Utilisée depuis plus d'un siècle en chirurgie esthétique, la greffe autologue de tissu adipeux, ou lipofilling, est une technique sûre permettant le comblement des tissus mous. Cependant, bien que la technique ait connue de nettes améliorations au cours du temps, les chirurgiens font toujours face à une résorption du greffon qui oblige dans la majorité des cas à planifier plusieurs autres interventions afin que le résultat esthétique soit en adéquation avec les attentes du patient. Le procédé MICROFILL® a été développé dans le but d'augmenter le taux de prise de greffe en favorisant la survie cellulaire au sein du greffon. Cette dernière est optimisée par : un prélèvement et une réinjection de lobules adipeux de petite taille permettant de diminuer l'ischémie et la mauvaise nutrition des cellules - une élimination des éléments délétères (anesthésiques, cytokines inflammatoires) par un protocole de lavages et centrifugations non traumatique. D'autre part, au cours de ces dernières années, le tissu adipeux s'est révélé posséder un pouvoir thérapeutique plus important par l'hébergement de cellules souches mésenchymateuses au fort potentiel. Ces cellules sont présentes en grande quantité et facilement accessibles à partir d'une simple lipoaspiration. Cependant, la lipoaspiration implique bien souvent l'usage d'un anesthésique local et d'un vasoconstricteur qui peuvent nuire aux cellules. Nos études ont en effet montré que la lidocaïne, un anesthésique couramment utilisé, est cytotoxique pour les cellules souches du tissu adipeux, ayant pour effets l'inhibition de la prolifération cellulaire (arrêt du cycle cellulaire en phase G0-G1) et la nécrose des cellules. En revanche, une manipulation appropriée du tissu adipeux, se rapprochant du protocole MICROFILL®, permet de diminuer la mortalité cellulaire. L'effet délétère de la lidocaïne semble lié à l'apparition d'une vacuolisation cytoplasmique dont la nature est à ce jour non élucidée. De plus, la lidocaïne induit également un processus d'autophagie, dont les mécanismes moléculaires d'induction sont eux aussi inconnus et dont la finalité physiologique serait le maintien en vie de la cellule malgré le stress provoqué. Les conclusions de ces études mènent à certaines recommandations à suivre quant à l'usage de la lidocaïne en vue de la réinjection extemporanée de cellules souches adipeuses chez un patient. Aussi, dans le but de traiter les tendinopathies équines, ces études ont permis d'optimiser le protocole de prélèvement du tissu adipeux chez le cheval ainsi que le protocole d'extraction des cellules souches du tissu adipeux. Cette thèse a finalement permis de développer un kit à usage vétérinaire permettant de traiter les tendinopathies équines. Ce nouveau procédé de thérapie cellulaire a été testé chez des chevaux et s'est avéré très prometteur, permettant la régénération de la structure tendineuse et un retour au travail rapide des chevaux. / Despite the dark side of obesity in the pathogenesis of metabolic diseases, adipose tissue has been shown to be a good therapeutic tool. First, autologous fat grafting, also named lipofilling, has been used for over a century and represents a safe technique for soft tissue filling. However, although the technique has seen marked improvements over time, surgeons are still facing graft resorption that often requires overcorrection of the treated area or other interventions so that the aesthetic result is in line with expectations of the patient. Thus, MICROFILL® process has been developed in order to increase the rate of engraftment by promoting cell survival within the graft. The latter is enhanced by: - sampling and reinjection of small fat lobules in order to reduce ischemia and poor nutrition of the cells- elimination of deleterious elements (anesthetics, inflammatory cytokines) by a non-traumatic protocol involving soft centrifugations and washings. Furthermore, in recent years, adipose tissue has been found to have a greater therapeutic power by hosting mesenchymal stem cells with great potential. These adipose stem cells (ASCs) are present in large quantities and can be easily obtained from a simple liposuction. However, liposuction procedure often involves the use of a local anesthetic and a vasoconstrictor that can harm cells. Our studies have shown that lidocaine, an anesthetic commonly used, exerts cytotoxic effects on adipose stem cells, inhibiting cell proliferation (cell cycle arrest in G0-G1 phase) and inducing necrosis. Nonetheless, appropriate handling of adipose tissue, quite similarly to MICROFILL® protocol, reduces cell death. The deleterious effects of lidocaine appear to be related to the occurrence of cytoplasmic vacuolization whose nature is so far unclear. In addition, lidocaine also induces a process of autophagy, including molecular mechanisms of induction also unknown and whose physiological purpose could be cell survival despite the stress. The findings of these studies lead to some recommendations to follow regarding the use of lidocaine for the extemporaneous reinjection of ASCs in a patient. Also, in order to treat equine tendinopathy, these studies have been used to optimize adipose tissue harvest by liposuction on horses and the protocol of extraction of ASCs.Finally, this thesis has allowed developing a kit for veterinary use to treat equine tendinopathy. This new method of cell therapy has been tested in horses and has shown very promising results for tendon regeneration, knowing that treated horses could rapidly return to work.

