ENHANCED AMPEROMETRIC DETECTOR FOR LOCAL-ANESTHETICS IN LIQUID-CHROMATOGRAPHY WITH METAL-OXIDE DISPERSED GLASSY-CARBON ELECTRODES

Chemically modified electrodes (CMEs) prepared by the dispersion of metal oxide particles on a glassy carbon (GC) substrate greatly enhance the voltammetric response and amperometric detection of local anesthetics following liquid chromatography (LC). The enhancement is more pronounced with the GC electrodes dispersed by the metal oxides of higher oxidation states (+3, +4) and for the species exhibiting relatively slow electrode kinetics under given conditions. With an applied potential of 1.2 V (vs. SCE), LC amperometric detection of the analytes at the alpha-alumina modified GC surface gives detection limits 2-5 times lower than those obtained at the bare electrode. The metal oxide-dispersed electrodes display significant improvement in sensitivity, and selectivity and indicate excellent preparation reproducibility and performance stability.

Pungent general anesthetics activate transient receptor potential-A1 to produce hyperalgesia and neurogenic bronchoconstriction

BACKGROUND: Volatile anesthetics such as isoflurane and halothane have been in clinical use for many years and represent the group of drugs most commonly used to maintain general anesthesia. However, despite their widespread use, the molecular mechanisms by which these drugs exert their effects are not completely understood. Recently, a seemingly paradoxical effect of general anesthetics has been identified: the activation of peripheral nociceptors by irritant anesthetics. This mechanism may explain the hyperalgesic actions of inhaled anesthetics and their adverse effects in the airways. METHODS: To test the hypothesis that irritant inhaled anesthetics activate the excitatory ion-channel transient receptor potential (TRP)-A1 and thereby contribute to hyperalgesia and irritant airway effects, we used the measurement of intracellular calcium concentration in isolated cells in culture. For our functional experiments, we used models of isolated guinea pig bronchi to measure bronchoconstriction and withdrawal threshold to mechanical stimulation with von Frey filaments in mice. RESULTS: Irritant inhaled anesthetics activate TRPA1 expressed in human embryonic kidney cells and in nociceptive neurons. Isoflurane induces mechanical hyperalgesia in mice by a TRPA1-dependent mechanism. Isoflurane also induces TRPA1-dependent constriction of isolated bronchi. Nonirritant anesthetics do not activate TRPA1 and fail to produce hyperalgesia and bronchial constriction. CONCLUSIONS: General anesthetics induce a reversible loss of consciousness and render the patient unresponsive to painful stimuli. However, they also produce excitatory effects such as airway irritation and they contribute to postoperative pain. Activation of TRPA1 may contribute to these adverse effects, a hypothesis that remains to be tested in the clinical setting.

Micro and nanosystems for delivering local anesthetics

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Benzocaine and eugenol as anesthetics for Brycon hilarii

A utilização de produtos anestésicos durante práticas de manejo é frequentemente empregada, porém doses corretas de diferentes fármacos e para espécies distintas ainda estão em fases de pesquisa. O objetivo do estudo foi determinar a melhor concentração de benzocaína e eugenol para juvenis de piraputanga (B. hilarii). Foram utilizados 104 juvenis de piraputanga com peso médio de 50,04 ± 20,80 g e comprimento total médio de 16,30 ± 12,32 cm adquiridos em uma piscicultura comercial localizada na região Oeste do Estado do Paraná. O trabalho foi conduzido no Laboratório de Aquicultura do Grupo de Estudos de Manejo na Aquicultura - GEMAq da Universidade Estadual do Oeste do Paraná (UNIOESTE). Os animais foram submetidos a cinco concentrações de benzocaína (50,0; 100,0; 150,0; 200,0 e 250,0 mg L-1) e sete concentrações de eugenol (50,0; 100,0; 150,0; 200,0; 250,0; 300,0 e 350 mg L-1), para a aferição dos tempos referentes à letargia. Para a recuperação, os animais foram mantidos em aquários livre do anestésico e observado o tempo em que retornaram às atividades normais. A melhor dose de benzocaína verificada foi de 100 mg L-1, enquanto a melhor dose de eugenol foi entre 100 e 150 mg L-1.

Gastric mucosal perfusion in dogs: Effects of halogenated anesthetics and of hemorrhage

The gastrointestinal tract is one of the first organs affected by hypoperfusion during hemorrhagic shock. The hemodynamics and oxygen transport variables during hemorrhagic shock and resuscitation can be affected by the anesthetics used. In a model of pressure-guided hemorrhagic shock in dogs, we studied the effects of three halogenated anesthetics - halothane, sevoflurane, and isoflurane - at equipotent concentrations on gastric oxygenation. Thirty dogs were anesthetized with 1.0 minimum alveolar anesthetic concentration (MAC) of either halothane, sevoflurane, or isoflurane. A gastric tonometer was placed in the stomach to determine mucosal gastric CO2 (PgCO(2)) and for the calculation of gastric-arterial PCO2 gradient (PCO2 gap). The dogs were splenectomized and hemorrhaged to hold mean arterial pressure at 40-50 mm Hg over 45 min and then resuscitated with the shed blood volume. Hemodynamics, systemic oxygenation, and PCO2 gap were measured at baseline, after 45 min of hemorrhage, and at 15 and 60 min after blood resuscitation. Hemorrhage induced reductions of mean arterial pressure and cardiac index, while systemic oxygen extraction increased (p < .05), without significant differences among groups (p > .05). Halothane group showed significant lower PCO2 gap values than the other groups (p < .05). After 60 min of shed blood replacement, all groups restored hemodynamics, systemic oxygenation, and PCO2 gap to the prehemorrhage levels (p > .05), without significant differences among groups (p > .05). We conclude that halothane is superior to preserve the gastric mucosal perfusion in comparison to isoflurane and sevoflurane, in dogs submitted to pressure-guided hemorrhagic shock at equipotent doses of halogenated anesthetics.

