Metabolic transformation of dinophysistoxin-3 into dinophysistoxin-1 causes human intoxication by consumption of O-acyl-derivatives dinophysistoxins contaminated shellfish.

This paper describes for the first time a massive intoxication episode due to consumption of shellfish contaminated with 7-O-acyl-derivative dinophysistoxin-1, named Dinophysistoxin-3 (DTX-3). 7-O-acyl-derivative dinophysistoxin-1, a compound recently described in the literature, was found in shellfish samples collected in the Chilean Patagonia fjords. This compound does not inhibit Protein Phosphatases and also does not elicit the symptoms described for Diarrheic Shellfish Poisoning (DSP). The data showed here, give evidence of metabolic transformation of 7-O-acyl-derivative dinophysistoxin-1 (DTX-3) into Dinophysistoxin-1 (DTX-1, Methyl-Okadaic acid) in intoxicated patients. This metabolic transformation is responsible for the diarrheic symptoms and the intoxication syndrome showed by patients that consumed contaminated shellfish, which showed only the presence of 7-O-acyl-derivative dinophysistoxin-1. Patients fecal bacterial analysis for the presence of enteropathogens was negative and the mouse bioassay for DSP, performed as described for regulatory testing, was also negative. The HPLC-FLD and HPLC-MS analysis showed only the presence of DTX-3 as the only compound associated to DSP toxins in the contaminated shellfish samples. No other DSP toxins were found in the shellfish sample extracts. However, the patient fecal samples showed DTX-1 as the only DSP toxins detected in fecal. Moreover, the patient fecal samples did not show DTX-3. Since 7-O-acyl-derivative dinophysistoxin-1 (DTX-3) was the only compound associated to DSP toxins detected in the shellfish samples, an explanation for the diarrheic symptoms in the intoxicated patients would be the metabolic transformation of DTX-3 into DTX-1. This transformation should occur in the stomach of the poisoned patients after consuming 7-O-acyl-derivatives dinophysistoxin-1 (DTX-3) contaminated bivalves.

Neosaxitoxin as a local anesthetic: preliminary observations from a first human trial.

BACKGROUND: Neosaxitoxin is a phycotoxin that reversibly blocks the voltage-gated sodium channels at the neuronal level. Its activity results in blocking the axonal conduction, stopping the propagation of the nerve impulse. The objective of the present work was to evaluate neosaxitoxin as a local anesthetic in a human trial. METHODS: The authors conducted a randomized, double-blind, placebo-controlled trial with 10 healthy volunteers. Subcutaneous injections were made in the middle posterior skin of the calf: one leg received 50 microg neosaxitoxin, and the contra-lateral leg received placebo. The anesthetic effect was evaluated using a standardized human sensory and pain model. TSA II Neurosensory Analyzer (Medoc Ltd, Minneapolis, MN) and von Frey technique were used to evaluate five parameters: sensory threshold for warm and cold, pain thresholds for heat and cold, and mechanical touch perception threshold. Measurements were made 0, 1, 3, 6, 9, 12, 16, 24, and 48 h after the injections. RESULTS: For all the patients, effective and complete blocking of the evaluated parameters was obtained. As the blocking began to revert gradually, heat pain was the first to return to normal values after 3 h. Cold pain was the longest sensation abolished, achieving 24 h of blockade. The toxin was undetected in blood and urine samples. No adverse reactions to neosaxitoxin were detected. CONCLUSIONS: Neosaxitoxin showed an effective local anesthetic effect when injected in the subcutaneous plane. The efficacy of a 50-microg dose of neosaxitoxin was shown. This is the first report of neosaxitoxin as a local anesthetic in a human trial.

Human intoxication with paralytic shellfish toxins: clinical parameters and toxin analysis in plasma and urine.

