Orientador: Wilter Ricardo Russiano Vicente / Coorientador: Marcus Antonio Rossi Feliciano / Banca: Leandro Zuccolotto Crivellenti / Banca: Rafael Ricardo Huppes / Banca: Márcia Rita Fernandes Machado / Banca: Roberto Thiesen / Resumo: Considerando a escassa informação disponível para a espécie Cuniculus paca que permita a adequação de um protocolo anestésico seguro para a aspiração folicular laparoscópica (LOPU) e a monitorização consciente dos parâmetros fisiológicos nestes pacientes, propôs-se avaliar a eficácia, os efeitos cardiorrespiratórios e sobre os constituintes celulares e bioquímicos sanguíneos, da associação de cetamina e midazolam para a contenção química, isofluorano para a manutenção anestésica e tramadol ou metadona para o controle da dor pós-operatória em pacas hígidas de cativeiro submetidas à LOPU. Oito animais foram submetidos a três protocolos experimentais com intervalo de 15 dias recebendo aleatoriamente 0,5 mg/kg de metadona, 5 mg/kg de tramadol ou placebo no período anestésico. Após contenção física, foi aplicada por via intramuscular a associação de 0,5 mg/kg de midazolam e 25 mg/kg de cetamina para contenção farmacológica (CF). Posteriormente, realizou-se indução e manutenção anestésica com isofluorano. Realizou-se exame eletrocardiográfico, análise de gases arteriais, dos constituintes celulares sanguíneos e das concentrações de proteínas plasmáticas (PPT), creatinina, alanina aminotransferase, sódio, potássio, cloreto e cálcio ionizado, após CF e ao final do procedimento cirúrgico. Os parâmetros frequência cardíaca (FC), e respiratória (fR), temperatura retal (TR), saturação da oxihemoglobina (SpO2), pressão de CO2 ao final da expiração (PE'CO2), concentração de isofluorano exp... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Given the limited information available in Cuniculus Paca that allows suitability and safe anesthetic protocol for laparoscopic ovum pick up (LOPU) and conscious physiological parameters monitoring in these patients, it was proposed to evaluate efficacy, cardiorespiratory, hematology and biochemical effects of ketamine/midazolam association chemical restraint, isoflurane anesthesia and tramadol or methadone for postoperative pain control in healthy, captivity pacas submitted to LOPU. Eight animals subjected to three experimental protocols with 15 days interval randomly receiving methadone 0.5 mg/kg, tramadol 5 mg/kg or placebo postinduction. After physical restraint midazolam 0.5 mg/kg plus ketamine 25 mg/kg was applied intramuscularly for pharmacological restraint (MFR). Anesthesia was induced and maintained with isoflurane. The electrocardiographic parameters, blood gas analysis, blood cell counts, plasma protein (PPT), creatinine, alanine aminotransferase, sodium, potassium, chloride and ionized calcium concentrations, were evaluated after MFR and at end of surgical procedure. Heart (HR), and respiratory rate (fR), rectal temperature (TR), oxyhemoglobin saturation (SpO2), End tidal CO2 (PE'CO2), isoflurane expiratory concentration (PE'ISO) and mean arterial pressure (MAP) were monitored from MFR and at LOPU stages. Pain intensity was evaluated for 24 hours after LOPU by visual analogic scale (VAS). The results were compared between treatments, moments and periods by Friedm... (Complete abstract click electronic access below) / Doutor

Orientador: Artur Udelsmann / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T17:18:24Z (GMT). No. of bitstreams: 1 Lorena_SilviaElaineRodolfodeSa_M.pdf: 3753839 bytes, checksum: 169d0a30b4fcf5178104cb80601ea003 (MD5) Previous issue date: 2007 / Resumo: Até recentemente, a bupivacaína tem sido o anestésico de escolha nos bloqueios locorregionais em razão da qualidade da anestesia proporcionada e pela sua duração. Apesar disso, sua toxicidade cardiovascular preocupa os anestesiologistas que procuram novas opções farmacológicas com menor grau desse inconveniente. Uma destas é o seu isômero levógiro, a levobupivacaína, que por uma menor afinidade aos receptores dos canais de sódio da célula cardíaca, seria menos cardiotóxica. Em nosso meio está disponível a apresentação contendo 75% do isômero levógiro e 25% do isômero dextrógiro, denominada