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Fulltext The Diagnostic Accuracy of the M2 Pyruvate Kinase Quick Stool Test--A Rapid Office Based Assay Test for the Detection of Colorectal Cancer

Sithambaram S, Hilmi I, Goh KL

PLoS One, 2015;10(7):e0131616.
PMID: 26158845 DOI: 10.1371/journal.pone.0131616

M2 pyruvate kinase (M2PK) is an oncoprotein secreted by colorectal cancers in stools. This the first report on the accuracy of a rapid stool test in the detection of colorectal cancer (CRC).
Fulltext Acute and subacute dermal toxicity of ethanolic extract of Melastoma malabathricum leaves in Sprague-Dawley rats

Reduan FH, Shaari RM, Sayuti NSA, Mustapha NM, Abu Bakar MZ, Sithambaram S, et al.

Toxicol Res, 2020 Jul;36(3):203-210.
PMID: 32685424 DOI: 10.1007/s43188-019-00013-5

Melastoma malabathricum is a well-known herb in Malaysia where it being used in various ways for treatment of different diseases and ailments including skin problems. The study aims to investigate acute and subacute dermal toxicity of ethanolic extract of M. malabathricum leaves following to a single or repeated doses exposure. A total of 30 female Sprague-Dawley rats were grouped into 5 groups (n = 6 per group) for both acute and subacute toxicity study. The duration for each study was determined at 14 days for acute toxicity and 28 days for subacute toxicity. The rats were topically applied with the plant extract at three different doses; 2.5%, 5.0% and 10.0% on the shaved area of dorsal skin. For acute toxicity study, rats in all three groups received single application of the extract on the first day of the experimental period, while rats in subacute toxicity study were topically applied with the extract once daily for 28 days. Throughout the respective 14-day and 28-day study periods, all rats were monitored for any changes in their physical appearance and behavioural patterns that might develop due to toxic effects of the plant. There were no mortality or abnormal physical appearance, and physiological and behavioural changes observed in all rats in both studies. Body weights, kidney and liver weights, and both haematology and serum biochemistry results showed no significant (p > 0.05) differences between all groups in both studies. All of the findings were supported by normal macroscopic and microscopic architectures of liver, kidneys and skin of all rats applied topically with the extract. This study suggests that topical application of M. malabathricum leaf ethanolic extract at 2.5%, 5% and 10% does not induce acute and subacute adverse effects on the skin or systemic toxic reactions in rats.
Mandarin version of the Leeds Dyspepsia Questionnaire: A valid instrument for assessing symptoms in Asians

Leow HR, Ching SM, Sujarita R, Yap CF, Chia YC, Ho SH, et al.

J Dig Dis, 2014 Nov;15(11):591-6.
PMID: 25139629 DOI: 10.1111/1751-2980.12183

OBJECTIVE:
To develop and validate a Mandarin version of the Leeds Dyspepsia Questionnaire (M-LDQ) in Asian patients with dyspepsia.

METHODS:
The M-LDQ was developed according to standardized methods. The validity, internal consistency, test-retest reliability and responsiveness of the instrument were evaluated in both primary and secondary care patients.

RESULTS:
A total of 184 patients (mean age 54.0 ± 15.8 years, of whom 59% were women and 72.3% of whom had at least secondary level education) were recruited between August 2012 and March 2013, from both primary (n = 100) and secondary care clinics (n = 84). Both the internal consistency of all components of the M-LDQ (Cronbach's α 0.79) and test-retest reliability (Spearman's correlation coefficient 0.78) were good. The M-LDQ was valid in diagnosing dyspepsia in primary care (area under the receiver operating characteristics curve 0.84) and was able to discriminate between secondary and primary care patients (median cumulative LDQ score 13.0 vs 3.0, P < 0.0001). Among eight patients with organic dyspepsia, the median M-LDQ score reduced significantly from 21.0 (pretreatment) to 9.5 (4 weeks post-treatment) (P < 0.0001).

CONCLUSION:
The M-LDQ is a valid and responsive instrument for assessing ethnic Chinese adults with dyspepsia.

KEYWORDS:
Mandarin; ethnic Chinese; functional dyspepsia; outcome measure; questionnaire; validation
Fulltext N-Ethyl-n-Nitrosourea Induced Leukaemia in a Mouse Model through Upregulation of Vascular Endothelial Growth Factor and Evading Apoptosis

Aliyu A, Shaari MR, Ahmad Sayuti NS, Reduan MFH, Sithambaram S, Noordin MM, et al.

