Tetrodotoxin Intoxication Research Articles

Is tetrodotoxin intoxication the cause of "zombi voice" in Haiti?

Zombification, a magical and religious process in Haiti, has been scientifically studied and remains relevant. Originating from the convergence of African, Caribbean, and Christian rites, it involves a comatose trance, transforming individuals into living dead through Voodoo practices. Haitian zombies consistently exhibit a preserved expression marked by a nasal voice, a result of nasalization-using nasal cavities as resonators during phonation. The aim of this study was to ascertain the mechanisms through which zombification could impact the voices of the subjects. A comprehensive investigation was conducted using both primary and secondary sources. Primary sources involved direct or reported testimonies of individuals undergoing zombification, with audio or video recordings available from the collections of the Laboratory of Anthropology, Archaeology, and Biology (UVSQ/Paris-Saclay University), as well as on the internet. Secondary sources encompassed the entirety of existing literature regarding zombification in Haiti on one hand, alterations in the voices of subjects when mentioned on the other hand, and toxicological hypotheses or evidence available on PubMed/Medline and Google Scholar. Few post-zombification observations exist, but 20th-century studies clarified the physio pathological process, confirming its reality. Wade Davis demonstrated in 1983 that zombification results from poisoning, with effects ranging from reversible to fatal, implicating substances like tetrodotoxin and datura. Nasalization can be natural or pathological, affecting various phonemes. No mutilating acts or surgery have been reported related to Haitian zombification. The pharmacological characteristics of tetrodotoxin, coupled with testimonials, present a medical hypothesis elucidating the biological mechanism underlying nasalization in this context. Given that tetrodotoxin induces flaccid paralysis as a neurotropic poison, its neurological impact could account for soft palate paralysis or spasms. Additionally, the severe hypotension induced by tetrodotoxin may elucidate oral and pharyngeal necrosis.

Acute paralysis after seafood ingestion

The first European case of tetrodotoxin intoxication is reported in a patient who ingested a trumpet shellfish from the Atlantic Ocean in Southern Europe. He suffered general acute paralysis with respiratory failure necessitating ventilation. Early neurophysiologic studies showed complete peripheral nerve inexcitability, with no recordable sensory or motor responses, and normal electroencephalography. Tetrodotoxin was detected in high quantities in the patient's blood and urine through high performance liquid chromatography-mass spectrometry analysis. Seventy-two hours after admission the patient recovered normal strength, reflexes and sensation.

Serial electrophysiological changes in uraemic patients with tetrodotoxin intoxication

Tetrodotoxin (TTX) is a well-known biological neurotoxin, predominantly isolated from the viscera of puffer fish. TTX binds to the voltage-gated sodium channels and reduces the membrane excitability of vital tissues (Narahashi et al., 1967). As a result, paraesthesia, paralysis, respiratory failure and, eventually, coma with absence of electrical brain activities can appear depending on the amounts of ingested toxin. There are only a few reports about the electrophysiological studies of peripheral nerves in TTX intoxication because of the rarity of this intoxication and rapid alteration of clinical and electrophysiological status. We conducted serial nerve-conduction studies (NCSs) in two uraemic patients with acute TTX intoxication during the recovery period and obtained the strength–duration curves with nerve-excitability test at each visit. A brief case summary is as follows: Patient #1 was a 38-year-old man, who received peritoneal dialysis with end-stage renal disease for 1 year. He was referred to our hospital due to rapidly progressive quadriparesis. Three days before admission, he ate cooked puffer fish for dinner. On the next morning, he felt dizziness and peri-oral tingling sensation. On neurologic examination, he showed symmetric muscle weakness of Medical Research Council grade 2. Although he complained of mild dyspnoea, he did not need mechanical ventilation. On the 5th day of intoxication, an NCS on the median nerve revealed slow conduction velocity (30 m s ) but normal compound muscle action potential (CMAP) amplitude (8 mV). Serum blood urea nitrogen (BUN) and creatinine (Cr) were 99 and 14.9 mg dl , respectively. Serum potassium level was normal (3.9 mEq l ). His neurologic deficits slowly improved and disappeared at 14 days after ingestion. In the follow-up NCS performed on the 17th day, CMAP was increased in amplitude (11 mV) and conduction velocity demonstrated improvement (51 m s ) over the previous value. A nerve-excitability test was performed. Recording electrodes were attached in the abductor pollicis brevis muscle and the median nerve at the wrist was stimulated. We set the initial stimulation duration to 0.05 ms of square wave, and stimulation intensities were serially increased with 1-mA intervals until visible muscle twitching was observed. We conducted the same procedure with each increment of 0.1 ms up to 1 ms to measure each threshold.