mistura com excesso enantiomérico de 50%. O objetivo desse estudo foi avaliar as repercussões hemodinâmicas da injeção intravascular de dose tóxica desses três agentes, buscando encontrar qual deles tem menor impacto em caso de acidente. Suínos da raça Large White foram anestesiados com tiopental, intubados e ventilados mecanicamente, sendo em seguida instalada monitorização hemodinâmica com cateter de Swan-Ganz e pressão invasiva para estudo das variáveis hemodinâmicas. Após repouso, foram divididos aleatoriamente em três grupos e realizada intoxicação duplamente encoberta com um dos agentes na dose de 4 mg.kg-1. Os resultados hemodinâmicos foram avaliados durante 30 minutos. Aos resultados foram aplicados testes estatísticos para comparação entre os grupos. A mistura com excesso enantiomérico de 50% e a levobupivacaína causaram maiores repercussões hemodinâmicas do que a mistura racêmica, sendo estas mais pronunciadas com o primeiro agente. Estes resultados se opõem aos encontrados em humanos, particularmente quando da utilização do isômero levógiro puro, mas estão de acordo com resultados recentes também em animais. Extrapolar dados obtidos em suínos para seres humanos exige muita cautela e novos estudos são necessários. Em suínos, a mistura com excesso enantiomérico de 50% particularmente, e a levobupivacaína mostraram-se mais tóxicas quando administradas por via venosa do que a bupivacaína racêmica / Abstract: Until recently, bupivacaine had been the anesthetic of choice for loco-regional blocks due to the quality and duration of the anesthesia. But its cardiovascular toxicity is a source of concern for anesthesiologists who seek new pharmacological options with a smaller degree ofthis problem. Its levorotatory isomer, levobupivacaine, that would be less cardiotoxicitydue a smaller affinity for the receptorsof the sodium channels of the cardiac cell, is one of these options. In Brazil, a presentation containing 75% of the levorotatory isomer and 25% of the destrorotatory isomer, called 50 % enantiomeric excess mixture is available. The aim of this studywas to evaluate thr hemodynamic repercurssions of the intravascular injectionof a toxic dose of those three agents to determine wich one hás the least impact in the case of na accident. Large White pigs were anesthetized with tiopental, intubated, and placed on mechanical ventilation. Hemodynamic monitoring was achieved with Swan-Ganz catheter and invasive blood pressure. After period of rest, the animals were randomlydivided in three groups. The intoxication was performed, on a double-blind fashion, with 4 mg. Kg -1 of one of the drugs. Hemodynamic parameters were evaluate during 30 minutes. Analytical tests were used to compare the results among the groups. The 50 % enantiomeric excess mixture and levobupivacaine hás greater hemadynamic repercussions than the racemic mixture, which were more pronounced with the first drug. These results go against those found in humans, especially regarding the pure levarotatoty isomer, but are similar to recent results reported in animals. One should be careful when extrapolating the data obtained in pigs to humans and further studies are necessary. In pigs, the 50% enantiomeric excess mixture, in particular, and levobupivacaine were more toxic when administered intravenously than racemic bupivacaine / Mestrado / Cirurgia / Mestre em Cirurgia

Orientadores: Francisco Carlos Groppo, Maria Cristina Volpato / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-20T01:18:43Z (GMT). No. of bitstreams: 1 Serpe_Luciano_M.pdf: 1055627 bytes, checksum: 5bd220cdbda1df9bd75a85c3d1bb9159 (MD5) Previous issue date: 2012 / Resumo: Este estudo teve como objetivo avaliar a eficácia anestésica da formulação de bupivacaína complexada com 2-hidroxipropil-ß-ciclodextrina, comparando-a com soluções comerciais de bupivacaína com e sem vasoconstritor, em dois modelos experimentais: bloqueio do nervo alveolar inferior (BNAI) e infiltração subcutânea em ferida cirúrgica (ISFC). Para o BNAI 30 ratos receberam, próximo ao forame mandibular, 0,2ml de uma das seguintes formulações: bupivacaína 0,5% (Bupi), bupivacaína 0,5% com epinefrina 1:200.000 (Bupi-Epi) e formulação