This study reports the data recorded from four patients intoxicated with shellfish during the summer 2002, after consuming ribbed mussels (Aulacomya ater) with paralytic shellfish toxin contents of 8,066 +/- 61.37 microg/100 gr of tissue. Data associated with clinical variables and paralytic shellfish toxins analysis in plasma and urine of the intoxicated patients are shown. For this purpose, the evolution of respiratory frequency, arterial blood pressure and heart rate of the poisoned patients were followed and recorded. The clinical treatment to reach a clinically stable condition and return to normal physiological parameters was a combination of hydration with saline solution supplemented with Dobutamine (vasoactive drug), Furosemide (diuretic) and Ranitidine (inhibitor of acid secretion). The physiological condition of patients began to improve after four hours of clinical treatment, and a stable condition was reached between 12 to 24 hours. The HPLC-FLD analysis showed only the GTX3/GTX2 epimers in the blood and urine samples. Also, these epimers were the only paralytic shellfish toxins found in the shellfish extract sample.

Human intoxication with paralytic shellfish toxins: clinical parameters and toxin analysis in plasma and urine

This study reports the data recorded from four patients intoxicated with shellfish during the summer 2002, after consuming ribbed mussels (Aulacomya ater) with paralytic shellfish toxin contents of 8,066 n 61.37 mg/100 gr of tissue. Data associated with clinical variables and paralytic shellfish toxins analysis in plasma and urine of the intoxicated patients are shown. For this purpose, the evolution of respiratory frequency, arterial blood pressure and heart rate of the poisoned patients were followed and recorded. The clinical treatment to reach a clinically stable condition and return to normal physiological parameters was a combination of hydration with saline solution supplemented with Dobutamine (vasoactive drug), Furosemide (diuretic) and Ranitidine (inhibitor of acid secretion). The physiological condition of patients began to improve after four hours of clinical treatment, and a stable condition was reached between 12 to 24 hours. The HPLC-FLD analysis showed only the GTX3/GTX2 epimers in the blood and urine samples. Also, these epimers were the only paralytic shellfish toxins found in the shellfish extract sample.

Veneno diarreico de moluscos y derivados del benzopireno en bivalvos ahumados / Diarrheal poison in molluscs and derivates of benzopyrene in smoked bivalves

Los florecimientos algales nocivos (FANs), corresponden al fenómeno comúnmente denominado marea roja. Esta se encuentra constituida por 5 tipos de venenos diferentes: veneno paralizante de moluscos (VPM); veneno diarreico de moluscos (VDM); veneno amnésico de moluscos (VAM); veneno neuro-tóxico de moluscos (VNM) y toxinas producidas por cianobacterias, cada una de las cuales presenta una distribución a nivel mundial. En Chile, sólo han sido identificados los venenos VPM y VDM, los que se encuentran endémicamente desde la X a XII regiones. Su identificación a nivel nacional, se realiza a través del método denominado bioensayo en ratón, el cual presenta una sensibilidad adecuada para la detección de VPM, no así para la detección de VDM, debido a las cualidades químicas que presentan estas toxinas, produciéndose cada año un número no estimado de personas intoxicadas. Dadas las características socioeconómicas del sur de Chile, la mayoría de los bivalvos son expendidos bajo condiciones de ahumado, de manera de aumentar su preservación para el consumo por parte de la población local. Esto ocasiona la fijación de hidrocarburos aromáticos policíclicos (HAPs) en los bivalvos de manera extrema. Considerando que los HAPs son iniciadores y el VDM promotor del proceso carcinogénico, sumándose a ello la importancia de este tipo de alimento en la dieta diaria de la población, en este trabajo se identificaron y cuantificaron las concentraciones HAP y VDM presentes en bivalvos de la X Región. Los resultados, muestran que los HAPs y VDM presentes en los bivalvos sobrepasan la norma internacional 10 µg/kg y 200 ng/g de hepatopáncreas, respectivamente. Siendo el HAP más relevante el benzopireno (71,62 ± 18,40 µg/kg en cholgas) y la toxina VDM identificada DTX-3 (217,33 ± 14,76 ng/g de hepatopáncreas en cholgas). Estos resultados ponen en evidencia la necesidad de realizar estudios epidemiológicos en la zona para determinar si existe una asociación entre la exposición a estos compuestos y la incidencia de cáncer gástrico de la población local.