臺灣博碩士論文加值系統

海洋生物毒中，河魨毒及麻痺性貝毒最為人們所熟知，為阻塞神經細胞上之鈉腔體神經性毒素，導致人類死亡和麻痺症狀。近年來，河魨毒及麻痺性貝毒在台灣所引發之食物中毒事件不斷，在2005-2008年之間，台灣共發生4件因食用不明螺貝類中毒案件，地點分別在小琉球、台南、高雄及澎湖地區，共有 9名中毒患者，其中1名患者腦死而成植物人。為對疑似症狀食物中毒之食物檢體或中毒患者檢體之毒素加以檢測和鑑定，本研究乃應用LC-MS和LC-MS/MS方法加以解析，另外物種不明者，乃應用基因技術加以鑑定物種。第一部分利用LC-MS方法，經毒性分析結果得知2005年中毒檢體織紋螺科的疣織紋螺和2007年球織紋螺體內，均含有河魨毒和麻痺性貝毒。另利用聚合?連鎖反應技術增幅粒線體DNA中16S rRNA基因，經基因序列分析證實未知扇貝肉之種類為江珧蛤科之牛角江珧蛤，再分析其有毒成分為麻痺性貝毒中之巨蛤毒素 (saxitoxin, STX) 所引發中毒。因此判定上述2件螺類中毒事件均是由河魨毒或麻痺性貝毒所引起。
基於水產食品安全性及中毒病患之診療，進一步了解河魨毒和麻痺性貝毒之代謝成為很重要之議題。接續以1/10口服半致死劑量之河魨毒和麻痺性貝毒，灌食Wistar系雄性大白鼠，收集不同時間點(2-60小時)之血液及尿液樣本，再以LC-FLD和LC-MS方法分析河魨毒和麻痺性貝毒的變化以了解毒素在大鼠中之代謝。分析結果發現麻痺性貝毒GTX1-4毒素型結構在生物體內相互轉換。另外研究結果發現血液及尿液之最高毒量分別在攝食後2小時及4小時出現。因此，當發生河魨毒和麻痺性貝毒中毒後尿液及血液在60小時內尚可被偵測。其次，於河魨毒和麻痺性貝毒中毒後接續餵食鹼性電解水及生理食鹽水可使毒素迅速代謝。上述成果可作為日後河魨毒和麻痺性貝毒醫療診斷參考。
食物中毒事件中致毒成分之鑑定，大多根據殘存食物來進行檢驗。由於食物中成分複雜，純化毒素需經過繁複步驟，先前研究室已經利用LC-MS方法針對中毒患者尿液及血液中河魨毒偵測，其偵測極限為1 ng TTX /ml。本研究第二部分則應用LC-MS/MS分析方法，其最低偵測極限為0.1 ng TTX/ml，比先前之LC-MS方法更為靈敏。LC-MS/MS 之檢量線範圍，尿液及血液分別介在0.1-900 ng/ml及0.1-50 ng/ml之間。自疣織紋螺和球織紋螺2件中毒案件中取得6名中毒患者之尿液及血液，經 C18 Sep-Pak cartridge column及3,000道爾頓分子量高速離心過濾膜純化河魨毒，而後以LC-MS/MS進行河魨毒的定性及定量分析。結果顯示3名中毒患者的尿液中均可檢出含有河魨毒，3件血液樣品中僅1件檢出含有河魨毒，且尿液中河魨毒的量高於血液。
台灣、中國、越南、泰國、柬埔塞、馬來西亞和菲律賓，河魨毒及麻痺性貝毒事件也頻繁的發生在東南亞其他國家的沿岸區域。基於進口貝類食品安全性之考量，則以LC-MS/MS作為螺貝類之分析方法，首次報告針對越南及菲律賓之螺類分析其毒性及毒成分。2005年從菲律賓宿霧市收集2種螺類共計20件樣品，包括鳳凰螺科之百肋鳳凰螺及法螺科之大法螺，分析結果證實其中腸腺含有河魨毒素，其他部位未檢出。2007年在越南芽庄市的沿岸，採集5種螺類共計34件樣品，經LC-MS/MS分析榧螺科之平瀨榧螺、蠟燭榧螺、寶島榧螺主要含有STX、膝溝藻毒素﹙gonyautoxin 2, 3 ;GTX 2, 3﹚ 和少量的河魨毒﹙tetrodotoxin, TTX﹚。玉螺科之腰帶玉螺及白玉螺含有STX、GTX 1, 4。
目前數種分析方法已經被使用於偵測河魨毒，包括老鼠生物毒性法、單株抗體、高效液相層析法及氣相層析法。但由於前述方法之分析前處理步驟較繁雜、耗費時間、需要較昂貴的設備和熟練的經驗。因此在毒理學領域有需要發展快速、即時及靈敏性之偵測技術。第三部分研究試圖利用表面增強拉曼散射技術來分析河魨毒之分子結構特性和偵測中毒患者尿液中之微量河魨毒。藉由控制奈米顆粒的大小、形狀與奈米顆粒間距之奈米銀顆粒陣列來增強其靈敏度。另利用Gauissan06模擬軟體計算出河魨毒的拉曼光譜與振動模式。拉曼光譜在1000 至1735 cm?1範圍，分析河魨毒濃度和表面增強拉曼散射強度面積相關性。在拉曼定量的實驗中，檢量線範圍介於0.9-50 ng TTX/ml之間，相關係數可達0.98，量測出河魨毒的濃度最低極限為0.9 ng/ml。接續，針對中毒患者尿液進行稀釋偵測微量之河魨毒，相關係數為0.97，由於真實尿液溶液干擾物質較多，經純化後以定量方式來偵測尿液中之微量河魨毒。結果顯示使用奈米銀顆粒陣列能偵測到低濃度的河魨毒分子，更有助於日後醫療診斷之發展。

Among marine biotoxins, tetrodotoxin (TTX) and paralytic shellfish poisons (PSP) are well known as sodium channel blocking neurotoxins. Recently, TTX and PSP associated with food poisoning incidents have caused human fatalities and many illnesses in Taiwan. Four food poisoning incidents due to ingesting unknown gastropod and scallop occurred in Taiwan during 2005-2008. There were total of 9 victims inclusive of 1 brain died in Liuchiu Island, Tainan, Kaohsiung and Penghu counties. Based on the data of toxin analysis, gastropods Nassariidae Nassarius papillosus and Niotha clathrata contained TTX and/or PSP. In addition, application of polymerase chain reaction (PCR) technique and mitochondrial DNA (mtDNA) 16S rRNA gene analysis are used to identify unknown scallop species Atrina pectinata in food poisoning incidents. Furthermore, the causative agent of unknown scallop food poisoning was identified as saxitoxin (STX). It was concluded that the causative agent of the above food poisoning incidents were TTX and/or PSP.
