Anestesia intravenosa contínua com cetamina racêmica ou dextrocetamina e detomidina em cadelas / [Continuous intravenous anesthesia with racemic ketamine or dextroketamine and detomidine in female dogs]

Objetivou-se com este estudo comparar a associação de detomidina e cetamina ou dextrocetamina, por via intravenosa contínua, em oito cadelas submetidas a dois protocolos: GCD - indução anestésica com 5mg/kg e infusão intravenosa contínua de 20mg/kg/h de cetamina; e GDD - indução com 3,5mg/kg e infusão de 14mg/kg/h de dextrocetamina. Associou-se detomidina, 30µg/kg/h, em ambos os grupos. Registraram-se frequência cardíaca (FC), pressão arterial (PA), frequência respiratória (f), temperatura (TC), miorrelaxamento, analgesia, hemogasometria e eletrocardiograma, antes e 15 minutos após a MPA (Mbasal e Mmpa); após o início da infusão (Mic); a cada 10 minutos até 90 minutos (M10, M20, M30, M40, M50, M60, M70, M80 e M90); e 30 minutos após o fim da infusão (M120). Foi observada bradicardia em Mmpa no GCD e de Mmpa a M10 no GDD. Ocorreu hipotensão em Mmpa e hipertensão a partir de Mic. A f diminuiu de M10 a M30. Foram observados: onda T de alta amplitude, bloqueios atrioventriculares e parada sinusal. Ocorreu acidose respiratória. O período de recuperação foi de 219,6±72,3 minutos no GCD e de 234,1±96,8 minutos no GDD. A cetamina e a dextrocetamina, associadas à detomidina por infusão contínua, causam efeitos cardiorrespiratórios e anestésicos similares.(AU)

The combination of detomidine and ketamine or dextrocetamine for continuous intravenous infusion was compared in eight female dogs submitted to two protocols: GCD - 5mg/kg of anesthetic induction and continuous intravenous infusion of ketamine 20mg/kg/h; and GDD - induction with 3.5mg/kg and infusion of 14mg/kg/h of dextrocetamine. Detomidine, 30µg/kg/h was associated in both groups. Heart rate (HR), blood pressure (BP), respiratory rate (RR), temperature (CT), myorelaxation, analgesia, blood gas analysis and electrocardiogram were recorded before and 15 minutes after MPA (Mbasal and Mmpa); after the start of infusion (Mic); every 10 minutes to 90 minutes (M10, M20, M30, M40, M50, M60, M70, M80 and M90); and 30 minutes after the end of infusion (M120). Bradycardia was observed in Mmpa in GCD and from Mmpa to M10 in GDD. There was hypotension in Mmpa and hypertension from Mic. The RR decreased from M10 to M30. High amplitude T wave, atrioventricular blocks and sinus arrest were observed. Respiratory acidosis occurred. The recovery period was 219.6±72.3 minutes in GCD and 234.1±96.8 minutes in GDD. Ketamine and S+ ketamine associated with detomidine for continuous infusion cause cardiorespiratory and similar anesthetic effects.(AU)

Assessment of neuropharmacological potential of low molecular weight components extracted from Rhinella schneideri toad poison

Studies on toad poison are relevant since they are considered a good source of toxins that act on different biological systems. Among the molecules found in the toad poison, it can be highlighted the cardiotonic heterosides, which have a known mechanism that inhibit Na+/K+-ATPase enzyme. However, these poisons have many other molecules that may have important biological actions. Therefore, this work evaluated the action of the low molecular weight components from Rhinella schneideri toad poison on Na+/K+-ATPase and their anticonvulsive and / or neurotoxic effects, in order to detect molecules with actions of biotechnological interest. Methods: Rhinella schneideri toad (male and female) poison was collected by pressuring their parotoid glands and immediately dried and stored at -20 °C. The poison was dialysed and the water containing the low molecular mass molecules (< 8 kDa) that permeate the dialysis membrane was collected, frozen and lyophilized, resulting in the sample used in the assays, named low molecular weight fraction (LMWF). Na+/K+ ATPase was isolated from rabbit kidneys and enzyme activity assays performed by the quantification of phosphate released due to enzyme activity in the presence of LMWF (1.0; 10; 50 and 100 µg/mL) from Rhinella schneideri poison. Evaluation of the L-Glutamate (L-Glu) excitatory amino acid uptake in brain-cortical synaptosomes of Wistar rats was performed using [3H]L-glutamate and different concentration of LMWF (10-5 to 10 µg/µL). Anticonvulsant assays were performed using pentylenetetrazole (PTZ) and N-methyl-D-aspartate (NMDA) to induce seizures in Wistar rats (n= 6), which were cannulated in the lateral ventricle and treated with different concentration of LMWF (0.25; 0.5; 1.0; 2.0; 3.0 and 4.0 µg/µL) 15 min prior to the injection of the seizure agent. Results: LMWF induced a concentration-dependent inhibition of Na+/K+-ATPase (IC50% = 107.5 μg/mL). The poison induces an increased uptake of the amino acid L-glutamate in brain-cortical synaptosomes of Wistar rats. This increase in the L-glutamate uptake was observed mainly at the lowest concentrations tested (10-5 to 10-2 µg/µL). In addition, this fraction showed a very relevant central neuroprotection on seizures induced by PTZ and NMDA. Conclusions: LMWF from Rhinella schneideri poison has low molecular weight compounds, which were able to inhibit Na+/K+-ATPase activity, increase the L-glutamate uptake and reduced seizures induced by PTZ and NMDA. These results showed that LMWF is a rich source of components with biological functions of high medical and scientific interest.(AU)

Assessment of neuropharmacological potential of low molecular weight components extracted from Rhinella schneideri toad poison

Background:Studies on toad poison are relevant since they are considered a good source of toxins that act on different biological systems. Among the molecules found in the toad poison, it can be highlighted the cardiotonic heterosides, which have a known mechanism that inhibit Na+/K+-ATPase enzyme. However, these poisons have many other molecules that may have important biological actions. Therefore, this work evaluated the action of the low molecular weight components from Rhinella schneideri toad poison on Na+/K+-ATPase and their anticonvulsive and / or neurotoxic effects, in order to detect molecules with actions of biotechnological interest.Methods:Rhinella schneideri toad (male and female) poison was collected by pressuring their parotoid glands and immediately dried and stored at -20 °C. The poison was dialysed and the water containing the low molecular mass molecules (< 8 kDa) that permeate the dialysis membrane was collected, frozen and lyophilized, resulting in the sample used in the assays, named low molecular weight fraction (LMWF). Na+/K+ ATPase was isolated from rabbit kidneys and enzyme activity assays performed by the quantification of phosphate released due to enzyme activity in the presence of LMWF (1.0; 10; 50 and 100 µg/mL) from Rhinella schneideri poison. Evaluation of the L-Glutamate (L-Glu) excitatory amino acid uptake in brain-cortical synaptosomes of Wistar rats was performed using [3H]L-glutamate and different concentration of LMWF (10-5 to 10 µg/µL). Anticonvulsant assays were performed using pentylenetetrazole (PTZ) and N-methyl-D-aspartate (NMDA) to induce seizures in Wistar rats (n= 6), which were cannulated in the lateral ventricle and treated with different concentration of LMWF (0.25; 0.5; 1.0; 2.0; 3.0 and 4.0 µg/µL) 15 min prior to the injection of the seizure agent.Results:LMWF induced a concentration-dependent inhibition of Na+/K+-ATPase (IC50% = 107.5 μg/mL)...(AU)

