Although microdialysis (MD) and solid-phase microextraction (SPME) are widely used sampling techniques, a comparison study has not been performed to date. The goal of the research presented was not only to address this issue but also to develop new analytical methods that were more suitable for in vivo study using MD and SPME. A new calibration method called kinetic microdialysis was developed for in vivo sampling. Two MD probes with different flow rates were simultaneously inserted into the symmetric parts of sampling system. A simple empirical equation was proposed to calculate the analyte concentrations in the sample matrix using two different dialysate concentrations. Several factors that influenced the correction factor in this equation were discussed. An excellent correlation was observed between the calculated and theoretical value. This method was subsequently applied for in vivo sampling, for the measurement of pesticide allocation in the different leaves of a jade plant (Crassula ovata). Compared to the other reported MD calibration methods, this novel approach offers several advantages including simplicity, speed, robustness, and increased accuracy. The on-fiber standardization technique for solid-coated SPME was studied and a theoretical model is proposed for the isotropic behavior of adsorption and desorption, based on Fick’s law of diffusion and the Langmuir model. The isotropy of the adsorption and desorption of analytes onto and from the surface of porous solid SPME fiber was validated with the use of a commercially available fiber, a 50 um carbowax/templated resin (CW/TPR) for carbamate pesticide analysis in various in vitro sample matrices. Time constants were comparable for the adsorption and desorption processes. Equilibrium constants and fiber capacities were calculated with the Langmuir Isotherm Model. A kinetic method was developed to calibrate adsorption using desorption. This calibration corrected for the sample matrix effects and minimized displacement effects as a pre-equilibrium extraction. The technique was successfully applied to the analysis of pesticides in river water and white wine. This developed method could be potentially applied for in vivo study. A new kinetic calibration was developed using dominant pre-equilibrium desorption by SPME. The calibration was based on isotropism between absorption and desorption, which was proved theoretically and experimentally in an aqueous solution and semi-solid matrix. This approach allows for the calibration of absorption using desorption to compensate for matrix effects. Moreover, concentration profiles are initially proposed to verify isotropism between the absorption and desorption, while providing a linear approach to obtain time constants for the purpose of quantitative analysis. This linear approach is more convenient, robust and accurate than the non-linear version with the previously used time profiles. Furthermore, the target analytes are used as the internal standards, thus radioactive or deuterated internal standards are not necessary. In addition, dominant pre-equilibrium desorption utilizes the pre-equilibrium approach and offers a shorter sample preparation time, which is typically suitable for in vivo sampling. This kinetic calibration method was successfully applied to prepare samples of polycyclic aromatic hydrocarbons (PAHs) in a flow-through system and in vivo pesticide sampling in a jade plant (Crassula ovata). Previous field studies utilizing SPME predominantly focused on volatile compounds in air or water. Earlier in vivo sampling studies utilizing SPME were limited to liquid matrices, namely blood. In this study, SPME was developed for in vivo laboratory and field sampling of pharmaceuticals in fish muscle. Pre-equilibrium extraction was used to shorten in vivo sampling time. The use of pre-equilibrium desorption rates are proposed as a means to calibrate pre-equilibrium extractions. Excellent linearity was found between the free concentrations determined by SPME from the muscle of living fish and the waterborne concentrations of several pharmaceuticals. It is also firstly proposed a simple SPME method to determine free and total concentrations simultaneously in a living tissue using the known protein binding value. The utility of in vivo SPME sampling under field conditions was evaluated in wild fish collected from a number of different river locations under varying degrees of influence from municipal wastewater effluents. Diphenhydramine and diltiazem were detected in the muscle of fish downstream of a local wastewater treatment plant. Based on this study, SPME technique has demonstrated several important advantages for laboratory and field in vivo sampling. The development of a rapid, robust, easy to deploy technique which combines sampling, extraction and concentration into one step is a potentially important tool for use in vivo field-based sampling. MD and SPME methods have been developed and compared through in vitro and in vivo study. For in vitro study (juice, milk and orange jelly), both methods offered accurate and precise results (recovery: 88-105% with RSD < 15%) for complex sample matrices by standard addition method. The limits of quantification (LOQs) of the two methods developed were below the tolerance levels in milk set by the United Nations Food and Agriculture Organization (FAO). Compared to MD, the fully automated SPME procedure offered several advantages including high-throughput and more efficient sampling, less labor intensity, and capability for batch analysis. For in vivo study, kinetic calibrations were performed using retrodialysis and in-fiber standardization techniques for MD and SPME, respectively. Quantitative analysis was performed to measure pesticide concentrations in living tissue, i.e., the leaves of a living jade plant (Crassula ovata). Although both techniques provided sampling with minimal perturbation to the system under study, SPME was more sensitive, precise and accurate, suitable for field sampling and had a wider application than MD. It demonstrated that SPME has the potential to replace MD for in vivo study.