de bupivacaína 0,5% complexada com 2-hidroxipropil-ß-ciclodextrina (Bupi-HP?CD). Os lados contralaterais (controle) receberam solução de NaCl 0,9% ou solução de 2-hidroxipropil-ß-ciclodextrina (HPßCD) sem anestésico local. Foram avaliadas latência, sucesso e duração da anestesia pulpar por meio da aplicação de estímulo elétrico ("pulp tester"). Para a ISFC, 30 animais receberam 0,1mL de cada uma das formulações anestésicas ou o respectivo controle na pata traseira direita, 24h após indução de hipernocicepção (ferida cirúrgica - incisão e sutura). A pata traseira esquerda também recebeu injeção, constituindo o controle sem hipernocicepção. A anestesia foi avaliada pela aplicação de força ao lado da ferida (analgesímetro de von Frey). Os resultados foram submetidos à ANOVA e aos testes de Tukey, Student-Newman-Keuls, Kruskal-Wallis, Log Rank e Qui-Quadrado (alfa = 5%). No BNAI não foram observada s diferenças na latência entre as formulações (p>0,05); Bupi apresentou menor duração de anestesia (p<0,05) que Bupi-Epi e Bupi-HPßCD, sem diferença entre estas (p>0,05). Bupi-Epi apresentou maior sucesso de anestesia que Bupi-HPßCD e esta, maior sucesso que Bupi (p<0,05). Para ISFC, nas patas sem hipernocicepção Bupi-Epi induziu maior duração de anestesia do que Bupi (p<0,05); Bupi-HPßCD não diferiu das demais (p>0,05); quanto ao sucesso, Bupi-Epi induziu maior sucesso que as demais soluções e Bupi-HPßCD, maior sucesso que Bupi (p<0,05). Nas patas com hipernocicepção Bupi-Epi induziu maior sucesso de anestesia do que as demais formulações (p<0,05), sem diferença entre estas (p>0,05). Não houve diferença entre as formulações quanto à duração da anestesia nas patas com hipernocicepção (p>0,05). Concluí-se que a complexação da bupivacaína em HP?CD aumentou a taxa de sucesso, mas não a duração da anestesia no BNAI e na ISFC na ausência de hipernocicepção, em relação à bupivacaína sem aditivos, não sendo eficaz em aumentar a eficácia da bupivacaína em tecido com hipernocicepção. A epinefrina aumentou a eficácia anestésica da bupivacaína, à exceção do modelo de ISFC com hipernocicepção, o qual diminuiu a eficácia de todas as soluções de bupivacaína estudadas / Abstract: The aim of the present study was to evaluate the anesthetic efficacy of 2-hydroxypropyl ß-cyclodextrin bupivacaine formulation, compared with commercial bupivacaine solutions, in two experimental models: inferior alveolar nerve block (IANB) and subcutaneous infiltration in surgical wound (SISW). For IANB, 30 rats received an injection of 0.2mL of one of the following formulations, near to the mandibular foramen: 0.5% bupivacaine (Bupi), 0.5% bupivacaine with 1:200.000 epinephrine (Bupi-Epi), and 0.5% bupivacaine in 2-hydroxypropyl-ß-cyclodextrin inclusion complex (Bupi-HPßCD). The contralateral sides (control) received 0.9% NaCl or anesthetic free 2-hydroxypropyl-ß-cyclodextrin (HPß CD) solution. The onset, success and duration of pulpal anesthesia were assessed by electrical stimulation ("pulp tester"). For SISW, 30 animals received 0.1 mL of each anesthetic formulation (both hind paws) or their respective control, 24 hours after hypernociception induction (surgical wound - incision and suture) in the right hind paw. The left hind paw also received the injection and was the control without hypernociception. Analgesia was evaluated by applying force lateral to the incision (von Frey aesthesiometer). Results were submitted to ANOVA and Tukey, Student-Newman-Keuls, Kruskal-Wallis, Log Rank and Chi-square tests (alfa = 5%). No differences were observed among the formulations concerning IANB onset (p>0.05); Bupi presented lower anesthesia duration (p<0.05) than Bupi-Epi and Bupi-HPßCD, with no difference between these two solutions (p>0.05). Bupi-Epi presented higher anesthesia success than Bupi-HP?CD, which showed higher success than Bupi (p<0.05). For SISW, Bupi-Epi showed higher anesthesia success than Bupi (p<0.05) in the non hypernociceptive paws; Bupi-HPßCD did not differ from the others (p>0.05). In this condition Bupi-Epi provided higher anesthesia success than the other formulations and Bupi-HPßCD presented higher anesthesia success than Bupi (p<0.05). In the hypernociceptive