Azacytidine (5-Aza) is a chemotherapeutic drug that has been known to restore the expression of Tumour suppressor genes by de-methylation and shown clinical efficacy inMyelodysplastic syndrome (MDS) [1-3]. Currently, 5-Aza is being used in UK for the treatment of some adults with MDS, chronic myelocytic leukemia (CML) and acute myelocytic leukemia (AML) [4]. Majority of CML patients treated with imatinib, a BCR/ABL inhibitor would develop resistance under prolonged therapy. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that is constitutively activated in various human cancers including hematological malignancies. Activation of STAT3 represents an important mechanism of imatinib resistant [5]. Methylation of SHP-1is involved in the constitutive activation of STAT3 [6], and a low level of SHP-1is not sufficient to inhibit activated STAT3 [7]. Epigenetic silencing of SHP-1also plays a role in the development of resistance to imatinib in BCR/ABL positive CML cells.
Screening for Tuberculosis (TB) using Chest X-Rays (CXR) among high-risk individuals is essential to help reach the End TB Strategy goal in reduction of 90% in TB incidence by 2035. Even though Ministry of Health Malaysia has made screening compulsory, the number of cases detected is not encouraging. Therefore, it is essential to identify factors contributing to positive screening that would improve case detection. High-risk groups are individuals that are compulsory to be screened using chest x-ray, regardless of presence or absence of TB symptoms. A cross sectional study was done in 2016 involving individuals belonging to TB high-risk groups who underwent screening in Kedah, Malaysia. Data was obtained from the TB information system (TBIS) 104 A, an information system used for TB screening monitoring and chest x-ray report of the selected individuals. It involved 1417 individuals who were randomly selected from various health facilities in six districts of Kedah. Among all 1417 study samples, 1036 (73.1%) individuals were asymptomatic. Among the asymptomatic individuals, only 91 (8.8%) had positive CXR findings. Smokers were found to have almost 3 times the odds of having positive CXR findings compared to non-smokers [Adjusted OR (95% CI): 2.71 (1.03, 7.15), p-value
The aims of the study were to investigate the anti-cancer effects of 5-
Aza and TSA in two leukemic cell lines (CCRF-CEM and HL-60). Inhibition
concentration of 5-Aza and TSA were measured using trypan blue exclusion
assay. 5-Aza and TSA at IC50 were treated to both CCRF-CEM and HL-60 cell
lines for 4-6 days. To confirm the inhibition effects of these agents, Annexin-V
stained cells were analyzed using flow cytometry to evaluate the apoptotic
induction. The IC50 values of CCRF-CEM were 2.01±0.1µM and 2.65±0.3µM for
5-Aza- and TSA-treated, respectively. Whereas, the IC50 values of HL-60 were
1.98±0.2µM and 2.35±0.2µM for 5-Aza- and TSA-treated, respectively. To
further substantiate the findings, the time-dependent exposure of both drugs was
studied. CCRF-CEM cells were reduced to 49.4%±5.0, 49.4%±2.5 and
41.5%±5.6 by 5-Aza; 56.5%±7.0, 45.3%±4.2 and 40.2%±4.2 by TSA treatment
at first, third and sixth day. HL-60 cells were reduced to 72.0%±4.5, 51.0%±1.5
and 40.6%±2.6 by 5-Aza at first, third and sixth day. Meanwhile, HL-60 cells
reduced to 55.6%±4.5, 45.2%±4.0 and 36.3%±2.9 by TSA at first, second and
fourth day. Both cell lines were significantly inhibited (p
Hospital-acquired infections (HAIs) are responsible for over 40% of cases in acute-care hospitals and commonly associated with catheter-sassociated urinary tract infections (CAUTIs). Current nanotechnology approach focus on improving the aseptic procedures for medical devices and manage the HAIs risk. TiO2 and ZnO nanoparticles (NPs) have been widely reported independently, to have a photocatalytic killing potential. The present study evaluates the antibacterial activity of heterojunction between TiO2 and ZnO NPs on several types bacterial pathogens model including Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The antibacterial screening test on TiO2/ZnO nanoparticles (NPs) were done under dark and light conditions with different molar ratio 25T75Z, 50T50Z and 75T25Z according to Clinical Laboratory Standards Institute (CLSI) guidelines MO2-A11. ZnO and TiO2/ZnO (25T75Z and 50T50Z) NPs at the highest concentration (1000µg/µL) showed mean diameters of the zones of inhibition (mm); (12.5 ± 0.58), (12.13 ± 0.85), and (7.25 ± 1.44) in dark condition. Increment in inhibition zones was obtained under light condition; (21.38 ± 0.48), (17.50 ± 1.0), and (12.38 ± 1.80). Findings from this study highlights the heterogeneous TiO2 and ZnO NPs could become a promising bacteriostatic and/or bactericidal agent to combat against the HAIs.
