Snake venom poisoning remains a medical problem and potent antivenoms are needed for effective treatment. However, production of potent antivenoms against the highly poisonous elapid venoms is difficult due to the relatively low molecular size of the toxins and thus the low immonogenicity. In our laboratory we successfully formulated a novel ‘low dose, low volume, multi-site' immunization protocol which has resulted in the production of highly potent polyvalent antivenom against all three major elapids (cobra, King cobra and krait) found in Thailand.

    The other important medical problem associated with snake venom poisoning is the local tissue necrosis caused by some venoms. The local effects can be so severe that they require skin graft or amputation and long hospitalization. The enzymes (e.g. metalloproteases, phospholipases) and toxins responsible for the tissue damage act extremely fast (within minutes). Thus, although antivenom administration can save life but it could not prevent or reduce the extent of tissue damage. In our laboratory we have studied various drugs used clinically in man that could inhibit these locally acting venom enzymes. Injection of these enzyme inhibitors within minutes into the sites of bite drastically reduce local tissue damage as studied in mice. Furthermore, inhibitors of hyaluronidase which hydrolyses connective tissue and helps ‘spreading' the toxin were shown to increase the survival time of the animals to the extent that some actually recovered completely. Experiments in pigs are underway and preliminary results show promise.

    Thailand has a highly diverse population of venomous snakes, especially the vipers in the genus Trimeresurus. About a dozen of these hematotoxic snakes are found in the country. These venoms are rich sources of biologically active compounds that affect the hematologic system. Some of these compounds may be useful in the elucidation of some physiological pathways. These highly specific and potent compounds may serve as leads for drug development. Currently we have carried out the fractionation, characterization and testing of proteins from the venoms of several Trimeresurus snakes. The biological activity that we are particularly interested in is the ability to affect the release of vascular endothelial growth factor (VEGF) and endostatin from platelets. VEGF and endostatin are proteins that stimulate and inhibit angiogenesis, respectively.

    With the collaboration of Prof. Somsak Ruchirawat at Laboratory of Medicinal Chemistry, we have synthesized and produced antigens and/or antibodies and used them to develop rapid diagnostic test kits based on the principle of immunochromatography (I.C.). The I.C. technique mastered in our laboratories has resulted in the development of Thailand 's first locally produced I.C. test kit for Ecstasy together with an I.C. test kit for methamphetamine. These tests are among the first ones to employ reagents totally synthesized/produced in this country. The knowledge and experience gained from this work are useful to the development of similar I.C. tests for other targets.

    In the past decades, many highly specific monoclonal antibodies against important antigens (hepatitis, malaria, Leptospirosis and pathogens of economic farm animals etc.) have been produced by Thai scientists. However these valuable reagents have rarely been used in diagnostic kits, primarily because of the difficulty in the development of I.C. tests. It would be very useful if I.C. tests could be developed to detect the clinically relevant antigens/antibodies using these readily available monoclonal antibodies. In the regard, we have currently collaborated with scientists and physicians from various institutions to develop rapid diagnostic tests based on I.C. for the detections of antigen/antibody of Vibrio cholerae , Fasciola gigantica and Pythium insidiosum . Moreover, tests based on the I.C. format using specific complimentary nucleotide sequences, instead of antigen/antibody, are now being studied and developed for the rapid detection of microorganisms.

    Orchid is an important agricultural product of Thailand both for local use and export. Due to the expanding orchid market, farmers have extensively used pesticides to increase productivity. The increasing use of pesticides, particularly as mixture of several components and at very high frequency without control measures and proper management will adversely affect human health and the environment. It is therefore important to study whether, and to what extent, Thai orchid farmers suffer from the exposure to pesticides. Moreover, immunotoxicity study of pesticide mixture has rarely been reported.

    The Laboratory of Immunology has carried out a study on the immunotoxicity of these pesticides on orchid farmers and also in experimental animals. Preliminary results obtained from the farmers have shown that these pesticides significantly altered various important components of the immune system. Experiments in laboratory animals should delineate the effects of these chemicals. It is believed that this study will provide direct and useful evidence of immunotoxicity of pesticide exposure to fully convince the farmers and the responsible authorities to enforce proper handling of these toxic chemicals. This will eventually lead to improved health of the farmers and improved quality of the environment.