Neosaxitoxin, a Paralytic Shellfish Poison phycotoxin, blocks pain and inflammation in equine osteoarthritis.

The Osteoarthritis is a chronic disease characterized by a progressive deterioration of the articular cartilage producing a strong inflammatory activity and chronic pain in patients. Horses also show osteoarthritis. Since the activation and progression of the disease are similar to that of human we developed a study model in horses.

Gonyautoxins 2/3 Local Periarticular Injection for Pain Management after Total Knee Arthroplasty: A Double-Blind, Randomized Study.

The purpose of this study was to compare the efficacy of periarticular infiltration of gonyautoxin 2/3 (GTX 2/3) and a mixture of levobupivacaine, ketorolac, and epinephrine for pain management after total knee arthroplasty (TKA). Forty-eight patients were randomly allocated to receive periarticular infiltration of 40 µg GTX 2/3 ( = 24) diluted in 30 mL of sodium chloride 0.9% (study group) or a combination of 300 mg of levobupivacaine, 1 mg of epinephrine, and 60 mg ketorolac ( = 24) diluted in 150 mL of sodium chloride 0.

Neosaxitoxin Inhibits the Expression of Inflammation Markers of the M1 Phenotype in Macrophages.

(1) Background: Neosaxitoxin (NeoSTX) has been used as a local anesthetic, but its anti-inflammatory effects have not been well defined. In the present study, we investigate the effects of NeoSTX on lipopolysaccharide (LPS)-activated macrophages. (2) Methods: Raw 264.

In vivo blockade of ovarian sympathetic activity by Neosaxitoxin prevents polycystic ovary in rats.

A high sympathetic tone is observed in the development and maintenance of the polycystic ovary (PCO) phenotype in rats. Neosaxitoxin (NeoSTX) specifically blocks neuronal voltage-dependent Na+ channels, and we studied the capacity of NeoSTX administered into the ovary to block sympathetic nerves and PCO phenotype that is induced by estradiol valerate (EV). The toxin was administered with a minipump inserted into the bursal cavity using two protocols: (1) the same day as EV administration and (2) 30 days after EV to block the final step of cyst development and maintenance of the condition.

Evaluation of Neosaxitoxin as a local anesthetic during piglet castration: A potential alternative for Lidocaine.

Objetive: To evaluate Neosaxitoxin (NeoSTX) as a local anesthetic drug, for pain control during and after piglet castration.

Study Design: Prospective, randomized and double-blind study.

Animals: 24 commercial hybrids, males, 23-day-old piglets.

Neosaxitoxin, a Paralytic Shellfish Poison toxin, effectively manages bucked shins pain, as a local long-acting pain blocker in an equine model.

Local anesthesia is an effective method to control pain. Neosaxitoxin is a phycotoxin whose molecular mechanism includes a reversible inhibition of voltage-gated sodium channels at the axonal level, impeding nerve impulse propagation. The present study was designed to evaluate the clinical efficacy of Neosaxitoxin as a local long-acting pain blocker in horse bucked shins, and it was found to effectively control pain.

Sublethal doses of dinophysistoxin-1 and okadaic acid stimulate secretion of inflammatory factors on innate immune cells: Negative health consequences.

One of the proposed mechanisms to explain why Diarrhetic Shellfish Poison (DSP) toxins are tumor promoters is founded on the capacity of these toxins to increase TNF-α secretion. Although macrophages are the principal cells in the activation of the inflammatory response, the immune profile that Okadaic acid (OA) and Dinophysistoxin-1 (DTX-1) trigger in these cells has not been fully explored. We have therefore investigated the effect of various concentrations of both toxins on the activity of several inflammatory factors.

Gonyautoxins: First evidence in pain management in total knee arthroplasty.

Improvements in pain management techniques in the last decade have had a major impact on the practice of total knee arthroplasty (TKA). Gonyautoxin are phycotoxins, whose molecular mechanism of action is a reversible block of the voltage-gated sodium channels at the axonal level, impeding nerve impulse propagation. This study was designed to evaluate the clinical efficacy of Gonyautoxin infiltration, as a long acting pain blocker in TKA.

First evidence of neosaxitoxin as a long-acting pain blocker in bladder pain syndrome.

Introduction And Hypothesis: Neosaxitoxin is a phycotoxin whose molecular mechanism of action shows a reversible inhibition of voltage-gated sodium channels at the axonal level, impeding nerve impulse propagation. This study was designed to evaluate the clinical efficacy of neosaxitoxin as a long-acting pain blocker in the treatment of bladder pain syndrome (BPS).

Methods: Five patients with a diagnosis of BPS received a total dose of 80 µg of neosaxitoxin in an isoosmotic solution of 0.

Management of Pregnancy in a Chilean Patient with Congenital Deficiency of Factor VII and Glanzmann's Thrombasthenia Variant.

Patients with inherited bleeding disorders are rare in obstetric practice but present with prolonged bleeding even after minor invasive procedures. They require a combined approach with obstetric and hematological management of each case, including the neonatal management of a possibly affected fetus. We present the case of a pregnancy in a patient with combined Factor VII deficiency and Glanzmann's thrombasthenia, the successful obstetric and hematological management of the case, and a review of the literature.

Okadaic acid toxin at sublethal dose produced cell proliferation in gastric and colon epithelial cell lines.

The aim of this study was to analyze the effect of Okadaic Acid (OA) on the proliferation of gastric and colon epithelial cells, the main target tissues of the toxin. We hypothesized that OA, at sublethal doses, activates multiple signaling pathways, such as Erk and Akt, through the inhibition of PP2A. To demonstrate this, we carried out curves of doses and time response against OA in AGS, MKN-45 and Caco 2 cell lines, and found an increase in the cell proliferation at sublethal doses, at 24 h or 48 h exposure.