Thyroid Storm and Reversible Thyrotoxic Cardiomyopathy After Ingestion of Seafood Stew Thought to Contain Marine Neurotoxin

Thyroid storm and severe decompensated thyrotoxicosis are life-threatening diseases, requiring immediate treatment in an intensive care unit. Thyrotoxic heart disease is common in patients with hyperthyroidism; thyrotoxic cardiomyopathy with poor left ventricular systolic function is rare. Here, we report a patient who presented with severe decompensated thyrotoxicosis and reversible thyrotoxic cardiomyopathy after ingestion of a mixed seafood stew thought to contain tetrodotoxin or a related marine neurotoxin. The patient was a 50-year-old woman who was seen at the emergency room of another hospital with altered mentality and flaccid quadriplegia after eating a mixed seafood stew. At the other hospital, she was diagnosed as having tetrodotoxin intoxication on the basis of her clinical presentation. The patient was placed on assisted ventilation and transferred to our hospital the following day because of persisting fever, tachycardia, and respiratory depression. Upon admission, thyroid storm was diagnosed on the basis of thyroid function tests (total triiodothyronine was 354 ng/dL, free thyroxine was 3.45 ng/dL, and thyroid-stimulating hormone was <0.01 mU/L) and clinical manifestations. On the third hospital day, she complained of chest discomfort and progressively worsening dyspnea. Echocardiography showed reduced left ventricular systolic function (left ventricular ejection fraction, 47%; left ventricular fractional shortening, 24.4%) with regional wall motion abnormality of anteroseptal wall and apex and diastolic dysfunction (grade 1, relaxation abnormality), suggesting thyrotoxic cardiomyopathy. She was treated with 10 mCi of radioactive iodine and methimazole, and her thyroid and cardiac function normalized. The patient reported here developed thyroid storm and cardiac decompensation shortly after a clinical event consistent with ingestion of marine neurotoxin. This adds to the list of stresses that have been associated with thyroid storm and emphasizes the need to fully evaluate patients who, on initial evaluation, appear to have only a single disorder.

Seafood Intoxication by Tetrodotoxin: First Case in Europe

Tetrodotoxin is considered the most lethal toxin in the marine environment. Prior cases of intoxication previously described correspond to consumption of tetrodotoxin in tropical or subtropical regions of Asia or the Pacific Islands. We present the first European case of tetrodotoxin intoxication in a patient who ingested part of a trumpet shellfish (Charonia sauliae) from the Atlantic Ocean in Southern Europe. Our patient suffered general paralysis, including the respiratory muscles, a few minutes after the consumption of a few grams of C. sauliae. Intubation and mechanical ventilation were necessary for 52 h after the intoxication. The corresponding electrophysiologic studies showed complete non-excitability, with no recordable sensory or motor nerve conduction. We detected the presence of tetrodotoxin in the mollusk and the patient's blood and urine by means of high-performance liquid chromatography-mass spectrometry analysis technique. A previous bioassay showed extremely high quantities of the toxin in the mollusk. This case alerts us to the possibility of a very harmful biotoxin in European coastal waters. This now should be included in the differential diagnosis of similar cases in Europe, and we must be vigilant for its possible presence in Europe.

Identification of novel genes related to tetrodotoxin intoxication in pufferfish

To investigate the genes related to the biosynthesis or accumulation of tetrodotoxin (TTX) in pufferfish, mRNA expression patterns in the liver from pufferfish, akamefugu Takifugu chrysops and kusafugu Takifugu niphobles, were compared by mRNA arbitrarily primed reverse transcription-polymerase chain reaction (RAP RT-PCR) with fish bearing different concentrations of TTX and its derivatives. RAP RT-PCR provided a 383 bp cDNA fragment and its transcripts were higher in toxic than non-toxic pufferfish liver. Its deduced amino acid sequence was similar to those of fibrinogen-like proteins reported for other vertebrates. Northern blot analysis and rapid amplification of cDNA ends (RACE) revealed that the cDNA fragment of 383 bp was composed of at least three fibrinogen-like protein (flp) genes, flp-1, flp-2 and flp-3. Relative mRNA levels of flp-1, flp-2 and flp-3 showed a linear correlation with toxicity of the liver for two pufferfish species.