Estudamos 62 pacientes, que com teste ergométrico positivo, manifestaram angina estável e estavam sob controle farmacológico. Todos apresentavam cinecoronariografia mostrando obstrução >70% em pelo menos uma das principais artérias coronárias. Objetivamos avaliar parâmetros eletrocardiográficos e de pressão arterial, durante procedimento odontológico restaurador sob anestesia local com e sem vasoconstritor em presença de doença arterial coronária. As idades variaram de 39 a 80, média de 58,7±8,8 anos, sendo 51 (82,3%) homens. Trinta pacientes foram randomizados para receber anestesia local com solução de lidocaína a 2% com adrenalina 1:100.000 e os demais para lidocaína a 2% sem vasoconstritor. Todos os pacientes foram submetidos à monitorização ambulatorial da pressão arterial (MAPA) e eletrocardiografia dinâmica por 24 horas, iniciados 2 horas antes do procedimento odontológico. Consideramos 3 períodos de registro: (1) basal - os 60 minutos que antecederam ao procedimento odontológico; (2) procedimento - desde o início da anestesia até o final do procedimento odontológico restaurador; (3) subseqüente completar das 24 horas. A análise de variância com medidas repetidas mostrou que houve elevação significativa da pressão arterial sistólica e diastólica do período basal para o procedimento nos dois grupos estudados (aproximadamente 14mmHg e 5 a 7mmHg) respectivamente, quando analisados separadamente e quando confrontados não apresentaram diferença de comportamento entre si. A freqüência cardíaca não se alterou nos dois grupos estudados. Depressão do segmento ST >1mm ocorreu em 10 (17,9%) pacientes; todos os eventos ocorreram no mínimo 2 horas após o término do procedimento odontológico. Extra - sístoles supra-ventriculares e/ou extra-sístoles ventriculares em número maior do que 10/hora estiveram presentes em 17 (30,4%) pacientes durante as 24 horas e durante o período do procedimento em 7 (12,5%), sendo 4 (13,8%) do grupo que recebeu anestesia sem adrenalina e 3 (11,1%) do grupo que recebeu anestesia com adrenalina e o teste Exato de Fisher não mostrou diferença entre os grupos. Concluímos que não houve diferença em relação ao comportamento de pressão arterial, freqüência cardíaca, evidência de isquemia e arritmias entre os grupos. O uso associado de vasoconstritor mostrou-se, portanto, seguro dentro dos limites do estudo. / We enrolled 62 patients with positive exercise stress test who presented with stable angina and were receiving drug therapy. All had a coronary angiography screening showing >70% obstruction in at least one of the main coronary arteries. The study aimed to compare electrocardiographic and blood pressure parameters during restorative dentistry procedure under local anesthesia, both with and without vasoconstrictor, in the presence of coronary artery disease. Ages ranged from 39 to 80, (mean ± SD) 58.7±8.8 years, 51 (82.3%) of them were male. Thirty patients were randomly assigned to receive 2% lidocaine local anesthesia with 1:100,000 epinephrine, the others receiving 2% lidocaine without vasoconstrictor. All the patients underwent ambulatory blood pressure and 24-hour Holter monitoring, beginning two hours ahead of the dental procedure. Recording were made during (1) baseline - 60-minute period before dental procedure began; (2) procedure - from beginning of anesthesia until the end of the procedure; and (3) subsequent 24-hour period. Analysis of variance with repeat measures showed significant diastolic and systolic blood pressure increases from baseline to the period of the procedure, in the two study groups (approximately 14 mm Hg, and 5 to 7 mm Hg, respectively); both in a separate analysis and in a comparative analysis no significant difference between them could be confirmed. Heart rate did not change in neither of the two groups. ST-segment >1 mm depression was detected in 10 (17.9%) patients; all these events occurred at least two hours after the end of the dentistry procedure. Premature supraventricular systoles and/or premature ventricular systoles in a greater number than 10/hour were seen in 17 (30.4%) patients in the 24-hours period after the procedure; during the procedure they occurred in 7 (12.5%) patients, of whom 4 (13.8%) were in the group without, and 3 (11.1%) in the group with vasoconstrictor. The Fisher\'s exact test revealed no difference between the groups. We concluded that there was no difference of blood pressure, heart rate, evidence of ischemia or arrhythmia episodes between the groups. Thus, the associated use of vasoconstrictor proved to be safe within the limits of this study