Determination of the variability of both hydrophilic and lipophilic toxins in endemic wild bivalves and carnivorous gastropods from the southern part of Chile.

The aim of this study was to analyse and determine the composition of paralytic shellfish poisoning (PSP) toxins and lipophilic toxins in the Region of Aysén, Chile, in wild endemic mussels (Mytilus chilensis, Venus antiqua, Aulacomya ater, Choromytilus chorus, Tagelus dombeii and Gari solida) and in two endemic carnivorous molluscs species (Concholepas concholepas and Argobuccinum ranelliforme). PSP-toxin contents were determined by using HPLC with fluorescence detection, while lipophilic toxins were determined by using LC-MS/MS. Mean concentrations for the total of PSP toxins were in the range 55-2505 μg saxitoxin-equivalent/100 g.

Lipophilic toxin profiles detected in farmed and benthic mussels populations from the most relevant production zones in Southern Chile.

Lipophilic toxins associated with diarrhoeic toxins were found in Mytilus chilensis (Blue mussels) and Aulacomya ater (Ribbed mussels). These shellfish samples were collected from Chiloe Island, Southern Chile. The samples were tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

First evidence of Okadaic acid acyl-derivative and Dinophysistoxin-3 in mussel samples collected in Chiloe Island, Southern Chile.

This paper shows the detection of Diarrhetic Shellfish Poison (DSP) phycotoxins, using HPLC-FLD with pre-column derivatization procedure and HPLC-MS methods, in the analysis of shellfish extracts tested positive with the official DSP mouse bioassay. The shellfish samples were collected in Chiloe Island, Southern of Chile. The amount of Dinophysistoxin-3 (DTX-3) measured in the shellfish extracts were in average above the international safe limits for DSP content in the shellfish extracts analyzed.

Highly toxic Microcystis aeruginosa strain, isolated from São Paulo-Brazil, produce hepatotoxins and paralytic shellfish poison neurotoxins.

While evaluating several laboratory-cultured cyanobacteria strains for the presence of paralytic shellfish poison neurotoxins, the hydrophilic extract of Microcystis aeruginosa strain SPC777--isolated from Billings's reservoir, São Paulo, Brazil--was found to exhibit lethal neurotoxic effect in mouse bioassay. The in vivo test showed symptoms that unambiguously were those produced by PSP. In order to identify the presence of neurotoxins, cells were lyophilized, and the extracts were analyzed by HPLC-FLD and HPLC-MS.

Potentiation of local anesthetic activity of neosaxitoxin with bupivacaine or epinephrine: development of a long-acting pain blocker.

Local anesthetics effectively block and relieve pain, but with a relatively short duration of action, limiting its analgesic effectiveness. Therefore, a long-acting local anesthetic would improve the management of pain, but no such agent is yet available for clinical use. The aim of this study is to evaluate the potentiation of the anesthetic effect of neosaxitoxin, with bupivacaine or epinephrine in a randomized double-blind clinical trial.

Route of metabolization and detoxication of paralytic shellfish toxins in humans.

Paralytic shellfish toxins (PST) are a collection of over 26 structurally related imidazoline guanidinium derivatives produced by marine dinoflagellates and freshwater cyanobacteria. Glucuronidation of drugs by UDP-glucuronosyltransferase (UGT) is the major phase II conjugation reaction in mammalian liver. In this study, using human liver microsomes, the in vitro paralytic shellfish toxins oxidation and sequential glucuronidation are achieved.

Evidence of in vitro glucuronidation and enzymatic transformation of paralytic shellfish toxins by healthy human liver microsomes fraction.

Paralytic Shellfish Toxins (PST) are endemic components found in filter bivalves in Southern Chile. Post-mortems analysis of fluid and tissue samples has shown biotransformation of PST in humans. The Gonyautoxin 3 (GTX3) and Gonyautoxin 2 (GTX2) are the major PST components in the toxin profile found in Chilean shellfish extracts, being as much as 65% of the total content of PST in filter bivalves.

GTX 2/3 epimers permeate the intestine through a paracellular pathway.

The aim of this work was to typify the mechanisms involved in gonyautoxins intestinal permeability. For this purpose, permeability of gonyautoxins through intestinal epithelium, and their effect on transepithelial resistance was investigated in excised human jejunal segments. The isolated mucosa segments were mounted in a Ussing chamber and experiments performed under voltage-controlled conditions.

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.

High amount of dinophysistoxin-3 in Mytilus chilensis collected in Seno de Reloncaví, chile, during massive human intoxication associated with outbreak of Vibrio parahaemolyticus.

This study describes the detection of high amount of 7-O-acyl-derivative dinophysistoxin-1 (Dinophysistoxin-3) in filter bivalves collected on February 2005 in the Seno de Reloncaví, Puerto Montt City, Southern Chile, in the same period of time where an intoxication episode was associated with the presence of Vibrio parahaemolyticus in shellfish. The Diarrhetic Shellfish Poisoning (DSP) mouse bioassay of mussel extract samples, performed as described for regulatory testing, were negative to DSP toxins. Therefore, the same mussel samples collected from 8 places of Seno de Reloncaví were then analyzed by the HPLC-FLD method with pre-column derivatization procedure for DSP toxins.

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).

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.

Gonyautoxin: new treatment for healing acute and chronic anal fissures.

Purpose: The mayor symptoms of chronic anal fissure are permanent pain, intense pain during defecation that lasts for hours, blood in the stools, and sphincter cramps. It is subsequent to formation of fibrosis infiltrate that leads to an increased anal tone with poor healing tendency. This vicious circle leads to fissure recurrence and chronicity.