The analysis of both TTX and PSP toxins is an important issue for seafood safety and diagnosis for patients. The purpose of this study was to understand the pharmacokinetic of TTX and PSP in the body. This research compared the methods of determining trace TTX and PSP component in the urine and blood of rat. Wistar rats were orally administered with 10% of LD50 dose of TTX and PSP. The LC-MS methods for detecting TTX and PSP in the urine and blood of rat were compared and the time course (2 to 60 hr) of serum and urine specimens in rats was investigated. The PSP conformation could be converted in the body. TTX can be detected from blood and urine within 60 hr when intoxicated poisoning occurs. When the rats took saline solution and AE water, it was found that GTX1-4 could be early secreted from the blood and urine. The AE water and saline solution also could rapidly metabolize PSP toxins. This has provided the development of an appropriate diagnostic test and investigation of human metabolism.
Usually, the causative agents of TTX and/or PSP food poisonings were identified from the toxin of food. However, the suspected food was sometimes discarded and no leftover was retained. Hence, the TTX diagnosis from patients is very important.
The detection limit of TTX by using LC-MS method in human urine and blood samples was 1 ng/ml. The second part of this research, we report the toxin of patient’s blood serum and urine in an outbreak of two cases of TTX poisoning were trace amount and analyzed by a new developed method LC-MS/MS. The detection limit of LC-MS/MS method was 0.1 ng/ml for TTX. The standard curves were linear in the range of 0.1–900 ng/ml for urine and 0.1–50 ng/ml for blood serum. The urine and blood samples from six patients who were intoxicated in both N. papillosus and N. clathrata food poisoning incidents, were cleansed using a C18 Sep-Pak cartridge column and 3,000 MW cut-off Ultrafree microcentrifuge filters, and the eluate was filtered and determined by LC-MS/MS. TTX was quantified in three samples of urine and three samples of serum from six patients who ingested gastropods and had clinical effects consistent with TTX poisoning. TTX was detected in all serum and urine samples of patients tested. It indicated that LC-MS/MS was a highly sensitive and reliable method for TTX determination compared to LC-MS method reported previously. Furthermore, the causative agent of gastropod food poisoning was identified as TTX. Therefore, the LC-MS/MS method is usable as a diagnostic technique for TTX intoxification in human.
Outbreak of PSP and TTX poisoning, have been reported from other place, such as China, Vietnam, Thailand, Cambodia, Malaysia and Philippines. Because of food safety concerns, we undertook examination of the toxicity potency of gastropods consumed in Vietnam and Philippines. Twenty specimens of 2 species gastropods (Strombus labiatus and Charonia tritonis ) were collected from Cebu City in 2005, Philippines. Both S. labiatus and C. tritonis specimens were found to be toxic, and TTX was found in the digestive gland only. In 2007, 34 specimens 5 species of gastropod species, Natica vitellus, N. tumidus, Oliva hirasei, O. lignaria and O. annulata, were collected from the coastal seawaters in the Nha-Trang City, Vietnam. Results of HPLC-FLD analysis indicated that the toxins of Olive shell (Oliva hirasei, O. lignaria and O. annulata) was mainly composed of STX, gonyautoxin (GTX) 2,3, along with minor TTX, and the toxins of N. vitellus and N. tumidus were mainly composed of STX and GTX1,4.
Several methods have been employed to detect TTX, including mouse bioassays, monoclonal antibodies, high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). However, all these methods are time-consuming and expensive equipments and sophisticated techniques are required. A fast and real-time detection technique with comparatively high sensitivity for detecting TTX would possibly shorten the time consuming in the analysis process and speed up the research in toxicology. The third part of this research, attempts were made to develop surface enhanced Raman scattering (SERS) method for analyzing TTX molecular structure characteristics and detecting the trace TTX in the urine of poisoned victims. Thereupon, the application of nanoparticle arrays were fabricated by using nanosphere lithography (NSL) and metallic lift-off process to control the size, shape, and particle spacing in the large arrays. The Raman spectrum of TTX was also calculated by using Gaussian06 software. Raman spectra between 1000 and 1735 cm?1 were analyzed to obtain the relationship between the SERS band area and TTX concentration. In the SERS quantitative experiment, we have obtained the correlation coefficient between SERS intensity and TTX concentration which ranged form 0.9-50 ng TTX/ml is 0.98. The concentration of TTX as small as 0.9 ng TTX/ml can be detectable by Raman spectra. In the detection of TTX for urine samples of patients, quantitative could be conducted by using SERS method. Judging from above data, using nanoparticle array could detect the low concentration of TTX and it may develop as the diagnostic method with advanced efficiency.

CONTENTS

PUBLICATION OF DISSERTATION……………………………V
ABBREVIATIONS…………………………………………………VIII
ABSTRACT (in Chinese)…………………………………………IX
ABSTRACT (in English)…………………………………………XIII

I. LITERATURE REVIEW
1. Properties of TTX……………………………………………………1
1.1 Molecular structure and chemical properties……………….1
1.2 Clinical characteristics and toxic dose of TTX……………2
2. Properties of PSP……………………………………………………2
2.1 Molecular structure and chemical properties………………2
2.2 Clinical characteristics and toxic dose of TTX…………3
3. Poisoning mechanism of TTX and STX……………………………4
3.1 Molecular structure of Na+ channels…………………………4
3.2 Mechanism of action on Na+ channels…………………………5
4. Origin sources of TTX and PSP in toxic gastropod…………7
4.1 Microbe.…………………………………………………………7
4.2 Food chain………………………………………………………7
5. Gastropod poisoning incidents……………………........ 8
5.1 Gastropod poisoning incident in Taiwan………………8
5.2 Gastropod poisoning incident in other place………10
6. Electrolyzed water…………………………………………………11
6.1 History…………………………………………………………11
6.2 Electrolyzed water producing machines……………………….12
6.3 Uses of ERW in clinical research……………………………12
7. Raman spectroscopy……………………………………………13
7.1 The principle of Raman spectroscopy…………………………13
7.2 The principle of surface enhanced Raman scattering……14
7.3 The application of Rama and SERS in biomedicine…………15

II. IDENTIFICATION OF TOXICITIES AND TOXIN COMPONENTS IN FOOD POISONING INCIDENTS BY LC-MS METHOD
1. OCCURRENCE OF TTX AND PSP IN A GASTROPOD IMPLICATED IN FOOD POISONING IN SOUTHERN TAIWAN
Abstract……………………………………………………………16
Introduction………………………………………………………17
Materials and methods………………………………………18
Results…………...………………………………………………21
Discussion…………………………………………………………23
Tables and figures………………………………………………25
2. IDENTIFICATION OF SPECIES AND PARALYTIC SHELLFISH POISONS IN AN UNKNOWN SCALLOP MEAT IMPLICATED IN FOOD POISONING IN TAIWAN
Abstract………………………………………………………30
Introduction……………………………………………………31
Materials and methods………………………………………33
Results…………...……………………………………………36
Discussion………………………………………………………38
Tables and figures…………………………………………40
3. METABOLISM OF GTXS AND TTX AFTER ORAL ADMINISTRATION IN RAT
Abstract………………………………………………………46
Introduction……………………………………………………48
Materials and methods…………………………………………50
Results…………...…………………………………………………53
Discussion…………………………………………………57
Tables and figures…………………………………………………61

III. DETECTION OF TOXICITIES AND TOXIN COMPONENTS OF SEVERAL GASTROPODS AND POISONED SAMPLES FROM BLOOD AND URINE BY LC-MS/MS METHOD
1. LC-MS/MS DETERMINATION FOR TRACE LEVEL OF TTX IN URINE AND BLOOD OF GASTROPOD POISONING PATIENTS
Abstract………………………………………………………73
Introduction………………………………………………………74
Materials and methods……………………………………………76
Results……………………………………………………………80
Discussion………………………………………………………83
Tables and figures………………………………………………….85
2. DETERMINATION OF TTX AND PSP IN SEVERAL GASTROPOD SPECIES FROM VIETNAM AND PHILIPPINES
Abstract………………………………………………………96
Introduction……………………………………………………98
Materials and methods…………………………………………100
Results…………………………………………………………102
Discussion……………………………………………105
Tables and figures…………………………………………………108

Ⅳ. SURFACE ENHANCED RAMAN SCATTERING SPECTROSCOPY TECHNIQUE APPLIED FOR TTX MEASUREMENT
Abstract………………………………………………………119
Introduction……………………………………………………120
Materials and methods…………………………………………122
Results and Discussion………………………………… 124
Tables and figures………………………………………………….127

Ⅴ. OVERALL CONCLUSION……………………………………134
Ⅵ. REFERENCES………………………………………………….135
ACKNOWLEDGEMENTS (in Chinese)………………………158

Akaki, K., Hatano, K. 2006. Determination of tetrodotoxin in puffer-fish tissues, and in serum and urine of intoxicated humans by liquid chromatography with tandem mass spectrometry. Shokuhin Eiseigaku Zasshi 47: 46-50.