INTRODUÇÃO: A segurança da administração de anestésicos locais com vasoconstritor em pacientes diabéticos submetidos à cirurgia oral não está bem fundamentada na literatura. OBJETIVO: Investigar a ocorrência de variação da glicemia nos períodos pré, trans e pós-operatório de exodontia de dentes superiores, sob anestesia local com lidocaína 2% sem e com adrenalina 1:100.000, em portadores de diabetes mellitus tipo 2. Secundariamente, avaliar os efeitos hemodinâmicos e o grau de ansiedade. MÉTODOS: Estudo prospectivo e randomizado com pacientes portadores de diabetes acompanhados na Unidade Clinica de Coronariopatia Crônica do Instituto do Coração do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo. A monitorização contínua da glicemia durante 24 horas foi realizada através do MiniMed Continuous Glucose Monitoring System (CGMS, Medtronic). Os pacientes foram divididos em dois grupos: LSA - que recebeu 5,4 mL lidocaína 2% sem adrenalina e LCA - que recebeu 5,4 mL de lidocaína 2% com adrenalina 1:100.000. Os níveis de glicemia foram avaliados nas 24 horas (período basal) e nos tempos determinados: uma hora antes, durantes e até uma hora após a exodontia (período de procedimento). Os parâmetros hemodinâmicos foram avaliados por meio de um medidor de pressão arterial digital automático e o nível de ansiedade através de uma escala. RESULTADOS: Dos 400 pacientes avaliados, 70 foram incluídos no estudo, sendo 35 randomizados no grupo LSA e 35 no grupo LCA. A análise das médias da glicemia nos grupos LSA e LCA durante os períodos (basal e procedimento) não demonstrou diferença estatisticamente significativa (p=0,229 e p=0,811, respectivamente). Também não houve diferença significativa (p=0,748) na glicemia entre os grupos em cada tempo avaliado. Entretanto, nos dois grupos houve decréscimo significativo da glicemia (p < 0,001) ao longo dos tempos avaliados. Os grupos LSA e LCA não apresentaram diferenças significativas em relação à PAS (p=0,176), à PAD (p=0,913), à FC (p=0,570) e ao nível de ansiedade. CONCLUSÃO: A administração de 5,4mL de lidocaína 2% com adrenalina 1:100.000 não provocou alteração significativa da glicemia, parâmetros hemodinâmicos e nível de ansiedade em relação ao grupo sem vasoconstritor / INTRODUCTION: The safety of administration of local anesthetics with epinephrine for diabetic patients undergoing oral surgery is not well grounded in the literature. OBJECTIVE: To investigate the occurrence of variation of glucose in the pre, intra and postoperative extraction of upper teeth under local anesthesia with lidocaine 2% with and without 1:100.000 epinephrine in patients with type 2 diabetes mellitus. Secondly, to evaluate the hemodynamic effects and degree of anxiety. METHODS: A prospective randomized study of patients with diabetes attended in Coronary Chronic Clinics Unit, Heart Institute, Hospital das Clinicas in University of São Paulo Medical School. Continuous monitoring of blood glucose for 24 hours was performed using MiniMed Continuous Glucose Monitoring System (CGMS, Medtronic) and the patients were divided into two groups: LSA - which received 5.4 mL of 2% lidocaine without epinephrine and LCA - which received 5.4 mL of 2% lidocaine with 1:100,000 epinephrine. Blood glucose levels were assessed at 24 hours (baseline period) and at certain times: one hour before, during, and up to one hour after oral surgery (procedure period). We evaluated the hemodynamic parameters through a digital automatic pressure meter and anxiety level was measured by the scale. RESULTS: Of 400 patients evaluated, 70 were included in these study, 35 were randomized in the LSA group and 35 in the group LCA. The analysis of mean glicemia in groups LSA and LCA during the baseline period and procedure showed no statistically significant difference (p = 0.229 and p = 0.811, respectively). There was no difference in blood glucose (p = 0.748) between the groups at each time evaluated. However, in both groups there was a significant decrease in blood glucose (p < 0.001) over the time periods studied. The groups showed no significant differences regarding SBP (p = 0.176), DBP (p = 0.913), HR (p = 0.570) and anxiety level. CONCLUSION: The administration of 5.4 mL of 2% lidocaine with epinephrine 1:100.000 caused no significant change in blood glucose, hemodynamic parameters and level of anxiety compared to the group without vasoconstrictor

No description available.

