RESUMO
BACKGROUND AND OBJECTIVES: Wound infiltration with available local anesthetics generally provides analgesia for less than 8 hrs. The site 1 sodium-channel toxin neosaxitoxin (neoSTX) produced analgesia for over 24 hrs in animals and human volunteers. In this randomized, double-blind trial, we examined the postoperative course of patients undergoing laparoscopic cholecystectomy under a standardized general anesthesia with wound infiltration using either neoSTX or bupivacaine. We hypothesized that neoSTX would reduce pain compared with bupivacaine at 12 hrs postoperatively. METHODS: Patients received preincisional infiltration of laparoscope entry sites with 20 mL containing either neoSTX (total dose, 100 µg) or bupivacaine 0.25% (total dose, 50 mg). The primary outcome measure was the visual analog pain score at 12 hrs postoperatively. Secondary outcomes included repeated pain scores at rest and with movement,analgesic use, functional recovery, and adverse effects. Groups were compared using Mann-Whitney U tests for pain scores, Fisher exact test for proportions of patients with severe pain and complete analgesia, and Kaplan-Meier curves for time to full recovery. RESULTS: Among 137 subjects, 69 were randomized to neoSTX and 68 to bupivacaine. Median pain scores at rest and with movement 12 hrs postoperatively were lower in the neoSTX group compared with the bupivacaine group (P<0.01). Additional pain measures and recovery parameters also favored neoSTX. No serious adverse events occurred,and no adverse events were more frequent in the neoSTX group. CONCLUSIONS: NeoSTX shows promise as a long-acting local anesthetic. Future studies will examine dose response, combination formulations, and safety with dose escalation.
Assuntos
Analgesia , Anestesia Local , Bupivacaína/administração & dosagem , Colecistectomia Laparoscópica , Dor Pós-Operatória/prevenção & controle , Saxitoxina/análogos & derivados , Adulto , Analgesia/métodos , Anestesia Local/métodos , Bupivacaína/farmacocinética , Colecistectomia Laparoscópica/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/metabolismo , Saxitoxina/administração & dosagem , Saxitoxina/farmacocinéticaRESUMO
Cyanobacterial waterblooms, such as the saxitoxin (STX) producer Cylindrospermopsis raciborskii, have been a worldwide concern in environmental health. However, the bioaccumulation of this neurotoxin in the trophic chain is not completely known. The aim of the present work was to evaluate STX bioaccumulation through chemical analyses and the toxic and trophic effects using biomarkers in the tropical freshwater fish Hoplias malabaricus. They were fed once every five days with Astyanax sp. before being subjected to intraperitoneal inoculation with STX extract (0.08 µg/100 g) obtained by lysis of toxic C. raciborskii strain (T3). After 20 days the brain was collected for acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione (GSH), lipoperoxidation (LPO), protein carbonylation (PCO), and comet assay analysis. The muscle was collected for STX chemical analysis. The activities of SOD and concentrations of PCO and LPO increased. The CAT, GST, and GPx activities decreased. Genotoxicity was observed in the experimental group. STX was not detected in muscle samples. Thus, an oxidative stress was observed in the brain, leading to the damage of lipids, proteins, and DNA. The mechanism of action of the neurotoxin in this subchronic exposure suggests an apoptotic cellular process.
Assuntos
Eutrofização , Peixes/metabolismo , Contaminação de Alimentos , Venenos/farmacocinética , Saxitoxina/farmacocinética , Animais , Biomarcadores/metabolismo , Ensaio Cometa , Dano ao DNA , Cadeia Alimentar , Água Doce , Músculo Esquelético/metabolismo , Mutagênicos/análise , Mutagênicos/farmacocinética , Mutagênicos/toxicidade , Estresse Oxidativo , Venenos/análise , Venenos/toxicidade , Saxitoxina/análise , Saxitoxina/toxicidade , Distribuição Tecidual , Clima TropicalRESUMO
In July 5, 2002 fishermen working in harvesting sea urchin (Loxechinus albus) in the Patagonia Chilean fjords were intoxicated by consumption of filter-feeder bivalve Aulacomya ater. After the ingestion of 7-9 ribbed mussel, two fishermen died 3-4 h after shellfish consumption. The forensic examination in both victims did not show pathological abnormalities with the exception of the lungs conditions, crackling to the touch, pulmonary congestion and edema. The toxic mussel sample showed a toxicity measured by mouse bioassay of 8575 microg of STX (saxitoxin) equivalent by 100 g of shellfish meat. Using post-column derivatization HPLC method with fluorescent on line detection was possible to measure mass amount of each paralytic shellfish poisoning (PSP) toxin yielding individual toxin concentrations. These PSP toxins were identified in the gastric content, body fluids (urine, bile and cerebrospinal fluid) and tissue samples (liver, kidney, lung, stomach, spleen, heart, brain, adrenal glands, pancreas and thyroids glands). The toxin profiles of each body fluid and tissue samples and the amount of each PSP toxin detected are reported. The PSP toxins found in the gastric content, were STX and the gonyautoxins (GTX4, GTX1, GTX5, GTX3 and GTX2) which showed to be the major amount of PSP toxins found in the victims biological samples. The PSP toxin composition in urine and bile showed as major PSP toxins neoSaxitoxin (neoSTX) and GTX4/GTX1 epimers, both STX analogues with an hydroxyl group (-OH) in the N(1) of the tetrahydropurine nucleus. The neoSTX was not present in the gastric content sample, indicating that the oxidation of N(1) in the STX tetrahydropurine nucleus resulted neoSTX, in a similar way that GTX3/GTX2 epimers were transformed in GTX4/GTX1 epimers. Beside this metabolic transformation, also the hydrolysis of carbamoyl group from STX to form its decarbomoyl analogue decarbamoylsaxitoxin was detected in liver, kidney and lung. These two findings show that PSP toxins went under metabolic transformation during the 3-4 h of human intoxication period, in which PSP toxins showed enzymatic oxidation of N(1) in the tetrahydropurine nucleus, producing neoSTX and GTX4/GTX1 epimers starting from STX and GTX3/GTX2 epimers, respectively. This study conclude, that PSP toxins are metabolically transformed by humans and that they are removed from the body by excretion in the urine and feces like any other xenobiotic compound.