Clinacanthus nutans or locally known as Belalai Gajah in Malaysia has been used in China in various manners to treat inflammatory conditions like hematoma, contusion, strains and rheumatism. Recently, C. nutans has become popular for the treatment of cancer among Malaysian. Thus, the aim of this present study is to prove the anti cancer activity of C. nutans extracts in a treatment of cervical cancer as claimed by local people. Aqueous and methanol extracts were extracted from the leaves of C. nutans and phytochemical screening was performed for determination of secondary metabolites. The cytotoxic activities of both aqueous and methanol extracts were investigated against HeLa cell by using MTT assay. The mode of cell death was examined by Hoechst 33258 nuclear staining. The secondary metabolite constituents detected in C. nutans aqueous extract are terpenoids and flavonoids, whereas methanol extract contains terpernoids, alkaloids and flavonoids. Results also showed that C. nutans aqueous extract exerted a significant cytotoxic effect on HeLa cells (IC50=13±0.82 μg/ml) but no IC50 was detected by methanol extract. No significant cytotoxic activities (IC50 = not detected) were observed in normal kidney cell line, Vero, treated with both aqueous and methanol extracts of C. nutans which showed the cytoselective property of the extracts. However, HeLa and Vero cells treated with control drug, tamoxifen showed a significant cytotoxicity effects with IC50 values of 3.8±0.19 μg/ml and 2.2±0.029 μg/ml respectively. Hoechst 33258 stained showed the aqueous extract of C. nutans induced cell death on HeLa cells via apoptosis. Thus, suggesting C. nutans aqueous extract as a potential promising alternate therapeutic substance for cancer prevention and treatment especially for cervical cancer treatment.
Ki67, a nuclear protein presents in cells that is usually associated
with tumor cell proliferation. Therefore, physical quantification of Ki67 is a direct
measure cell proliferation activity. Immunohistochemical staining is known to be
an effective method of assessing the proportion of tumor cells. Currently, there
are various techniques for counting Ki67 in different types of cancer. This paper
provides an overview of recent scoring methods of Ki67, which includes ‘eyeballing’ estimation, vision counting with a microscope or viewer software,
manual counting of the camera-captured or digital image and automated
counting.
