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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 (n = 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 (n = 24) diluted in 150 mL of sodium chloride 0.9% (control group). Intraoperative anesthetic and surgical techniques were identical for both groups. Postoperatively, all patients received patient-controlled analgesia (morphine bolus of 1 mg; lockout interval of 8 minutes), acetaminophen, and ketoprofen for 72 hours. A blinded investigator recorded morphine consumption, which was the primary outcome. Also, the range of motion (ROM) and static and dynamic pain were assessed at 6, 12, 36, and 60 hours after surgery. The incidence of adverse events, time to readiness for discharge, and length of hospital stay were also recorded. The median of total cumulative morphine consumption was 16 mg (range, 0-62 mg) in the GTX 2/3 group and 9 mg (range, 0-54 mg) in control group, which did not reach statistical difference (median test, p = 0.40). Furthermore, static and dynamic pain scores were similar at all time intervals. GTX 2/3 was inferior in range of motion at 6 and 12 hours; nevertheless, we noted no difference after 36 hours. No differences between groups were found in terms of complications, side effects, or length of hospital stay. No significant differences were found between groups in terms of breakthrough morphine requirement. However, local anesthetic use resulted in an increased ROM in the first 12 hours. This prospective randomized clinical trial shows that GTX 2/3 is a safe and efficient drug for pain control after TKA; nevertheless, more studies using GTX 2/3 with larger populations are needed to confirm the safety profile and efficiency. This is level 1 therapeutic study, randomized, double-blind clinical trial.

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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. In this study, we test the effect of Neosaxitoxin, a phycotoxin from Paralytic Shellfish Poison, in the remediation of osteoarthritis equine clinical symptoms such as pain (showed in lameness) and inflammation quantifying the amounts of pro-inflammatory markers like cellular infiltration, TNF-alpha and nitric oxide in the synovial fluid obtained from the horse damaged joint. The outcomes show that Neosaxitoxin blocks pain for long lasting period (average 24.7 days). Furthermore, the amounts of pro-inflammatory markers were reduced and consequently an enhanced horse's well-being was obtained. Neosaxitoxin showed to be a candidate for establishing treatment protocols for OA, being safe and effective as a pain blocker in equine osteoarthritis.

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(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 264.7 and equine PBMC cells were incubated with or without 100 ng/mL LPS in the presence or absence of NeoSTX (1µM). The expression of inflammatory mediators was assessed: nitric oxide (NO) content using the Griess assay, TNF-α content using the ELISA assay, and mRNA of inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) using a real-time polymerase chain reaction. (3) Results: NeoSTX (1 µM) significantly inhibited the release of NO, TNF-α, and expression of iNOS, IL-1ß, and TNF-α in LPS-activated macrophages of both species studied. Furthermore, our study shows that the LPS-induced release of inflammatory mediators was suppressed by NeoSTX. Additionally, NeoSTX deactivated polarized macrophages to M1 by LPS without compromising its polarization towards M2. (4) Conclusions: NeoSTX inhibits LPS-induced release of inflammatory mediators from macrophages, and these effects may be mediated by the blockade of voltage-gated sodium channels (VGSC).

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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. We studied the estrous cycling activity, follicular morphology, steroid plasma levels, and norepinephrine concentration. NeoSTX administered together with EV decreased NA intraovarian levels that were induced by EV, increased the number of corpora lutea, decreased the number of follicular cyst found after EV administration, and decreased the previously increased testosterone plasma levels induced by the PCO phenotype. Estrous cycling activity also recovered. NeoSTX applied after 30 days of EV administration showed near recovery of ovary function, suggesting that there is a specific window in which follicular development could be protected from cystic development. In addition, plasma testosterone levels decreased while those of progesterone increased. Our data strongly suggest that chronic inhibition of sympathetic nerves by a locally applied long-lasting toxin is a new tool to manage the polycystic phenotype in the rat and could be applied to other mammals depending on sympathetic nerve activity.

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RESUMEN No hay guías específicas para el manejo de pacientes embarazadas con la deficiencia de Factor VII; no hay una correlación entre el nivel de FVII y el riesgo de hemorragia y el nivel del Factor VII aumento durante el embarazo. Presentamos un caso clínico, el manejo y las recomendaciones del consenso.

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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. While Neosaxitoxin and Gonyautoxin, another Paralytic Shellfish Poison (PSP) toxin, have been successfully used in humans as long-lasting pain blockers, this finding marks the first time a PSP has been shown to have an established effect in veterinary medicine.

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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. Fifteen patients received a total dose of 40 µg of Gonyautoxin during the TKA operation. Postoperatively, all patients were given a standard painkiller protocol: 100 mg of intravenous ketoprofen and 1000 mg of oral acetaminophen every 8 hours for 3 days. The Visual Analog Scale (VAS) pain score and range of motion were recorded 12, 36, and 60 hours post-surgery. All patients reported pain of 2 or less on the VAS 12 and 36 hours post-surgery. Moreover, all scored were less than 4 at 60 hours post-surgery. All patients achieved full knee extension at all times. No side effects or adverse reactions to Gonyautoxin were detected in the follow-up period. The median hospital stay was 3 days. For the first time, this study has shown the effect of blocking the neuronal transmission of pain by locally infiltrating Gonyautoxin during TKA. All patients successfully responded to the pain control. The Gonyautoxin infiltration was safe and effective, and patients experienced pain relief without the use of opioids.

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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 0.9 % NaCl, pH 6.5. Infiltration was performed via cystoscopy under spinal anesthesia. Questionnaires were administered immediately before and 7, 30 and 90 days after the procedure to measure the patients' reported pain severity and quality of life. RESULTS: This study, for the first time, showed the effect of blocking the neuronal transmission of pain by local infiltration of neosaxitoxin into the bladder submucosa. All five patients successfully responded to the treatment. Furthermore, the analgesic effect lasted for the entire 90 days of follow-up without the need for a second infiltration, and no adverse reactions to neosaxitoxin were detected. CONCLUSIONS: Neosaxitoxin infiltration was shown to be a safe and effective intervention to control pain related to BPS. It was well tolerated by patients, who experienced extended pain relief and associated beneficial effects over a follow-up of 90 days. These results confirm the effectiveness of neosaxitoxin as a long-acting local pain blocker.

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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.

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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. Indeed, cells can withstand high concentrations of the toxin at 4 h exposure, the time chosen considering the maximum time before total gastric emptying. We have proved that this increased proliferation is due to an overexpression of Cyclin B, a cyclin that promotes the passage from G2 to mitosis. In addition, we have demonstrated that OA induces activation of Akt and Erk in the three cells lines, showing that OA can activate pathways involved in oncogenesis. In conclusion, this study contributes to the knowledge about the possible effects of chronic OA consumption.

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