Al-Haq, M. I., Seo, Y., Oshita, S., Kawagoe, Y. 2002. Disinfection effects of electrolyzed oxidizing water on suppressing fruit rot of pear caused by Botryosphaeria berengeriana. Food Res. Intl. 35: 657-664.
Al-Haq, M. I., Sugiyama, J., Isobe, S. 2005. Applications of electrolyzed water in agriculture and food industries. Food Sci. Technol. Res. 11: 135-150.
Anderson, D. M., Sullivan, J. J., Reguera, B. 1989. Paralytic shellfish poisonings in northwest Spain: The toxicity of the dinoflagellate Gymnodinium catenatum. Toxicon 27: 665-674.
Anderson, D. M., Kulis, D. M., Qi, Y. Z., Zheng, L., Lu, S., Lin, Y. T. 1996. Paralytic shellfish poisoning in southern China. Toxicon 34: 579-590.
Andrinolo, D., Michea, L. F., Lagos, N. 1999. Toxic effects, pharmacokinetic and clearance of saxitoxin, a component of paralytic shellfish poison (PSP), in cat. Toxicon 37: 447-464.
Andrinolo, D., Gomes, P., Fraga, S., Soaresda-Silva, P., Lagos, N. 2002. Transport of the organic cations gonyautoxin 2/3 epimers, a paralytic shellfish poison toxin, through the human and rat intestinal epitheliums. Toxicon 40: 1389-1397.
AOAC (Association of Official Analytical Chemists). 1995. Paralytic shellfish poisons biological method final action. In Official Methods of the Association of Official Analytical Chemists, 15th Ed., Horowitz, W. pp. 21-22. AOAC, Washington, D.C.
Aranishi, F., Okimoto, T. A. 2003. Simple and reliable method for DNA extraction from bivalve mantle. Journal of Applied Genetics 47: 251-254.
Arbuckle, J. B., Docherty, R. J. 1995. Expression of tetrodotoxin-resistant sodium channels in capsaicin-sensitive dorsal root ganglion neurons of adult rats. Neuroscience Lett. 185: 70-73.
Asakawa, M., Nishimura, F., Miyazawa, K., Noguchi, T. 1997. Occurrence of paralytic shellfish poison in the starfish Asterias amurensis in Kure Bay, Hiroshima Prefecture, Japan. Toxicon 35: 1081-1087.
Asakawa, M., Takayama, H., Beppu, R., Miyazzwa, K. 2005. Occurrence of paralytic shellfish poison producing dinoflagellate Alexandrium tamarense in Hiroshima Bay, Hiroshima Prefecture, Japan, during 1993-2004 and its PSP profiles. Shokuhin Eiseigaku Zasshi 46: 246-250.
Baia, L., Baia, B., Popp, J., Astilean, S. 2006. Gold films deposited over regular arrays of polystyrene nanospheres as highly effective SERS substrates from visible to NIR. J. Phys. Chem. B 110: 23982-23986.
Bakker-Schut, T. C., Puppels, G. J., Kraan, Y. M., Greve, J., van-der Maas, L. L., Figdor, C. G. 1997. Intracellular carotenoid levels measured by Raman microspectroscopy: Comparison of lymphocytes from lung cancer patients and healthy individuals. Int. J. Cancer 74: 20-25.
Bougrier, S., Lassus, P., Bardouil, M., Masselin, P., Truquet, P. 2003. Paralytic shellfish poison accumulation yields and feeding time activity in the Pacific oyster (Crassostrea gigas) and king scallop (Pecten maximus). Aquatic Living Resources 16: 347-352.
Breuzard, G., Angiboust, J. F., Jeannesson, P., Manfait, M., Millot, J. M. 2004. Surface-enhanced Raman scattering reveals adsorption of mitoxantrone on plasma membrane of living cells. Biochem. Biophys. Res. Commun. 320: 615-621.
Carmichael, W. W., Evans, W. R., Yin, Q. Q., Bell, P., Moczydlowski, E. 1997. Evidence for paralytic shellfish poisons in the freshwater cyanobacteria Lyngbya wollei (Farlow ex Gamont) comb. nov. Appl. Environ. Microbiol. 63: 3104-3110.
Catterall, W. A. 1992. Cellular and molecular biology of voltage-gated sodium channel. Physiology Rev. 72: 15-48.
Cestele, S., Catterall, W. A. 2000. Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie. 82: 883-892.
Chao, Y. C., Jin, R., Mirkin, C. A. 2002. Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science 297: 1536-1540.
Cheng, C. A., Hwang, D. F., Tsai, Y. H., Chen, H. C., Jeng, S. S. 1995. Microflora and tetrodotoxin-producing bacteria in a gastropod Niotha clathrata. Food Chem. Toxic. 33: 929-934.
Cong, N. H., Tuan, Le. T. Q. 2006. Electrodiagnosis in puffer fish poisoning - A case report. Electromyography and Clinical Neurophysiology 46: 291- 294.
Culha, M., Stokes, D., Allain, L. R., Vo-Dinh, T. 2003. Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics. Anal. Chem. 75: 6196-6201.
Daigo, K., Noguchi, T., Miwa, A., Kawai, N., Hashimoto, K. 1988. Resistance of nerves from certain toxic crabs to paralytic shellfish poison and tetrodotoxin. Toxicon 26: 485-490.
Dell’Aversano, C., Hess, P., Quilliam, M. A. 2005. Hydrophilic interaction liquid chromatography-mass spectrometry for the analysis of paralytic shellfish poisoning toxins. Journal of chromatography A 1081: 190-201.