Although microdialysis (MD) and solid-phase microextraction (SPME) are widely used sampling techniques, a comparison study has not been performed to date. The goal of the research presented was not only to address this issue but also to develop new analytical methods that were more suitable for in vivo study using MD and SPME. A new calibration method called kinetic microdialysis was developed for in vivo sampling. Two MD probes with different flow rates were simultaneously inserted into the symmetric parts of sampling system. A simple empirical equation was proposed to calculate the analyte concentrations in the sample matrix using two different dialysate concentrations. Several factors that influenced the correction factor in this equation were discussed. An excellent correlation was observed between the calculated and theoretical value. This method was subsequently applied for in vivo sampling, for the measurement of pesticide allocation in the different leaves of a jade plant (Crassula ovata). Compared to the other reported MD calibration methods, this novel approach offers several advantages including simplicity, speed, robustness, and increased accuracy. The on-fiber standardization technique for solid-coated SPME was studied and a theoretical model is proposed for the isotropic behavior of adsorption and desorption, based on Fick’s law of diffusion and the Langmuir model. The isotropy of the adsorption and desorption of analytes onto and from the surface of porous solid SPME fiber was validated with the use of a commercially available fiber, a 50 um carbowax/templated resin (CW/TPR) for carbamate pesticide analysis in various in vitro sample matrices. Time constants were comparable for the adsorption and desorption processes. Equilibrium constants and fiber capacities were calculated with the Langmuir Isotherm Model. A kinetic method was developed to calibrate adsorption using desorption. This calibration corrected for the sample matrix effects and minimized displacement effects as a pre-equilibrium extraction. The technique was successfully applied to the analysis of pesticides in river water and white wine. This developed method could be potentially applied for in vivo study. A new kinetic calibration was developed using dominant pre-equilibrium desorption by SPME. The calibration was based on isotropism between absorption and desorption, which was proved theoretically and experimentally in an aqueous solution and semi-solid matrix. This approach allows for the calibration of absorption using desorption to compensate for matrix effects. Moreover, concentration profiles are initially proposed to verify isotropism between the absorption and desorption, while providing a linear approach to obtain time constants for the purpose of quantitative analysis. This linear approach is more convenient, robust and accurate than the non-linear version with the previously used time profiles. Furthermore, the target analytes are used as the internal standards, thus radioactive or deuterated internal standards are not necessary. In addition, dominant pre-equilibrium desorption utilizes the pre-equilibrium approach and offers a shorter sample preparation time, which is typically suitable for in vivo sampling. This kinetic calibration method was successfully applied to prepare samples of polycyclic aromatic hydrocarbons (PAHs) in a flow-through system and in vivo pesticide sampling in a jade plant (Crassula ovata). Previous field studies utilizing SPME predominantly focused on volatile compounds in air or water. Earlier in vivo sampling studies utilizing SPME were limited to liquid matrices, namely blood. In this study, SPME was developed for in vivo laboratory and field sampling of pharmaceuticals in fish muscle. Pre-equilibrium extraction was used to shorten in vivo sampling time. The use of pre-equilibrium desorption rates are proposed as a means to calibrate pre-equilibrium extractions. Excellent linearity was found between the free concentrations determined by SPME from the muscle of living fish and the waterborne concentrations of several pharmaceuticals. It is also firstly proposed a simple SPME method to determine free and total concentrations simultaneously in a living tissue using the known protein binding value. The utility of in vivo SPME sampling under field conditions was evaluated in wild fish collected from a number of different river locations under varying degrees of influence from municipal wastewater effluents. Diphenhydramine and diltiazem were detected in the muscle of fish downstream of a local wastewater treatment plant. Based on this study, SPME technique has demonstrated several important advantages for laboratory and field in vivo sampling. The development of a rapid, robust, easy to deploy technique which combines sampling, extraction and concentration into one step is a potentially important tool for use in vivo field-based sampling. MD and SPME methods have been developed and compared through in vitro and in vivo study. For in vitro study (juice, milk and orange jelly), both methods offered accurate and precise results (recovery: 88-105% with RSD < 15%) for complex sample matrices by standard addition method. The limits of quantification (LOQs) of the two methods developed were below the tolerance levels in milk set by the United Nations Food and Agriculture Organization (FAO). Compared to MD, the fully automated SPME procedure offered several advantages including high-throughput and more efficient sampling, less labor intensity, and capability for batch analysis. For in vivo study, kinetic calibrations were performed using retrodialysis and in-fiber standardization techniques for MD and SPME, respectively. Quantitative analysis was performed to measure pesticide concentrations in living tissue, i.e., the leaves of a living jade plant (Crassula ovata). Although both techniques provided sampling with minimal perturbation to the system under study, SPME was more sensitive, precise and accurate, suitable for field sampling and had a wider application than MD. It demonstrated that SPME has the potential to replace MD for in vivo study.

