tetrodotoxin and Acute-Disease

Acute otitis media (AOM) commonly causes pain and distress in children. Existing analgesic ototopical drops have limited effectiveness due to the impermeable nature of the tympanic membrane. We developed a local drug delivery system to provide sustained pain relief in patients with AOM, achieved by applying a single dose of a hydrogel formulation onto the tympanic membrane. Successful drug delivery across intact tympanic membranes was demonstrated using the amino-amide anesthetic, bupivacaine, and a highly potent site 1 sodium channel blocker anesthetic, tetrodotoxin. The chemical permeation enhancers incorporated in the delivery system increased the permeability of the tympanic membrane to the anesthetics considerably. The drug levels measured using a previously developed ex vivo model reflect the potential for highly effective local anesthesia.

Topics: Acute Disease; Anesthetics, Local; Bupivacaine; Drug Delivery Systems; Humans; Otitis Media; Pain; Tetrodotoxin

To explore the role of histamine in acute pain perception and its possible mechanisms.. Pain-like behaviors induced by four types of noxious stimuli (hot-plate, tail-pressure, acetic acid, and formalin) were accessed in mice. Nav 1.8 expression and functions in primary afferent neurons were compared between histidine decarboxylase knockout (HDC(-/-) ) mice and their wild-types.. HDC(-/-) mice, lacking in endogenous histamine, showed elevated sensitivity to all these noxious stimuli, as compared with the wild-types. In addition, a depletion of endogenous histamine with α-fluoromethylhistidine (α-FMH), a specific HDC inhibitor, or feeding mice a low-histamine diet also enhanced nociception in the wild-types. Nav 1.8 expression in primary afferent neurons was increased both in HDC(-/-) and in α-FMH-treated wild-type mice. A higher Nav 1.8 current density, a lower action potential (AP) threshold, and a higher firing rate in response to suprathreshold stimulation were observed in nociception-related small DRG neurons of HDC(-/-) mice. Nav 1.8 inhibitor A-803467, but not TTX, diminished the hyperexcitability and blocked repetitive AP firing of these neurons.. Our results indicate that histamine participates in acute pain modulation in a dose-related manner. The regulation of Nav 1.8 expression and the excitability of nociceptive primary afferent neurons may be involved in the underlying mechanisms.

Topics: Action Potentials; Acute Disease; Animals; Ganglia, Spinal; Histamine; Histidine Decarboxylase; Methylhistidines; Mice; NAV1.8 Voltage-Gated Sodium Channel; Neurons, Afferent; Nociception; Tetrodotoxin

We report three cases of a collective tetrodotoxin poisoning, after ingestion of puffer fish eggs. This neurotoxin is the most potent membrane stabilizer, blocking the nervous conduction and resulting in death from respiratory paralysis in case of massive ingestion. The father died at admission, the mother and her daughter presented an acute respiratory failure and a flaccid tetraplegia, with favourable outcome after 24 hours.

Topics: Acute Disease; Adolescent; Adult; Animals; Cranial Nerve Diseases; Eggs; Fatal Outcome; Female; Fishes, Poisonous; Gastrointestinal Contents; Humans; Ion Channels; Ion Transport; Male; Mice; Middle Aged; Neural Conduction; Paresthesia; Quadriplegia; Respiration, Artificial; Respiratory Insufficiency; Respiratory Paralysis; Tetrodotoxin

In an ex situ organ perfusion system, that of the isolated nonrecirculating joint perfusion of rat small intestine and liver, insulin infused into the portal vein increased intestinal glucose absorption. This insulin action against the bloodstream can be blocked by TTX, indicating a propagation of the insulin signal via hepatoenteral nerves, which conforms with previous studies with atropine and carbachol. Insulin action could also be mimicked by dibutyryl cAMP (DBcAMP) acting directly on the absorptive enterocytes. Because autonomic neuropathy is a common late complication of diabetes mellitus, the possible impairment of these nerves in the diabetic state was studied in streptozotocin-diabetic rats. In the isolated joint intestine-liver perfusion, glucose was applied as a bolus into the lumen; its absorption was measured in the portal vein. In 5-day diabetic as well as in control rats, portal insulin, arterial carbachol, and arterial DBcAMP increased intestinal glucose absorption. In 3-mo diabetic rats portal insulin and arterial carbachol failed to stimulate glucose absorption, whereas arterial DBcAMP still did so, indicating an undisturbed function of the absorptive enterocytes. The lack of an effect of portal insulin and arterial carbachol and the unchanged action of DBcAMP in the chronically diabetic rats indicated that the signaling chain via the hepatoenteral nerves was impaired, which is in line with a diabetic neuropathy.