Globally, α-thalassaemia is a highly prevalent disease. In Malaysia, this disorder is a well-known public health problem [1]. The three most common deletional α-thalassaemia found in this region include --SEA deletion, -α3.7 and -α4.2 deletions [2]. The prevalence rate of triplication alpha cases such as αααanti3.7 and αααanti4.2 is unknown in Malaysia although it plays a pivotal role in exacerbating the clinical phenotypes in beta thalassaemia carriers [3]. Therefore, the purpose of this study was to design an assay for the detection of triplications and common deletional alpha thalassaemia using droplet digital PCR (ddPCR). Copy number changes were analysed using Quanta-SoftTM software version 1.6.6 after performing ddPCR. Sensitivity and validation analysis were also performed on the DNA samples. The changes in copy number changes (common deletions, duplications and triplications) in the alpha globin gene has been quantitatively detected using ddPCR. For the samples validation as determined by ddPCR, the mean copy number values for αα/αα are 2.0275±0.0177 (HS-40), 1.8175±0.0389 (HBA2), 2.0450±0.0848 (HB 3.7), 2.0050±0.0000 (HBA1). For -α3.7 /--SEA, the mean copy number values are 2.0225±0.2180 (HS-40), 0.9325±0.1213 (HBA2), 0 (HB 3.7), 0.9984±0.1333 (HBA1). As for –α4.2 /--SEA, the mean copy number values are 1.9350 (HS-40), 0 (HBA2), 0.7945 (HB 3.7), 0.8480 (HBA1). The mean copy number values for --SEA/αα samples are 1.9067±0.1327 (HS-40), 0.8164±0.0364 (HBA2), 0.8920±0.0434 (HB 3.7), 0.9148±0.0338 (HBA1) respectively. This study has found that the use of ddPCR is convenient as it allows direct quantification without the requirement of a calibration curve unlike qPCR [4]. Secondly, this study also showed that ddPCR is accurate and precise in the detection of alpha thalassaemia deletions and triplications based on the gene dosages using absolute quantification. In addition, the non-requirement of post-PCR work has minimised the risk of PCR carryover contamination. Thirdly, ddPCR saves time with less turnaround time and minimise the labour work required as compared to techniques such as MLPA which requires DNA denaturation and hybridisation reaction on day 1 while ligation and PCR reaction on day 2. Fourthly, this study found that the detection of α-thalassaemia using ddPCR is sensitive. DNA samples with low concentration as low as 1 ng were able to be detected for α-thalassaemia using ddPCR. The ability to detect minute amount of DNA concentration is crucial particularly in the diagnosing of the lethal HbH hydrops foetalis during the neonatal stage in α-thalassaemia. In conclusion, this is an alternative method (ddPCR) that can be employed for rapid detection of alpha thalassaemia variants in Malaysia.
Trisomy 8 is a condition where every cell of an individual presents with an extra copy (three copies of chromosome 8. This disorder occurs when a pair of chromosomes fails to divide evenly, which results in cells containing more than two of this chromosome. Here, we report a case of mosaic trisomy 8 in a Malaysian Malay boy.Although patient in this case confirmed with T8M, he exhibited few of the characteristic features that previously were reported to be associated with T8M. However, the patient’s very young age might explain the lack of clinical presentation of these features.
Thalassaemia is one of the most common autosomal recessive blood disorders in the world and its carrier status is prevalent in nearly 15% of Malaysian population. The global and economic burden for lifelong care of those affected increases every year. Currently, there is no policy on thalassaemia-carrier screening for couples prior to marriage besides HIV/AIDS screening in Malaysia. Other countries such as Iran, Iraq, Turkey, Bahrain and Saudi Arabia have established a policy for thalassaemia prevention by conducting premarital thalassaemia screening. Zero thalassaemia cases in new-born child in Cyprus have proven that thalassaemia can be prevented. This study aimed to investigate the willingness of premarital Malays on premarital thalassaemia screening.
A set of questionnaire was distributed to 57 persons at premarital course sites and wedding fairs and expositions held in Kuala Lumpur and Selangor. Components in the questionnaire included: 1) demographic 2) knowledge about thalassaemia, signs and screening method 3) attitudes towards thalassaemia premarital screening 4) practices of premarital thalassaemia screening. Analysis for the questionnaire was performed using IBM SPSS Statistics 23.0.
