O objetivo deste estudo foi comparar a eficácia anestésica da articaína 4%, da lidocaína 2%, ambas associadas à epinefrina 1:100.000, e da bupivacaína 0.5%, associada à epinefrina 1:200.000, durante pulpectomia em pacientes com pulpite irreversível em molares inferiores. Cento e cinco voluntários do Setor de Urgência da Faculdade de Odontologia da Universidade de São Paulo receberam, aleatoriamente, 3,6mL de um dos anestésicos locais para o convencional bloqueio do nervo alveolar inferior (BNAI). No caso de falha do BNAI, foram administrados 3,6mL da mesma solução como injeção complementar no ligamento periodontal. O sinal subjetivo de anestesia do lábio, a presença de anestesia pulpar e ausência de dor durante a pulpectomia foram avaliados, respectivamente, por indagação ao paciente, por meio do aparelho estimulador pulpar elétrico (pulp tester) e por uma escala analógica verbal. A análise estatística foi realizada por meio dos testes Qui-quadrado, Kruskal Wallis e Razão de Verossimilhanças. Foi adotado nível de significância de 0,05 (P <= 0,05). Todos os pacientes reportaram anestesia no lábio após o BNAI. A lidocaína apresentou valores superiores (42,9%) para a anestesia pulpar após o BNAI e após a injeção no ligamento periodontal (61,5%). A bupivacaína apresentou valores superiores para a analgesia (80%) após o BNAI e a lidocaína (92,3%) após a injeção no ligamento periodontal. Após a falha do BNAI, a dor na câmara pulpar foi a mais frequente para articaína e lidocaína e na dentina para a bupivacaína e após a falha da injeção no ligamento periodontal, a dor foi similar para articaína nas diferentes regiões; câmara, canal e dentina; para a bupivacaína foi mais frequente na dentina e para a lidocaína no canal. No entanto, essas diferenças não foram estatisticamente significantes. Portanto as três soluções anestésicas locais se comportam de forma semelhante e não apresentam efetivo controle da dor no tratamento da pulpite irreversível em molares inferiores. / The aim of this study was to compare the anesthetic efficacy of 4% articaine and 2% lidocaine both associated with 1:100,000 epinephrine and 0.5% bupivacaine associated with 1:200,000 epinephrine in patients with irreversible pulpitis of the mandibular molars during a pulpectomy procedure. One hundred and five volunteers from the Emergency Center of the School of Dentistry at University of São Paulo randomly received 3.6 mL of local anesthetic as a conventional inferior alveolar nerve block (IANB). The subjective signal of lip numbness, pulpal anesthesia and the absence of pain during the pulpectomy procedure were, respectively, evaluated by questioning the patient, stimulation using an electric pulp tester and a verbal analogue scale. Statistical analysis was performed using the chi-square test, Kruskal Wallis and likelihood rations. The level for significance of differences was P <= .05. All patients reported the subjective signal of lip numbness after the application of either IANB. Lidocaine showed higher values for pulpal anesthesia after the IANB (42.9%) and after injection in the periodontal ligament (61.5%). Bupivacaine presented higher values for analgesia after the IANB (80,0%) and lidocaine after injection in the periodontal ligament (92,3%). After the failure of the IANB, the pain in the pulp chamber was the most frequent to articaine and lidocaine and bupivacaine for dentin and after the failure of the periodontal ligament injection, the pain was equal to articaine in different regions, chamber, canal and dentin; for bupivacaine was greater in dentin and lidocaine was higher in the channel. However, these differences were not statistically significant. So the three local anesthetic solutions behave similarly and not present any effective pain control in the treatment of irreversible pulpitis in mandibular molars.