Infusão contínua de duas doses de fentanil associadas à lidocaína e cetamina em fêmeas caninas anestesiadas com sevoflurano e submetidas à ovariohisterectomia eletiva / Continuous infusion of two doses of fentanyl associated with lidocaine and ketamine for female dogs anesthetized with sevoflurane and undergoing elective ovariohysterectomy / Infusión continua de dos dosis de fentanila asociada a lidocaína y ketamina en perras anestesiadas con sevoflurane y sometidas a ovariohisterectomía electiva

O objetivo deste trabalho foi avaliar os efeitos cardiorrespiratórios de duas doses de fentanil associadas à lidocaína e cetamina em fêmeas caninas anestesiadas com sevoflurano e submetidas à ovariohisterectomia eletiva. Foram utilizados 18 animais distribuídos aleatoriamente em dois grupos. Os animais do grupo A (GA) receberam pela via intravenosa um bolus de fentanil de 0,0018 mg/kg e os do grupo B (GB) 0,0036 mg/kg, ambos associados a lidocaína 3 mg/kg e cetamina 0,6 mg/kg. Imediatamente após o bolus realizou-se a indução com propofol seguido do início da infusão contínua (IC) de fentanil na dose de 0,0018 mg/kg/h para o GA e 0,0036 mg/kg/h para GB, ambos associados a 3 e 0,6 mg/kg/h de lidocaína e cetamina. A anestesia foi mantida com sevoflurano diluído em oxigênio 100% a 1,5V% por meio de vaporizador calibrado que foi ajustado para a manutenção do plano anestésico cirúrgico. Os animais foram posicionados em decúbito dorsal e permaneceram sob ventilação espontânea. Foram avaliados os valores basais (T0), após indução (T1) e 5 (T5), 20 (T20) e 35 (T35) minutos de IC dos seguintes parâmetros: frequência cardíaca (FC), frequência respiratória (f), pressão arterial sistólica (PAS), diastólica (PAD) e média (PAM), saturação de oxigênio na hemoglobina (SatO2), pressão parcial de dióxido de carbono (EtCO2) e o sevoflurano expirado (EtSevo). A análise estatística foi realizada através da análise de variância seguida do teste de Scott-knott. As diferenças foram consideradas significativas quando P< 0,05. A FC reduziu após 20 minutos de IC e a f, PAS, PAD e PAM diminuíram após indução anestésica. Tais diferenças não foram relevantes clinicamente e os valores se mantiveram dentro do limite fisiológico. Pode-se concluir que as duas doses de infusão contínua de fentanil produziram estabilidade cardiovascular e respiratória, além de permitirem a diminuição do requerimento de sevoflurano para a realização da ovariohisterectomia eletiva.(AU)

The aim of this study was to evaluate the cardiorespiratory effects of two doses of fentanyl associated with lidocaine and ketamine in canine females anesthetized with sevoflurane and submitted to elective ovariohysterectomy. 18 animals were randomly assigned to two groups. Group A (GA) animals received a loading dose intravenously of fentanyl 0.0018 mg/kg and those of group B (GB) 0.0036 mg/kg, both associated with lidocaine 3 mg/kg and ketamine 0, 6 mg/kg. Immediately after the loading dose, induction with propofol was realized followed by continuous infusion (CI) of fentanyl at the dose of 0.0018 mg/kg/h for GA and 0.0036 mg/kg/h for GB, both associated to 3 and 0.6 mg/kg/h of lidocaine and ketamine. The anesthesia was maintained with sevoflurane diluted in 100% oxygen at 1.5% by a calibrated vaporizer that was adjusted for the maintenance of the surgical anesthetic plane. The animals were placed in dorsal decubitus position and remained under spontaneous ventilation. Was evaluated the baseline values (T0), after induction (T1) and 5 (T5), 20 (T20) and 35 (T35) minutes of following parameters: heart rate (HR), respiratory rate (f), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MAP), oxygen saturation in hemoglobin (SatO2), partial carbon dioxide (EtCO2) pressure and expired sevoflurane (EtSevo). Statistical analysis was performed through analysis of variance followed by the Scott-knott test. Differences were considered significant when P< 0.05. HR decreased after 20 minutes of CI and f, SBP, DBP and MAP decreased after anesthetic induction. These differences were not clinically relevant and the values remained within the physiological limit. It can be concluded that the two doses of continuous infusion of fentanyl produced cardiovascular and respiratory stability, besides allowing the reduction of the sevoflurane requirement for elective ovariohysterectomy.(AU)

El objetivo de este trabajo fue evaluar los efectos cardiorrespiratorios de dos dosis de fentanil asociadas a la lidocaína y cetamina en perras anestesiadas con sevoflurane y sometidas a la ovariohisterectomía electiva. Se utilizaron 18 animales distribuidos aleatoriamente en dos grupos. Los animales del grupo A (GA) recibieron por vía intravenosa un bolus de fentanil de 0,0018 mg/kg y los del grupo B (GB) 0,0036 mg/kg, ambos asociados a lidocaína 3 mg/kg y cetamina 0,6 mg/kg. Inmediatamente después del bolus se realizó la inducción con propofol seguido del inicio de la infusión continua (IC) de fentanil a la dosis de 0,0018 mg/kg/h para el GA y 0,0036 mg/kg/h para GB, ambos asociados a 3 y 0,6 mg/kg/h de lidocaína y cetamina. La anestesia fue mantenida con sevoflurane diluido en oxígeno 100% a 1,5V% a través de vaporizador calibrado que fue ajustado para el mantenimiento del plano anestésico quirúrgico. Los animales fueron colocados en decúbito dorsal y permanecieron bajo ventilación espontánea. Se evaluaron los valores basales (T0), después de la inducción (T1) y 5 (T5), 20 (T20) y 35 (T35) minutos de IC de los siguientes parámetros: frecuencia cardíaca (FC), frecuencia respiratoria (f), presión arterial sistólica (PAS), presión arterial diastólica (PAD) y presión arterial media (PAM), saturación de oxígeno en la hemoglobina (SatO2), presión parcial de dióxido de carbón (EtCO2) y el sevoflurane expirado (EtSevo). El análisis estadístico fue realizado a través del análisis de varianza seguida de la prueba de Scott-knott. Las diferencias se consideraron significativas cuando P< 0,05. La FC redujo después de 20 minutos de IC y la f, PAS, PAD y PAM disminuyeron después de la inducción anestésica. Estas diferencias no fueron relevantes clínicamente y los valores se mantuvieron dentro del límite fisiológico. Se puede concluir que las dos dosis de infusión continua de fentanil produjeron estabilidad cardiovascular y respiratoria, además de permitir la disminución del requerimiento de sevoflurane para la realización de la ovariohisterectomía electiva.(AU)

Infusão contínua de duas doses de fentanil associadas à lidocaína e cetamina em fêmeas caninas anestesiadas com sevoflurano e submetidas à ovariohisterectomia eletiva / Continuous infusion of two doses of fentanyl associated with lidocaine and ketamine for female dogs anesthetized with sevoflurane and undergoing elective ovariohysterectomy / Infusión continua de dos dosis de fentanila asociada a lidocaína y ketamina en perras anestesiadas con sevoflurane y sometidas a ovariohisterectomía electiva

