Memory-impairing effects of local anesthetics in an elevated plus-maze test in mice

Post-training intracerebroventricular administration of procaine (20 µg/µl) and dimethocaine (10 or 20 µg/µl), local anesthetics of the ester class, prolonged the latency (s) in the retention test of male and female 3-month-old Swiss albino mice (25-35 g body weight; N = 140) in the elevated plus-maze (mean ± SEM for 10 male mice: control = 41.2 ± 8.1; procaine = 78.5 ± 10.3; 10 µg/µl dimethocaine = 58.7 ± 12.3; 20 µg/µl dimethocaine = 109.6 ± 5.73; for 10 female mice: control = 34.8 ± 5.8; procaine = 55.3 ± 13.4; 10 µg/µl dimethocaine = 59.9 ± 12.3 and 20 µg/µl dimethocaine = 61.3 ± 11.1). However, lidocaine (10 or 20 µg/µl), an amide class type of local anesthetic, failed to influence this parameter. Local anesthetics at the dose range used did not affect the motor coordination of mice exposed to the rota-rod test. These results suggest that procaine and dimethocaine impair some memory process(es) in the plus-maze test. These findings are interpreted in terms of non-anesthetic mechanisms of action of these drugs on memory impairment and also confirm the validity of the elevated plus-maze for the evaluation of drugs affecting learning and memory in mice

Anestésicos locais: interação com membranas de eritrócitos de sangue humano, estudada por ressonância magnética nuclear de ¹H e 31P

The literature carries many theories about the mechanism of action of local anesthetics (LA). We can highlight those focusing the direct effect of LA on the sodium channel protein and the ones that consider the interaction of anesthetic molecules with the lipid membrane phase. The interaction between local anesthetics and human erythrocyte membranes has been studied by ¹H and 31P nuclear magnetic resonance spectroscopy. It was found that lidocaine (LDC) and benzocaine (BZC) bind to the membranes, increase the mobility of the protons of the phospholipid's acyl chains, and decrease the mobility and/or change the structure of the polar head groups. The results indicate that lidocaine molecules are inserted across the polar and liquid interface of the membrane, establishing both electrostatic (charged form) and hydrophobic (neutral form) interactions. Benzocaine locates itself a little deeper in the bilayer, between the interfacial glycerol region and the hydrophobic core. These changes in mobility or conformation of membrane lipids could affect the Na+-channel protein insertion in the bilayer, stabilizing it in the inactivated state, thus causing anesthesia.

Preparação e caracterização físico-química de complexos de inclusão entre anestésicos locais e hidroxipropil-beta-ciclodextrina

S(-) Bupivacaine (S(-)BVC) and Lidocaine (LDC) are widely used local anesthetics (LA). Hydroxypropyl beta-cyclodextrin (HP-beta-CD) is used as a drug-carrier system. The aim of this work was to characterize inclusion complexes between LA and HP-beta-CD. The affinity constants determined at different pHs show favourable complexation. The release kinetics experiments showed that S(-)BVC and LDC changed the released profiles in the presence of HP-beta-CD. Nuclear magnetic resonance experiments gave information about the interaction between LA and the cyclodextrin cavity. This study focused on the physicochemical characterization of drug-delivery formulations that come out as potentially new therapeutic options for pain treatment.

Anestésicos locais: interação com membranas biológicas e com o canal de sódio voltagem-dependente

Many theories about the mechanism of action of local anesthetics (LA) are described in the literature. Two types of theories can be distinguished: those that focus on the direct effects of LA on their target protein in the axon membranes, i.e. the voltage-gated sodium channel and the ones that take into account the interaction of anesthetic molecules with the lipid membrane phase for the reversible nerve blockage. Since there is a direct correlation between LA hydrophobicity and potency, it is crucial to take this physico-chemical property into account to understand the mechanism of action of LA, be it on the sodium channel protein, lipid(s), or on the whole membrane phase.

Effects of hypertonic sodium chloride solution on the electrophysiologic alterations caused by bupivacaine in the dog heart

The effects of various hypertonic solutions on the intraventricular conduction, ventricular repolarization and the arrhythmias caused by the intravenous (iv) injection of bupivacaine (6.5 mg/kg) were studied in sodium pentobarbital-anesthetized mongrel dogs. Hypertonic solutions, given iv 5 min before bupivacaine, were 7.5% (w/v) NaCl, 5.4% (w/v) LiCl, 50% (w/v) glucose (2,400 mOsm/l, 5 ml/kg), or 20% (w/v) mannitol (1,200 mOsm/l, 10 ml/kg). Bupivacaine induced severe arrhythmias and ventricular conduction and repolarization disturbances, as reflected by significant increases in QRS complex duration, HV interval, IV interval and monophasic action potential duration, as well as severe hemodynamic impairment. Significant prevention against ventricular electrophysiologic and hemodynamic disturbances and ventricular arrhythmias was observed with 7.5% NaCl (percent increase in QRS complex duration: 164.4 ± 21.8% in the non-pretreated group vs 74.7 ± 14.1% in the pretreated group, P<0.05; percent increase in HV interval: 131.4 ± 16.1% in the non-pretreated group vs 58.2 ± 7.5% in the pretreated group, P<0.05; percent increase in monophasic action potential duration: 22.7 ± 6.8% in the non-pretreated group vs 9.8 ± 6.3% in the pretreated group, P<0.05; percent decrease in cardiac index: -46 ± 6% in the non-pretreated group vs -28 ± 5% in the pretreated group, P<0.05). The other three hypertonic solutions were ineffective. These findings suggest an involvement of sodium ions in the mechanism of hypertonic protection.

Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group) were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg) was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg) increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s) and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN) at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg) blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics.

Paradigma da disseminação local do carcinoma epidermóide da base de língua

OBJETIVO: Analisar o padrão de disseminação local através da delimitação clínica da extensão da lesão primária assim como os subsítios invadidos. FORMA DE ESTUDO: Clínico retrospectivo. MATERIAL E MÉTODO: Foram analisados os prontuários de 290 pacientes com carcinoma epidermóide de base de língua no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital Heliópolis, Hosphel, São Paulo - Brasil, de 1977 a 2000, sendo estadiados pelo TNM da UICC, e os resultados analisados pelo teste do Quiquadrado para tabelas Z x N (Cochran) para estudo da associação dos sítios e dimensão da neoplasia em relação à invasão da linha média. RESULTADOS: Com predomínio dos homens (8:1) e da 6ª década de vida (41,0%), 83,8% eram etilistas e tabagistas e em 4,7% os hábitos estavam ausentes. Quanto aos sintomas, odinofagia (37,6%), linfonodo (21,7%) e a média de tempo entre o 1º sintoma e o diagnóstico de 6 meses (62,0%). Quanto ao estadiamento, tivemos T1-T2 (18,3%), T3 (32,4%), T4(50,7%). Quanto à disseminação local, em direção à valécula (25,3%), epiglote (18,7%), glote (2,7%), anteriormente para o v lingual em (22,4%) e póstero lateralmente para a prega faringloepiglótica (6,6%) e seio piriforme (2,2%). Quanto a ultrapassagem da linha média, isso ocorreu em 66,2% dos casos, sendo 42,2% (T2), 54,2% (T3) e 82,9% (T4). CONCLUSÃO: o carcinoma epidermóide no estádio T4 ultrapassa a linha média da base da língua em 82,9%.

Multi-level governance and social cohesion in the European Union: the assessment of local agents, a study case inside Galicia

Implementing multi-level governance has been a key priority in EU cohesion policy. This study assesses the perceived achievements and shortcomings in implementing European Social Fund by analyzing the deficits and weaknesses as well as the poor participation of local agents who are in direct contact with the beneficiaries in order to design and implement this fund, which is the main financial instrument of EU social policy.

Understanding local governance: an international perspective

Enormous change and innovation in governmental practices are occurring throughout the world. Local governance, in particular, has become a concern in many countries. Processes such as redemocratization and decentralization and imperatives of international lending agencies have focused attention on developing good governance practices. Improvement in local government remains a high priority in most countries, but unless the relationship between citizens and government is more fully developed the actions of local government will not necessarily lead to improvement in the conditions of people's lives. This paper will explore the concept of governance and propose an analytical framework for the study of local governance in an international context. The article concludes with recommendations on strategies to improve governance systems and government performance.

The rights approach to local public management: experiences from Brazil

The Fundação Getulio Vargas, São Paulo, Public Management and Citizenship Program was set up in 1996 with Ford Foundation support to identify and disseminate Brazilian subnational government initiatives in service provision that have a direct effect on citizenship. Already, the program has 2,500 different experiences in its data bank, the results of four annual cycles. The article draws some initial conclusions about the possibilities of a rights-based approach to public management and about the engagement of other agencies and civil society organizations.

FATORES QUE AFETAM A TRANSFERÊNCIA DA APRENDIZAGEM PARA O LOCAL DE TRABALHO

O treinamento visa responder às necessidades de desenvolvimento das pessoas e das organizações (Grohmann & Kauffeld, 2013). Baseado no modelo de Holton, realizou-se um estudo que procura identificar e compreender os fatores envolvidos no processo de transferência de aprendizagem para o posto de trabalho de duas ações de treinamento distintas quanto ao design e às competências. O estudo decorreu numa organização portuguesa e envolveu 98 participantes. Realizaram-se entrevistas com ex-formandos com o objetivo de explorar os fatores que facilitaram ou dificultaram a transferência das aprendizagens e aplicou-se o Inventário do Sistema de Transferência da Aprendizagem, versão portuguesa (Holton, Bates, Seyler & Carvalho, 1997; Velada & Caetano, 2009). Os resultados sugerem que o modelo de Holton model (2005) mostra o que os treinandos identificaram como importante para a transferência da aprendizagem e que há diferenças em relação aos fatores de transferência de acordo com o tipo de treinamento.

DETERMINANTS OF THE SUCCESS OF GLOBAL AND LOCAL BRANDS IN LATIN AMERICA

ABSTRACTThe purpose of this paper is to address the issue of the implementation of global and local brands in Latin America by drawing on contingency theory to develop and test hypotheses relating to how product category characteristics affect the success of global and local brands in the region. Hypotheses are tested using data obtained from top brands rankings reported in five Latin American markets (Argentina, Brazil, the Caribbean and Central America, Chile and Mexico). The study design considers estimating a logistic regression on a binomial dependent variable measuring whether 475 top brands are global or local brands, with product category characteristics as independent variables. Results reveal that product categories related to subscriptions, local tastes, high-tech, and global citizenship do have an impact on the success of global and local brands in Latin America.

Proposta para construção de um índice local de preços de imóveis a partir dos lançamentos imobiliários de condomínios residenciais

Este artigo propõe um modelo para construção de índices de mercados locais a partir das informações fornecidas nos lançamentos imobiliários residenciais, pois construir um índice de preços nacional para unidades residenciais em um país de dimensões continentais e com uma diversidade cultural e econômica como a do Brasil é muito difícil. Além disso, mesmo nas grandes regiões metropolitanas, faltam informações sobre os preços reais praticados nas transações imobiliárias e sobre as características dos imóveis negociados.