115.
PMID: 28413551 DOI: 10.4103/1793-5482.144197

Metastatic tumors are the most common mass lesions in the brain. This case reports a rare form of sarcoma with metastasis to the brain. The appropriate management of a patient with metastatic alveolar soft part sarcoma to the brain is discussed. Author describes a 32-year-old gentleman diagnosed with primary tumor at gluteus and distant metastases at lower lobe of right lung and the brain. Histopathology proves diagnosis as alveolar soft part sarcoma. Craniotomy with excision of brain lesion was done. Repeated magnetic resonance imaging of the brain after 2 months showed rapidly growing new lesions. The next step of management was made by the oncology team as recurrence rate was high and due to multi-systemic involvement. Patient was planned for palliative chemotherapy and to be reassessed later. This case report discusses the appropriate approach to any form of brain metastases and the role of early follow-up especially after surgery for better outcome and choice of post operative management such as radiotherapy or chemotherapy or both for malignant tumors. Based on this report, it was concluded that every brain tumor patient should be frequently monitored even in the outpatient setting as most of them are metastatic and rapidly spreading. The patient should be considered for radiotherapy or chemotherapy or both after surgery if the histopathology result is suggestive of malignancy.
Fulltext CYP2C9 polymorphism: prevalence in healthy and warfarin-treated Malay and Chinese in Malaysia

Ngow HA, Wan Khairina WM, Teh LK, Lee WL, Harun R, Ismail R, et al.

Singapore Med J, 2009 May;50(5):490-3.
PMID: 19495518

Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different. CYP2C9 has been reported to be the enzyme responsible for the metabolism of many drugs, including warfarin and other drugs with a narrow therapeutic index. Realising the importance of inter-individual differences in the genetic profile in determining the outcome of a drug therapy, this study was conducted to explore the types and frequencies of CYP2C9 alleles in healthy and warfarin-treated Malays and Chinese, the two major ethnic groups in Malaysia. We aimed to evaluate the prevalence of the types and frequencies of common CYP2C9 alleles (*1, *2, *3 and *4) among the healthy unrelated individuals and diseased patients prescribed with warfarin.
Role of pharmacodiagnostic of CYP2C9 variants in the optimization of warfarin therapy in Malaysia: a 6-month follow-up study

Ngow H, Teh LK, Langmia IM, Lee WL, Harun R, Ismail R, et al.

Xenobiotica, 2008 Jun;38(6):641-51.
PMID: 18570163 DOI: 10.1080/00498250801999087

1. A retrospective study was conducted to explore the importance of CYP2C9 genotyping for the initiation and maintenance therapy of warfarin in clinical practice. A total of 191 patients on warfarin therapy in a local hospital were recruited after written informed consent. Their medical records were reviewed and no intervention of warfarin dose was performed. 2. A total of 5 ml of blood were taken from each subject for DNA extraction and identification of 1, 2, 3 and 4 CYP2C9 alleles, using a nested-allele-specific-multiplex-polymerase chain reaction (PCR). Half the patients were Malays and the remaining were Chinese. 3. Two genotypes were detected; 93.2% had CYP2C9 1/1 and 6.8% were CYP2C9 1/3. Warfarin doses were higher in patients with CYP2C91/1. Patients with the 1/3 genotype experienced a higher rate of serious and life-threatening bleeding; 15.4 versus 6.2 per 100 patients per 6 months. 4. The observation clearly highlights the inadequacy of the current dosing regimens and the need to move toward a more individualized approach to warfarin therapy. Prospective clinical studies are now being conducted to assess dosing algorithms that incorporate the contribution of the genotype to allow the individualization of warfarin dose.

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