The rare condition of neutrophils agglutination in-vitro may give inaccurate neutrophils count. We reported a case of a 71-year-old female admitted with a diagnosis of extended-spectrum beta-lactamase (ESBL) Escherichia Coli (E.coli) septicaemia secondary to the left lower limb cellulitis. Despite underlying infection, total white blood cell count (TWBC) and absolute neutrophil count remained in a normal range. An accidental finding of full blood picture (FBP) using K2 ethylenediaminetetraacetic acid (EDTA) tube presented numerous neutrophils agglutination. Further tests were carried out using citrated and heparinised tubes and tested at room temperature, 4 C, and 37 ͦC. The findings showed a significant reduction in neutrophils agglutination in both citrated and heparinised tubes, including when tested at room temperature (RT) and 4 ͦC. Surprisingly, at 37 ͦC, no neutrophil agglutination was observed. This indicates that temperature-dependent anti-neutrophil IgM antibody may be found in the patient's serum that reacted with the EDTA anticoagulant. In conclusion, white blood cells (WBC) agglutination has been associated with malignancy, sepsis, liver disease, and autoimmune disease. Thus, a baseline FBP is recommended, especially in these categories of patients to optimise their clinical management.
It has been recognized extensively that studies of pharmacogenetics provide massive examples of causal relationship between genotypes and drug effectiveness to account for interindividual phenotypic variations in drug therapy. In most cases, cytochrome P450 (CYP) polymorphisms are one of the major variables that affecting those drug plasma concentration, drug detoxification and drug activation in humans. Thus, understanding of CYP polymorphisms can be crucially valuable in order to allow early and more accurate drug dosage prediction and improve the drug response accordingly. Despite the high level of homologous amino acid sequences, CYP2C9 and CYP2C19 genes are among the most important CYP genes which metabolize a wide range of clinically therapeutic drugs. Several critical reviews have been published relating to the aforementioned genes. However, this minireview aims to systematically merge reported studies on the SNPs frequencies of both genes concentrating only on Malaysian population. It is hoped that, the minireview can be an opener for new opportunities to reevaluate the evidence on the prevalence of CYP2C genes as a potential genetic factor influencing a particular drug efficacy and safety among Malaysian. Such evaluation can be developed to the next level of early prediction of better and specific drug treatment, thereby improving the drug response while helping the government in minimising the drug expenditures.
HRQOL is referring to patients' perceptions that is related to physical and mental of thalessemia patients. HRQOL measurement is crucial in assessing the extent of impact that this chronic disease has affected the thalassaemia patients’ lives. HRQOL measurement also includes identifying the effects of the treatment and disease towards wellbeing of the patients. Quality of Life (QOL) of individuals with thalassaemia major are affected by many influence factors such as the effect of diagnosis and treatment, chronic conditions state, appearances, treatment’s components such as frequent hospital visits for the transfusion, nightly mixture of subcutaneous, late arrival or absence, sexual development and complications from the disease[1-2].
The study aims to assess the Health Related Quality of Life (HRQoL) among thalassaemia patients and identify the significant factors that contribute to HRQoL in thalassaemia patients in Malaysia. A cross sectional based study was conducted at Kedah Thalassaemia Society Club in Kedah, Malaysia. The HRQoL was measured using a Short form survey version 2 (SF-36). Descriptive study was used to describe the demographic and disease related to the thalassaemia patients. The HRQoL was compared using the Mann-Whitney and Kruskal-Wallis test. The analyses were performed using the Quality Metric Health Outcomes Scoring software for SF-36 and SPSS v 22. Three hundred and ninety thalassaemia patients were enrolled in the study. The majority of the participants (n = 221, 58.5%) were categorized in the age group of 18-27 years (25.40 ± 10.2). The HRQoL measure of less than 50 for the physical component summary (PCS) and mental component summary (MCS) among thalassaemia patients were rated as poor. Patients with higher education levels were significantly associated with PCS (p=0.002) and showed higher mean scores for PCS (52.0) compared to the others. Age, marital status, employment status, monthly income, health check-ups before screening of thalassaemia and medical insurance was associated with PCS levels compare to the others. The type of thalassaemia, the medical treatment received and the side effects of the conventional treatment were significantly associated with p-values of less than 0.001 and PCS and MCS scores of below 50.