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Fulltext Rare cases of haemoglobin variant presented with isolated erythrocytosis

Subithira N, Hafidzah NM, Syirah N, Ezalia E, Faridah, Sabariah MN

Malaysian Journal of Medicine and Health Sciences, 2020;16(109):114-116.
MyJurnal

Haemoglobinopathies presenting with erythrocytosis is relatively rare. The clinicians might mistakenly diagnose such patients with other causes of erythrocytosis such as myeloproliferative neoplasm, etc instead of haemoglobinopathies. Here, we described two cases of haemoglobin variant, namely Haemoglobin Johnstown (Hb Johnstown) and Haemoglobin Bethesda (Hb Besthesda) that were detected following various futile investigations for persistent erythrocytosis. For both cases, the two main screening methods used were capillary electrophoresis (CE) and high performance liquid chromatography (HPLC). Approximately 30% of the high affinity haemoglobin (Hb) are not detected by electrophoresis method, however, in some cases, a variant Hb peak can be seen in chromatography method. Thus, a high index of suspicion of such diagnosis is utmost important as to not to miss the definitive diagnostic test by DNA analysis.
Fulltext Antigen expression pattern of acute promyelocytic leukaemia cases in Malaysia

Ambayya A, Zainina S, Salmiah MS, Sabariah MN

Med J Malaysia, 2014 Apr;69(2):64-9.
PMID: 25241814 MyJurnal

INTRODUCTION: Acute Promyelocytic Leukaemia (APL) is associated with devastating coagulopathy and life threatening condition which requires immediate medical attention. It is crucial to establish an expedited diagnosis as early therapeutic intervention has led to optimal patient management. In this study, we assessed the type and frequency of antigen expressions in APL and correlated these findings with genetic studies.

METHODS: Multiparametric immunophenotyping was performed on 30 samples and findings were correlated with karyotypes, FISH for t(15;17) translocation and RT-PCR for PML-RARΑ for detection of breakpoint cluster regions (bcr1,bcr2 and bcr3).

RESULTS: On SSC/CD45, APL cells displayed high to moderate SSC, with the expression of CD33 (100%), CD13 (96.8%), cMPO (71%) but lacked CD34 (3.2%) and HLA-DR (9.7%). Aberrant expression of CD4 was seen in 12.9% and CD56 in 6.5% of the cases. A significant association between cumulative aberrant antigen expression and bcr1 were observed bcr1 (X2(2) =6.833,p.05) and (X2(2)=4.599,p>.05) respectively.

CONCLUSIONS: Flow cytometry is a rapid and effective tool in detecting APL. It is interesting to note that there is significant association between cumulative aberrant antigen expression and genotype analysis. Further validation is required to corroborate this relationship.
Fulltext Qualitative flow cytometric analysis of Malaysian myelodysplastic syndromes (MDS) patients

Mohadese Hashem B, Ramasamy R, Sabariah MN, Seman Z

Med J Malaysia, 2012 Feb;67(1):77-80.
PMID: 22582553 MyJurnal

Myelodysplastic syndromes (MDS) are a group of haematological malignancies categorized by ineffective hematopoiesis that result in dysplasia. Although morphological diagnosis is a traditional and standard technique that is used for the diagnosis of MDS, the heterogeneous blood and bone marrow characteristics of MDS patients can potentially obscure the right diagnosis. Thus, we have utilized flow cytometric immunophenotyping as a supportive mechanism to obtain a more accurate and faster method for detection of abnormal markers in MDS. Flow cytometry was used for analyzing bone marrow samples from newly diagnosed MDS patients to investigate the abnormal antigen expression patterns in granulocytic, monocytic, erythroid, lymphoid lineages and myeloid precursors. The results were compared with those obtained from cases that had Idiopathic Thrombocytopenic Purpura (ITP) as a control. The most common abnormality found in the granulocytic lineage was the decrease of CD10. Low expressions of CD13 were the most frequent abnormality in the monocytic lineage. The erythroid lineage was found to have low expression of CD235A+/CD71+, reduce of CD71 and decreased CD235a. In conclusion, this method is useful for confirming cases in which it is difficult to make a diagnosis by morphology.
Fulltext Childhood idiopathic myelofibrosis: a case report and review of literature

Noor-Fadzilah Z, Leong CF, Sabariah MN, Cheong SK

Malays J Pathol, 2009 Dec;31(2):129-32.
PMID: 20514856 MyJurnal

Idiopathic myelofibrosis occurs predominantly in older adults. It is very rarely seen in children. We describe a 3-year-old girl with Down's syndrome who presented with recurrent chest infections associated with anaemia and easy bruising. There was mild hepatosplenomegaly. Full blood picture revealed pancytopaenia with leucoerythroblastosis with absence of circulating blast cells. Repeated attempts at bone marrow aspiration and trephine biopsy were unsuccessful. A trephine biopsy from the tibia showed depressed myelopoiesis and erythropoiesis, megakaryocytes with atypical morphology and increased bone marrow reticulin fibres, findings compatible with idiopathic myelofibrosis. She was treated symptomatically as she was clinically stable. Review of the English literature online yielded 46 reported cases of childhood idiopathic myelofibrosis with variable outcome from spontaneous remission to an indolent course with shortened survival. 6 cases evolved to another malignancy. 5 cases were associated with Down's syndrome.
Fulltext MTHFR C677T polymorphism, homocysteine and B-vitamins status in a sample of Chinese and Malay subjects in Universiti Putra Malaysia

Choo SC, Loh SP, Khor GL, Sabariah MN, Rozita R

Malays J Nutr, 2011 Aug;17(2):249-58.
PMID: 22303578 MyJurnal

Methylenetetrahydrofolate reductase (MTHFR) C677T is involved in folate and homocysteine metabolism. Disruption in the activity of this enzyme will alter their levels in the body.
Fulltext Andrographolide effect on both Plasmodium falciparum infected and non infected RBCs membranes

Zaid OI, Abd Majid R, Sabariah MN, Hasidah MS, Al-Zihiry K, Yam MF, et al.