O objetivo deste trabalho foi avaliar os efeitos cardiorrespiratórios de duas doses de fentanil associadas à lidocaína e cetamina em fêmeas caninas anestesiadas com sevoflurano e submetidas à ovariohisterectomia eletiva. Foram utilizados 18 animais distribuídos aleatoriamente em dois grupos. Os animais do grupo A (GA) receberam pela via intravenosa um bolus de fentanil de 0,0018 mg/kg e os do grupo B (GB) 0,0036 mg/kg, ambos associados a lidocaína 3 mg/kg e cetamina 0,6 mg/kg. Imediatamente após o bolus realizou-se a indução com propofol seguido do início da infusão contínua (IC) de fentanil na dose de 0,0018 mg/kg/h para o GA e 0,0036 mg/kg/h para GB, ambos associados a 3 e 0,6 mg/kg/h de lidocaína e cetamina. A anestesia foi mantida com sevoflurano diluído em oxigênio 100% a 1,5V% por meio de vaporizador calibrado que foi ajustado para a manutenção do plano anestésico cirúrgico. Os animais foram posicionados em decúbito dorsal e permaneceram sob ventilação espontânea. Foram avaliados os valores basais (T0), após indução (T1) e 5 (T5), 20 (T20) e 35 (T35) minutos de IC dos seguintes parâmetros: frequência cardíaca (FC), frequência respiratória (f), pressão arterial sistólica (PAS), diastólica (PAD) e média (PAM), saturação de oxigênio na hemoglobina (SatO2), pressão parcial de dióxido de carbono (EtCO2) e o sevoflurano expirado (EtSevo). A análise estatística foi realizada através da análise de variância seguida do teste de Scott-knott. As diferenças foram consideradas significativas quando P< 0,05. A FC reduziu após 20 minutos de IC e a f, PAS, PAD e PAM diminuíram após indução anestésica. Tais diferenças não foram relevantes clinicamente e os valores se mantiveram dentro do limite fisiológico. Pode-se concluir que as duas doses de infusão contínua de fentanil produziram estabilidade cardiovascular e respiratória, além de permitirem a diminuição do requerimento de sevoflurano para a realização da ovariohisterectomia eletiva.

The aim of this study was to evaluate the cardiorespiratory effects of two doses of fentanyl associated with lidocaine and ketamine in canine females anesthetized with sevoflurane and submitted to elective ovariohysterectomy. 18 animals were randomly assigned to two groups. Group A (GA) animals received a loading dose intravenously of fentanyl 0.0018 mg/kg and those of group B (GB) 0.0036 mg/kg, both associated with lidocaine 3 mg/kg and ketamine 0, 6 mg/kg. Immediately after the loading dose, induction with propofol was realized followed by continuous infusion (CI) of fentanyl at the dose of 0.0018 mg/kg/h for GA and 0.0036 mg/kg/h for GB, both associated to 3 and 0.6 mg/kg/h of lidocaine and ketamine. The anesthesia was maintained with sevoflurane diluted in 100% oxygen at 1.5% by a calibrated vaporizer that was adjusted for the maintenance of the surgical anesthetic plane. The animals were placed in dorsal decubitus position and remained under spontaneous ventilation. Was evaluated the baseline values (T0), after induction (T1) and 5 (T5), 20 (T20) and 35 (T35) minutes of following parameters: heart rate (HR), respiratory rate (f), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MAP), oxygen saturation in hemoglobin (SatO2), partial carbon dioxide (EtCO2) pressure and expired sevoflurane (EtSevo). Statistical analysis was performed through analysis of variance followed by the Scott-knott test. Differences were considered significant when P< 0.05. HR decreased after 20 minutes of CI and f, SBP, DBP and MAP decreased after anesthetic induction. These differences were not clinically relevant and the values remained within the physiological limit. It can be concluded that the two doses of continuous infusion of fentanyl produced cardiovascular and respiratory stability, besides allowing the reduction of the sevoflurane requirement for elective ovariohysterectomy.

El objetivo de este trabajo fue evaluar los efectos cardiorrespiratorios de dos dosis de fentanil asociadas a la lidocaína y cetamina en perras anestesiadas con sevoflurane y sometidas a la ovariohisterectomía electiva. Se utilizaron 18 animales distribuidos aleatoriamente en dos grupos. Los animales del grupo A (GA) recibieron por vía intravenosa un bolus de fentanil de 0,0018 mg/kg y los del grupo B (GB) 0,0036 mg/kg, ambos asociados a lidocaína 3 mg/kg y cetamina 0,6 mg/kg. Inmediatamente después del bolus se realizó la inducción con propofol seguido del inicio de la infusión continua (IC) de fentanil a la dosis de 0,0018 mg/kg/h para el GA y 0,0036 mg/kg/h para GB, ambos asociados a 3 y 0,6 mg/kg/h de lidocaína y cetamina. La anestesia fue mantenida con sevoflurane diluido en oxígeno 100% a 1,5V% a través de vaporizador calibrado que fue ajustado para el mantenimiento del plano anestésico quirúrgico. Los animales fueron colocados en decúbito dorsal y permanecieron bajo ventilación espontánea. Se evaluaron los valores basales (T0), después de la inducción (T1) y 5 (T5), 20 (T20) y 35 (T35) minutos de IC de los siguientes parámetros: frecuencia cardíaca (FC), frecuencia respiratoria (f), presión arterial sistólica (PAS), presión arterial diastólica (PAD) y presión arterial media (PAM), saturación de oxígeno en la hemoglobina (SatO2), presión parcial de dióxido de carbón (EtCO2) y el sevoflurane expirado (EtSevo). El análisis estadístico fue realizado a través del análisis de varianza seguida de la prueba de Scott-knott. Las diferencias se consideraron significativas cuando P< 0,05. La FC redujo después de 20 minutos de IC y la f, PAS, PAD y PAM disminuyeron después de la inducción anestésica. Estas diferencias no fueron relevantes clínicamente y los valores se mantuvieron dentro del límite fisiológico. Se puede concluir que las dos dosis de infusión continua de fentanil produjeron estabilidad cardiovascular y respiratoria, además de permitir la disminución del requerimiento de sevoflurane para la realización de la ovariohisterectomía electiva.

Antinociceptive effect of PnTx4(5-5), a peptide from Phoneutria nigriventer spider venom, in rat models and the involvement of glutamatergic system

Background:The venom of Phoneutria nigriventer spider is a source of numerous bioactive substances, including some toxins active in insects. An example is PnTx4(5-5) that shows a high insecticidal activity and no apparent toxicity to mice, although it inhibited NMDA-evoked currents in rat hippocampal neurons. In this work the analgesic activity of PnTx4(5-5) (renamed Γ-ctenitoxin-Pn1a) was investigated.Methods:The antinociceptive activity was evaluated using the paw pressure test in rats, after hyperalgesia induction with intraplantar injection of carrageenan or prostaglandin E2 (PGE2).Results:PnTx4(5-5), subcutaneously injected, was able to reduce the hyperalgesia induced by PGE2 in rat paw, demonstrating a systemic effect. PnTx4(5-5) administered in the plantar surface of the paw caused a peripheral and dose-dependent antinociceptive effect on hyperalgesia induced by carrageenan or PGE2. The hyperalgesic effect observed in these two pain models was completely reversed with 5 µg of PnTx4(5-5). Intraplantar administration of L-glutamate induced hyperalgesic effect that was significantly reverted by 5 μg of PnTx4(5-5) injection in rat paw.Conclusion:The antinociceptive effect for PnTx4(5-5) was demonstrated against different rat pain models, i.e. induced by PGE2, carrageenan or glutamate. We suggest that the antinociceptive effect of PnTx4(5-5) may be related to an inhibitory activity on the glutamatergic system.(AU)

