Vishna Devi Nadarajah

Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol

ETHNOPHARMACOLOGICAL RELEVANCE Zingiber officinale Rosc. (Zingiberaceae) has been traditionally used in Ayurvedic, Chinese and Tibb-Unani herbal medicines for the treatment of various illnesses that involve inflammation and which are caused by oxidative stress. Although gingerols and shogaols are the major bioactive compounds present in Zingiber officinale, their molecular mechanisms of actions and the relationship between their structural features and the activity have not been well studied. AIM OF THE STUDY The aim of the present study was to examine and compare the antioxidant and anti-inflammatory activities of gingerols and their natural analogues to determine their structure-activity relationship and molecular mechanisms. MATERIALS AND METHODS The in vitro activities of the compounds [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol were evaluated for scavenging of 1,1-diphenyl-2-picyrlhydrazyl (DPPH), superoxide and hydroxyl radicals, inhibition of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) induced reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN), inhibition of lipopolysaccharide induced nitrite and prostaglandin E(2) production in RAW 264.7 cells. RESULTS In the antioxidant activity assay, [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol exhibited substantial scavenging activities with IC(50) values of 26.3, 19.47, 10.47 and 8.05 microM against DPPH radical, IC(50) values of 4.05, 2.5, 1.68 and 0.85 microM against superoxide radical and IC(50) values of 4.62, 1.97, 1.35 and 0.72 microM against hydroxyl radical, respectively. The free radical scavenging activity of these compounds also enhanced with increasing concentration (P<0.05). On the other hand, all the compounds at a concentration of 6 microM have significantly inhibited (P<0.05) f-MLP-stimulated oxidative burst in PMN. In addition, production of inflammatory mediators (NO and PGE(2)) has been inhibited significantly (P<0.05) and dose-dependently. CONCLUSIONS 6-Shogaol has exhibited the most potent antioxidant and anti-inflammatory properties which can be attributed to the presence of alpha,beta-unsaturated ketone moiety. The carbon chain length has also played a significant role in making 10-gingerol as the most potent among all the gingerols. This study justifies the use of dry ginger in traditional systems of medicine.

The Multiple Mini-Interview (MMI) for student selection in health professions training – A systematic review

Background: The Multiple Mini-Interview (MMI) has been used increasingly for selection of students to health professions programmes. Objectives: This paper reports on the evidence base for the feasibility, acceptability, reliability and validity of the MMI. Data sources: CINAHL and MEDLINE Study eligibility criteria: All studies testing the MMI on applicants to health professions training. Study appraisal and synthesis methods: Each paper was appraised by two reviewers. Narrative summary findings on feasibility, acceptability, reliability and validity are presented. Results: Of the 64 citations identified, 30 were selected for review. The modal MMI consisted of 10 stations, each lasting eight minutes and assessed by one interviewer. The MMI was feasible, i.e. did not require more examiners, did not cost more, and interviews were completed over a short period of time. It was acceptable, i.e. fair, transparent, free from gender, cultural and socio-economic bias, and did not favour applicants with previous coaching. Its reliability was reported to be moderate to high, with Cronbachs alpha = 0.69–0.98 and G = 0.55–0.72. MMI scores did not correlate to traditional admission tools scores, were not associated with pre-entry academic qualifications, were the best predictor for OSCE performance and statistically predictive of subsequent performance at medical council examinations. Conclusions: The MMI is reliable, acceptable and feasible. The evidence base for its validity against future medical council exams is growing with reports from longitudinal investigations. However, further research is needed for its acceptability in different cultural context and validity against future clinical behaviours.