Asian Pac J Trop Med, 2015 Jul;8(7):507-12.
PMID: 26276279 DOI: 10.1016/j.apjtm.2015.06.007

OBJECTIVE: To explore whether its antiplasmodium effect of andrographolide is attributed to its plausible effect on the plasma membrane of both Plasmodium falciparum infected and non-infected RBCs.
METHODS: Anti-plasmodium effect of andrographolide against Plasmodium falciparum strains was screened using the conventional malaria drug sensitivity assay. The drug was incubated with uninfected RBCs to monitor its effect on their morphology, integrity and osmotic fragility. It was incubated with the plasmodium infected RBCs to monitor its effect on the parasite induced permeation pathways. Its effect on the potential of merozoites to invade new RBCs was tested using merozoite invasion assay.
RESULTS: It showed that at andrographolide was innocuous to RBCs at concentrations approach its therapeutic level against plasmodia. Nevertheless, this inertness was dwindled at higher concentrations.
CONCLUSIONS: In spite of its success to inhibit plasmodium induced permeation pathway and the potential of merozoites to invade new RBCs, its anti-plasmodium effect can't be attributed to these functions as they were attained at concentrations higher than what is required to eradicate the parasite. Consequently, other mechanisms may be associated with its claimed actions.
Berberis vulgaris fruit crude extract as a novel anti-leukaemic agent

Saedi TA, Ghafourian S, Jafarlou M, Sabariah MN, Ismail P, Eusni RM, et al.

J Biol Regul Homeost Agents, 2015 Apr-Jun;29(2):395-9.
PMID: 26122228

Tumor protein p53 encoded by the TP53 gene in humans is known as a cancer biomarker in patients diagnosed with cancer, and it plays an essential role in apoptosis, genomic stability, and inhibition of angiogenesis. Cancer therapies with common chemotherapy methods are effective, as known, but have some side effects. Berberis vulgaris is traditionally administrated as a cancer drug. The current research aims to evaluate p53 as a biomarker in WEHI-3 cell line and to demonstrate the Berberis vulgaris fruit crude extract (BVFCE) as a new anticancer drug. For this purpose, we evaluated the effect of BVFCE in different concentrations against WEHI-3cell line in vitro and determined the quantitative level of p53 gene in the treated WEHI-3 cells. The results demonstrated that even at only 1 mg/ml concentration of Berberis vulgaris crude extract, there was a low level of p53 biomarker expression on WEHI-3 cells in comparison with doxorubicin. Therefore, the current study suggests BVFCE as a reliable anti-leukaemic drug and candidate for anticancer therapy. However, further investigation need be carried out to confirm its efficiency in vivo.
Fulltext Anti-plasmodial and Chloroquine Resistance Suppressive Effects of Embelin

Zaid OI, Majid RA, Hasidah MS, Sabariah MN, Al-Zihiry K, Rahi S, et al.

Pharmacogn Mag, 2017 Jan;13(Suppl 1):S48-S55.
PMID: 28479726 DOI: 10.4103/0973-1296.203982

BACKGROUND: Emergence of chloroquine (CQ) resistance among different strains of Plasmodium falciparum is the worst catastrophe that has ever perplexed the dedicated efforts to eradicate malaria. This urged the scientists to search for new alternatives or sensitizers to augment its antiplasmodium effect.
MATERIALS AND METHOD: In this experiment, the potential of embelin, isolated from Embelia ribes, to inhibit the growth and sensitize CQ action was screened using SYBRE-green-I based drug sensitivity and isobologram assays, respectively. Its effect on red blood cells stability was screened to assess its safety. To explore its molecular mechanism, its effect on plasmodial Hemozoin and the in vitro β-hematin formation was screened as well. Furthermore, its anti-oxidant activity was measured using the conventional in vitro tests and its molecular characters were obtained using Molispiration program.
RESULTS: The results showed that its anti-plasmodial effect was weaker than CQ but synergism was obtained when they were combined at ratios lower than 5:5 CQ/embelin. Furthermore, β-hematin formation was inhibited by embelin without showing any synergism after mixing with CQ.
CONCLUSION: Overall, embelin is not ideal to be suggested as a conventional antiplasmodium but it has a potential to ameliorate CQ resistance. Furthermore, its action is not related to its impact on hemozoin formation. Further, investigations are recommended to illustrate its detailed mechanism of action. Abbreviation used: CQ-DV-PBS-HEPES: Chloroquine-Digestive vacuole-Phosphate-buffer-saline-4-(2-hydroxyethyl-1-piperazin-ethan-sulphoni-acid), EDTA: Ethylen-diamin-tetra-acetic-acid, g.m.wt: Gram molecular weight, cMCM: Complete-malaria-culture-medium, Hct: Hematocrite, PRBCs: Parasitized-redblood-cells, nRBCs: Normal-red-blood-cells, RT: Room temperature, IC: Inhibitory concentration, FIC: Fractional inhibitory concentration, iCM: Incomplete-culturemedium, BSA: Bovin serum albumin, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DPPH: 2,2-diphenyl-1- picrylhydrazy, BHT: Butylatedhydroxyl-toleuen, PSA: Polar surface area, ClogP: Log partition coefficient (octanol/water), GPCR: G-protein-coupled-receptors, DMSO: Dimethylsulphoxide, NaOH: Sodium hydroxide.