Antinociceptive effect of PnTx4(5-5), a peptide from Phoneutria nigriventer spider venom, in rat models and the involvement of glutamatergic system

The venom of Phoneutria nigriventer spider is a source of numerous bioactive substances, including some toxins active in insects. An example is PnTx4(5-5) that shows a high insecticidal activity and no apparent toxicity to mice, although it inhibited NMDA-evoked currents in rat hippocampal neurons. In this work the analgesic activity of PnTx4(5-5) (renamed Γ-ctenitoxin-Pn1a) was investigated. Methods: The antinociceptive activity was evaluated using the paw pressure test in rats, after hyperalgesia induction with intraplantar injection of carrageenan or prostaglandin E2 (PGE2). Results: PnTx4(5-5), subcutaneously injected, was able to reduce the hyperalgesia induced by PGE2 in rat paw, demonstrating a systemic effect. PnTx4(5-5) administered in the plantar surface of the paw caused a peripheral and dose-dependent antinociceptive effect on hyperalgesia induced by carrageenan or PGE2. The hyperalgesic effect observed in these two pain models was completely reversed with 5 µg of PnTx4(5-5). Intraplantar administration of L-glutamate induced hyperalgesic effect that was significantly reverted by 5 μg of PnTx4(5-5) injection in rat paw. Conclusion: The antinociceptive effect for PnTx4(5-5) was demonstrated against different rat pain models, i.e. induced by PGE2, carrageenan or glutamate. We suggest that the antinociceptive effect of PnTx4(5-5) may be related to an inhibitory activity on the glutamatergic system.(AU)

In silico analysis of binding interaction of conantokins with NMDA receptors for potential therapeutic use in Alzheimers disease

Abstract Background The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist. Among several antagonists, conantokins from cone snails are reported to bind to NMDA receptors. Methods This study was designed to analyze the binding mode of conantokins with NMDA receptors in both humans and rats. To study interactions, dockings were performed using AutoDock 4.2 and their results were further analyzed using various computational tools. Results Detailed analyses revealed that these ligands can bind to active site residues of both receptors as reported in previous studies. Conclusions In light of the present results, we suggest that these conantokins can act as antagonists of those receptors and play an important role in understanding the importance of inhibition of NMDA receptors for treatment of Alzheimers disease.

In silico analysis of binding interaction of conantokins with NMDA receptors for potential therapeutic use in Alzheimer's disease

Background The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist. Among several antagonists, conantokins from cone snails are reported to bind to NMDA receptors. Methods This study was designed to analyze the binding mode of conantokins with NMDA receptors in both humans and rats. To study interactions, dockings were performed using AutoDock 4.2 and their results were further analyzed using various computational tools. Results Detailed analyses revealed that these ligands can bind to active site residues of both receptors as reported in previous studies. Conclusions In light of the present results, we suggest that these conantokins can act as antagonists of those receptors and play an important role in understanding the importance of inhibition of NMDA receptors for treatment of Alzheimer's disease.(AU)

Total Intravenous Anesthesia with Propofol Associated with Fentanyl, Lidocaine or Ketamine in Bitches Submitted to Elective Ovariohysterectomy

Background: Total intravenous anesthesia with propofol is an alternative to inhalation anesthesia because it offers smoother anesthetic recovery, however, since propofol does not have adequate analgesic action, it is necessary to associate it with some drug to avoid the pain process. In addition, the combination may minimize cardiovascular depression resulting from continuous infusion of propofol by reducing infusion rate. The aim of this study was to evaluate cardiorespiratory parameters and anesthetic recovery in bitches submitted to continuous infusion of fentanyl, lidocaine and ketamine associated with total intravenous anesthesia with propofol and submitted to elective ovariohisterectomy.Materials, Methods & Results: Twenty-four bitches were medicated intramuscularly with 0.03 mg/kg of acepromazine. After 30 min, they were divided into three groups with different analgesic treatments: group F (GF) received a loading dose (LD) of 0.0036 mg/kg fentanyl, followed by continuous infusion of 0.0036 mg/kg/h; group L (GL), LD of 3 mg/kg lidocaine, followed by 3 mg/kg/h and group K (GK), LD of 0.6 mg/kg ketamine, followed by 0.6 mg/kg/h. First a LD of analgesic treatment was administered, followed by induction (to the effect) and beginning of continuous infusion of the analgesic treatment and propofol. The animals were intubated with endotracheal tube of adequate size, and conn

Anestesia total intravenosa com propofol associado ao fentanil, lidocaínaou cetamina em cadelas submetidas à ovariossalpingohisterectomia eletiva / Total intravenous anesthesia with propofol associated with fentanyl, lidocaine or ketamine in bitches submitted to elective ovariohysterectomy

Background: Total intravenous anesthesia with propofol is an alternative to inhalation anesthesia because it offers smoother anesthetic recovery, however, since propofol does not have adequate analgesic action, it is necessary to associate it with some drug to avoid the pain process. In addition, the combination may minimize cardiovascular depression resulting from continuous infusion of propofol by reducing infusion rate. The aim of this study was to evaluate cardiorespiratory parameters and anesthetic recovery in bitches submitted to continuous infusion of fentanyl, lidocaine and ketamine associated with total intravenous anesthesia with propofol and submitted to elective ovariohisterectomy. Materials, Methods & Results: Twenty-four bitches were medicated intramuscularly with 0.03 mg/kg of acepromazine. After 30 min, they were divided into three groups with different analgesic treatments: group F (GF) received a loading dose (LD) of 0.0036 mg/kg fentanyl, followed by continuous infusion of 0.0036 mg/kg/h; group L (GL), LD of 3 mg/kg lidocaine, followed by 3 mg/kg/h and group K (GK), LD of 0.6 mg/kg ketamine, followed by 0.6 mg/kg/h. First a LD of analgesic treatment was administered, followed by induction (to the effect) and beginning of continuous infusion of the analgesic treatment and propofol. The animals were intubated with endotracheal tube of adequate size, and connected to 100% oxygen, being kept under spontaneous ventilation during the entire period of anesthetic maintenance. The infusion of propofol started at 0.34 mg/kg/min and was adjusted so as to maintain the surgical anesthesia plane of Guedel and the cardiovascular parameters within the physiological limits for the species. The cardiorespiratory parameters were measured at different moments: basal (before application of any drug) and 5, 15, 20, 30, 40, 50, 60, 70 and 80 min after induction. The surgery started 20 min after anesthetic induction and lasted 60 min. […](AU)

Minimum alveolar concentration of isoflurane in dogs administered a single intramuscular injection of racemic or S (+)-ketamine after premedication with acepromazine-morphine / Concentração alveolar mínima do isoflurano em cães tratados com dose única intramuscular de cetamina racêmica ou S (+) após premedicação com acepromazina-morfina

The present study evaluated the minimum alveolar concentration of isoflurane (ISOMAC) in twenty three dogs premedicated with acepromazine (0.02mgkg-1) and morphine (0.5mgkg-1) and administered racemic (RK) or S(+)-ketamine (SK). Dogs randomly received a single dose (3mgkg-1, IM) of either RK or SK 15minutes after anesthetic induction with propofol. The ISOMAC was determined by the up-and-down method. Approximately 20 minutes after administration of RK or SK, a surgical noxious stimulus was applied and the response evaluated. The ISOMAC was 0.50±0.01% in the RK group (n=10) and 0.31±0.04% in the SK group (n=13). The ISOMAC was 38% lower in the SK group compared to the RK group. Results of the present study revealed that in dogs premedicated with acepromazine and morphine, IM administration of 3mgkg-1 ketamine approximately 20 minutes before the noxious stimulus produced clinically important reduction in the ISOMAC and the MAC-sparing effect was significantly greater with SK compared to RK.