Tesis por compendio / [ES] La ablación por radiofrecuencia (RF) se ha convertido en una técnica ablativa importante, ampliamente utilizada en el área de las terapias mínimamente invasivas de la medicina moderna. El avance en el campo de las tecnologías basadas en RF a lo largo de los años ha llevado a un número creciente de aplicaciones en diferentes áreas terapéuticas tales como arritmias cardíacas, epilepsia, oncología, resección asistida, apnea, dolor o cirugía estética. Sin embargo, existe una constante necesidad de desarrollar estudios computacionales y experimentales para mejorar el rendimiento de estas técnicas. El enfoque principal de esta tesis doctoral está centrado en examinar los efectos térmicos y eléctricos de ablación por radiofrecuencia de tejidos para mejorar la eficacia y la seguridad de las terapias y dispositivos basados en energía de radiofrecuencia. Las dos áreas principales de interés han sido el tratamiento del dolor y la cirugía hepática oncológica, que se han organizado en tres estudios independientes. La metodología de los estudios se ha basado en modelos computacionales y estudios experimentales sobre phantom de agar, modelos ex vivo e in vivo y ensayos clínicos. El estudio focalizado en el tratamiento del dolor ha incluido el análisis de los efectos eléctricos y térmicos del tratamiento con radiofrecuencia pulsada (PRF) y el riesgo relacionado con el daño térmico al tejido. Se han estudiado diferentes protocolos pulsados empleados en la práctica clínica utilizando modelos computacionales. La exactitud del modelo se ha validado mediante un modelo en phantom de agar. Se han propuesto también modelos computacionales adicionales para los protocolos pulsados alternativos en los cuales se reduciría el efecto térmico sin afectar al efecto eléctrico. En el estudio se ha discutido también el concepto de electroporación leve como el resultado de PRF. En el área de la cirugía hepática oncológica se han analizado dos técnicas diferentes. El primer estudio se ha centrado en examinar la hidratación del tejido durante la ablación por RF con un nuevo electrodo ICW. El nuevo diseño ha incluido dos agujas de perfusión expandibles integradas en el catéter. El objetivo principal ha sido mejorar la precisión del modelo computacional de ablación por RF de tumor utilizando una geometría realista de la distribución de solución salina en el tejido y evaluar el rendimiento del catéter de RF. Se han modelado diferentes casos de tumor infundido con solución salina y los resultados simulados se han comparado con los datos clínicos de un ensayo en 17 pacientes con cáncer hepático. Con el fin de obtener una distribución espacial realista de la solución salina infundida, se ha empleado un estudio in vivo sobre el modelo de hígado de cerdo. El segundo estudio se ha centrado en el desarrollo de una nueva técnica de sellado endoluminal basada en catéter, como una alternativa más efectiva para el manejo del remanente pancreático. El método ha consistido en una ablación por radiofrecuencia guiada por impedancia con la técnica de pullback. El ajuste del tipo de catéter de RF y del protocolo de ablación se ha realizado mediante modelos porcinos ex vivo. Posteriormente, la efectividad del sellado se ha evaluado sobre un modelo de cerdo in vivo. / [CA] L'ablació per radiofreqüència (RF) s'ha convertit en una tècnica ablativa important, àmpliament utilitzada en l'àrea de les teràpies mínimament invasives de la medicina moderna. L'avanç en el camp de les tecnologies basades en RF al llarg dels anys ha portat a un número creixent d'aplicacions en diferents àrees terapèutiques com ara arítmies cardíaques, epilèpsia, oncologia, resecció assistida, apnea, dolor o cirurgia estètica. No obstant això, hi ha una constant necessitat de desenvolupar estudis computacionals i experimentals per a millorar el rendiment d'aquestes tècniques. Aquesta tesi doctoral ha estat centrada en examinar els efectes tèrmics i elèctrics de l'ablació per radiofreqüència de teixits per tal de millorar l'eficàcia i la seguretat de les teràpies i dispositius basats en energia de radiofreqüència. Dos