Authors: Chin-Eng Ong, Yan Pan, Kai-Hung Tiong, Beow-Chin Yiap, Eng-Lai Tan, Peter Pook, Joon-Wah Mak.

ABSTRACT

Pharmacogenomics (or pharmacogenetics), the study of the effects of genetic differences on a person’s response to drugs, can help in optimizing drug efficacy and minimizing adverse drug reactions. Interperson difference in drug metabolism is one of the important consequences of such genetic variation. This variation is determined in part by mutations in cytochrome P450 enzymes (CYPs). IMU is part of a major collaborative research project in the area of phamacogenetics and drug metabolism. Working together with USM and UiTM, our group has, since 2000, generated useful population database on genetic polymorphism of various CYP isoforms. We have successfully genotyped three major ethnic groups, Malay, Indian and Chinese for their allelic frequency of important isoforms. These include CYP2D6, CYP2C9, CYP2C8 and CYP2A6. Data generated so far collectively have contributed to our effort in mapping and constructing genomic database for Malaysian population.

Since early 2002, our research has been focusing on developing in vitro methods in studying the functional consequences of genetic polymorphism of CYP enzymes. Using site-directed mutagenesis, CYP mutants, carrying nucleotide changes as reported in known alleles in human populations, were generated and expressed in E. coli system, and the expressed recombinant proteins were characterized using enzyme assays to determine the functional consequences of mutations. We have established a series of HPLC (high performance liquid chromatography)-based and fluorescence-based assays to investigate CYP activities. Assays that have been developed include tolbutamide methylhydroxylase, paclitaxel 6a-hydroxylase, dextromethorphan O-demethylation, testosterone 6b-hydroxylation and coumarin 7-hydroxylase assays. These assays serve as activity markers allowing comparison of catalytic activities of mutant proteins generated. Another focus of our work is to use the developed assays as a screening tool to investigate drug-herb interactions. This was achieved by co-incubation of herbal extracts and active constituents with the probe substrates in the assays followed by characterization of the kinetic behaviors of the enzymes involved using various pharmacokinetic parameters such as Km, Vmax, IC50 and Ki. This work is currently carried out with collaboration from the Institute for Medical Research (IMR) and is supported by MOSTI’s eScienceFund under RM9. It is envisaged that this screening work will give us insights on the potential of the commonly used herbs to cause pharmacokinetic interactions with other drug substrates, and allow us to elucidate the mechanisms involved in the interactions.

Keywords: Pharmacogenomics, Pharmacogenetics, Drug Interaction, Drug Therapy, Cytochromes P450.

Citation: IeJSME 2008: 2 (Suppl 1): S6-S10

DOI: https://doi.org/10.56026/imu.2.Suppl1.S6

Authors: Stephen Ambu, Wan-Loy Chu, Joon-Wah Mak, Shew-Fung Wong, Li-Li Chan, Siew-Tung Wong.

ABSTRACT

Malaysia has good environmental laws to protect the outdoor environment and public health. However there are no laws governing indoor air quality (IAQ) and the knowledge among the public about its importance is also lacking. Environmental professionals think it is not a priority and this influences the policy decisions in the country. Therefore there is a need to create awareness by way of research, education and other promotional activities. What is much needed at this time is the establishment of standards for the conduct of risk assessment studies. To establish standards we need reliable data which can be used to develop appropriate guidelines for the purpose of mitigation and adaptation programmes. IAQ can have significant influence on health resulting in drop in productivity and economy of a country. It has been estimated that in the US, building related illnesses (BRI) symptoms have a relationship with decrease (3 to 5%) in work performance in an affected population resulting in an annual loss of US$60 billion in revenue. However, based on efficient management programmes they have also projected that the potential annual savings can be in the region of US$10 to 30 billion. This establishes that fact that good management programmes based on efficient guidelines is of economic value to a country and wellbeing of the population. The IMU has embarked on a research programme to collect the much-needed data for the framing of a good IAQ guideline for Malaysia.

Keywords: Indoor air quality, health.

Citation: IeJSME 2008: 2 (Suppl 1): S11-S18

DOI: https://doi.org/10.56026/imu.2.Suppl1.S11

Authors: Ramesh Chandra Jutti, Vishna Devi Nadarajah, Victor Lim.

ABSTRACT

Medical Education research is a relatively new field but one that is progressing rapidly worldwide. This article is an attempt to take stock of the current status of Medical Education research in International Medical University and to explore the various factors that have influenced its direction. It also shares some of the initiatives that have been instituted or intended to be instituted at our university.

Keywords: Medical education, research.