No presente estudo, foi avaliada a concentração alveolar mínima do isoflurano (CAMISO) em vinte e três cães premedicados com acepromazina (0,02mgkg-1) e morfina (0,5mgkg-1) e tratados com cetamina racêmica (CR) ou S(+) (CS). Os cães receberam aleatoriamente dose única (3mgkg-1, IM) de CR ou CS, decorridos 15 minutos da indução anestésica com propofol. A CAMISO foi determinada pelo método up-and-down. Aproximadamente 20 minutos após a administração da CR ou CS, um estímulo nociceptivo (cirúrgico) foi aplicado e a resposta avaliada. A CAMISO foi 0,50±0,01% no CR (n=10) e 0,31±0,04% no CS (n=13). A CAMISO foi 38% menor no CS comparado ao CR. Os resultados deste estudo revelaram que, em cães premedicados com acepromazina e morfina, a administração IM de 3mgkg-1 de cetamina, aproximadamente 20 minutos antes do estímulo nociceptivo, causou redução clinicamente importante na CAMISO e o efeito redutor na CAMISO é significativamente maior com CS do que com CR.

In silico analysis of binding interaction of conantokins with NMDA receptors for potential therapeutic use in Alzheimer's disease

Background The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist. Among several antagonists, conantokins from cone snails are reported to bind to NMDA receptors. Methods This study was designed to analyze the binding mode of conantokins with NMDA receptors in both humans and rats. To study interactions, dockings were performed using AutoDock 4.2 and their results were further analyzed using various computational tools. Results Detailed analyses revealed that these ligands can bind to active site residues of both receptors as reported in previous studies. Conclusions In light of the present results, we suggest that these conantokins can act as antagonists of those receptors and play an important role in understanding the importance of inhibition of NMDA receptors for treatment of Alzheimer's disease.(AU)

Anestesia total intravenosa com propofol associado ao fentanil, lidocaínaou cetamina em cadelas submetidas à ovariossalpingohisterectomia eletiva / Total intravenous anesthesia with propofol associated with fentanyl, lidocaine or ketamine in bitches submitted to elective ovariohysterectomy

Background: Total intravenous anesthesia with propofol is an alternative to inhalation anesthesia because it offers smoother anesthetic recovery, however, since propofol does not have adequate analgesic action, it is necessary to associate it with some drug to avoid the pain process. In addition, the combination may minimize cardiovascular depression resulting from continuous infusion of propofol by reducing infusion rate. The aim of this study was to evaluate cardiorespiratory parameters and anesthetic recovery in bitches submitted to continuous infusion of fentanyl, lidocaine and ketamine associated with total intravenous anesthesia with propofol and submitted to elective ovariohisterectomy. Materials, Methods & Results: Twenty-four bitches were medicated intramuscularly with 0.03 mg/kg of acepromazine. After 30 min, they were divided into three groups with different analgesic treatments: group F (GF) received a loading dose (LD) of 0.0036 mg/kg fentanyl, followed by continuous infusion of 0.0036 mg/kg/h; group L (GL), LD of 3 mg/kg lidocaine, followed by 3 mg/kg/h and group K (GK), LD of 0.6 mg/kg ketamine, followed by 0.6 mg/kg/h. First a LD of analgesic treatment was administered, followed by induction (to the effect) and beginning of continuous infusion of the analgesic treatment and propofol. The animals were intubated with endotracheal tube of adequate size, and connected to 100% oxygen, being kept under spontaneous ventilation during the entire period of anesthetic maintenance. The infusion of propofol started at 0.34 mg/kg/min and was adjusted so as to maintain the surgical anesthesia plane of Guedel and the cardiovascular parameters within the physiological limits for the species. The cardiorespiratory parameters were measured at different moments: basal (before application of any drug) and 5, 15, 20, 30, 40, 50, 60, 70 and 80 min after induction. The surgery started 20 min after anesthetic induction and lasted 60 min. […]

Minimum alveolar concentration of isoflurane in dogs administered a single intramuscular injection of racemic or S (+)-ketamine after premedication with acepromazine-morphine / Concentração alveolar mínima do isoflurano em cães tratados com dose única intramuscular de cetamina racêmica ou S (+) após premedicação com acepromazina-morfina

The present study evaluated the minimum alveolar concentration of isoflurane (ISOMAC) in twenty three dogs premedicated with acepromazine (0.02mgkg-1) and morphine (0.5mgkg-1) and administered racemic (RK) or S(+)-ketamine (SK). Dogs randomly received a single dose (3mgkg-1, IM) of either RK or SK 15minutes after anesthetic induction with propofol. The ISOMAC was determined by the up-and-down method. Approximately 20 minutes after administration of RK or SK, a surgical noxious stimulus was applied and the response evaluated. The ISOMAC was 0.50±0.01% in the RK group (n=10) and 0.31±0.04% in the SK group (n=13). The ISOMAC was 38% lower in the SK group compared to the RK group. Results of the present study revealed that in dogs premedicated with acepromazine and morphine, IM administration of 3mgkg-1 ketamine approximately 20 minutes before the noxious stimulus produced clinically important reduction in the ISOMAC and the MAC-sparing effect was significantly greater with SK compared to RK.(AU)

No presente estudo, foi avaliada a concentração alveolar mínima do isoflurano (CAMISO) em vinte e três cães premedicados com acepromazina (0,02mgkg-1) e morfina (0,5mgkg-1) e tratados com cetamina racêmica (CR) ou S(+) (CS). Os cães receberam aleatoriamente dose única (3mgkg-1, IM) de CR ou CS, decorridos 15 minutos da indução anestésica com propofol. A CAMISO foi determinada pelo método up-and-down. Aproximadamente 20 minutos após a administração da CR ou CS, um estímulo nociceptivo (cirúrgico) foi aplicado e a resposta avaliada. A CAMISO foi 0,50±0,01% no CR (n=10) e 0,31±0,04% no CS (n=13). A CAMISO foi 38% menor no CS comparado ao CR. Os resultados deste estudo revelaram que, em cães premedicados com acepromazina e morfina, a administração IM de 3mgkg-1 de cetamina, aproximadamente 20 minutos antes do estímulo nociceptivo, causou redução clinicamente importante na CAMISO e o efeito redutor na CAMISO é significativamente maior com CS do que com CR.(AU)

INFLUÊNCIA DA ADMINISTRAÇÃO PERIOPERATÓRIA DO SULFATO DE MAGNÉSIO EM CADELAS ANESTESIADAS COM PROPOFOL E FENTANIL PARA OVARIOHISTERECTOMIA