àrees principals són el tractament del dolor i la cirurgia hepàtica. Aquestos han sigut organitzats en tres estudis independents. La metodologia dels estudis ha estat basada en models computacionals i experimentals sobre phantom d'agar, models ex vivo i in vivo i assajos clínics. L'estudi enfocat en el tractament del dolor ha inclòs l'anàlisi dels efectes elèctrics i tèrmics del tractament amb radiofreqüència polsada (PRF) i el risc relacionat amb el dany tèrmic al teixit. S'han estudiat diferents protocols polsats emprats en la pràctica clínica utilitzant models computacionals. L'exactitud del model ha estat validada per mitjà d'un model de phantom d'agar. S'han proposat també models computacionals addicionals per a protocols polsats alternatius en els quals es reduiria l'efecte tèrmic sense afectar l'efecte elèctric. En aquest estudi s'ha discutit també el concepte d'electroporació lleu com el resultat de PRF. A l'àrea de la cirugía hepàtica han sigut analitzades dos tècniques diferents. El primer estudi s'ha centrat en la hidratació del teixit durant l'ablació per RF amb un nou elèctrode ICW. El nou disseny ha inclòs dos agulles de perfusió expandibles integrades en el catèter. L' objetiu principal ha sigut millorar la precisió del model computacional d' ablació de tumors per RF utilitzant una geometria realista per a la distribució de sèrum salií en el teixit i evaluar el rendiment del catèter de RF. S'han modelat diferents casos de tumor infundit amb sèrum salí i els resultats simulats han sigut comparats amb les dades clíniques d'un assaig dut a terme sobre 17 pacients amb càncer hepàtic. Amb l'objetiu d'obtenir una distribució espacial realista del sèrum salí injectat, s'ha du a terme un estudi in vivo basat en un model de fetge de porc. El segon estudi s'ha centrat en el desenvolupament d'una nova tècnica de tancament endoluminal bassat en catèter, com una alternativa més efectiva per a gestionar el romanent pancreàtic. El mètode ha consistit en una ablació per radiofreqüència guiada per impedància amb la tècnica de pullback. L'ajust del tipus de catèter de RF i del protocol d'ablació ha sigut realitzat per mitjà de models porcins ex vivo. Posteriorment, l'efectivitat del tancament ha sigut avaluada sobre un model de porc in vivo. / [EN] Radiofrequency (RF) ablation has become an important ablative technique widely used in the area of minimally invasive therapies of the modern medicine. The advancement in the field of RF-based technologies over the years has led to a growing number of applications in different therapeutic areas such as cardiac arrhythmias, epilepsy, oncology, assisted resection, apnea, pain or aesthetic surgery. There is, however, a constant need for the development of computer and experimental studies, which would enhance the performance and safety of these techniques. The main focus of this PhD Thesis was on examining the thermal and electrical phenomena behind tissue radiofrequency ablation in order to improve the efficacy and safety of the RF-based therapies and applicators. Two main areas of interest were pain management and oncology, which were organized into three independent studies. The research methodology was based on computer modeling and experimental studies on phantoms, ex vivo and in vivo models, and clinical trials. The research on pain management involved the analysis of electrical and thermal effects of the pulsed radiofrequency (PRF) treatment and the related risk of tissue thermal damage. Different pulse protocols used in clinical practice were studied using computer modeling and the study accuracy was validated by means of agar phantom model. Additional computer models for alternative pulse protocols were also proposed, in which thermal effect would be reduced but the electrical effect would remain unchanged. The study also discussed the concept of a mild electroporation from PRF. In the area of oncology, two different techniques were analyzed. First study focused on examining tissue hydration technique during RF ablation with a novel internally cooled wet (ICW) electrode. The new design involved two expandable