The effect of consequent exposure of stress and dermal application of low doses of chlorpyrifos on the expression of glial fibrillary acidic protein in the hippocampus of adult mice

BackgroundChlorpyrifos (CPF), a commonly used pesticide worldwide, has been reported to produce neurobehavioural changes. Dermal exposure to CPF is common in industries and agriculture. This study estimates changes in glial fibrillary acidic protein (GFAP) expression in hippocampal regions and correlates with histomorphometry of neurons and serum cholinesterase levels following dermal exposure to low doses of CPF with or without swim stress.MethodsMale albino mice were separated into control, stress control and four treatment groups (n = 6). CPF was applied dermally over the tails under occlusive bandage (6 hours/day) at doses of 1/10th (CPF 0.1) and 1/5th dermal LD50 (CPF 0.2) for seven days. Consequent treatment of swim stress followed by CPF was also applied. Serum cholinesterase levels were estimated using spectroflurometric methods. Paraffin sections of the left hippocampal regions were stained with 0.2% thionin followed by the counting of neuronal density. Right hippocampal sections were treated with Dako Envision GFAP antibodies.ResultsCPF application in 1/10th LD50 did not produce significant changes in serum cholinesterase levels and neuronal density, but increased GFAP expression significantly (p < 0.001). Swim stress with CPF 0.1 group did not show increase in astrocytic density compared to CPF 0.1 alone but decreased neuronal density.ConclusionsFindings suggest GFAP expression is upregulated with dermal exposure to low dose of CPF. Stress combined with sub-toxic dermal CPF exposure can produce neurotoxicity.

Identification of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a binding protein for a 68-kDa Bacillus thuringiensis parasporal protein cytotoxic against leukaemic cells

BackgroundBacillus thuringiensis (Bt), an ubiquitous gram-positive spore-forming bacterium forms parasporal proteins during the stationary phase of its growth. Recent findings of selective human cancer cell-killing activity in non-insecticidal Bt isolates resulted in a new category of Bt parasporal protein called parasporin. However, little is known about the receptor molecules that bind parasporins and the mechanism of anti-cancer activity. A Malaysian Bt isolate, designated Bt18 produces parasporal protein that exhibit preferential cytotoxic activity for human leukaemic T cells (CEM-SS) but is non-cytotoxic to normal T cells or other cancer cell lines such as human cervical cancer (HeLa), human breast cancer (MCF-7) and colon cancer (HT-29) suggesting properties similar to parasporin. In this study we aim to identify the binding protein for Bt18 in human leukaemic T cells.MethodsBt18 parasporal protein was separated using Mono Q anion exchange column attached to a HPLC system and antibody was raised against the purified 68-kDa parasporal protein. Receptor binding assay was used to detect the binding protein for Bt18 parasporal protein in CEM-SS cells and the identified protein was sent for N-terminal sequencing. NCBI protein BLAST was used to analyse the protein sequence. Double immunofluorescence staining techniques was applied to localise Bt18 and binding protein on CEM-SS cell.ResultsAnion exchange separation of Bt18 parasporal protein yielded a 68-kDa parasporal protein with specific cytotoxic activity. Polyclonal IgG (anti-Bt18) for the 68-kDa parasporal protein was successfully raised and purified. Receptor binding assay showed that Bt18 parasporal protein bound to a 36-kDa protein from the CEM-SS cells lysate. N-terminal amino acid sequence of the 36-kDa protein was GKVKVGVNGFGRIGG. NCBI protein BLAST revealed that the binding protein was Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Double immunofluorescence staining showed co-localisation of Bt18 and GAPDH on the plasma membrane of the CEM-SS cells.ConclusionsGAPDH has been well known as a glycolytic enzyme, but recently GAPDH was discovered to have roles in apoptosis and carcinogenesis. Pre-incubation of anti-GAPDH antibody with CEM-SS cells decreases binding of Bt18 to the susceptible cells. Based on a qualitative analysis of the immunoblot and immunofluorescence results, GAPDH was identified as a binding protein on the plasma membrane of CEM-SS cells for Bt18 parasporal protein.

Maternal plasma soluble fms‐like tyrosine kinase‐1 and placental growth factor levels as biochemical markers of gestational hypertension for Malaysian mothers

Aims:  To establish baseline levels of maternal plasma soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) among normotensive Malaysian mothers and to compare the marker levels between normotensives and mothers with gestational hypertension (GH).