Cancers (Basel), 2020 Mar 13;12(3).
PMID: 32183192 DOI: 10.3390/cancers12030678

Chemical carcinogens are commonly used to investigate the biology and prognoses of various cancers. This study investigated the mechanism of leukaemogenic effects of n-ethyl-n-nitrosourea (ENU) in a mouse model. A total of 14 3-week-old male Institute of Cancer Research (ICR)-mice were used for the study. The mice were divided into groups A and B with seven mice each. Group A served as the control while group B received intraperitoneal (IP) injections of 80 mg/kg ENU twice with a one-week interval and were monitored monthly for 3 months for the development of leukaemia via blood smear examination. The mice were sacrificed humanely using a CO2 chamber. Blood, spleen, lymph nodes, liver, kidney and lung samples were collected for blood smear examination and histopathological evaluation. The expression of angiogenic protein (VEGF), and pro and anti-apoptotic proteins (BCL2 and BAX), was detected and quantified using Western blot technique. Leukaemia was confirmed by the presence of numerous blast cells in the peripheral blood smear in group B. Similarly, the VEGF and BCL2 proteins were significantly (p < 0.05) upregulated in group B compared to A. It is concluded that IP administration of 80 mg/kg ENU induced leukaemia in ICR-mice 12 weeks post administration through upregulation of angiogenic and anti-apoptotic proteins: VEGF and BCL2.
Fulltext Moringa oleifera hydorethanolic leaf extract induced acute and sub-acute hepato-nephrotoxicity in female ICR-mice

Aliyu A, Shaari MR, Ahmad Sayuti NS, Reduan FH, Sithambaram S, Mohamed Mustapha N, et al.

Sci Prog, 2021 Oct;104(4):368504211004272.
PMID: 34886737 DOI: 10.1177/00368504211004272

Moringa oleifera (M. oleifera) Lam belongs to the family Moringaceae. It is an important multipurpose tree that is largely distributed globally and has been used almost in every aspect of traditional medicine for the treatment of various illnesses including cancers, diabetes mellitus, asthma, arthritis, etc. This study investigated the effects of oral acute and sub-acute administration of M. oleifera hydroethanolic leaf extract (MOHE) in ICR-mice. Its major phenolic compounds were also determined. Ten (10) female, 8-week old mice were grouped into control and treatment groups for acute toxicity study. A dose of 2000 mg/kg MOHE was given once to the treatment group via oral gavage. However, for the sub-acute toxicity study, 25 mice were grouped into groups A (control), B (125 mg/kg), C (250 mg/kg), D (500 mg/kg) and E (1000 mg/kg). MOHE was given via oral gavage to groups B, C, D and E daily for 28 days. Group A received only distilled water. The mice were sacrificed at the end of the experiments and samples were collected for evaluation. The results of the chemical profiling of MOHE revealed the presence of glucomoringin, niaziminine, quercetin and kaempferol as the major compounds. The treated mice in the acute toxicity study were slightly anaemic and showed evidence of stress leukogram. Moreover, a slight increase in creatinine, significant increases in AST and CK, hepatic degeneration and necrosis, none-obstructive sinusoidal dilatation, renal tubular necrosis, interstitial nephritis and renal interstitial oedema were observed. It is concluded that the LD50 of MOHE is higher than 2000 mg/kg. However, oral administration of MOHE causes acute mild anaemia and moderate hepato-nephrotoxicity in ICR-mice. Its major phenolic compounds are glucomoringin, niaziminine, quercetin and kaempferol.
The development of a novel, multilingual IBD knowledge questionnaire for Asian patients with inflammatory bowel disease

Razima Wan Ibrahim N, Danaee M, Khoo XH, Sithambaram S, Shahrani S, Hwong-Ruey Leow A, et al.

BMC Gastroenterol, 2023 May 25;23(1):185.
PMID: 37231353 DOI: 10.1186/s12876-023-02817-0

BACKGROUND: Inflammatory bowel disease is an uncommon disease in developing nations whereby patient's knowledge on the disease may be limited. The CCKNOW questionnaire, a widely known questionnaire to assess patient's knowledge on the disease, may be too complex to comprehend for patients in developing countries. The aim of this study is to develop a new tool known as AIBDKQ questionnaire to evaluate the local inflammatory bowel disease patient's knowledge.
METHODS: This was a prospective study carried out in four phases. In phase 1, three gastroenterologists with expertise in IBD generated a total of 21 questions related to the general knowledge of the disease in the English language. Phase 2 involved content and face validity whereby the questions were further validated by other gastroenterologists. In phase 3, the validated questions were translated into three languages namely Malay, Mandarin and Tamil which are commonly used in Malaysia. In phase 4 (statistical validity), administration of the questionnaires to patients and hospital staff were conducted to assess the construct validity, discriminative ability, predictive validity and reliability of the questionnaires.
RESULTS: A total of 21 questions were generated initially. Further evaluation indicated that 20 items had adequate kappa and content validity index for relevance (CVI: 0.714 to 1, Kapp: 0.645 to 1) and clarity (CVI: 0.714 to 1, Kapp: 0.645 to 1). The questionnaires in four languages were administered to 213 patients to assess the construct validity. Six items were removed (three for low communality, one for small loading factors, two for cross loading), resulting in 16 final questions. Assessment with 34 hospital staff involving nurses, doctors and clerks showed significant differences in knowledge between the groups (F = 14.007, p