<p>One of the aims of this thesis was to investigate the involvement of efflux proteins, such as the P-glycoprotein (Pgp), in the drug transport in different regions of the rat and the human intestine. The intestinal extrusion of intracellularly formed CYP3A4 metabolites, including whether this extrusion might be mediated by Pgp, was also studied. The model drugs used were local anaesthetics (LA), which have been evaluated for inflammatory bowel disease, such as ropivacaine, lidocaine and bupivacaine. The intestinal permeability to LAs was found to be high throughout all intestinal regions of the rat and human intestine. Results from the Ussing chamber model indicated only minor efflux involvement as the drug permeability was higher in the serosa to mucosa transport direction than in the opposite direction. However, the involvement of efflux in the absorption of LAs could not be verified using in situ single-pass perfusion of rat jejunum. The extrusion of the ropivacaine metabolite, 2´,6´-pipecoloxylidide (PPX), was polarized to the mucosal reservoir of the Ussing chamber for both rat and human intestinal samples, and was probably not caused by any Pgp involvement. The expression levels of CYP3A4 and efflux transporters were consistent with the enzymes’ activity in human intestine. PPX formation was mediated by CYP3A4 in human intestine, and cyp2c and cyp2d in rat intestine. Species differences were observed, as PPX was formed in rat colon, but not human colon. In conclusion, the permeability of ropivacaine, lidocaine and bupivacaine was not subjected to efflux transport of significance for their intestinal uptake. The transport of ropivacaine metabolites to the mucosal compartment was probably not mediated by Pgp. The Ussing chamber model showed consistent results with those from intestinal microsomes as far as intestinal metabolism is concerned, making it a suitable model for investigations of the interplay of efflux and metabolism. </p>

One of the aims of this thesis was to investigate the involvement of efflux proteins, such as the P-glycoprotein (Pgp), in the drug transport in different regions of the rat and the human intestine. The intestinal extrusion of intracellularly formed CYP3A4 metabolites, including whether this extrusion might be mediated by Pgp, was also studied. The model drugs used were local anaesthetics (LA), which have been evaluated for inflammatory bowel disease, such as ropivacaine, lidocaine and bupivacaine. The intestinal permeability to LAs was found to be high throughout all intestinal regions of the rat and human intestine. Results from the Ussing chamber model indicated only minor efflux involvement as the drug permeability was higher in the serosa to mucosa transport direction than in the opposite direction. However, the involvement of efflux in the absorption of LAs could not be verified using in situ single-pass perfusion of rat jejunum. The extrusion of the ropivacaine metabolite, 2´,6´-pipecoloxylidide (PPX), was polarized to the mucosal reservoir of the Ussing chamber for both rat and human intestinal samples, and was probably not caused by any Pgp involvement. The expression levels of CYP3A4 and efflux transporters were consistent with the enzymes’ activity in human intestine. PPX formation was mediated by CYP3A4 in human intestine, and cyp2c and cyp2d in rat intestine. Species differences were observed, as PPX was formed in rat colon, but not human colon. In conclusion, the permeability of ropivacaine, lidocaine and bupivacaine was not subjected to efflux transport of significance for their intestinal uptake. The transport of ropivacaine metabolites to the mucosal compartment was probably not mediated by Pgp. The Ussing chamber model showed consistent results with those from intestinal microsomes as far as intestinal metabolism is concerned, making it a suitable model for investigations of the interplay of efflux and metabolism.

Este é um estudo clínico, prospectivo, aleatório, e duplamente encoberto realizado em 40 crianças submetidas a cirurgia infra-umbilical de pequeno porte, sob anestesia epidural sacra realizada com a mistura enantiomérica de bupivacaína (S75R25) comparada com a bupivacaína racêmica (SR50) isoladas ou em associação com a clonidina. O objetivo foi avaliar a duração do bloqueio motor e sensitivo, o consumo de sevoflurano e as variações da pressão arterial sistólica (PAS) e freqüência cardíaca (FC). O bloqueio motor foi avaliado pela escala de Bromage, durante o período de oito horas de observação no pós-operatório. A analgesia foi avaliada pelos escores obtidos com escala objetiva para análise da dor e a duração da analgesia foi considerada como o tempo entre a administração do anestésico local no espaço epidural sacro e a primeira dose de analgésico administrado. Os resultados obtidos foram submetidos à análise estatística onde p< 0,05 foi considerado significante. Os resultados mostraram que houve aumento significativo do bloqueio motor somente na primeira hora quando a bupivacaína SR50 foi associada a clonidina, mas não ocorreu o mesmo com a bupivacaína S75R25. Em relação a analgesia não houve diferença significante entre a bupivacaína SR50 e a bupivacaína S75R25 associadas ou não à clonidina. Não houve diferença significativa no consumo de sevoflurano entre os grupos estudados quando a clonidina foi associada aos anestésicos. Os valores da PAS e FC no pós-operatório, nos grupos onde a clonidina foi associada com ambos anestésicos locais, foram inferiores em todos os momentos de avaliação, porém sem significância estatística / This is a prospective, randomized double-blind clinical trial performed in 40 children using an enantiomeric mixture of bupivacaine (S75R25) compared to racemic bupivacaine SR50 plain or associated with clonidine, to caudal blockade. The aim of this study was to investigate the motor and sensitive block, sevoflurane requirement, blood pressure (PAS) and heart rate (FC) in children scheduled to sub-umbelical surgeries. The motor block was evaluated by Bromage scale for eight hours during the postoperative period. The analgesia was evaluated postoperatively for eight hours by an objective pain scale and the analgesia duration was taken as the time between the local anesthetic administration into epidural space and the first analgesic rescue. The results obtained were submitted to statistical analysis test where p< 0,05 was considered significant. There was a significant increase in the motor block at first hour on postoperative period when bupivacaine SR50 was associated to clonidine, but it did not occurr with the enantiomeric mixture of bupivacaine S75R25. There was no difference between bupivacaine SR50 and bupivacaine S75R25 associated or not to clonidine regarding to analgesia duration. There was no difference in the requirement of sevoflurane between groups in spite of the clonidine admixture to the local anesthetics. There was an absolut decrease in the PAS and FC values on the postoperative evaluation, but it was not statistically significant