perfusion needles built into the catheter. The main aim was to improve the accuracy of computer model of tumor RF ablation using a realistic geometry of saline distribution in tissue, and to assess the performance of the RF catheter. Different cases of saline-infused tumor were modeled and the simulated results were compared with the clinical data from a trial on 17 hepatic cancer patients. An in vivo study on pig liver model was used to obtain a realistic spatial distribution of the infused saline. The second study focused on the development of a new catheter-based endoluminal sealing technique as more effective alternative for management of the pancreatic stump. The method consisted of the impedance-guided radiofrequency ablation with pullback. Fine-tuning involving RF catheter type and ablation protocol was performed using ex vivo porcine models, and posteriorly, sealing effectiveness was assessed on an in vivo pig model. / The completion of this work would have not been possible without the financial support of the Spanish Ministerio de Economía, Industría y Competitividad that provided funding for the development of this research project, my Predoctoral scholarship, and also Travel Grant for the research stay in The Wellman Center for Photomedicine / Ewertowska, E. (2019). Computer modeling and experimentation in radiofrequiency-based minimally invasive therapies [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/134057 / Compendio

La rupture du Ligament Croisé Antérieur (LCA) est la blessure ligamentaire la plus fréquente avec une incidence de 1/3000. Elle est efficacement traitée aujourd’hui par une reconstruction par autogreffe tendineuse. Cependant, les problèmes causés par le prélèvement du greffon demeurent une limitation importante. Des substituts artificiels offrent une solution alternative mais la rupture et la génération de débris d’usure ont causé l’échec de la majorité des systèmes développés jusqu’à présent. Récemment, des travaux ont montré que des assemblages de fibres synthétiques d’hydrogel d’Alcool PolyVinylique (APV) reproduisent le comportement en traction du LCA humain. L’objectif principal de cette thèse a été d’explorer le potentiel de ces fibres pour la reconstruction ligamentaire en concevant et caractérisant des systèmes implantables pour une étude in vivo chez l’animal. Pour cela, j’ai réalisé une étude expérimentale depuis l’échelle de la fibre jusqu’à celle de l’implant complet. Deux types de fibres d’APV ont été caractérisés, obtenues par filage voie sèche (VS) et voie humide (VH). A l’échelle de la fibre, une étude microscopique et mécanique a mis en évidence un fort effet de l’orientation moléculaire sur le comportement en traction qui permet d’atteindre des modules élastiques très supérieurs à celui de films isotropes ayant un taux de gonflement équivalent. En particulier, les fibres VS présentent à 20°C un comportement en traction proche de celui du LCA. Cette étude montre également une forte dépendance en température du comportement mécanique et l’existence d’un phénomène de recouvrance par lequel des fibres étirées récupèrent leur comportement initial après un repos. Des observations in situ en diffraction des rayons X aux grands angles ont montré que la structure semi-cristalline des fibres résiste au gonflement et à une déformation représentative des sollicitations physiologiques. Un mécanisme microscopique basé sur ces résultats a été proposé qui explique le comportement mécanique des fibres par la dissociation et la reformation de liaisons hydrogène dans la phase amorphe. A l’échelle des assemblages de fibres, une étude systématique sur des structures torsadées et un modèle mécanique de structure double-hélice ont révélé que le gonflement confiné des fibres au sein des structures induit des états de contrainte interne permettant d’augmenter la rigidité des assemblages. A l’échelle de l’implant, des substituts compatibles avec le geste chirurgical ont été conçus grâce à une collaboration avec des partenaires cliniciens et biomécaniciens. Une étude in vivo sur modèle petit animal (lapin) de ligamentoplastie