Topics: Acute Disease; Animals; Autonomic Nervous System; Bucladesine; Carbachol; Chronic Disease; Cyclic AMP; Diabetes Mellitus, Experimental; Glucose; In Vitro Techniques; Insulin; Intestinal Absorption; Kidney; Liver; Male; Portal Vein; Rats; Rats, Wistar; Signal Transduction; Tetrodotoxin

Short-circuit current (Isc) and transepithelial potential difference (PD) of rat distal colon decrease during acute hypoxia and overshoot on reoxygenation. It is not known whether tonic intrinsic nervous activity may influence these responses.. Preparations lacking the submucosal plexus (islet mucosa) and preparations retaining it (mucosa-submucosa) were mounted in Ussing chambers at 37 degrees C and gassed with 95% O2-5% CO2; Isc and PD were monitored. A 5-min hypoxia with 95% N2-5% CO2 was followed by reoxygenation. The procedure was repeated in the presence of the nervous blocking agent, tetrodotoxin (10(-6)M) in the serosal side of the chamber.. In the isolated mucosa (n = 10) hypoxia reduced Isc by -55 +/- 5% and PD by -54 +/- 6% below baseline; reoxygenatory overshoots were, respectively, +60 +/- 17% and +/- 16%. Tetrodotoxin slightly and transiently reduced baseline Isc (-16 +/- 2%) and PD (-14 +/- 3%), with a small resistivity increase. It did not significatively modify the responses to responses to either hypoxia or reoxygenation. In mucosa-submucosa preparations (n = 9) hypoxia reduced Isc (-54 +/- 8%) and PD (-61 +/- 4%). On reoxygenation Isc and PD were increased, respectively, +30 +/- 5% and +19 +/- 6% over baseline. Tetrodotoxin reduced baseline Isc (-59.6 +/- 5%) and PD (61.3 +/- 6%). It enhanced hypoxic Isc and PD decreases (-80 +/- 5%), but not the reoxygenatory overshoots.. 1) Tetrodotoxin affects baseline Isc and PD more intensely in submucosal plexus innervated preparations than in the isolated mucosa. 2) The epithelial electrical response to acute hypoxia appears to be modulated by tonic neural activity.

Topics: Acute Disease; Animals; Colon; Electrophysiology; Hypoxia; Intestinal Mucosa; Male; Rats; Rats, Wistar; Submucous Plexus; Tetrodotoxin

The purpose of the present study was to quantify the inhibitory effect of inhaled halothane and isoflurane on acute hypercapnia-induced responses of capacitance-regulating veins and related cardiovascular variables in response to sequential 40-s periods of 5%, 10%, 15%, and 20% inspired CO2 (FICO2). Measurements were made in normoxic alpha-chloralose-anesthetized rabbits before, during, and after either 0.75 minimum alveolar anesthetic concentration inhaled halothane or isoflurane. The graded hypercapnia caused graded venoconstriction and bradycardia but minimal pressor responses. Hypercapnia-induced venoconstriction was blocked by prior local superfusion of the exposed veins with 3 x 10(-6) M tetrodotoxin. Both the hypercapnia-induced venoconstriction and bradycardia responses were significantly attenuated by halothane or isoflurane and did not fully recover after removal of the anesthetics from the circulation. Both anesthetics produced a significant baseline (i.e., prehypercapnia) hypotension and a tendency toward a resultant tachycardia. The baseline hypotension did not recover completely after elimination of the anesthetic. Neither anesthetic altered baseline vein diameter. These results agree with previous studies demonstrating that hypercapnic acidosis produces mesenteric venoconstriction by elevating excitatory sympathetic efferent neural input via activation of peripheral and central chemoreceptors and that bradycardia results from activation of compensatory baroreflexes. The neural components of these reflexes are possible primary sites for attenuation of these cardiovascular responses by halothane and isoflurane.

Topics: Acute Disease; Anesthetics, Inhalation; Animals; Blood Pressure; Bradycardia; Halothane; Heart Rate; Hypercapnia; Isoflurane; Mesenteric Veins; Rabbits; Tetrodotoxin; Vasoconstriction

Tetrodotoxin (TTN) is a marine neurotoxin that is sometimes responsible for the mortality of pufferfish consumers. A case of human tetrodotoxication caused by ingestion of Goby is reported. The patient developed perioral numbness, acroparesthesia, generalized weakness and respiratory failure within hours after ingestion. The electrophysiological studies at the 16th hour of intoxication revealed generalized sensorimotor axonopathy, but no disturbance on the neuromuscular junction motor endplate. Human electrophysiological studies of acute TTX intoxication have rarely been documented in literature.

Topics: Acute Disease; Adult; Animals; Electrophysiology; Female; Fishes; Foodborne Diseases; Humans; Tetrodotoxin