Post-mortem analysis of samples from a human victim of a fatal poisoning caused by the xanthid crab, Zosimus aeneus

After ingestion of a specimen of the crab Zosimus aeneus (Xanthidae), an East Timorese adult male died within several hours. Xanthid crabs are known to harbour paralytic shellfish toxins (PSTs), tetrodotoxin and palytoxin. A post-mortem examination did not find any obvious pathological abnormalities. This absence of pathologies is more often associated with PSTs and tetrodotoxin intoxication. A second, yet uneaten specimen of Z. aeneus from the same meal, contained a significant amount of PSTs and these same toxins were identified in the gut contents, blood, liver and urine of the victim. Metabolism of the PSTs occurred with the ingested crab harbouring gonyautoxin 2, gonyautoxin 3 and saxitoxin (STX) whereas neoSTX, decarbamoylSTX and STX dominated the PSTs in the victim's urine. The PST composition in the gut contents, in both their identity and proportion, was intermediate between the eaten crab and the urine suggesting that toxin conversion commenced in the victim's gut. The dose consumed by the victim was calculated to be between 1 and 2 μg STX equivalents/kg based upon the concentration in the remains of the cooked crab. The victim's meal did not consist solely of the toxic crab eaten and the possibility of other food items acting in a synergistic manner with the consumed PSTs cannot be discounted.

Detection of cardiomyocyte apoptosis in forensic autopsy cases.

The purpose of the present study was to determine reliable parameters for the detection of apoptotic cells for use as a diagnostic marker during the early stage of acute myocardial infarction (AMI) in forensic autopsy cases. Myocardial tissues taken from forensic autopsy cases were examined by immunohistochemical and molecular-biological methods using the terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labelling (TUNEL) and the DNA laddering methods. In cases of AMI with a time period between 2 h from onset to death and 20 h post-mortem time, the nuclei of cardiomyocytes were stained positive with the TUNEL method and DNA fragmentation of myocardial cells was detected by agarose gel electrophoresis. Similar findings were obtained in cases of carbon monoxide (CO) intoxication. However, no apoptotic cells were found in other cases such as methamphetamine (MAP) intoxication, tetrodotoxin intoxication, alcohol intoxication, asphyxia, head injury, heart injury or myocarditis. These findings suggested that it would be possible to apply TUNEL-positive cells as a diagnostic marker during the early stages of AMI.

Activity influences on neuronal connectivity within the auditory pathway.

Sensorineural hearing loss may be associated with altered patterns of neuronal connections within the central auditory pathway. The cat auditory system was used to address the relative importance of impulse traffic within the auditory nerve in maintaining central nervous system connections. Acute, unilateral deafness was induced by tetrodotoxin intoxication of cochlear hair cells. Analysis focused on the structural patterns of contact between auditory nerve endings called end bulbs of Held and their target neurons. Specifically, end bulb morphology and target cell size within the cochlear nucleus were examined. Highly specialized synaptic contacts at this junction provide a powerful site for study. The principal finding was that abolished activity in the auditory nerve caused nerve endings to assume a different shape, typified by more branching and smaller terminal swellings. The new shape is one typically associated with only a subpopulation of fibers in normal-hearing cats--those exhibiting a high-threshold, low-spontaneous activity profile. This result implies that abolished activity alters patterns of nerve fiber contact with second-order neurons. Tetrodotoxin produced differential effects on subpopulations of target neurons within the brainstem and is interpretable on the basis of "weighing" synaptic inputs. Second-order neurons that receive large axosomatic inputs from their parent fiber were significantly smaller than neurons that receive small, axodendritic terminals. Thus, attenuated auditory activity may produce differential effects across the auditory pathway, thereby disrupting the normal balance of inputs into synaptic stations. Impulse traffic is a critical factor in the interaction between the ear and central auditory stations and appears necessary for the maintenance of key synapses. As hearing disorders with impaired comprehension may be modeled by studies of auditory deafferentation, these observations extend the possibility that changes in central neuronal connections underlie reduced capabilities for processing restored auditory input.

Food poisoning due to consumption of the freshwater puffer Tetraodon fangi in Thailand

S. Laobhripatr, K. Limpakarnjanarat, O. Sangwonloy, S. Sudhasaneya, B. Anuchatvorakul, S. Leelasitorn and K. Saitanu. Food poisoning due to consumption of the freshwater puffer Tetraodon fangi in Thailand. Toxicon 28, 1372–1375, 1990.—In October 1988, food poisoning due to the freshwater puffer Tetraodon fangi occurred. Six out of eight people who consumed spicy soup (Tom Yam) of puffer developed clinical signs of tetrodotoxin intoxication. The incubation period varied from 30 min to 3 hr and there were no deaths. Puffers were collected one week after the occurrence of the food poisoning and their content of toxin was determined. All organs of puffer were toxic with skin having the highest toxicity followed by gonad, muscle, liver and intestine.