nÃo hà / A s(+)cetamina à o isÃmero levÃgiro da cetamina, antagonista do receptor NMDA para glutamato que està envolvido na gÃnese e manutenÃÃo do processo doloroso. A analgesia multimodal consiste na utilizaÃÃo de combinaÃÃo de fÃrmacos objetivando controle adequado da dor com reduÃÃo dos efeitos adversos. O objetivo deste estudo foi avaliar a eficiÃncia da s(+)cetamina isoladamente e da associaÃÃo morfina/cetamina comparadas à morfina isoladamente combinadas a mistura enantiomÃrica de bupivacaÃna (R75l25%) na anestesia peridural e analgesia pÃs-operatÃria em pacientes submetidas à histerectomia abdominal. Foi realizado estudo prospectivo, duplo cego e aleatÃrio, com aprovaÃÃo do Comità de Ãtica e Pesquisa da Universidade Federal do CearÃ. Participaram do estudo 36 pacientes ASA I ou II com idade de 20 a 60 anos submetidas à histerectomia abdominal com anestesia peridural. As pacientes foram alocadas em trÃs grupos: Grupo 1 - Grupo Cetamina (GC): administraÃÃo de mistura enantiomÃtrica (R75-S25) de bupivacaÃna associada à s(+)cetamina; Grupo 2 â Grupo Morfina (GM): administraÃÃo de mistura enantiomÃtrica (R75-S25) de bupivacaÃna associada à morfina e Grupo 3 - Grupo Cetamina/Morfina(GCM): administraÃÃo de mistura enantiomÃtrica (R75-S25) de bupivacaÃna associada à morfina e s(+)cetamina. Foram avaliados nÃvel de bloqueio motor e sensitivo, grau de sedaÃÃo e parÃmetros hemodinÃmicos: pressÃo arterial e frequÃncia cardÃaca a cada 15 minutos durante a cirurgia. No perÃodo pÃs-operatÃrio foi avaliado o consumo de analgÃsicos em 6 e 24 horas, alÃm da incidÃncia de nÃuseas, vÃmitos e prurido. A anÃlise estatÃstica foi realizada utilizando os softwares graphpad prisma 4.0 e Excel 2007. NÃo houve diferenÃa entre a idade, tempo cirÃrgico e o estado fÃsico (ASA) entre os grupos (p<0,05). A frequÃncia cardÃaca e pressÃo arterial mantiveram-se dentro dos valores estabelecidos como normal sem variaÃÃo significativa entre os grupos. A avaliaÃÃo da incidÃncia de efeitos adversos (nÃuseas, vÃmitos e prurido) nÃo foi diferente entre os grupos. A analgesia pÃs-operatÃria avaliada por consumo de analgÃsicos nas primeiras 6 horas nÃo foi diferente entre os grupos. Houve maior grau de bloqueio motor no grupo Cetamorf no tempo T15. Houve conversÃo para anestesia geral em 4 pacientes por falha de bloqueio, nos grupos cetamina-morfina (02 pacientes) e morfina (02 pacientes). Os dados sugerem que a adiÃÃo de s(+)cetamina e morfina nas doses avaliadas à segura, eficaz e permite a reduÃÃo de 50% na dose da morfina epidural mantendo-se o perfil de controle de dor no pÃs operatÃrio. No entanto, nÃo se verificou reduÃÃo da incidÃncia de nÃuseas, vÃmitos e prurido. / The association of drugs with different mechanisms of action in the dorsal horn of the spinal cord decreases postoperative pain, with a reduction in the incidence of side effects. The aim of this study was to evaluate some intraoperative parameters as well as postoperative analgesia and sedation by epidural morphine, S(+)ketamine and S(+) ketamine- morphine associated with Bupivacaine Enantiomeric Mixture (R75L25%) for abdominal hysterectomy. In this prospective, randomized, and double-blinded clinical trial, the efficacy and safety of the administration of epidural S(+)ketamine alone or with morphine were compared with epidural morphine alone (control group) for efficacy and safety comparisons after abdominal hysterectomy. 36 female patients, physical status ASA I and II, participated in this study. These patients were randomly allocated to one of the three treatment groups for having the following drugs administered epidurally: 1. Ketamine Group - Bupivacaine Enantiomeric Mixture (R75L25%) associated with S(+) ketamine (0.4 mg.kg-1); 2. Ketamine-Morphine Group - Bupivacaine Enantiomeric Mixture (R75L25%) associated S(+) ketamine (0.4 mg.kg-1) and morphine (1 mg) 3. Morphine Group, Bupivacaine Enantiomeric Mixture (R75L25%) was associated with morphine (2mg). During the intraoperative period the parameters analyzed were: blood pressure, heart rate, motor blockade level, sensitive level, intraoperative use of vasoconstrictor and sedation level. The time interval between each dada collection was 15 minutes. In the postoperative period, analgesia were evaluated using analogue visual scale 2h, 6h and 24h after the end of the surgery as well as the total amount of analgesics drugs requirement during the first 24 postoperative hours. Values were analyzed statistically using GraphPad Prisma 4.0 and Excel 2007. There were no differences between the three groups with respect to age, sex, weight, or duration of the surgical procedures (p<0,05). No differences were found between the groups during intraoperative analysis related to blood pressure, heart rate, Ramsay scores, vasoconstrictor use, and sensitive blockade level. Bromageâs scores were lower in the morpine/s+ketamine group during the first fifteen minutes analysis. Sedation scores were similar in both groups. The epidural blockade alone was not enough for surgical anesthesia resulting in conversion to general anesthesia in 4 patients who belong to Ketamine-morphine (02 patients) and Morphine (02 patients) groups, respectively. None of the patients in either group developed respiratory depression. Other side effects, such as pruritus, nausea, and vomiting, were also similar in both groups. The addiction of s(+) ketamine was safety and efficient to Bupivacaine Enantiomeric Mixture (R75L25%) in comparison with morphine.