A anestesia balanceada envolve a administração de diferentes agentes para criar o estado anestésico. Essa abordagem evita a dependência exclusiva de opióides para controlar a nocicepção no período transoperatório e a dor no pós-operatório. Com base no fato de que o sulfato de magnésio (MgSO4) impede a sensibilização central causada pela estimulação nociceptiva periférica atuando como um antagonista do receptor NMDA, seu efeito analgésico e redutor de anestésico, foi demonstrado em modelos animais e humanos. Dessa maneira, o objetivo do presente estudo foi avaliar o efeito da administração de sulfato de magnésio no requerimento anestésico de propofol e fentanil, na resposta ao estímulo nociceptivo durante o período transoperatório e na analgesia pós-operatória imediata de cadelas submetidas à ovariohisterectomia. Trinta e duas cadelas, sedadas com acepromazina 0,02 mg/kg intramuscular, foram divididas aleatoriamente por sorteio em quatro grupos: PMFA - MgSO4 e fentanil alta dose; PFA - NaCl 0,9% e fentanil alta dose; PMFB- MgSO4 e fentanil baixa dose; PFB - NaCl 0,9% e fentanil baixa dose. As pacientes foram induzidas com propofol 1mg/kg/min dose efeito, ato contínuo permaneceram em infusão contínua dos tratamentos selecionados, com titulação da taxa de propofol de acordo com as variáveis cardiorrespiratórias e plano anestésico. Caso houvesse incremento de 20% da FC, FR ou PAS, foi administrado fentanil 2,5mcg/kg. Durante o transoperatório, avaliou-se a dose de propofol necessária para indução e manutenção anestésica, efeito antinociceptivo transoperatório através das variáveis cardiorrespiratórias, com o requerimento de doses adicionais de fentanil, qualidade de indução, de intubação e de relaxamento muscular transoperatório. Após o término da cirurgia foram avaliados os tempos de extubação, de sustentação de cabeça e posicionamento espontâneo em esternal, a qualidade de recuperação anestésica e a avaliação da dor utilizando a escala de Glasgow e os parâmetros fisiológicos. A concentração sérica de magnésio total foi mensurada em três diferentes tempos. Quanto aos resultados, houve diferença estatística entre os grupos quanto ao número cadelas que necessitaram doses adicionais de fentanil no transoperatório PMFA (4/8) PFA (4/8), PMFB (5/8) e PFB (7/8). No pós-operatório não houve diferença significativa na avaliação de dor pela escala de Glasgow, porém mais cadelas do grupo PFB, necessitaram resgate analgésico. No trans e pós-operatório, a concentração média de magnésio sérico total foi estatisticamente maior do que o valor pré-operatório (p <0,005) nos grupos PMFA e PMFB. Nas demais variáveis avaliadas, não houve diferença estatística entre os grupos. Este estudo não encontrou benefício clínico evidente na administração de sulfato de magnésio em cadelas sedadas com acepromazina e anestesiadas com fentanil e propofol em cirurgia de ovariohisterectomia

Balanced anesthesia involves administering different agents to create an optimal anesthetic state. This approach avoids exclusive dependence on opioids to control intraoperative nociception and postoperative pain. Magnesium sulfate (MgSO4) prevents central sensitization caused by peripheral nociceptive stimulation by acting as an NMDA receptor antagonist, its analgesic and anesthetic-reducing effects have been demonstrated in animal and human models. Thus, the aim of the present study was to evaluate the effect of magnesium sulphate administration on the anesthetic requirement of propofol and fentanyl, on the response to nociceptive stimulus during the intraoperative period and on the immediate postoperative analgesia of bitches undergoing ovariohysterectomy. Thirty-two bitches sedated with acepromazine 0.02 mg/kg intramuscularly, were randomly divided into four groups: PMFA - MgSO4 and high dose fentanyl; PFA - 0.9% NaCl and high dose fentanyl; PMFB - MgSO4 and low dose fentanyl; PFB - 0.9% NaCl and low dose fentanyl. Anesthesia was induced with propofol (1 mg/kg/min) to effect and maintained with continuous rate infusion of selected treatments. Propofol rate was titrated to maintain cardiorespiratory variables within normal range and an adequate anesthetic plan. If a 20% increase in HR, RR or SAP were noted, 2.5mcg/kg fentanyl was administered. The total dose of propofol necessary for anesthetic induction and maintenance was evaluated. Intraoperative antinociceptive effect was assessed through cardiorespiratory variables and the requirement of additional doses of fentanyl. Other variables such as quality of induction, intubation and intraoperative degree of muscle relaxation were evaluated. Time to extubation, head support and spontaneous sternal recumbency were recorded. The quality of anesthetic recovery and pain were assessed using subjective scales. Serum magnesium concentrations were measured at three different time points (pre-, intra- and postoperatively). The present study demonstrated a significant difference among the groups regarding the number of bitches that needed additional doses of fentanyl in the intraoperative period PMFA (4/8) PFA (4/8), PMFB (5/8) and PFB (7/8). There was no significant difference in pain assessment using the Glasgow pain scale in the postoperative period, however, more bitches in the PFB group required analgesic rescue (2/8). The mean serum magnesium concentration was higher in the postoperative than its preoperative values (p <0.005) in the PMFA and PMFB groups. The other variables evaluated did not differ significantly among the groups. This study did not find clear clinical benefits in administering magnesium sulfate in bitches sedated with acepromazine and anesthetized with fentanyl and propofol undergoing ovariohysterectomy.

Subarachnoid injection of ifenprodil and ketamine association improves the anti-hyperalgesic action of ketamine in dogs / Injeção subaracnoidea da associação ifenprodil e cetamina melhora a ação anti-hiperalgésica da cetamina em cães

To test clinically whether a small dose of ifenprodil can enhance the anti-hyperalgesic effect of ketamine in dogs, a prospective randomized cross-over study was done with eight mongrel dogs (weighing 16.9 ± 3.7kg). Animals received two distinct treatments: ketamine (0.3mg kg-1; KT) and an ifenprodil plus ketamine combination (0.03mg kg-1 and 0.3mg kg-1, respectively; IKT). Dogs were anesthetized with propofol (5mg kg-1 intravenously) and a subarachnoid needle was placed between the 5th and 6th lumbar vertebrae. Five minutes after subarachnoid injection of KT or IKT, an incision including cutaneous and subcutaneous tissues was made on the common pad of one hind limb and was immediately closed with a simple interrupted suture pattern. The dogs were treated again 20 days later, using the contralateral pad and the opposite treatment. Sedation score (SS), lameness score (LS), heart rate (HR), respiratory rate (fR), and mechanical nociceptive threshold using von Frey filaments, were evaluated before anesthesia and at 1, 1.5, 2, 3, 4, 8, 12, and 24 hours after subarachnoid injection. There were no differences in SS, LS, HR or fR between treatments. The intensity of hyperalgesia was higher in KT than in IKT for 24 hours. The anti-hyperalgesic effect of IKT remained without statistical significant difference between 1 and 24 h. Prior subarachnoid administration of ifenprodil enhances the anti-hyperalgesic effect of subarachnoid ketamine in dogs. Ifenprodil can be co-administrated with ketamine to enhance its anti-hyperalgesic effect and to reduce acute post-incisional hyperalgesia without motor impairment and sedation(AU)