a permis de vérifier la bonne tolérance aux implants avec une encapsulation fibreuse modérée et a montré que le gonflement in vivo d’implants secs n’entraîne pas une réaction biologique délétère. L’ensemble de ces résultats a conduit à la conception d’implants complets à l’échelle du LCA humain qui ont été évalué dans un modèle grand animal (brebis) de ligamentoplastie. L’étude nécropsique et histologique sur les animaux implantés a montré une biocompatibilité comparable à celle observée sur les animaux reconstruits par autogreffe. En revanche, l’étude biomécanique révèle un taux de rupture intra-articulaire important (92%) des implants en fibres d’APV. Ces résultats permettent d’identifier des causes possibles d’endommagement et de proposer des pistes d’amélioration. Plus généralement, la bonne biocompatibilité des fibres d’hydrogel d’APV et leurs propriétés mécaniques en font des systèmes intéressants pour la reconstruction de tissus souples nécessitant une tenue en traction élevée. / The anterior cruciate ligament (ACL) rupture is the most frequent ligament injury with an occurrence of 1/3000. It is effectively treated nowadays by a reconstruction with tendinous autograft. However, the problems caused by the transplant harvest remain an important limitation. Artificial substitutes offer an alternative but the rupture rate and the generation of wear debris caused the failure of the majority of the systems developed until now. Recently, studies showed that assemblies of Poly(Vinyl Alcohol) hydrogel fibers mimic the human ACL behavior. The main objective of this thesis was to explore the potential of theses fibers for the ligament reconstruction by designing and characterizing implantable systems for an in vivo animal study. For that purpose, I conducted an experimental study from the fiber scale to the complete implant scale. Two types of PVA fibers were characterized, one obtained from dry spinning (DS) and the other from wet spinning (WS). At the fiber scale, a microscopic and mechanical study highlighted a strong effect of the molecular orientation on the tensile behavior, which allows to reach a much higher elastic modulus than that of an isotropic film with the same swelling ratio. In particular, DS fibers at 20°C exhibit a tensile behavior close to that of the ACL. This study also shows a strong temperature dependence of the mechanical behavior and the existence of recovery phenomenon by which the stretched fibers recover their initial behavior after a rest. In situ wide angle X-rays scattering showed that the fibers semi-crystalline structure resists to swelling and physiological range stretching. A microscopic mechanism based on these results was proposed to explain the fibers mechanical behavior by the dissociation and reformation of hydrogen bonds in the amorphous phase. At the fiber assemblies scale, a systematic study on twister structures and a l double-helix structure mechanical model revealed that the fibers confined swelling inside a structure induce internal stress leading to an increase of the assemblies stiffness. At the implant scale, substitutes compatible with the surgery were conceived in collaboration with clinicians and biomechanists. An in vivo study on a small animal ligamentoplasty model (rabbit) allowed to verify the implants tolerance with a moderate fibrous encapsulation and showed that the implants in vivo swelling does not induce noxious biological reaction. These results led to the conception of human scale implants which were evaluated in a large animal ligamentoplasty model (sheep). The necropsy and histological study on implanted animals showed a biocompatibility similar to that observed with animals reconstructed with an autograft. However, the biomechanical study revealed an important intra-articular rupture rate (92%) for PVA fibers implants. These results allow to identify possible damage causes and to offer ways of improvement. In general, the good biocompatibility of PVA hydrogel fibers and their mechanical properties make them interesting systems for the reconstruction of soft tissues with high tensile strength.