paws, Bupi-Epi promoted higher anesthesia success than the other formulations (p<0.05), with no difference between Bupi-HPß CD and Bupi (p<0.05). No difference among formulations were observed in relation to anesthesia duration in the hypernociceptive paws (p>0.05). In conclusion, the complexation of bupivacaine in HPßCD increased anesthesia success, but not duration in IANB and SISW without hypernociception in relation to bupivacaine; in the presence of hypernociception it did not improved bupivacaine efficacy. Epinephrine increased bupivacaine efficacy, except in SISW model with hypernociception, which decreased efficacy of all bupivacaine solutions studied / Mestrado / Farmacologia, Anestesiologia e Terapeutica / Mestre em Odontologia

Orientadores: Francisco Carlos Groppo, Maria Cristina Volpato / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-20T03:45:44Z (GMT). No. of bitstreams: 1 Nolasco_FabianaPinchetti_M.pdf: 1683899 bytes, checksum: b9140ed1fab0d06207e5a084fc6ea01e (MD5) Previous issue date: 2012 / Resumo: O presente estudo avaliou a eficácia anestésica das formulações: prilocaína 3% encapsulada em lipossomas unilamelares (Prilo-LUV, concentração lipídica 4mM), prilocaína 3% encapsulada em lipossomas multilamelares (Prilo-MLV, concentração lipídica 8mM) e prilocaína 3% com felipressina 0,03UI/mL (Prilo-Feli), em três modelos, bloqueio do nervo infraorbital (BNIO), bloqueio do nervo alveolar inferior (BNAI) e infiltração subcutânea em ferida cirúrgica (ISFC). Foram usadas como controle formulações lipossomais unilamelar e multilamelar sem anestésico e solução de NaCl 0,9%. No BNIO e BNAI as formulações anestésicas foram injetadas do lado direito e os controles no esquerdo. Para o BNIO, 30 ratos (10 animais/grupo) receberam 0,1 mL de uma das formulações próximo ao forame infraorbital. Foi avaliada a duração da anestesia por pinçamento do lábio superior, a cada 5 minutos. Para o BNAI 45 ratos (15 animais/grupo) receberam 0,2 mL das formulações próximo ao forame mandibular. Foram avaliados sucesso, latência e duração da anestesia pulpar com estímulo elétrico ("pulp tester"). Para a ISFC 36 ratos (6 animais/grupo) foram submetidos à incisão na pata traseira direita e 24 horas após, receberam 0,1 mL das formulações nas duas patas traseiras (com e sem incisão); a anestesia foi avaliada pelo analgesímetro de von Frey. Os resultados foram submetidos aos testes de Log-Rank, Kruskal-Wallis, Student-Newman-Keuls e Friedman (?= 5%). No BNIO, a Prilo-Feli proporcionou duração de anestesia maior que a Prilo-LUV (p<0,05); Prilo-MLV não diferiu das demais (p>0,05). A Prilo-Feli proporcionou maior sucesso de anestesia (p<0,05) que a Prilo-LUV e Prilo-MLV, sem diferença entre estas (p>0,05). Para o BNAI Prilo-Feli proporcionou maior sucesso e duração de anestesia que as formulações lipossomais (p<0,05); Prilo-MLV apresentou maior sucesso de anestesia que Prilo-LUV (p<0,05), mas não diferiu desta com relação à duração da anestesia (p>0,05). Não houve diferenças entre formulações com relação à latência (p>0,05). Para a ISFC, nas patas com hipernocicepção Prilo-Feli proporcionou maior duração de anestesia que Prilo-LUV e Prilo-MLV (p<0,05), sem diferença entre estas (p>0,05); nas patas sem hipernocicepção não houve diferenças entre as formulações (p>0,05). Com relação ao sucesso da anestesia, em ambas as condições, com e sem hipernocicepção, Prilo-Feli mostrou maior sucesso que Prilo-LUV e Prilo-MLV (p<0,05), sem diferença entre estas (p>0,05). Conclui-se que a encapsulação da prilocaína em lipossomas unilamelares e multilamelares resultou em menor eficácia anestésica em comparação á solução de prilocaína com felipressina nos modelos avaliados / Abstract: The present study assessed the anesthetic efficacy of the following formulations: 3% prilocaine with 0.03 UI/mL felypressin (Prilo-Fely), 3% prilocaine encapsulated in unillamellar liposomes (Prilo-LUV, 4 mM lipid concentration) and 3% prilocaine encapsulated in multillamelar liposomes (Prilo-MLV, 8 mM lipid concentration) in three models, in rats: infraorbital nerve block (IONB), inferior alveolar nerve block (IANB), and subcutaneous infiltration in surgical wound (SISW). The following