Eastaugh, J., Shepherd, S. 1989. Infections by Octopus maculosus Hoyle. Toxicol. Appl. Pharmacol. 16: 681-690.
Emory, S. R., Jensen, R. A., Wenda, T., Han, M., Nie, S. 2006. Re-examining the origins of spectral blinking in single-molecule and single-nanoparticle SERS. Faraday Discuss. 132: 249-259.
Fang, C., Agarwal, A., Buddharajua, K. D. 2008. DNA detection using nanostructured SERS substrates with Rhodamine B as Raman label. Biosensors and Bioelectronics 24: 216-221.
Faulds, K., Stewart, L., Smith, W. E., Graham, D. 2005. Quantitative detection of dye labelled DNA using surface enhanced resonance Raman scattering from silver nanoparticles. Talanta 67: 667-671.
Fernandez, A., Garc?a, T., Asensio, L., Rodr?guez, M. A., Gonzalez, I., Cespedes, A., Hernandez, P. E., Mart?n, R. 2000. Identification of the clam species Ruditapes decussatus (grooved carpet shell), Venerupis pullastra (pullet carpet shell), and Ruditapes philippinarum (Japanese carpet shell) by PCR-RFLP. Journal of Agricultural and Food Chemistry 48: 3336-3341.
Garcia, C., Carmen, D., Bravo, M., Lagos, M., Lagos, N. 2004. Paralytic shellfish poisoning: Post-mortem analysis of tissue and body fluid samples from human victims in the Patagonia fjords. Toxicon 43: 149-158.
Garland, E. D., Zimmer, C. A. 2002. Techniques for the identification of bivalve larvae. Marine Ecology Progress Series 225: 299-310.
Goto, T., Hishi, Y., Takahashi, S., Hirata, Y. 1965. Tetrodotoxin. Tetrahedron 21: 2059-2088.
Grand, J., Kostcheev, S., Bijeon, J. L., Lamy-Dela, C. M., Adam, P. M., Rumyantseva, A., Lerondel, G., Royer, P. 2003. Optimization of SERS-active substrates for near-field Raman spectroscopy. Synthetic Metals 139: 621-624.
Hall, S., Strichartz, G., Moczydlowski, E., Ravindran, A., Reichardt, P. B. 1990. The saxitoxins; sources, chemistry, and pharmacology. In: Hall, A., Strichartz, G. (Eds.). Marine Toxins: Origin, Structure and Molecular Pharmacology, American Chemical Society Symposium, series 418, pp. 29-65. American Chemical Society, Washington, DC.
Hallegraeff, G. M. 1993. A review of harmful algal blooms and their apparent global increase. Phycologia 32: 79-99.
Hanaoka, K., Sun, D., Lawrence, R., Kamitani, Y., Fernandes, G. 2004. The mechanism of the enhanced antioxidant effects against superoxide anion radicals of reduced water produced by electrolysis. Biophys. Chem. 107: 71-82.
Hanifin, C. T., Yamashita, M., Yamumoto, T., Brodie, E. D., Brodie, Jr. E. D. 1999. Toxicity of dangerous prey: Variation of tetrodotoxin levels within and among populations of the newt Taricha granulose. J. Chem. Ecol. 25: 2161-2175.
Hartshorne, R. P., Messner, D. J., Coppersmith, J. C., Catterall, W. A. 1982. The saxitoxin receptor of the sodium channel from rat brain: Evidence for two nonidentical beta subunits. J. Biol. Chem. 257: 13888-13891.
Hashimoto, Y. 1979. Marine Toxins and Other Bioactive Marine Metabolites. Japan Scientific Societies, Tokyo, Japan. p. 91.
Hashimoto, T., Matsuoka, S., Yoshimatsu, S. A., Miki, K., Nishibori, N., Nushio, S., Noguchi, T. 2002. First paralytic shellfish poison (PSP) infestation of bivalves due to toxic dinoflagellate Alexandrium tamiyavanichii, in the southeast coasts of the Seto Inland Sea, Japan. J. Food Hyg. Soc. Jpn. 43: 1-5.
Hayashida, M., Hayakawa, H., Wada, K., Yamada, T., Nihira, M., Ohno, Y. 2003. A column-switching LC/MS/ESI method for detecting tetrodotoxin and Aconitum alkaloids in serum. Legal Medicine 5: S101-S104.
Heipel, D. A., Bishop, J. D. D., Brand, A. R., Thorpe, J. P. 1998. Population genetic differentiation of the great scallop Pecten maximus in western Britain investigated by randomly amplified polymorphic DNA. Marine Ecology Progress Series 162: 163-171.
Hille, B., Ritchie, J. M., Strichartz, G. R. 1975. The effect of surface charge on the nerve membrane on the action of tetrodotoxin and saxitoxin in frog myelinated nerve. J. Physiol. 250: 34-35.
Hines, H. B., Naseem, S. M., Wannemacher, R. W. Jr. 1993. 3H-Saxitoxinol metabolism and elimination in the rat. Toxicon 31: 905-908.
Hirano, H., Ueda, O. 1997. Characteristics of electrolyzed neutral water possibility of the practical use for food hygiene. Shokuhin Kogyo Japan 40: 23-35.
Ho, P. H., Tsai, Y. H., Hwang, C. C., Hwang, P. A., Hwang, J. H., Hwang, D. F. 2006. Paralytic toxins in four species of coral reef crabs from Kenting National Park in southern Taiwan. Food Control 17: 439-445.
Horie, M., Kobayashi, S., Shimizu, N., Nakazawa, H. 2002. Determination of tetrodotoxin in puffer-fish by liquid chromatography-electrospray ionization mass spectrometry. Analyst 127: 755-759.
Hosoi, M., Hosoi-Tanabe, S., Sawada, H., Ueno, M., Toyohara, H., Hayashi, I. 2004. Sequence and polymerase chain reaction–restriction fragment length polymorphism analysis of the large subunit rRNA gene of bivalve: Simple and widely applicable technique for multiple species identification of bivalve larva. Fisheries Science 70: 629 - 637.
How, C. K., Chern, C. H., Huang, Y. C., Wang, L. M., Lee, C. H. 2003. Tetrodotoxin poisoning. The American Journal of Emergency Medicine 21: 51-54.
Huang, K., Yan, C., Lee, K., Chien, C. 2003. Reduced hemodyalisis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced water. Kidney International 64: 704-714.
Huang, Y. R., Hung,Y. C., Hsu, S. Y., Huang, Y. W., Hwang, D. F. 2008. Application of electrolyzed water in the food industry. Food Control 19: 329-345.
Hulteen, J. C., Treichel, D. A., Smith, M. T., Duval, M. L., Jensen, T. R., Van-Duyne, R. P. 1999. Nanosphere lithography: Size-tunable silver nanoparticle and surface cluster arrays. J. Phys. Chem. B 103: 3854-3863.
Huu, C. N., Tu, Q. 2006. Electrodiagnosis in puffer fish poisoning- a case report. Electromyography and Clinical Neurophysiology 46: 291-294.
Hwang, D. F., Jeng, S. S. 1991. Bioassay of tetrodotoxin by using ICR strain male mouse. J. Chin. Biochem. Soc. 20: 80-86.