As lesões cervicais não cariosas (LCNCs) são caracterizadas pela perda de estrutura dental no terço cervical dos dentes, que se origina a partir de mecanismos não relacionados com o processo de cárie. Este trabalho buscou investigar a correlação das LCNCs (severidade e acometimento), com os seguintes fatores: idade, sexo, dieta, hábitos parafuncionais, hábitos de higiene dental, distúrbios gástricos e aspectos oclusais. Foram estudados cinquenta pacientes (36 mulheres e 14 homens), com idades entre 20 e 62 anos (média de 40.9 anos). A avaliação consistiu na aplicação de questionários e exame clínico intraoral. Um índice de desgaste dental foi utilizado para classificação da severidade das LCNCs e do desgaste da borda incisal/face oclusal. Os resultados mostraram que os primeiros pré-molares (20,5%), segundos pré-molares (19,5%), caninos (14%), primeiros molares (13,9%) e segundos molares (11,6%) foram os dentes mais acometidos pelas LCNCs. Foi constatada correlação positiva entre idade e o percentual de dentes acometidos, ou seja, quanto maior a idade do paciente, maior foi o percentual de dentes acometidos com LCNC (p=0,003). Foi constatado que os pacientes com ingestão diária de alimentos e bebidas ácidas apresentaram relação significante com a severidade das LCNCs (p=0,038) e também apresentaram maior percentual de dentes acometidos pelas LCNCs (p=0,014). Não foi verificada relação significante entre as LCNCs (severidade e percentual de dentes acometidos) com o sexo dos pacientes, número de escovações diárias, apertamento dental, bruxismo, distúrbios gástricos, força durante a escovação e tipo de cerdas da escova. Quanto aos aspectos relacionados à oclusão, foi observada pequena correlação (r=0,079) entre o desgaste cervical e o desgaste da borda incisal/face oclusal. Em nenhum caso foi observada diferença estatística significante da severidade das LCNCs entre dentes que participam ou não do movimento de lateralidade. / Noncarious cervical lesions (NCCL) are characterized by loss of tooth structure in the cervical area, and originated by mechanisms unrelated to dental caries process. This study investigated the correlation of NCCL (severity and involvement) with the following factors: age, gender, diet, parafunctional habits, dental hygiene, gastric disorders and occlusal aspects. Fifty patients (36 female and 14 male) aged between 20 and 62 years (mean age of 40.9 years) were evaluated. The evaluation consisted of questionnaires and intraoral clinical examination. A Tooth Wear Index was used to classify the severity of NCCL and wear of the incisal/ occlusal surface. Results indicate that first premolars (20,5%), second premolars (19,5%), canine (14%), first molars (13,9%) and second molars (11,6%) were the teeth most affected by NCCL. There was correlation between the age of patients and the percentage of teeth affected, meaning that the older the patient, the higher the percentage of teeth affected with NCCL (p=0,003). Patients with daily intake of acidic foods and beverages presented a significant relationship with the severity of NCCL (p=0,038) and also a higher percentage of teeth affected by NCCL (p=0,014). There was no significant relationship between NCCL (severity and percentage of affected teeth) and gender of patients, number of daily brushings, teeth clenching, bruxism, gastric disorders, force applied during toothbrushing and characteristics of the toothbrushes. There was a small correlation (r=0,079) between NCCL and the wear of incisal/occlusal surface. Regarding the severity of NCCL, no significant statistical differences were observed between the teeth involved or not in the lateral excursive movement.

As lesões cervicais não cariosas (LCNCs) são caracterizadas pela perda de estrutura dental no terço cervical dos dentes, que se origina a partir de mecanismos não relacionados com o processo de cárie. Este trabalho buscou investigar a correlação das LCNCs (severidade e acometimento), com os seguintes fatores: idade, sexo, dieta, hábitos parafuncionais, hábitos de higiene dental, distúrbios gástricos e aspectos oclusais. Foram estudados cinquenta pacientes (36 mulheres e 14 homens), com idades entre 20 e 62 anos (média de 40.9 anos). A avaliação consistiu na aplicação de questionários e exame clínico intraoral. Um índice de desgaste dental foi utilizado para classificação da severidade das LCNCs e do desgaste da borda incisal/face oclusal. Os resultados mostraram que os primeiros pré-molares (20,5%), segundos pré-molares (19,5%), caninos (14%), primeiros molares (13,9%) e segundos molares (11,6%) foram os dentes mais acometidos pelas LCNCs. Foi constatada correlação positiva entre idade e o percentual de dentes acometidos, ou seja, quanto maior a idade do paciente, maior foi o percentual de dentes acometidos com LCNC (p=0,003). Foi constatado que os pacientes com ingestão diária de alimentos e