Com a finalidade de testar se uma dose baixa de ifenprodil pode melhorar a ação anti-hiperalgésica da cetamina em cães, um estudo randomizado prospectivo no formato cross-over foi realizado em oito cães sem raça definida (pesando 16,9±3.7kg). Os animais receberam dois tratamentos distintos: cetamina (0,3mg kg-1; KT) e a associação de ifenprodil com cetamina (0,03mg kg-1 e 0,3mg kg-1, respectivamente; IKT). Os cães foram anestesiados com propofol (5mg kg-1, via intravenosa), e uma agulha subaracnoidea foi introduzida entre a quinta e sexta vértebras lombares. Após cinco minutos da injeção subaracnoidea de KT ou IKT, uma incisão abrangendo os tecidos cutâneo e subcutâneo foi realizada no coxim plantar comum de um dos membros pélvicos e imediatamente fechada com um padrão de sutura simples e interrompido. Os cães foram novamente tratados após 20 dias, usando-se o coxim plantar contralateral e o outro tratamento. Os escores de sedação (SS) e claudicação (LS); as frequências cardíacas (HR) e respiratória (fR) e o limiar nociceptivo ao estímulo mecânico, utilizando os filamentos de von Frey, foram avaliados antes da anestesia e uma, uma e meia; duas; três; quatro; oito; 12 e 24 horas após a injeção subaracnoidea. Não foram observadas diferenças significativas em SS, LS, HR ou na fR entre os tratamentos. A intensidade da hiperalgesia foi maior em KT que em IKT nas 24 horas. O efeito anti-hiperalgésico de IKT se manteve sem diferença significativa entre os tempos uma hora e 24 horas. A administração prévia de ifenprodil aumentou a ação anti-hiperalgésica da cetamina subaracnoidea em cães. O ifenprodil pode ser coadministrado com cetamina para aumentar seu efeito anti-hiperalgésico e reduzir a hiperlagesia aguda pós-incisional, sem alterações motoras e sedação(AU)

AVALIAÇÃO DOS EFEITOS ANTINOCICEPTIVOS E ANTIOXIDANTE DA AMANTADINA EM MODELO DE NEUROPATIA PERIFÉRICA INDUZIDA PELA QUIMIOTERAPIA EM RATOS.

Amantadina é um antagonista não competitivo dos receptores glutamatérgicos do tipo NMDA amplamente utilizada no tratamento do Parkinson e como antiviral, com possível efeito analgésico em algumas enfermidades. Estudos recentes demonstraram que esse fármaco inibe a neuroinflamação, exercendo uma função de neuroproteção. Objetivou-se avaliar os efeitos antinociceptivo e antioxidante da amantadina em ratos após indução de dor neuropática periférica com sulfato de vincristina. Foram utilizados 64 ratos igualmente divididos em oito grupos (n=8): G1: Os animais não receberão nenhum fármaco (Naive), G2: Animais receberam 0,2ml de solução salina via IP, G3: Animais receberam vincristina (0,05mg/kg/IP), G4, G5, G6, G7 e G8: Animais receberam vincristina (0,05mg/kg/IP) e uma hora depois, receberam amantadina nas doses 25, 50, 75, 100 e 125mg/kg/VO, respectivamente, durante oito dias consecutivos. Após o tratamento os animais foram eutanasiados com sobredose de propofol 150mg/kg, via intravenosa, logo após foi coletado 9mm da medula espinal. Foi utilizado o analgesímetro digital para avaliação do limiar nociceptivo mecânico. Através da amostra colhida, a função antioxidante das enzimas catalase (CAT) e superóxido dismutase (SOD) foi analisada por meio da mensuração da reação enzimática e imunohistoquímica. Os resultados foram submetidos ao teste Bartlett's, os dados, então, foram submetidos à análise de variância (ANOVA) e o teste de Bonferroni para comparação das médias e para as variáveis sem distribuição normal foi utilizado o teste de Kruskal-Wallis (P<0,05). Foi visto que a dor neuropática foi instituída com a administração do sulfato de vincristina como o protoloco mencionado e a amantadina aumentou significativamente o limiar mecânico dos animais, porém sem diferença entre as doses utilizadas. Em relação à atividade da CAT e SOD, a amantadina não interferiu na ativação de CAT e SOD. Conclui-se que a amantadina teve efeito inibidor da neuropatia periférica, porém seu efeito neuroprotetor não age pelas vias de antioxidativas da catalase e da superóxido dismutase

Amantadine is a non-competitive antagonist of NMDA-type glutamatergic receptors widely used in the treatment of Parkinson's and as an antiviral, with possible analgesic effect in some diseases. Recent studies have shown that this drug inhibits neuroinflammation, exercising a function of neuroprotection. The objective was to evaluate the antinociceptive and antioxidant effects of amantadine in rats after induction of peripheral neuropathic pain with vincristine sulfate. 64 rats were equally divided into eight groups: G1: Animals will not receive any drugs (Naive), G2: Animals received 0.2 ml of saline via IP, G3: Animals received vincristine (0.05mg / kg / IP), G4, G5, G6, G7 and G8: Animals received vincristine (0.05mg / kg / IP) and one hour later, received amantadine in doses 25, 50, 75, 100 and 125mg / kg / VO, respectively, for eight days . After treatment, the animals were euthanized with an overdose of propofol 150mg / kg, intravenously, just after 9mm of the spinal cord was collected. A digital analgesometer was used to assess the mechanical nociceptive threshold. Through the collected sample, the antioxidant function of the enzymes catalase (CAT) and superoxide dismutase (SOD) was analyzed by measuring the enzymatic and immunohistochemical reaction. The results were submitted to the Bartlett's test, the data were then subjected to analysis of variance (ANOVA) and the Bonferroni test to compare the means and for the variables without normal distribution, the KruskalWallis test (P <0, 05). It was seen that neuropathic pain was instituted with the administration of vincristine sulfate as the aforementioned protoloco and amantadine significantly increased the mechanical threshold of the animals, but without difference between the doses used. Regarding the activity of CAT and SOD, amantadine did not interfere with the activation of CAT and SOD. It is concluded that amantadine had an inhibitory effect on peripheral neuropathy, but its neuroprotective effect does not act through the SOD AND CAT pathways.

AVALIAÇÃO DOS EFEITOS CLÍNICOS E ANALGÉSICOS DA AMANTADINA EM GATAS SUBMETIDAS A OVARIOHISTERECTOMIA

A amantadina possui eficácia no tratamento de distúrbios do sistema nervoso por inibir respostas nos receptores NMDA, podendo apresentar potencial como agente analgésico por bloquear a sensibilização central. Dessa forma, objetivou-se avaliar o efeito preemptivo da amantadina como adjuvante na analgesia pós-operatória da ovariohisterectomia em gatas. Foram utilizadas 20 gatas sem padrão racial definido, com idade entre1 e 4 anos. Realizou-se avaliação clínica e exames laboratoriaispreviamente a cirurgia. Os animais foram anestesiados com protocolo anestésico padrão: medicação pré-anestésica com acepromazina (0,03 mg/kg/IM) associado a meperidina (3 mg/kg/IM), indução anestésica com propofol (5mg/kg/IV) seguida de manutenção anestésica de isofluorano. Os animais foram distribuidos em dois grupos (n=10) aleatoriamente e receberam os seguintes tratamentos: GC- protocolo anestésico padrão e cápsulas de placebo por via oral, meia hora antes da MPA; GA protocolo anestésico padrão, e amantadina (5mg/kg/VO) meia hora antes da MPA. Avaliou-se a presença de efeitos adversos após a administração da cápsula. Os momentos avaliados durante o transoperatório foram: M1 (antes do início do procedimento cirúrgico); M2 (incisão da linha alba); M3 (após pinçamento do primeiro pedículo); M4 (após pinçamento do segundo pedículo); M5 (após ligadura no corpo do útero); M6 (sutura da musculatura abdominal) e M7 (fim da cirurgia). Houve monitoração de: T°, f, SpO2, ETCO2, ETIso, FC, PAS. A avaliação da analgesia por meio dos escores foi realizada a cada hora, totalizando 06 horas, após fim da cirurgia. Avaliou-se o grau de analgesia através de duas escalas: Escala Analógica Visual e Escala Multidimensional. Os resultados foram avaliados pelo Teste t-Student, Teste de Mann-whitney e Friedman. Houve uma redução do escore de dor, com menor número de resgate analgésico no GA comparado ao GC. Além disso, nota-se que não houve alteração cardiovascular e respiratória no GA, mantendo-se os parâmetros estáveis no transoperatorio. As gatas tratadas com amantadina não apresentaram efeitos adversos. Concluiu-se que a administração da amantadina no pré-operatório foi eficaz para analgesia pós-operatória, promovendo controle da dor e maior conforto ao paciente.