Hwang, D. F., Tsai, Y. H. 1999. Toxins in toxic Taiwanese crabs. Food Rev. Int. 15: 145-162.
Hwang, D. F., Lu, Y. H. 2000. Influence of environmental and nutritional factors on growth, toxicity, and toxin profile of dinoflagellate Alexandrium minutum. Toxicon 38: 1491-1503.
Hwang, D. F., Noguchi, T. 2007. Tetrodotoxin poisoning. Advances in Food and Nutrition Research 52: 141-236.
Hwang, D. F., Noguchi, T., Nagashima, Y., Lioa, I C., Hashimoto, K. 1987. Occurrence of paralytic shellfish poison in the purple clam Soletellina diphos (bivalve). Nippon Suisan Gakkaishi 53: 623-626.
Hwang, D. F., Arakawa, O., Saito, T., Noguchi, T., Simidu, U., Tsukamoto, K., Shida, Y., Hashimoto, K. 1989. Tetrodotoxin-producing bacteria from the blue-ringed octopus. Mar. Biol. 100: 327-332.
Hwang, D. F., Chueh, C. H., Jeng, S. S. 1990. Tetrodotoxin sectetion from the lined moon shell Natica lineata in response to external to stimulation. Toxicon 28: 1133-1136.
Hwang, D. F., Chueh, C. H., Jeng, S. S. 1991a. Occurrence of tetrodotoxin in the gastropods Rapana rapiformis and R. venosa venosa. Mar. Biol. 111: 65-69.
Hwang, D. F., Tai, K. P., Chueh, C. H., Jeng, S. S. 1991b. Tetrodotoxin and derivatives in several species of the gastropod Naticidae. Toxicon 29: 1019-1024.
Hwang, D. F., Lin, L. C., Jeng, S. S. 1992. Occurrence of a new toxin and tetrodotoxin in two species of the gastropod mollusk Nassariidae. Toxicon 30: 41-46.
Hwang, D. F., Cheng, C. A., Jeng, S. S. 1994. Gonyautoxin-3 as a minor toxin gastropod Niotha clathrata in Taiwan. Toxicon 32: 1573-1579.
Hwang, D. F., Cheng, C. A., Tsai, H. T., Shih, Y. C., Ko, H. C., Yang, R. Z., Jeng, S. S. 1995. Identification of tetrodotoxin and paralytic shellfish toxins in marine gastropods implicated in food poisoning. Fisheries Science 61: 675-679.
Hwang, D. F., Tsai, Y. H., Liao, H. J., Matsuoka, K., Noguchi, T., Jeng, S. S. 1999. Toxins of Alexandrium minutum Halim from the coastal waters and aquaculture ponds in southern Taiwan. Fisheries Science 64: 171-172.
Hwang, D. F., Shiu, Y. C., Hwang, P. A., Lu, Y. H. 2002. Tetrodotoxin in gastropods (snails) implicated in food poisoning in northern Taiwan. J. Food Protect. 65: 1341-1344.
Hwang, P. A., Tsai, Y. H., Lu, Y. H., Hwang, D. F. 2003. Paralytic toxins in three new gastropod (Olividae) species implicated in food poisoning in southern Taiwan. Toxicon 41, 529-533.
Hwang, P. A., Noguchi, T., Hwang, D. F. 2004. Neurotoxin tetrodotoxin as attractant for toxic snails. Fisheries Science 70: 1106-1112.
Hwang, P. A., Tsai, Y. H., Deng, J. F., Cheng, C. A., Ho, P. H., Hwang, D. F. 2005. Identification of tetrodotoxin in a marine gastropod (Nassarius glans) responsible for human morbidity and mortality in Taiwan. Journal of Food Protection 68: 153-158.
Hwang, P. A., Tsai, Y. H., Lin, S. I., Hwang, D. F. 2007. The gastropods possessing TTX and/or PSP. Food Reviews International 23: 321-340.
Iseki, M., Takaoka, T., Kondo, Y., Ikematsu, M., Rakuma, T., Takizawa, K. 2002. The sterilization system of water with electrolysis technology. 26th Seminar Soc. Study Water. pp. 5-10.
Ito, K., Asakawa, M., Beppu, R., Takayama, H., Miyazawa, K. 2004. PSP-toxicification of the carnivorous gastropod Rapana venosa inhabiting the estuary of Nikoh River, Hiroshima Bay, Hiroshima Prefecture, Japan. Mar. Pollut. Bull. 48: 1116-1121.
Jen, H. C., Lin, S. J., Lin, S. Y., Hwang, Y. W., Liao, I C., Arakawa, O., Hwang, D. F. 2007. Occurrence of tetrodotoxin and paralytic shellfish poisons in a gastropod implicated in food poisoning in southern Taiwan. Food Additives Contaminants 24: 902-909.
Jen, H. C., Lin, S. J., Tsai, Y. H., Chen, C. H., Lin, Z. C., Hwang, D. F. 2008. Tetrodotoxin poisoning evidenced by solid-phase extraction combining with liquid chromatography-tandem mass spectrometry. J. Chromatography B 871: 95-100.
Jensen, T. R., Duval, M. L., Kelly, K. L., Lazarides, A. A., Schatz, G. C., Van-Duyne, R. P. 1999. Nanosphere lithography: Effect of the external dielectric medium on the surface plasmon resonance spectrum of a periodic array of silver nanoparticles. J. Phys. Chem. B 103: 9846-9853.
Jiang, L., Wu. W. L., Lin,Y. S. 1997. Efficient methods for isolating mitochondrial DNAs from molluscan specimens of different conditions. Zoological Studies 36: 74-78.
Jiang, T., Chen, J., Zou, Y., Liu, J., Yang, W. 2003. Paralytic shellfish toxins in shellfish from the coast of high frequent harmful algae blooms occurrence areas in East China Sea and South China Sea. Ying Yong Sheng Tai Xue Bao 14: 1156-1160.
Jiang, T. J., Niu, T., Xu, Y. X. 2006. Transfer and metabolism of paralytic shellfish poisoning from scallop (Chlamys nobilis) to spiny lobster (Panulirus stimpsoni). Toxicon 48: 988-994.
Kan, S. K., Chan, M. K., David, P. 1987. Nine fatal cases of puffer fish poisoning in Sabah, Malaysia. Med. J. Malaysia 42: 199-200.
Kanchanapongkul, J. 2008. Tetrodotoxin poisoning following ingestion of the toxic eggs of the horseshoe crab Carcinoscorpius rotundicauda, a case series from 1994 through 2006. Southeast Asian J. Trop. Med. Public Health 39: 303-306.
Kao, P. N., James-Kracke, M. R., Kao, C. Y. 1983. The active guanidinium group of saxitoxin and neosaxitoxin identified by the effects of pH on their activities on squid axon. Pflugers Arch. Eur. J. Physiol. 398: 199-203.
Kawatsu, K., Shibata, T., Hamano, Y. 1999. Application of immunoaffinity chromatography for detection of tetrodotoxin from urine samples of poisoned patients. Toxicon 37: 325-333.