Orientador: Jose Ranali / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-04T11:51:15Z (GMT). No. of bitstreams: 1 Palma_FabianoRodrigues_D.pdf: 466426 bytes, checksum: abc9540e10df2749efca61cad2ebc0ff (MD5) Previous issue date: 2005 / Resumo: Vários estudos têm demonstrado as vantagens do uso de anestésicos locais de longa duração em cirurgias bucais. O objetivo deste estudo foi avaliar a eficácia anestésica (latência e duração da anestesia pulpar e em tecidos moles) proporcionada pela injeção de 3,6 ml de bupivacaína e ropivacaína na concentração de 0,5% e associadas à epinefrina 1:200.000, no bloqueio do nervo alveolar inferior, para cirurgias de terceiros molares inferiores inclusos, em 30 voluntários sadios. Também foi avaliada a sensibilidade dolorosa ao procedimento anestésico. O estudo foi cruzado e duplo cego, com a seqüência e lado de aplicação das soluções aleatorizados. As avaliações do tempo de latência e duração da anestesia foram feitas através da aplicação de estímulo elétrico ("pulp tester") nos caninos, segundos pré-molares e segundos molares inferiores. A ausência de resposta ao estímulo elétrico máximo do aparelho foi considerada como critério de anestesia pulpar. A Escala Analógica Visual (EAV) foi utilizada para avaliar a sensibilidade dolorosa. Os resultados foram submetidos à análise estatística através do Teste t (p<0,05). Não foram observadas diferenças entre as soluções, com exceção do tempo de latência em tecidos moles, que foi menor com o uso de ropivacaína (p = 0,016). Nas condições deste estudo a bupivacaína e a ropivacaína apresentaram eficácia anestésica semelhante. Assim, a ropivacaína mostra-se um anestésico útil para o bloqueio de longa duração do nervo alveolar inferior e poderia substituir a bupivacaína em cirurgias orais, em função de sua menor toxicidade, demonstrada na literatura / Abstract: The advantages of using long-acting local anesthetics in oral surgery have been demonstrated in a limited number of clinical studies. The purpose of this double-blind and cross-over study, was to evaluate and compare the efficacy of 2 local anesthetics - bupivacaine and ropivacaine - in the concentration of 0.5% containing 1:200,000 epinephrine for inferior alveolar nerve block. Thirty healthy individuals participated in the study on a voluntary basis. All subjects received bupivacaine and ropivacaine injections (3,6 ml), one anesthetic for each side of the mandible, for surgical removal of impacted mandibular third molar teeth, on separate occasions. The onset time and duration of pulpal anesthesia were assessed by electric pulp tester in the inferior canines, second pre-molars and second molars; no response from the subject to the maximum output (80 reading) of the pulp testes was used as the criterion for pulpal anesthesia; the onset time and duration of lip anesthesia were also assessed. Injection discomfort was assessed by Visual Analogue Scale. The results were evaluated by using Student-t test (p<0.05). No differences were found between the solutions, except for a lower onset of lip anesthesia (p=0,016) with the use of ropivacaine. Under the conditions of this study bupivacaine and ropivacaine showed similar anesthetic efficacy. This leads to the conclusion that ropivacaine can be useful as a long acting anesthetic for inferior alveolar nerve block and could replace bupivacaine in oral surgery due to the decreased toxicity related in the literature / Doutorado / Farmacologia, Anestesiologia e Terapeutica / Doutor em Odontologia