Periodic assessment of plasma sFlt-1 and PlGF concentrations and its association with placental morphometry in gestational hypertension (GH) - a prospective follow-up study

BackgroundHypertensive disorders in pregnancy contributes to about 12% of maternal deaths in Malaysia and similarly worldwide. Early detection and adequate management are preventable strategies. Biochemical markers of abnormal angiogenesis would be more specific in early detection than routine blood pressure and proteinuria measurements. The aim of this study was to estimate maternal plasma PlGF and sFlt-1 levels in pregnant women with gestational hypertension at three intervals of pregnancy and correlate these biomarker levels with placental morphometry.MethodsVenous blood samples (antepartum, intrapartum and post partum periods) were drawn to estimate for sFlt-1 and PlGF levels while placental tissue samples were examined for placental morphometry.ResultsPlGF levels were lower in gestational hypertension (GH) compared to normotensive during antepartum and intrapartum period, whereas sFlt-1 levels were elevated in GH at antepartum, intrapartum and postpartum intervals during pregnancy. An inverse relationship between these two biomarkers was observed through correlation analysis. PlGF levels were inversely correlated with total villous surface area of the placental periphery (TCsa-C) and villous capillarization (VC-C) of the placental periphery.ConclusionWe established periodic values of for sFlt-1 and PlGF levels for the first time in an ethnically diverse Malaysian setting. We suggest the development of GH in women is related to defective capillarization. In demonstrating periodic changes, this study suggest the possibility of developing GH and other long term health complications as a result of prolonged exposure to sFlt-1. The correlation between PlGF levels and morphometric findings also support possible capillarization defect.

The near-peer tutoring programme: embracing the ‘doctors-to-teach’ philosophy - a comparison of the effects of participation between the senior and junior near-peer tutors

Background While there is an increasing pool of literature documenting the benefits of near-peer tutoring programme, little is known about the benefits for junior and senior peer tutors. Knowledge of the peer tutors’ perceived benefits at different levels of seniority will aid in the development of a near-peer tutoring programme that will better fulfil both curricula and personal aspirations of near-peer tutors. We, therefore, investigated the perceived benefits of participation in a near-peer tutoring programme for junior as well as senior near-peer tutors. Methods Pre- and post-participation questionnaires were distributed to near-peer tutors after their clinical skills teaching sessions with Phase I undergraduate medical students. The Peer Tutor Assessment Instrument questionnaires were distributed to the 1) students, and to the 2) near-peer tutors (junior and senior) after each teaching and learning session for self-evaluation. Results The senior near-peer tutors felt that their participation in the programme had enhanced their skills (p=0.03). As a whole, the near-peer tutors were more motivated (Pre 5.32±0.46; Post 5.47±0.50; p=0.210) to participate in future teaching sessions but did not expect that having teaching experiences would make teaching as their major career path in the future (Pre 4.63±1.07; Post 4.54±0.98; p=0.701). The senior near-peer tutors were evaluated significantly higher by the students (p=0.0001). Students’ evaluations of near-peer tutors on the domain of critical analysis was higher than self-evaluations (p=0.003). Conclusions Generally, the near-peer tutors perceived that they have benefited most in their skills enhancement and these near-peer tutors were scored highly by the students. However, senior near-peer tutors do not perceive that the programme has a lasting impact on their choice of career path.

Assessment of attitudes for interprofessional team working and knowledge of health professions competencies for final year health professional students