<p>In this thesis some multivariate spectroscopic methods for the analysis of solutions are proposed. Spectroscopy and multivariate data analysis form a powerful combination for obtaining both quantitative and qualitative information and it is shown how spectroscopic techniques in combination with chemometric data evaluation can be used to obtain rapid, simple and efficient analytical methods. These spectroscopic methods consisting of spectroscopic analysis, a high level of automation and chemometric data evaluation can lead to analytical methods with a high analytical capacity, and for these methods, the term high-capacity analysis (HCA) is suggested. It is further shown how chemometric evaluation of the multivariate data in chromatographic analyses decreases the need for baseline separation. </p><p>The thesis is based on six papers and the chemometric tools used are experimental design, principal component analysis (PCA), soft independent modelling of class analogy (SIMCA), partial least squares regression (PLS) and parallel factor analysis (PARAFAC). The analytical techniques utilised are scanning ultraviolet-visible (UV-Vis) spectroscopy, diode array detection (DAD) used in non-column chromatographic diode array UV spectroscopy, high-performance liquid chromatography with diode array detection (HPLC-DAD) and fluorescence spectroscopy. The methods proposed are exemplified in the analysis of pharmaceutical solutions and serum proteins.</p><p>In Paper I a method is proposed for the determination of the content and identity of the active compound in pharmaceutical solutions by means of UV-Vis spectroscopy, orthogonal signal correction and multivariate calibration with PLS and SIMCA classification. Paper II proposes a new method for the rapid determination of pharmaceutical solutions by the use of non-column chromatographic diode array UV spectroscopy, i.e. a conventional HPLC-DAD system without any chromatographic column connected. In Paper III an investigation is made of the ability of a control sample, of known content and identity to diagnose and correct errors in multivariate predictions something that together with use of multivariate residuals can make it possible to use the same calibration model over time. In Paper IV a method is proposed for simultaneous determination of serum proteins with fluorescence spectroscopy and multivariate calibration. Paper V proposes a method for the determination of chromatographic peak purity by means of PCA of HPLC-DAD data. In Paper VI PARAFAC is applied for the decomposition of DAD data of some partially separated peaks into the pure chromatographic, spectral and concentration profiles. </p>

Au cours des vingt dernières années, l’anesthésie régionale est devenue, autant en médecine vétérinaire qu’humaine, un outil essentiel à l’élaboration de protocoles analgésiques péri-opératoires. Parmi l’éventail de techniques mises au point en anesthésie canine, le bloc paravertébral du plexus vertébral (PBPB) et sa version modifiée sont d’un grand intérêt pour toute procédure du membre thoracique, dans sa portion proximale. Toutefois, l’essentiel des données publiées à ce jour provient d’études colorimétriques, sans évaluation clinique, et peu d’information est disponible sur les techniques de localisation nerveuse envisageables à ce site. Notre étude visait à décrire une approche échoguidée du PBPB modifié, puis à caractériser ses paramètres pharmacocinétiques et pharmacodynamiques après administration de lidocaïne (LI) ou lidocaïne adrénalinée (LA). Huit chiens ont été inclus dans un protocole prospectif, randomisé, en aveugle et croisé, réparti sur trois périodes. L’impact pharmacodynamique du bloc effectué avec LI ou LA a été évalué régulièrement pour 180 min suivant son exécution. Le traitement à l’adrénaline n’a pas démontré d’impact significatif (P = 0,845) sur la durée du bloc sensitif, tel qu’évalué par un stimulus douloureux mécanique appliqué aux dermatomes