Keller, M. D., Guillar, R. R. L. 1985. Factors significant to marine dinoflagellate culture. In Toxic dinoflagellates. Proceedings of the Third International Conference on Toxic Dinoflagellates, D. M. Anderson et al. (Eds.), pp. 113-116. Elsevier, New York.
Kerker, M., Wang, D. S., Chew H. 1980. An optical model for fluorescence of mammalian sperm in flow cytometry. Cytometry 1: 161-167.
Kim, M. J., Kim, H. K. 2006. Anti-diabetic effects of electrolyzed reduced water in streptozotocin-induced and genetic diabetic mice. Life Sciences 79: 2288-2292.
Kim, J. D., Ahn, D. G., Oh, J. W., Park, W., Jung, H. 2008. Ribosome display and Dip-Pen nanolithography for the fabrication of protein nanoarrays. Adv. Mater. 20: 3349-3353.
Kobayashi, T., Shiomi, K., Nagashima, T., Fuji, T., Okuzumi, M. 1992. Effect of culture conditions on bacterial production of tetrodotoxins. Nippon Suisan Gakkaishi 58: 1365-1372.
Kungsuwan, A., Nagashima, Y., Noguchi, T., Shida, Y., Suvapeepan, S., Suwansakornkul, P., Hashimoto, K. 1987. Tetrodotoxin in the horseshoe crab Carcinoscorpius rotundicauda inhabiting Thailand. Nippon Suisan Gakkaishi 53: 261-266.
Kungsuwan, A., Arakawa, O., Promdet, M., Onoue, Y. 1997. Occurrence of paralytic shellfish poisons in Thai freshwater puffers. Toxicon 35: 1341-1346.
Lagos, N., Onodera, H., Zagatto, P., Andrinolo, D., Azevedo, S., Oshima, Y. 1999. The first evidence of paralytic shellfish toxins in the freshwater cyanobacterium Cylindrospermopsis raciborskii, isolated from Brazil. Toxicon 37: 1359-1373.
Lapegue, S., Boutet, I., Leitao, A., Heurtebise, S., Garcia, P., Thiriot-Quievreux, C., Boudry, P. 2002. Trans-atlantic distribution of a mangrove oyster species revealed by 16S mtDNA and karyological analyses. The Biological Bulletin 202: 232-242.
Larsson, K., Hellgren, L. 1974. A study of the combined Raman and fluorescence scattering from human blood plasma. Experientia 30: 481-483.
Lehane, L. 2001. Paralytic shellfish poisoning: A potential public health problem. The Medical Journal of Australia 175: 29-31.
Li, A., Zhou, R., Li, M. J. 2008. A primary study on anatomical distribution of tetrodotoxin and its analogs in gastropod Nassarius succinctus. Wei Sheng Yan Jiu 37: 448-451.
Liao, H. J., Hwang, D. F. 2000. Survey of paralytic toxins in shellfish in southern Taiwan between 1995 and 1997. J. Nat. Toxins 9: 63-71.
Lim, P. T., Sato, S., Thuoc, C. V., Tu, P. T., Huyen, N. T. M., Takata, Y., Yoshida, M., Kobiyama, A., Koike, K., Ogata, T. 2007. Toxic Alexandrium minutum (Dinophyceae) from Vietnam with new gonyautoxin analogue. Harmful Algae 6: 321-331.
Lin, S. J., Hwang, D. F. 2001. Possible source of tetrodotoxin in the starfish Astropecten scoparius. Toxicon 39: 573-579.
Lin, W. F., Hwang, D. F. 2008. Application of species specific PCR for the identification of dried bonito product (katsuobushi). Food Chemistry 106: 390-396.
Liu, F. M., Fu, Y. M., Daniel, Y. C. 2004. Occurrence of tetrodotoxin poisoning in Nassarius (Alectrion) papillosus and Nassarius (Niotha) gruneri. Yaowu Shipin Fenxi 12: 189-192.
Llewellyn, L. E., Endean, R. 1988. Toxic coral reef crabs from Australian waters. Toxicon 26: 1085-1088.
Llewellyn, L. E., Doyle. J., Negri, A. P. 1998. A high-throughput, microtiter plate assay for paralytic shellfish poisons using the saxitoxin-specific receptor, saxiphilin. Analytical Biochemistry 261: 51-56.
Lyandres, O., Shah, N. C., Yonzon, C. R., Walsh, J. T. Jr., Glucksberg, M. R., Van-Duyne, R. P. 2005. Real-time glucose sensing by surface-enhanced Raman spectroscopy in bovine plasma facilitated by a mixed decanethiol and mercaptohexanol partition layer. Anal. Chem. 77: 6134-6139.
Mahesh, T., Menon, V. P. 2004. Quercetin allievates oxidative stress in streptozotocin-induced diabetic rats. Phytotherapy Research 18: 123-127.
Manger, R. L., Leja, L. S., Lee, S. Y., Hungerford, J. M., Kirkpatrick, M. A., Yasumoto, T., Wekell, M. M. 2003. Detection of paralytic shellfish poison by rapid cell bioassay: Antagonism of voltage-gated sodium channel active toxins in vitro. J. AOAC Int. 86: 540-543.
Maruyama, J., Noguchi, T., Jeon, J. K., Harada, T., Hashimoto, K. 1984. Occurrence if tetrodotoxin in the starfish Astropecten latespinosus. Experientia 40: 1395-1396.
Matthaus, C., Boydston-White, S., Miljkovic, M., Romeo, M., Diem, M. 2006. Raman and infrared microspectral imaging of mitotic cells. Appl. Spectrosc. 60: 1-8.
Mclean, M. J., Bennet, P. B., Thomas, R. M. 1988. Subtypes of dorsal root ganglion neurons based upon different inward currents as measured by whole cell voltage clamp. Molecular Cell Biochemistry 80: 95-107.
Miyazawa, K., Noguchi, T. 2001. Distribution and origin of tetrodotoxin. J. Toxicol. Toxin Rev. 20: 11–33.
Moczydlowski, E., Garber, S. S., Miller, C. 1984. Batrachotoxin activated Na+ channels in planar lipid bilayers. J. Gen. Physiol. 84: 665-686.
Montojo, U. M., Sakamoto, S., Cayme, M. F., Gatdula, N. C., Furio, E. F., Relox, J. R., Sato, S., Fukuyo, Y., Kodama, M. 2006. Remarkable difference in accumulation of paralytic shellfish poisoning toxins among bivalve species exposed to Pyrodinium bahamense var. compressum bloom in Masinloc bay, Philippines. Toxicon 48: 85-92.
Morse, E. V. 1977. Paralytic shellfish poisoning: A review. Journal of the American Veterinary Medical Association 171: 1178-1180.
Mosher, H. S., Fuhrman, F. A., Bruchward, H. D., Fisher, H. G. 1964. Tarichatoxin-tetrodotoxin: A potent neurotoxin. Science 144: 1100-1101.
Nagashima, T., Maruyama, J., Noguchi, T., Hashimoto, K. 1987. Analysis of paralytic shellfish poison and tetrodotoxin by ion-pairing high performance liquid chromatography. Nippon Suisan Gakkaishi 53: 819-823.