Citation: IeJSME 2008: 2 (Suppl 1): S19-S20

DOI: https://doi.org/10.56026/imu.2.Suppl1.S19

Authors: Wan-Loy Chu, Ammu Kutty Radhakrishnan.

ABSTRACT

Research on bioactive molecules is one of the thrust areas of research at the International Medical University (IMU). The bioactive molecules that have attracted the interest of IMU researchers include tocotrienol, astaxanthin, zingerone, apigenin, carrageenan and phycocyanin. There are also projects which focus on the screening of extracts from local plants such as Elephantopus mollis, Morinda citrifolia, Pereskia bleo, Euphorbia hirta, Zinger officinale, Mangifera indica and Nephelium lappaceum and algae such as Spirulina and Gracilaria. Characterisation of the toxin from Bacillus thuringiensis is another area of active research at IMU. The compounds and extracts from the various organisms are screened for anticancer, antioxidative, antiviral and immuno-modulating activity. There are also studies on the production of recombinant molecules, especially monoclonal antibodies for the detection of house dust mites, Salmonella typhi and Candida. The pool of faculty with diverse expertise and the active collaboration with public universities and institutions have enhanced the progress of bioactive research at IMU. With the current postgraduate and Bachelor of Medical Science (B. MSc.) programme and the introduction of new programmes in health sciences, there are good opportunities for training of students in the research on bioactive molecules. The future research direction should focus on the mechanisms of action of the bioactive molecules using new approaches such as ‘omic’ technologies and in silico modelling.

Keywords: Algae, anticancer, antioxidant, antiviral, bioactive compounds, recombinant molecules, tocotrienol.

Citation: IeJSME 2008: 2 (Suppl 1): S21-S24

DOI: https://doi.org/10.56026/imu.2.Suppl1.S21

Author: Sivalingam Nalliah

ABSTRACT

Clinical research refers to any field of research involving human subjects. Clinicians as researchers are well placed in contributing to research as they have access to human subjects and are able to apply research results for better patient outcome. The need for clinician-scientists as a dedicated breed is hence implied. Clinical research has low priority in the agenda of academic clinicians for various reasons. Strategies to overcome such a malady include training in research methodology and creating a permissive environment for the conduct of research. The IMU has introduced several measures to enhance clinical research and has a vibrant postgraduate program. The BMedSc programme has seen an increase in MBBS students taking this degree. Research is part of the curriculum before the Semester 7 examinations. Clinicians have been increasingly seen to be involved in research. The enhancement of clinical research through encouraging formal clinical research training and development of the MBBS-PhD programs could further enhance clinical research at the IMU. Attention to logistic constraints, improvement in collaboration with the CRC-MOH and other agencies and the close working relationship with scientists will propel clinical research to higher levels.

Keywords: Clinical research, clinical methodology training, clinician-scientist, collaboration with scientists.

Citation: IeJSME 2008: 2 (Suppl 1): S25-S34

DOI: https://doi.org/10.56026/imu.2.Suppl1.S25

Authors: Abu Bakar Suleiman, Joon-Wah Mak.

ABSTRACT

A better educated public has started to challenge the way decisions are made in medical research activities. Although Institutional and National Guidelines on Research are in place, there are fears that Institutional Review Boards (IRBs) and funding agencies are only fairly active in scientific and ethical reviews of research proposals but not on oversight of projects after their initiation. These issues are integral to good research governance and researchers and custodians of research ethics must ensure that public interest is not compromised.

Medical progress is based on research including human experimentation carried out according to guiding principles as enunciated in the Declaration of Helsinki (2000), but the quality of compliance with the Declaration is an important issue.

Better choice and appropriate training of members of IRBs to improve the quality of decision making and governance processes are urgently needed. Competency in evaluation of proposals requires not only the appropriate scientific knowledge but also access to relevant preclinical and other data. Unfortunately, the completeness and quality of such data may not be adequate.

Public interest demands that injury to trial subjects in clinical trials is minimized if not avoided completely. Unfortunately this is not always possible with trials where novel biological modes of action are tested. A more robust evaluation mechanism for project approval may minimize but not completely avoid injury to subjects; thus insurance cover to provide care and compensation to subjects must be compulsory.

The decision to approve or reject a project must be based on the balance of potential risks and benefits, taking into consideration justifiable distributive risks to target communities and populations. Economic considerations should never be the primary focus, especially when there are real concerns that the migration of early phase clinical trials including vaccine trials to developing countries is based on the perceived less stringent ethical requirements and oversight there.

Keywords: Declaration of Helsinki, ethics, Institutional Review Boards, research governance, research oversight.

Citation: IeJSME 2008: 2 (Suppl 1): S35-S38

DOI: https://doi.org/10.56026/imu.2.Suppl1.S35