ciblés. À l’opposé, l’atteinte proprioceptive évaluée par la démarche a été trouvée prolongée (P = 0,027) et le bloc moteur mesuré par le pic de force verticale (PVF) au trot sur la plaque de force s’est avéré plus marqué (PVF réduit; P = 0,007) sous LA. À l’arrêt comme au trot, le nadir de la courbe PVF-temps a été trouvé retardé (P < 0,005) et la pente ascendante de retour aux valeurs normales adoucie (P = 0,005). Parallèlement aux évaluations cliniques, des échantillons plasmatiques ont été collectés régulièrement afin de quantifier et décrire le devenir pharmacocinétique de la lidocaïne. Parmi les trois élaborés, un modèle bi-compartimental doté d’une double absorption asynchrone d’ordre zéro a finalement été sélectionné et appliqué aux données expérimentales. Sous LA, la Cmax a été trouvée significativement diminuée (P < 0,001), les phases d’absorption prolongées [P < 0,020 (Dur1) et P < 0,001 (Dur2)] et leurs constantes réduites [P = 0,046(k01) et P < 0,001 (k02)], le tout en concordance avec les effets proprioceptifs et moteurs rapportés. Bien que l’extrapolation du dosage soit maintenant théoriquement envisageable à partir du modèle mis en lumière ici, des études supplémentaires sont encore nécessaires afin d’établir un protocole de PBPB d’intérêt clinique. L’analyse sur plaque de force pourrait alors devenir un outil de choix pour évaluer l’efficacité du bloc dans un cadre expérimental. / Over the last decade, regional anaesthesia has become a gold standard for peri-surgical management in veterinary medicine. Among the many techniques developed for analgesia in dogs, the paravertebral brachial plexus block (PBPB) is of great interest when targeting the proximal half of the thoracic limb. Yet, most available data on this technique is based on colorimetric protocols rather than clinical evaluation, and there are very few published results for PBPB execution using nerve location techniques. Through this work, we wished to describe an ultrasound-guided approach of the PBPB and characterize its pharmacokinetic/ pharmacodynamic parameters when executed with either lidocaine alone (LI) or combined to adrenaline (LA). Eight dogs were included in a prospective, randomised, blinded, crossover protocol performed over three distinct periods. Pharmacodynamic impact of LI and LA was compared for 180 minutes after block administration. No significant difference (P = 0.845) was noted between treatments regarding length of the sensitive block, as evaluated regularly through a mechanical painful stimulus applied to selected dermatomes. On the opposite, gait examination showed a longer proprioceptive deficit using LA (P = 0.027). Motor block measured with dynamic force plate analysis showed a lower peak vertical force with LA than LI (P = 0.007). For both dynamic and static evaluations, nadir was clearly delayed (P < 0.005) and the ascending slope back to baseline significantly softened (P = 0.005) in the LA group. Throughout block execution and evaluation, blood samples were collected regularly in order to quantify and describe lidocaine kinetics. Models where developed and compared. A two-compartment model with dual zero-order absorption processes was selected as the best fit for our experimental data. Cmax proved to be significantly reduced with LA (P < 0.001), thus reducing potential toxicity. Absorption phase was prolonged [P < 0.020 (Dur1) and P < 0.001 (Dur2)] and zero-order absorption constant rates lowered [P = 0.046(k01) and P < 0.001 (k02)] following adrenaline addition, in accordance with the previously noted prolonged gait and motor effects. Though dosage extrapolation is now possible using the model developed and tested here, further studies would be needed to establish a PBPB protocol of more clinical interest. Then, force plate analysis could become a key tool for block quality assessment, as both dynamic and static measurements proved to be the reliable ways to collect ground reaction force (GRF) data.