bebidas ácidas apresentaram relação significante com a severidade das LCNCs (p=0,038) e também apresentaram maior percentual de dentes acometidos pelas LCNCs (p=0,014). Não foi verificada relação significante entre as LCNCs (severidade e percentual de dentes acometidos) com o sexo dos pacientes, número de escovações diárias, apertamento dental, bruxismo, distúrbios gástricos, força durante a escovação e tipo de cerdas da escova. Quanto aos aspectos relacionados à oclusão, foi observada pequena correlação (r=0,079) entre o desgaste cervical e o desgaste da borda incisal/face oclusal. Em nenhum caso foi observada diferença estatística significante da severidade das LCNCs entre dentes que participam ou não do movimento de lateralidade. / Noncarious cervical lesions (NCCL) are characterized by loss of tooth structure in the cervical area, and originated by mechanisms unrelated to dental caries process. This study investigated the correlation of NCCL (severity and involvement) with the following factors: age, gender, diet, parafunctional habits, dental hygiene, gastric disorders and occlusal aspects. Fifty patients (36 female and 14 male) aged between 20 and 62 years (mean age of 40.9 years) were evaluated. The evaluation consisted of questionnaires and intraoral clinical examination. A Tooth Wear Index was used to classify the severity of NCCL and wear of the incisal/ occlusal surface. Results indicate that first premolars (20,5%), second premolars (19,5%), canine (14%), first molars (13,9%) and second molars (11,6%) were the teeth most affected by NCCL. There was correlation between the age of patients and the percentage of teeth affected, meaning that the older the patient, the higher the percentage of teeth affected with NCCL (p=0,003). Patients with daily intake of acidic foods and beverages presented a significant relationship with the severity of NCCL (p=0,038) and also a higher percentage of teeth affected by NCCL (p=0,014). There was no significant relationship between NCCL (severity and percentage of affected teeth) and gender of patients, number of daily brushings, teeth clenching, bruxism, gastric disorders, force applied during toothbrushing and characteristics of the toothbrushes. There was a small correlation (r=0,079) between NCCL and the wear of incisal/occlusal surface. Regarding the severity of NCCL, no significant statistical differences were observed between the teeth involved or not in the lateral excursive movement.

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Children with high-risk SHH/TP53-mut and Group 3 medulloblastoma (MB) have a 5-year overall survival of only 40%. Innovative approaches to enhance survival while preventing adverse effects are urgently needed. We investigated an innovative therapy approach combining irradia- tion (RT), decitabine (DEC), and abacavir (ABC) in a patient-derived orthotopic SHH/TP53-mut and Group 3 MB mouse model. MB-bearing mice were treated with DEC, ABC and RT. Mouse survival, tumor growth (BLI, MRT) tumor histology (H/E), proliferation (Ki-67), and endothelial (CD31) staining were analyzed. Gene expression was examined by microarray and RT-PCR (Ki-67, VEGF, CD31, CD15, CD133, nestin, CD68, IBA). The RT/DEC/ABC therapy inhibited tumor growth and enhanced mouse survival. Ki-67 decreased in SHH/TP53-mut MBs after RT, DEC, RT/ABC, and RT/DEC/ABC therapy. CD31 was higher in SHH/TP53-mut compared to Group 3 MBs and decreased after RT/DEC/ABC. Microarray analyses showed a therapy-induced downregulation of cell cycle genes. By RT-PCR, no therapy-induced effect on stem cell fraction or immune cell inva- sion/activation could be shown. We showed for the first time that RT/DEC/ABC therapy improves survival of orthotopic SHH/TP53-mut and Group 3 MB-bearing mice without inducing adverse effects suggesting the potential for an adjuvant application of this multimodal therapy approach in the human clinic.

In der vorliegenden Arbeit wurde mit Hilfe von Gefäßversuchen der Transfer von ausgewählten organischen (m-Kresol, Simazin, Lindan, Anthracen, Galaxolid) und anorganischen Umweltschadstoffen (As, Cd, Pb, Cr, Zn, Ni) aus dotiertem Substrat in Nutzpflanzen (Tomaten, Paprika) untersucht. Zum besseren Verständnis des Schadstofftransfers der organischen Verbindungen und als Möglichkeit einer kosten- und zeitsparenden Alternative zu den herkömmlichen Untersuchungsverfahren, wurden ergänzend in vivo – Experimente durchgeführt. Weitere Schwerpunkte der Arbeit waren Untersuchungen zur Schadstoffaufnahme durch Pflanzen in Abhängigkeit von der Substratkonzentration sowie der Vegetationsdauer. Ein weiterer Schwerpunkt der Arbeiten waren Studien über mögliche Einflüsse eines neuartigen Bodenverbesserungsmaterials auf die Schadstoffmobilität und Bioverfügbarkeit der oben genannten potentiellen Schadstoffe sowie die damit verbundene mögliche Aufnahme durch die Untersuchungspflanzen.