were used as controls: unillamelar liposomal suspension, multillamelar liposomal suspension and 0.9% NaCl solution. For IONB and IANB the anesthetic formulations were injected in the right side and the respective controls in the left side. For IONB, 30 rats (10 animals per group) received 0.1mL of the anesthetic formulations near the infraorbital foramen. The duration of anesthesia was assessed by upper lip pinching every 5 minutes. For IANB, 45 rats (15 animals per group) received 0.2mL of the anesthetic formulations near the right mandibular foramen. The success, onset and duration of pulpal anesthesia were assessed by electric pulp tester. For SISW, 36 animals (6 animals per group) were submitted to incision in the right hind paw and 24h after they received 0.1mL of the formulations in both hind paws (with and without incision). Anesthesia was evaluated with von Frey anesthesiometer. Data were submitted to Log-Rank, Kruskal-Wallis, Student-Newman-Keuls and Friedman tests (?= 5%). For IONB Prilo-Fely presented longer anesthesia duration than Prilo-LUV (p<0.05); Prilo-MLV did not differ from the others (p>0.05). Prilo-Fely promoted higher anesthesia success (p<0.05) than Prilo-LUV and Prilo-MLV, with no difference between these two formulations (p>0.05). For IANB Prilo-Fely provided higher success and duration of anesthesia than the liposomal formulations (p<0.05); Prilo-MLV presented higher anesthesia success than Prilo-LUV (p<0.05), but did not differ from the latter concerning anesthesia duration (p>0.05). No differences among the formulations were observed for BNAI anesthesia onset (p>0.05). For SISW in the hypernociceptive paws, Prilo-Fely provided longer anesthesia duration than Prilo-LUV and Prilo-MLV (p<0.05), with no difference between these two formulations (p>0.05); in the non hypernociceptive paws no differences were observed among the formulations (p>0.05). In both conditions, with and without hypernociception, Prilo-Fely presented higher anesthesia success (p<0.05) than Prilo-LUV e Prilo-MLV, whith no difference between these two formulations (p>0.05). It can be concluded that the encapsulation of prilocaine in unillamelar and multillamelar liposomes provided lower anesthetic efficacy when compared to prilocaine with feypressin in the evaluated models / Mestrado / Farmacologia, Anestesiologia e Terapeutica / Mestre em Odontologia

D.Sc. (Zoology) / Please refer to full text to view abstract

Bupivacaine is one of the amide type local anesthetics and is widely used for epidural anesthesia and blockade of nerves. Bupivacaine administration locally could result in neuron injury showing transient neurologic symptoms. Dexamethasone is a synthetic glucocorticoid and may exert cytoprotective properties against damage induced by some stimuli. In the present study, we evaluated the effects of dexamethasone on bupivacaine-induced toxicity in mouse neuroblastoma N2a cells. N2a cells were exposed to bupivacaine in the presence or absence of dexamethasone. After treatment, the cell viability, nuclear condensation, and lactate dehydrogenase levels were evaluated. Mitochondrial potential and Akt (threonine-serine protein kinase B) activation were also examined. In a separate experiment, we examined the effect of Akt inhibition by triciribine on cell viability following dexamethasone treatment. We also investigated whether dexamethasone could prevent lidocaine-induced neurotoxicity. Treatment of N2a cells with bupivacaine resulted in significant cell injury as evidenced by morphological changes, LDH leakage, and nuclear condensation. Pretreatment of the cells with dexamethasone significantly attenuated bupivacaine- and lidocaine-induced cell injury. Dexamethasone treatment prevented the decline of mitochondrial potential caused by bupivacaine and increased the levels of Akt phosphorylation. Importantly, pharmacological inhibition of Akt abolished the protective effect of dexamethasone against bupivacaine-induced cell injury. Our data suggest that pretreatment of neuroblastoma cells with dexamethasone exerts a protective effect on bupivacaine-induced neuronal cell injury. The mechanisms involve activating the Akt signaling pathway.