Modificações na fisiologia do organismo da mulher ocorrem durante a gravidez em conseqüência às alterações hormonais, anatômicas e metabólicas. No sistema circulatório a modificação mais significativa é o aumento do débito cardíaco a partir do primeiro trimestre da gestação. Mulheres portadoras de cardiopatias podem apresentar graves complicações durante o período gestacional devido à inapropriada adaptação à sobrecarga hemodinâmica, mesmo em pacientes consideradas em capacidade funcional favorável, no início da gestação. A literatura carece de estudos dos efeitos dos anestésicos locais com ou sem vasoconstritor utilizados nos procedimentos odontológicos, sobre os parâmetros cardiovasculares de mulheres gestantes portadoras de valvopatias e seus conceptos. A escassez científica fez deste tema nosso objetivo de estudo: avaliar e analisar parâmetros da cardiotocografia, como freqüência cardíaca, motilidade fetal e contrações uterinas e de pressão arterial e eletrocardiográficos da gestante portadora de doença valvar reumática quando submetida à anestesia local com lidocaína, com e sem vasoconstritor, durante procedimento odontológico restaurador. Para tanto, a monitorização ambulatorial da pressão arterial (MAPA) e a eletrocardiografia ambulatorial (Holter) materna, ambas obtidas durante 24 horas e a cardiotografia (CTG) de 31 portadoras de cardiopatia reumática entre a 28ª e 37ª semana de gestação, nos períodos: (1) basal - 60 minutos antes do procedimento para MAPA e Holter e 20 minutos para CTG; (2) procedimento - 56+15,5minutos (média+desvio padrão); (3) pós-procedimento - 20 minutos; e (4) média das 24 horas para freqüência cardíaca e extra-sístoles e média da vigília e do sono para pressão arterial, permitiu a análise da variação desses parâmetros, utilizando-se lidocaína 2% sem vasoconstritor e lidocaína 2% com epinefrina 1:100.000, compondo-as em dois grupos. Demonstrou-se redução significativa nos valores de freqüência cardíaca materna durante o procedimento somente quando comparado aos demais períodos (p<0,001). Quando comparados os dois grupos, não houve diferença (p>0,05). Houve ocorrência de arritmia cardíaca em 9 (29,0%) pacientes, sendo 7 (41,8%) do grupo que recebeu anestesia com adrenalina. A pressão arterial materna não apresentou diferença quando comparamos os períodos ou os grupos (p>0,05). O mesmo ocorreu (p>0,05) nas análises comparativas dos parâmetros fetais obtidos por meio da CTG - número de contrações, nível e variabilidade da linha de base, número de acelerações da freqüência cardíaca fetal e padrão de reatividade fetal. Concluiu-se que o uso da lidocaína 2% associado à adrenalina mostrou-se seguro em procedimento odontológico durante a gestação de mulheres com cardiopatia valvar reumática. / During pregnancy, the organic systems of a woman are subjected to physiological modifications consequential to hormonal, anatomic and metabolical alterations. The most significant modification in the circulatory system is an increased cardiac output from the first three months of gestation. Women with heart disease may present with severe complications during the gestational period, because of inappropriate adaptation of her body to this hemodynamic overload, even those patients who are thought to have an appropriate functional capacity during early pregnancy. There are scant studies in the literature on the effects of local anesthetics, with and without vasoconstrictor, used in dental procedures on the cardiovascular variables of pregnant women with valvar disease, as well as on their concepti. Driven by this shortage, we decided to have this subject studied, by assessing and analyzing cardiotachographic parameters, such as heart rate, fetal motility and uterine contractions, in addition to blood pressure and electrocardiographic variables, in pregnant women with rheumatic valvar disease who undergo local anesthesia with lidocaine, with and without vasoconstrictor, during restorative dental procedure. For this, 31 rheumatic heart disease patients who were in their 28th to 37th week of gestation, had 24-hour ambulatory monitoring of their blood pressure (BP) and Holter electrocardiography (Holter-ECG), and cardiotocography (CTG), performed during: (1) baseline - 60 minutes before the procedure for BP and Holter- ECG monitoring, and 20 minutes before the procedure for CTG; (2) procedure - 56±15.5 minutes (mean±SD); (3) post-procedure - 20 minutes; and (4) mean 24-hour heart rate and extrasystoles measurement, and mean wake and sleeping periods BP monitoring. Variation of the above variables was analyzed in two groups, one with infusion of a 2% solution of lidocaine with vasoconstrictor, and the other with infusion of a 2% solution of lidocaine with epinephrine 1:100.000. The maternal heart rate values obtained during the procedure showed a significant reduction only in comparison with the other time periods (P<0.001). The comparison of the two groups did not reveal any significant difference (P>0.05). Cardiac arrhythmia was detected in 9 (29.0%) patients, 7 of them (41.8%) from the group who received anesthetics with epinephrine. Maternal blood pressure did not show any significant difference neither between time periods, nor between groups (P>0.05). The same occurred in the comparative analysis of the fetal parameters obtained during CTG -number of contractions, level and variability from baseline, number of fetal heart rate accelerations and fetal reactivity pattern. Our conclusion was that the use of 2% solution of lidocaine in association with epinephrine proved safe during dental procedure in pregnant women with rheumatic valvar cardiopathy.