Inter-professional education (IPE) contributes to the development of an ‘inter-professional, collaborative and practice-ready’ healthcare workforce that is well prepared to respond to local healthcare needs. Little is known about the extent, to which health professional students who are nearing graduation understand the competencies of diverse health professions. The aim of this study was to investigate the perception of final-year undergraduate students’ towards interprofessional team working and their knowledge of the competencies of 6 health professions. This study evaluated the final-year health professional students’ from six (6) health professions programmes namely medical, dental, nursing, pharmacy, dietetics and biomedical sciences programmes. Attitudes towards Health Care Team Scale (ATHCTS) was used to measure students’ attitudes towards teamwork while a checklist was used measure students’ knowledge of 6 health professionals competencies. Construct validity was ascertain and findings from ATHCTS showed mean scores ranges from 48.57 to 54.23 indicating positive attitudes toward working within interprofessional health care teams. While the ACTHS findings were positive, the competencies checklist showed mixed findings in that students correctly identified some competencies and had misconceptions for others. For example, the majority of students regarded physicians as competent in ‘assessment and evaluation’ and ‘medication management’ while less than 50% of participants recognised the importance of assessment of patient’s health-illness as a competency for dieticians. Gaps identified in final year students’ knowledge of the roles and competencies of health professions has an impact on future interprofessional collaborative practice suggesting a need to further improve curriculum design and delivery of IPE.

Drug-like dietary vanilloids induce anticancer activity through proliferation inhibition and regulation of bcl-related apoptotic proteins

In this study, a series of 20 structurally similar vanilloids (Vn) were tested for their antiproliferative effects against 12 human cancer cells: human breast (MCF‐7 and MDA‐MB‐231), cervical (HeLa), ovarian (Caov‐3), lung (A549), liver (HepG2), colorectal (HT‐29 and HCT116), nasopharyngeal (CNE‐1 and HK‐1), and leukemic (K562 and CEM‐SS) cancer cells. Among all the tested vanilloids, Vn16 (6‐shogaol) exhibited the most potent cytotoxic effects against human colorectal cancer cells (HT‐29). The apoptotic induction effects exhibited by Vn16 on HT‐29 cells were confirmed using dual staining fluorescence microscopy and enzyme‐linked immunosorbent assay. The effects of Vn16 on regulation of 43 apoptotic‐related markers were determined in HT‐29. The results suggested that 8 apoptotic markers (caspase 8, BAD, BAX, second mitochondrial‐derived activator, caspase 3, survivin, bcl‐2, and cIAP‐2) were either upregulated or downregulated. These results further support the chemopreventive properties of foods that contain vanilloids.

Personal domains assessed in multiple mini interviews (MMIs) for healthcare student selection: A narrative synthesis systematic review

OBJECTIVES To examine the personal domains multiple mini interviews (MMIs) are being designed to assess, explore how they were determined and contextualise such domains in current and future healthcare student selection processes DESIGN: A systematic review of empirical research reporting on MMI model design was conducted from database inception to November 2017. DATA SOURCES Twelve electronic bibliographic databases. REVIEW METHODS Evidence was extracted from original studies, and integrated in a narrative synthesis guided by the PRISMA statement for reporting systematic reviews. Personal domains were clustered into themes using a modified Delphi technique. RESULTS A total of 584 articles were screened. 65 unique studies (80 articles) matched our inclusion criteria of which seven were conducted within nursing/midwifery faculties. Six in 10 studies featured applicants to medical school. Across selection processes, we identified 32 personal domains assessed by MMIs, the most frequent being: communication skills (84%), teamwork/collaboration (70%), and ethical/moral judgement (65%). Domains capturing ability to cope with stressful situations (14%), make decisions (14%), and resolve conflict in the workplace (13%) featured in fewer than ten studies overall. Intra- and inter-disciplinary inconsistencies in domain profiles were noted, as well as differences by entry level. MMIs deployed in nursing and midwifery assessed compassion and decision-making more frequently than in all other disciplines. Own programme philosophy and professional body guidance were most frequently cited (~50%) as sources for personal domains; a blueprinting process was reported in only 8% of studies. CONCLUSIONS Nursing, midwifery and allied healthcare professionals should develop their theoretical frameworks for MMIs to ensure they are evidence-based and fit-for-purpose. We suggest a re-evaluation of domain priorities to ensure that students who are selected, not only have the capacity to offer the highest standards of care provision, but are able to maintain these standards when facing clinical practice and organisational pressures.