Influence of glyceryl guaiacolate ether on anesthetics in tilapia compared to benzocaine and eugenol

Objective. The study aimed to investigate the effectiveness of glyceryl guaiacolate ether (GGE) and compare the times of induction, recovery, hematological changes, total protein and glycaemia among anesthetics in Nile tilapia, Oreochromis niloticus. Materials and methods. A total of 60 tilapia distributed in 3 aquariums (N=20) were used, which formed the group benzocaine (100 mg/L), eugenol (50 mg/L) and guaiacol glyceryl ether (9.000 mg/L). After the induction of anesthesia fish blood samples were collected to determine the complete hemogram and glycemia. Then the animals were placed in aquariums with running water for assessing the anesthesia recovery. Results. It was verified that GGE showed longer induction and recovery times as well a significant increase (p<0.05) of glycemia, when compared with the other groups (p<0.05). The concentration of total protein did not differ between groups (p>0.05). An increase in the number of monocytes in the group treated with benzocaine (p<0.05) was observed in the analysis of the hematological parameters with no difference between groups for other variables. Conclusions. Eugenol and benzocaine allow rapid induction and recovery in Nile tilapia, without evidence of stress during handling and GGE showed high induction and recovery times, being inadequate for anesthetic use in Nile tilapia.

Genotoxicity of anesthetics evaluated in vivo (animals)

The anesthesia has been improved all over the years. However, it can have impact on health, in both patients and animals anesthetized, as well as professionals exposed to inhaled anesthetics. There is continuing effort to understand the possible effects of anesthetics at molecular levels. Knowing the effects of anesthetic agents on genetic material could be a valuable basic support to better understand the possible mechanisms of these agents. Thus, the purpose of this review is to provide an overview on the genotoxic potential, evaluated in animal models, of many anesthetics that have already been used and those currently used in anesthesia.

Ocular effects of retrobulbar block with different local anesthetics in healthy dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dental students familiarity with the implications of using local anesthetics and dental materials

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury

Disruption of the blood-brain barrier (BBB) results in cerebral edema formation, which is a major cause for high mortalityrnafter traumatic brain injury (TBI). As anesthetic care is mandatory in patients suffering from severe TBI it may be importantrnto elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ) such as zonularnoccludens-1 (ZO-1) and claudin-5 (cl5) play a central role for BBB stability. First, the influence of the volatile anestheticsrnsevoflurane and isoflurane on in-vitro BBB integrity was investigated by quantification of the electrical resistance (TEER) inrnmurine brain endothelial monolayers and neurovascular co-cultures of the BBB. Secondly brain edema and TJ expression ofrnZO-1 and cl5 were measured in-vivo after exposure towards volatile anesthetics in native mice and after controlled corticalrnimpact (CCI). In in-vitro endothelial monocultures, both anesthetics significantly reduced TEER within 24 hours afterrnexposure. In BBB co-cultures mimicking the neurovascular unit (NVU) volatile anesthetics had no impact on TEER. In healthyrnmice, anesthesia did not influence brain water content and TJ expression, while 24 hours after CCI brain water contentrnincreased significantly stronger with isoflurane compared to sevoflurane. In line with the brain edema data, ZO-1 expressionrnwas significantly higher in sevoflurane compared to isoflurane exposed CCI animals. Immunohistochemical analysesrnrevealed disruption of ZO-1 at the cerebrovascular level, while cl5 was less affected in the pericontusional area. The studyrndemonstrates that anesthetics influence brain edema formation after experimental TBI. This effect may be attributed tornmodulation of BBB permeability by differential TJ protein expression. Therefore, selection of anesthetics may influence thernbarrier function and introduce a strong bias in experimental research on pathophysiology of BBB dysfunction. Futurernresearch is required to investigate adverse or beneficial effects of volatile anesthetics on patients at risk for cerebral edema.

Comparative efficacy of 2 topical anesthetics for the placement of orthodontic temporary anchorage devices.

This study compared the effectiveness of topical benzocaine 20% versus a combination of lidocaine, tetracaine, and phenylephrine in providing sufficient analgesia for the placement of orthodontic temporary anchorage devices (TADs). The 2 topical anesthetics were tested against each other bilaterally using a randomized, double-blind, crossover design. The agents were left in place for the amount of time prescribed by the manufacturer. The TAD was then placed, and each subject rated the degree of pain on a Heft-Parker visual analogue scale. A pulse oximeter was used to record the preoperative and postoperative pulse rates. Statistically significant differences in perceived pain (P < .05) and success rate (P < .01) between drugs were seen, but no significant difference in pulse rate change between the topical anesthetics was observed (P > .05). It was concluded that when the efficacy of topical benzocaine and of a combination product was compared as the sole anesthetic to facilitate acceptable pain control for placement of orthodontic temporary anchorage devices, the combination product was considerably more efficacious.