Amantadine has efficacy in the treatment of disorders of the nervous system by inhibiting responses at NMDA receptors and may present potential as analgesic agent by blocking central sensitization. The aim of this study was to evaluate the preemptive effect of amantadine as an adjuvant in postoperative analgesia of ovariohysterectomy in cats. Twenty cats with no defined racial pattern were used, aged between 1 and 4 years. Clinical evaluation and laboratory tests were performed prior to surgery. The animals were anesthetized with standard anesthetic protocol: pre-anesthetic medication with acepromazine (0.03 mg / kg / IM) associated with meperidine (3 mg / kg / IM), anesthetic induction with propofol (5mg / kg / IV) followed by anesthetic maintenance of isofluorane. The animals were randomly assigned to two groups (n = 10) and received the following treatments: GC- standard anesthetic protocol and placebo capsules orally, half an hour before MPA; GA - standard anesthetic protocol, and amantadine (5mg / kg / VO) half an hour before MPA. Adverse effects were evaluated after administration of the capsule. The moments evaluated during the intraoperative period were: M1 (before the beginning of the surgical procedure); M2 (incision of the alba line); M3 (after clamping of the first pedicle); M4 (after clamping of the second pedicle); M5 (after ligation in the body of the uterus); M6 (abdominal muscle suture) and M7 (end of surgery). There was monitoring of: T°, f, SpO2, ETCO2, ETIso, FC, PAS. The evaluation of analgesia by means of the scores was performed every hour, totaling 06 hours, after the end of the surgery. The degree of analgesia was evaluated through two scales: Visual Analog Scale and Multidimensional Scale. The results were evaluated by Student's t-Test, Mann-Whitney test and Friedman test. There was a reduction in the pain score, with a lower number of analgesic rescue in GA compared to CG. In addition, it was noted that there was no cardiovascular and respiratory changes in GA, and the parameters were stable in the intraoperative period. Cats treated with amantadine had no adverse effects. It was concluded that pre-operative amantadine administration was effective for postoperative analgesia, promoting pain control and patient comfort.

EFEITO PREEMPTIVO DA AMANTADINA COMO ADJUVANTE NA ANALGESIA PÓS-OPERATÓRIA DE OVARIOHISTERECTOMIA EM CÃES

A amantadina, antagonista não competitivo de receptores N-metil-D-aspartato (NMDA), por apresentar propriedades inibitórias na modulação do estímulo nociceptivo visceral, acredita-se que apresente uma alternativa segura e eficaz para o controle da dor pós-operatória. Dessa forma, objetivou-se avaliar o efeito preemptivo da amantadina, como adjuvante na analgesia pós-operatória de ovariohisterectomia em cães. Foram utilizadas 20 cadelas sem raça definida, com idade entre 1,5 e 08 anos. Os animais receberam como medicação pré-anestésica meperidina (3 mg/kg/IM). Após 10 minutos, realizouse indução anestésica com propofol (5mg/kg/IV) seguida de manutenção anestésica de isofluorano. Os animais foram distribuídos em dois grupos (n=10) aleatoriamente, e receberam os seguintes tratamentos: GC protocolo anestésico padrão e cápsulas de placebo por via oral; GA protocolo anestésico padrão, e amantadina (5mg/kg/VO) meia hora antes da MPA. Os momentos avaliados durante o transoperatório foram: M0 (antes da MPA); M1 (antes do início do procedimento cirúrgico); M2 (incisão da musculatura abdominal); M3 (após pinçamento do pedículo esquerdo); M4 (após pinçamento do pedículo direito); M5 (após ligadura no corpo do útero); M6 (sutura da musculatura abdominal) e M7 (no fim da cirurgia). No decorrer desses momentos houve monitorações de: FC, f, SatO2, ETCO2, ETIso, T° corporal por meio de termômetro esofágico, PAS, PAM e PAD. A avaliação de dor, por meio dos escores, foi realizada a cada hora, totalizando 06 horas, após extubação. Avaliou-se os graus de analgesia e sedação através de quatro escalas: Escala Analógica Visual Interativa e Dinâmica; Escala Composta de Glasgow Modificada; Escala de Taxa Numérica Dimensionamento, Escala Descritiva Simples. E para limiar mecânico nociceptivo, analgesímetro digital, modelo EFF 301(Insight, Brasil). Concluiu-se que a administração da amantadina no pré-operatório foi eficaz para analgesia pós-operatória melhorando o conforto do paciente e diminuindo o requerimento de resgates analgésicos.

Amantadine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, for presenting inhibitory properties in the modulation of the visceral nociceptive stimulus, it is believed that it presents a safe and effective alternative for the control of postoperative pain. In this way, the objective was to evaluate the preemptive effect of amantadine as an adjunct to postoperative analgesia of ovariohysterectomy in dogs. Twenty non-breed bitches, aged between 1.5 and 8 years. The animals received meperidine as preanesthetic medication (3 mg / kg / IM). After 10 minutes, anesthesia was induced with propofol (5mg / kg / IV) followed by anesthetic maintenance of isoflurane. The animals were randomly divided into two groups (n = 10) and received the following treatments: GC - standard anesthetic protocol and oral placebo capsules; GA - standard anesthetic protocol, and amantadine (5mg / kg / VO) half an hour before MPA. The moments evaluated during the intraoperative period were: M0 (before MPA); M1 (before the beginning of the surgical procedure); M2 (incision of the abdominal musculature); M3 (after clamping of the left pedicle); M4 (after clamping of the right pedicle); M5 (after ligature in the body of the uterus); M6 (abdominal muscle suture) and M7 (at the end of surgery). In the course of these moments there were monitoring of: FC, f, SatO2, ETCO2, ETIso, body T ° by means of esophageal thermometer, SBP, MAP and PAD. The pain evaluation, using the scores, was performed every hour, totaling 06 hours, after extubation. The degrees of analgesia and sedation were evaluated through four scales: Analogical Visual Scale and Dynamic Scale; Composite Glasgow Modified Scale; Numerical Rate Scale Sizing, Simple Descriptive Scale. And for nociceptive mechanical threshold, digital analgesimeter, model EFF 301 (Insight, Brazil). It was concluded that preoperative amantadine administration was effective for postoperative analgesia, improving patient comfort and reducing the need for analgesic rescues.