No description available.

No description available.

<p>The thesis describes the synthesis of chromatographic media using several different approaches, their characterizations and applications in liquid chromatography. The steps to achieve a separation column for a specific analyte are presented. The main focus of the study was the design of novel molecularly imprinted polymers.</p><p>Attachment of monolithic polymeric substrates to the walls of fused silica capillaries was studied in Paper I. With a broad literature survey, a set of common methods were tested by four techniques and ranked by their ability to improve anchoring of polymers. The best procedure was thus used for all further studies.</p><p>Synthesis of monoliths in capillary columns was studied in Paper II. With the goal of separating proteins without denaturation, various monoliths were polymerized in situ using a set of common monomers and cross-linkers mixed with poly(ethylene glycol) as porogen. The resulting network was expected to present “protein-friendly pores”. Chemometrics were used to find and describe a set of co-porogens added to the polymerization cocktails in order to get good porosity and flow-through properties.</p><p>Assessment of the macroporous structure of a monolith was described in Paper III. An alternative method to mercury intrusion porosimetry was proposed. The capillaries were embedded in a stained resin and observed under transmission electron microscope. Images were then computed to determine the pore sizes.</p><p>Synthesis of molecularly imprinted polymers grafted to a core mono-lith in a capillary was described in Paper IV. The resulting material, imprinted with local anaesthetics, was tested for its chromatographic performance. Similar imprinted polymers were characterized by microcalorimetry in Paper V. Finally, imprinted monoliths were also synthesized in a glass tube and further introduced in a NMR rotor to describe the interactions between stationary phase and template in Paper VI.</p>

The thesis describes the synthesis of chromatographic media using several different approaches, their characterizations and applications in liquid chromatography. The steps to achieve a separation column for a specific analyte are presented. The main focus of the study was the design of novel molecularly imprinted polymers. Attachment of monolithic polymeric substrates to the walls of fused silica capillaries was studied in Paper I. With a broad literature survey, a set of common methods were tested by four techniques and ranked by their ability to improve anchoring of polymers. The best procedure was thus used for all further studies. Synthesis of monoliths in capillary columns was studied in Paper II. With the goal of separating proteins without denaturation, various monoliths were polymerized in situ using a set of common monomers and cross-linkers mixed with poly(ethylene glycol) as porogen. The resulting network was expected to present “protein-friendly pores”. Chemometrics were used to find and describe a set of co-porogens added to the polymerization cocktails in order to get good porosity and flow-through properties. Assessment of the macroporous structure of a monolith was described in Paper III. An alternative method to mercury intrusion porosimetry was proposed. The capillaries were embedded in a stained resin and observed under transmission electron microscope. Images were then computed to determine the pore sizes. Synthesis of molecularly imprinted polymers grafted to a core mono-lith in a capillary was described in Paper IV. The resulting material, imprinted with local anaesthetics, was tested for its chromatographic performance. Similar imprinted polymers were characterized by microcalorimetry in Paper V. Finally, imprinted monoliths were also synthesized in a glass tube and further introduced in a NMR rotor to describe the interactions between stationary phase and template in Paper VI.