Nakashima, K., Osamu, A., Taniyama, S., Nonaka, M., Takatani, T., Yamamori, K., Fuchi, Y., Noguchi, T. 2004. Occurrence of saxitoxins as a major toxin in the ovary of a marine puffer Arothron firmamentum. Toxicon 43: 207-212.
Narahashi, T. 2001. Pharmacology of tetrodotoxin. J. Toxicol. 20: 67-84.
Narahashi, T., Haas, H. G., Therren, E. F. 1967. Saxitoxin and tetrodotoxin: Comparison of nerve blocking mechanism. Science 157: 1441-1442.
Narita, H., Noguchi, T., Maruyama, J., Ueda, Y., Hashimoto, K., Watanabe, Y., Hida, K. 1981. Occurrence of tetrodotoxin in a trumpet shell “Boshubora” Charonia sauliae. Nippon Suisan Gakkaishi 47: 935-941.
Narita, H., Matsubara, S., Miwa, N., Akahane, M., Murakami, M., Goto, T., Nara, M., Noguchi, T., Saito, T., Shida, Y., Hashimoto, K. 1987. Vibrio alginolyticus, a TTX-producing bacterium isolated from the starfish Astropecten polyacanthus. Nippon Suisan Gakkaishi 53: 617-621.
Negri, A., Llewellyn, L. 1998. Comparative analyses by HPLC and the sodium channel and saxiphilin 3H-saxitoxin receptor assays for paralytic shellfish toxins in crustaceans and molluscs from tropical North West Australia. Toxicon 36: 283-298.
Nguyen-Ngoc, L. 2004. An autecological study of the potentially toxic dinoflagellate Alexandrium affine isolated from Vietnamese waters. Harmful Algae 3: 117-129.
Ngy, L., Yu, C. F., Takatani, T., Arakawa, O. 2007. Toxicity assessment for the horseshoe crab Carcinoscorpius rotundicauda collected from Cambodia. Toxicon 49: 843-847.
Ngy, L., Tada, K., Yu, C. F., Takatani, T., Arakawa, O. 2008. Occurrence of paralytic shellfish toxins in Cambodian Mekong pufferfish Tetraodon turgidus: Selective toxin accumulation in the skin. Toxicon 51: 280-288.
Noguchi, T., Ebesu, J. S. M. 2001. Puffer poisoning: Epidemiology and treatment. J. Toxicol. 20: 1-10.
Noguchi, T., Maruyama, J., Ueda, Y., Hashimoto, K., Harada, T. 1981. Occcurrence of tetrodotoxin in the Japanese ivory shell Babylonia japonica.. Nippon Suisan Gakkaishi 47: 909-913.
Noguchi, T., Koyama, K., Uzu, A., Hashimoto, K. 1983. Local variation of toxicity and toxin composition in a xanthid crab Atergatis floridus. Bull. Japan. Soc. Sci. Fish. 49: 1883-1886.
Noguchi, T., Maruyama, J., Narita, H., Hashimoto, K. 1984. Occurrence of tetrodotoxin in the gastropod mollusk Tutufa lissostoma (frog shell). Toxicon 22: 219-226.
Noguchi, T., Jeon, J. K. Arakawa, O., Sugita, H., Deguchi, Y., Hashimoto, K. 1986. Local differences in toxin composition of a xanthid crab Atergatis floridus inhabiting Ishigaki Island, Okinawa Toxicon 24: 705-711.
Noguchi, T., Hwang, D. F., Arakawa, O., Sugita, H., Deguchi, Y., Shida, Y., Hashimoto, K. 1987. Vibrio alginolyticus, a tetrodotoxin-producing bacterium, in the intestines of the fish Fugu vermicularis. Mar. Biol. 94: 625-630.
Noguchi, T., Arakawa, O., Takatani, T. 2006. TTX accumulation in pufferfish. Comparative Biochemistry and Physiology Part D: Genomics and Proteomics 1: 145-152.
O’Leary, M. A., Schneider, J. J., Isbister, G. K. 2004. Use of high performance liquid chromatography to measure tetrodotoxin in serum and urine of poisoned patients. Toxicon 44: 549-553.
Oda, K., Araki, K., Totoki, T., Shibasaki, H. 1989. Nerve conduction study of human tetrodotoxication. Neurology 39: 743-745.
Oshima, Y. 1995. Post column derivatization liquid chromatographic method for paralytic shellfish toxins. Journal of AOAC International 78: 528–532.
Oshima, Y., Hasegawa, M., Yasumoto, G. H., Hallegraeff, G. M., Blackburn, S. 1987. Dinoflagellate Gymnodinium catenatum as the source of paralytic shellfish toxins in Tasmanian shellfish. Toxicon 25: 1105-1111.
Pires, O. R., Sebben, A., Schwartz, E. F., Largura, S. W. R., Bloch, C., Morales, R. A. V., Schwartz, C. A. 2002. Occurrence of tetrodotoxin and its analogues in the Brazilian frog Brachycephalus ephippium (Anura: Brachycephalidae). Toxicon 40: 761-766.
Pires, O. R., Sebben, A., Schwartz, E. F., Morales, R. A., Bloch, C. Jr., Schwartz, C. A. 2005. Further report of the occurrence of tetrodotoxin and new analogues in the Anuran family Brachycephalidae. Toxicon 45: 73-79.
Sato, S., Kodama, M., Ogata, T., Saitanu, K., Hirayama, K., Kakinuma, K. 1997. Saxitoxin as a toxin principle of a fresh water puffer, Tetraodon fangi, in Thailand. Toxicon 35: 137-140.
Sato, S., Ogata, T., Borja, V., Gonzales, C., Fukuyo, Y., Kodama, M. 2000. Frequent occurrence of paralytic shellfish poisoning toxins as dominant toxins in marine puffer from tropical water. Toxicon 38: 1101-1109.
Schantz, E. J. 1960. Biochemical studies on paralytic shellfish poisons. Ann. N. Y. Acad. Sci. 90: 843-855.
Schantz, E. J. 1984. Historical perspective on paralytic shellfish poison. In: Seafood Toxins (ed. by Ragelis, E. P.). ACS Symposium Series 262, American Chemical Society, Washington, DC. pp. 99-111.
Shirahata, S. 2001. Reduced water for prevention of diseases. Animal Cell Technology: Basics and Applied Aspects 12: 25-31.
Shirahata, S., Kabayama, S., Nakano, M., Miura, T., Kusumoto, K., Gotoh, M., Hayashi, H., Otsubo, K., Morisawa, S., Katakura, Y. 1997. Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage. Biochem. Biophys. Res. Commun. 234: 269-274.
Shiu, Y. C., Lu, Y. H., Hsai, Y. H., Chen, S. K., Hwang, D. F. 2003. Occurrence of tetrodotoxin in the causative gastropod Polinices didyma and another gastropod Natica lineata collected from western Taiwan. Journal of Food and Drug Analysis 11: 159-163.