Bupivacaine ((R, S)-1-butyl-2-piperidylformo-2', 6'-xylidide), an anilide type local anaesthetic is manufactured in the standard racemic form and is widely used in the practice of regional anaesthesia. Despite its popularity as a local anesthetic, it has the potential to produce severe cardiotoxicity. Enantiomers, which are a pair of chiral isomers that are direct, nonsuperimposable mirror images of each other, vary in their chemical, pharmacological and toxicological profiles due to different stereospecific recognition in the body. Single enantiomeric drugs, when compared to racemic drugs, exert similar clinical effects but produce decreased risks of cardiac and neurotoxicity. This has led to the development of the single enantiomeric drugs ropivacaine ((S)-1-propyl-2-piperidylformo-2', 6'-xylidide) and levobupivacaine ((S)-1-butyl-2-piperidylformo-2', 6'-xylidide). Since local anaesthetics are extensively bound (>90%) to plasma protein in blood such as album and alpha1-acid-glycoprotein, it is only the free form of the flowing drug that can exert its pharmacological effects and are believed to be closely related to systemic toxicity. Although the safety and efficacy of these newer local anaesthetics have been ascertained in the literatures, but there are limited data on their pharmacokinetic profiles; thus it is envisioned that further pharmacokinetic trials would be required to elucidate their pharmacological and clinical effects. The aim of this thesis was to develop sensitive, reproducible and reliable methods of local anaesthetic assays to support such clinical trials. / The assays described in the thesis have been applied to numerous clinical research projects. Out of the various studies, the following will be discussed: Ropivacaine undergoes slower systemic absorption from the caudal epidural space in children than bupivacaine; Arterial and venous pharmacokinetics of ropivacaine with and without epinephrine after thoracic paravertebral block; Pharmacokinetics of levobupivacaine after thoracic paravertebral block. / The first method developed is the simultaneous determination of ropivacaine and bupivacaine in human plasma using high performance chromatography (HPLC). Most published methods of determining ropivacaine in human plasma use gas chromatography and a review of literature to date shows no data describing the use of HPLC to simultaneously determine both drugs. This is the first report describing a simple, isocratic, reversed-phase, liquid-liquid extraction procedure of high-performance liquid chromatographic method that allows the simultaneous detection of both local anaesthetics in one single injection. The chromatography was achieved using a reversed-phase chromatographic system with a Waters Novapak C18 column. 0.5 ml plasma was used for the sample preparation procedures. Bupivacaine and ropivacaine concentrations ranging from 10ng/ml to 3000 ng/ml and fixed amounts of pentycaine (internal standard) were spiked into the plasma samples for calculating the calibration graphs. Calibration graphs were linear over the range 10-3000 ng/ml (r=0.9978 for bupivacaine and r=0.9986 for ropivacaine). The within-day (intra-assay) coefficient of variation of the assay varied between 13.84% at 100 ng/ml, 1.84% at 500 ng/ml and 3.34% at 2000 ng/ml for bupivacaine; and 5.29% at 100 ng/ml, 1.38% at 500 ng/ml and 3.93% at 2000 ng/ml for ropivacaine. The between-day (inter-assay) coefficient of variation was 8.43% at 100 ng/ml, 4.06% at 500 ng/ml and 9.15% at 2000 ng/ml for bupivacaine, and 5.66% at 100 ng/ml, 4.40% at 500 ng/ml and 8.14% at 2000 ng/ml for ropivacaine. The limit of detection for both drugs was 10 ng/ml. / The fourth analytical technique describes the successful development of an ultrafiltration protein binding procedure to detect the free levels of the local anaesthetics in human plasma. Sample plasma was deposited in the ultrafiltration apparatus and ultrafiltrate containing the free