In this thesis some multivariate spectroscopic methods for the analysis of solutions are proposed. Spectroscopy and multivariate data analysis form a powerful combination for obtaining both quantitative and qualitative information and it is shown how spectroscopic techniques in combination with chemometric data evaluation can be used to obtain rapid, simple and efficient analytical methods. These spectroscopic methods consisting of spectroscopic analysis, a high level of automation and chemometric data evaluation can lead to analytical methods with a high analytical capacity, and for these methods, the term high-capacity analysis (HCA) is suggested. It is further shown how chemometric evaluation of the multivariate data in chromatographic analyses decreases the need for baseline separation. The thesis is based on six papers and the chemometric tools used are experimental design, principal component analysis (PCA), soft independent modelling of class analogy (SIMCA), partial least squares regression (PLS) and parallel factor analysis (PARAFAC). The analytical techniques utilised are scanning ultraviolet-visible (UV-Vis) spectroscopy, diode array detection (DAD) used in non-column chromatographic diode array UV spectroscopy, high-performance liquid chromatography with diode array detection (HPLC-DAD) and fluorescence spectroscopy. The methods proposed are exemplified in the analysis of pharmaceutical solutions and serum proteins. In Paper I a method is proposed for the determination of the content and identity of the active compound in pharmaceutical solutions by means of UV-Vis spectroscopy, orthogonal signal correction and multivariate calibration with PLS and SIMCA classification. Paper II proposes a new method for the rapid determination of pharmaceutical solutions by the use of non-column chromatographic diode array UV spectroscopy, i.e. a conventional HPLC-DAD system without any chromatographic column connected. In Paper III an investigation is made of the ability of a control sample, of known content and identity to diagnose and correct errors in multivariate predictions something that together with use of multivariate residuals can make it possible to use the same calibration model over time. In Paper IV a method is proposed for simultaneous determination of serum proteins with fluorescence spectroscopy and multivariate calibration. Paper V proposes a method for the determination of chromatographic peak purity by means of PCA of HPLC-DAD data. In Paper VI PARAFAC is applied for the decomposition of DAD data of some partially separated peaks into the pure chromatographic, spectral and concentration profiles.