Shoji, Y., Yotsu-Yamashita, M., Miyazawa, T., Yasumoto, T. 2001. Electrospray ionization mass spectrometry of tetrodotoxin and its analogs: Liquid chromatography/mass spectrometry, tandem mass spectrometry, and liquid chromatography/tandem mass spectrometry. Analytical Biochemistry 290: 10-17.
Shui, L. M., Chen, K., Wang, J. Y., Mei, H. Z., Wang, A. Z., Lu, Y. H., Hwang, D. F. 2003. Paralytic snail poisoning in Zhoushan: A 25-year retrospective analysis. Journal of Food Protection 66: 110-114.
Sierra-beltran, A. P., Cruz, A., Nunez, E., Del-Villar, L. M., Ochoa, J. L. 1998. An overview of the marine food poisoning in Mexico. Toxicon 36: 1493-1502.
Simidu, U., Noguchi, T., Hwang, D. F., Shida, Y., Hashimoto, K. 1987. Marine bacteria which produce tetrodotoxin. Appl. Environ. Microbiol. 53: 1714-1715.
Smith, D. R., Snyder, M. 2007. Complete mitochondrial DNA sequence of the scallop Placopecten magellanicus: Evidence of transposition leading to an uncharacteristically large mitochondrial genome. Journal of Molecular Evolution 65: 380-391.
Stuart, D. A., Yuen, J. M., Shah, N., Lyandres, O., Yonzon, C. R., Glucksberg, M. R., Walsh, J. T., Van-Duyne, R. P. 2006. In vivo glucose measurement by surface-enhanced Raman spectroscopy. Anal. Chem. 78: 7211-7215.
Suenaga, K., Kotoku, S. 1980. Detection of tetrodotoxin in autopsy material by gas chromatography. Arch. Toxicol. 44: 291-297.
Sui, L. M., Chen, K., Hwang, P. A., Hwang, D. F. 2002. Identification of tetrodotoxin in marine gastropods implicated in food poisoning. J. Nat. Toxin 11: 213-220.
Sullivan, J., Iwaoka, W. 1983. High pressure liquid chromatographic determination of toxins associated with paralytic shellfish poisoning. Journal of the Association of Official Agricultural Chemists 66: 297-303.
Sumida, O. 1998. Redox water and usage of oxidized water using redox water maker. Fresh Food System 26: 21-28.
Tani, I. 1945. Toxicological Studies of Puffers in Japan. Teikokutosho, Tokyo.
Tsai, Y. H., Hwang, D. F., Cheng, C. A., Hwang, C. C., Deng, J. F. 2006. Determination of tetrodotoxin in human urine and blood using C18 cartridge column, ultrafitration and LC-MS. J. Chromat. B 832: 75-80.
Tsuda, K., Ikuma, S., Kawamura, M., Tachikawa, R., Sakai, K., Tamura, C., Amakasu, O. 1964. Tetrodotoxin. VII. On the structures of tetrodotoxin and its derivatives. Chem. Pharm. Bull. 12: 1357-1374.
Tsuruda, K., Arakawa, O., Kawatsu, K., Hamano, Y., Takatani, T., Noguchi, T. 2002. Secretory glands of tetrodotoxin in the skin of the Japanese newt Cynops pyrrhogaster. Toxicon 40: 131-136.
Vale, P., Bire, R., Hess, P. 2008. Confirmation by LC-MS/MS of azaspiracids in shellfish from the Portuguese north-western coast. Toxicon 51: 1449-1456.
Vessal, M., Hemmati, M., Vasei, M., 2003. Antidiabetic effects of quercetin in streptozotocin-induced diabetic rats. Comparative Biochemistry and Physiology C 135: 357-364.
Vo-Dinh, T., Stokes, D. L., Griffin, G. D., Volkan, M., Kim, U. J., Simon, M. I. 1999. Surface enhanced Rama scattering method and instrumentation for genomics and biomedical analysis. J. Rama Spectrosc. 30: 785-793.
Vo-Dinh, T., Kasili, P., Wabuyele, M. 2006. Nanoprobes and nanobiosensors for monitoring and imaging individual living cells. Nanomedicine 2: 22-30.
Weiser, T. 2004. A novel toxicity-based assay for the identification of modulators of voltage-gated Na+ channels. Journal of Neuroscience Methods 137: 79-85.
Wilding, C. S., Beaumont, A. R., Latchford, J. W. 1997. Mitochondrial DNA variation in the scallop Pecten maximus assessed by a PCR-RFLP method. Heredity 79: 178-189.
Woodward, R. B. 1964. The structure of tetrodotoxin. Pure Appl. Chem. 9: 49-74.
Wu, Z., Yang, Y., Xie, L., Xia, G., Hu, J., Wang, S., Zhang, R. 2005. Toxicity and distribution of tetrodotoxin-producing bacteria in puffer fish Fugu rubripes collected from the Bohai Sea of China. Toxicon 46: 471-476.
Xia, Y., Halas, N. J. 2005. Shape-controlled synthesis and surface plasmonic properties of metallic nanostructures. MRS Bulletin 30: 338-348.
Yamashita, M. Y., Mebs, D. 2001. The levels of tetrodotoxin and its analogue 6-epi tetrodotoxin in the red-spotted newts, Notophthalumus viridescens. Toxicon 39: 1261-1263.
Yang, L., Kao, C. Y. 1992. Actions of chiriquitoxin on frog skeletal muscle fibers and implications for the tetrodotoxin/saxitoxin receptor.
J. Gen. Physiol. 100: 609-622.
Yang, C. C., Liao, S. C., Deng, J. F. 1996. Tetrodotoxin poisoning in Taiwan: An analysis of poison center data. Veterinary and Human Toxicology 38: 282–286.
Yasumura, D., Oshima, Y., Yasumoto, T., Alcala, A. C., Alcala, L. C. 1986. Tetrodotoxin and paralytic shellfish toxins in Philippine crabs. Agric. Biol. Chem. 50: 593-598.
Yoshida, S. 1994. Tetrodotoxin-resistant sodium channels. Cell Molecular Neurobiology 14: 227-44.
Yoshida, M., Ogata, T., Thuoc, C. V., Matsuoka, K., Fukuyo, Y., Hoi, N. C., Kodama, M. 2000. The first finding of toxic dinoflagellate Alexandrium minutum in Vietnam. Fisheries Science 66: 177–179.
Yu, F. H., Catterall, W. A. 2003. Overview of the voltage-gated sodium channel family. Genome Biology 4: 207.1-207.7.
Zeiri, L., Bronk, B. V., Shabtai, Y., Eichler, J., Efrima, S. 2004. Surface-enhanced Raman spectroscopy as a tool for probing specific biochemical components in bacteria. Appl. Spectrosc. 58: 33-40.
Zhang, Q., Allen, S. K. Jr., Reece, K. S. 2005. Genetic variation in wild and hatchery stocks of Suminoe Oyster (Crassostrea ariakensis) assessed by PCR-RFLP and microsatellite markers. Marine Biotechnology 7: 588-599.
Zhang, X., Young, M. A., Lyandres, O., Van-Duyne, R. P. 2005. Rapid detection of an anthrax biomarker by surface-enhanced Raman spectroscopy. J. Am. Chem. Soc. 127: 4484- 4489.