local anaesthetics was forced thru a membrane under a fixed-angle rotor centrifugal force. Experiments were done to establish the optimum parameters for the ultrafiltration apparatus' binding capacities. The validated procedures use 0.5 ml plasma as the starting volume and it was deposited into the ultrafiltration apparatus. It was then subjected to 1750g centrifugal force for 20 minutes at centrifugal temperature of 37&deg;C. The resultant ultrafiltrate was processed according to the described LC-MS/MS method to detect the free local anaesthetic levels. / The second analytical methodology describes the assay of levobupivacaine in human plasma using HPLC. Calibration graphs relating peak height ratios and concentrations were linear over the range 10-3000 ng/ml (r=0.9995). The chromatography was achieved with an XTerra MS C18 column with the ultraviolet monitor set at 210 nm. The sample preparation steps were similar to the first analytical method, but with a different internal standard used. Precision and accuracy were assessed by performing analysis on replicate control plasma samples. The within-day (intra-assay) coefficient of variation of the assay varied between 4.25% at 50 ng/ml, 3.38% at 500 ng/ml, 3.76% at 1000 ng/ml and 3.14% at 2000 ng/ml. The between-day (inter-assay) coefficient of variation of the assay varied between 4.68% at 50 ng/ml, 4.94% at 500 ng/ml, 4.25% at 1000 ng/ml and 2.94% at 2000 ng/ml. The limit of detection was 10 ng/ml. / The third analytical methodology details the development and validation of a chiral analytical technique. This is the first report describing the development of a simple, isocratic, reversed-phase, liquid-liquid extraction procedure of a direct chiral method that allows the simultaneous detection of either free or total concentrations of bupivacaine enantiomers and ropivacaine in one single injection. It is also a novel technique to assay bupivacaine enantiomers with the use of vancomycin CSP column and liquid chromatography-mass spectrometry (LC-MS/MS) analysis, which achieved the lowest published detection limit with the lowest volume of plasma used. Calibration graphs were linear over the range 0.1-2000 ng/ml. Precision and accuracy were assessed by performing analysis on replicate control plasma samples. The within-day (intrassay) coefficient of variations of the assay for the drugs ropivacaine, levobupivacaine, dextrobupivacaine varied from 2.20% to 5.78%, 1.96% to 9.64%, 1.78% to 6.34%, respectively, for concentrations between 0.5 ng/ml to 2000 ng/ml. The between-day (interassay) coefficient of variations of the assay for the drugs ropivaciane, levobupivacaine, dextrobupivacaine varied from 3.66% to 9.61%, 3.18% to 8.34%, 2.22% to 10.59%, respectively, for concentrations between 0.5 ng/ml to 2000 ng/ml. The limit of detection was 0.05 ng/ml. / Wong Sum Yee April. / "November 2005." / Advisers: Manoj Karmakar; Tony Gin. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6370. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 207-217). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Bibliography :leaves 350-384. / xv, 384 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Introduces possible neural mechanisms of action of general anaesthesia. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1994

Bibliography: p. 207-236. / 236 p. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis examines the systemic and cerebral pharmacokinetics and pharmacodynamics of propofol following rapid administration, using regional pharmacokinetic techniques in a sheep preparation. New methods for measurement of cerebral blood flow, cerebral metabolic rate and depth of anaesthesia are developed and validated. The final studies show that distribution of propofol to the brain is dependent on cardiac output. / Thesis (Ph.D.)--University of Adelaide, Dept. of Anaesthesia and Intensive Care, 1997?

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 4 uppsatser.