Modificações na fisiologia do organismo da mulher ocorrem durante a gravidez em conseqüência às alterações hormonais, anatômicas e metabólicas. No sistema circulatório a modificação mais significativa é o aumento do débito cardíaco a partir do primeiro trimestre da gestação. Mulheres portadoras de cardiopatias podem apresentar graves complicações durante o período gestacional devido à inapropriada adaptação à sobrecarga hemodinâmica, mesmo em pacientes consideradas em capacidade funcional favorável, no início da gestação. A literatura carece de estudos dos efeitos dos anestésicos locais com ou sem vasoconstritor utilizados nos procedimentos odontológicos, sobre os parâmetros cardiovasculares de mulheres gestantes portadoras de valvopatias e seus conceptos. A escassez científica fez deste tema nosso objetivo de estudo: avaliar e analisar parâmetros da cardiotocografia, como freqüência cardíaca, motilidade fetal e contrações uterinas e de pressão arterial e eletrocardiográficos da gestante portadora de doença valvar reumática quando submetida à anestesia local com lidocaína, com e sem vasoconstritor, durante procedimento odontológico restaurador. Para tanto, a monitorização ambulatorial da pressão arterial (MAPA) e a eletrocardiografia ambulatorial (Holter) materna, ambas obtidas durante 24 horas e a cardiotografia (CTG) de 31 portadoras de cardiopatia reumática entre a 28ª e 37ª semana de gestação, nos períodos: (1) basal - 60 minutos antes do procedimento para MAPA e Holter e 20 minutos para CTG; (2) procedimento - 56+15,5minutos (média+desvio padrão); (3) pós-procedimento - 20 minutos; e (4) média das 24 horas para freqüência cardíaca e extra-sístoles e média da vigília e do sono para pressão arterial, permitiu a análise da variação desses parâmetros, utilizando-se lidocaína 2% sem vasoconstritor e lidocaína 2% com epinefrina 1:100.000, compondo-as em dois grupos. Demonstrou-se redução significativa nos valores de freqüência cardíaca materna durante o procedimento somente quando comparado aos demais períodos (p<0,001). Quando comparados os dois grupos, não houve diferença (p>0,05). Houve ocorrência de arritmia cardíaca em 9 (29,0%) pacientes, sendo 7 (41,8%) do grupo que recebeu anestesia com adrenalina. A pressão arterial materna não apresentou diferença quando comparamos os períodos ou os grupos (p>0,05). O mesmo ocorreu (p>0,05) nas análises comparativas dos parâmetros fetais obtidos por meio da CTG - número de contrações, nível e variabilidade da linha de base, número de acelerações da freqüência cardíaca fetal e padrão de reatividade fetal. Concluiu-se que o uso da lidocaína 2% associado à adrenalina mostrou-se seguro em procedimento odontológico durante a gestação de mulheres com cardiopatia valvar reumática. / During pregnancy, the organic systems of a woman are subjected to physiological modifications consequential to hormonal, anatomic and metabolical alterations. The most significant modification in the circulatory system is an increased cardiac output from the first three months of gestation. Women with heart disease may present with severe complications during the gestational period, because of inappropriate adaptation of her body to this hemodynamic overload, even those patients who are thought to have an appropriate functional capacity during early pregnancy. There are scant studies in the literature on the effects of local anesthetics, with and without vasoconstrictor, used in dental procedures on the cardiovascular variables of pregnant women with valvar disease, as well as on their concepti. Driven by this shortage, we decided to have this subject studied, by assessing and analyzing cardiotachographic parameters, such as heart rate, fetal motility and uterine contractions, in addition to blood pressure and electrocardiographic variables, in pregnant women with rheumatic valvar disease who undergo local anesthesia with lidocaine, with and without vasoconstrictor, during restorative dental procedure. For this, 31 rheumatic heart disease patients who were in their 28th to 37th week of gestation, had 24-hour ambulatory monitoring of their blood pressure (BP) and Holter electrocardiography (Holter-ECG), and cardiotocography (CTG), performed during: (1) baseline - 60 minutes before the procedure for BP and Holter- ECG monitoring, and 20 minutes before the procedure for CTG; (2) procedure - 56±15.5 minutes (mean±SD); (3) post-procedure - 20 minutes; and (4) mean 24-hour heart rate and extrasystoles measurement, and mean wake and sleeping periods BP monitoring. Variation of the above variables was analyzed in two groups, one with infusion of a 2% solution of lidocaine with vasoconstrictor, and the other with infusion of a 2% solution of lidocaine with epinephrine 1:100.000. The maternal heart rate values obtained during the procedure showed a significant reduction only in comparison with the other time periods (P<0.001). The comparison of the two groups did not reveal any significant difference (P>0.05). Cardiac arrhythmia was detected in 9 (29.0%) patients, 7 of them (41.8%) from the group who received anesthetics with epinephrine. Maternal blood pressure did not show any significant difference neither between time periods, nor between groups (P>0.05). The same occurred in the comparative analysis of the fetal parameters obtained during CTG -number of contractions, level and variability from baseline, number of fetal heart rate accelerations and fetal reactivity pattern. Our conclusion was that the use of 2% solution of lidocaine in association with epinephrine proved safe during dental procedure in pregnant women with rheumatic valvar cardiopathy.