名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成5年10月13日 柴田佳久氏の博士論文として提出された

Orientador: Taís maria Bauab / Banca: Luis Vitor Silva do Sacramento / Banca: Carlos Henrique Gomes Martins / Resumo: A família Eriocaulaceae é amplamente distribuída no Brasil, popularmente são conhecidas como "sempre viva" porque, mesmo após o corte e secagem, conservam a cor e forma por vários anos. O objetivo deste trabalho foi determinar o potencial biológico de P. geniculatus, estudando a atividade antimicrobiana, antioxidante e a motilidade intestinal dos extratos diclorometânico, metanólico e hexânico. Para determinação da atividade antimicrobiana foram utilizadas as técnicas de difusão em ágar e microdiluição. Para determinação do potencial antioxidante foram realizados os ensaios espectrofotométricos: radical ABTS●+, DPPH, determinação dos teores de fenóis e flavonóides totais, utilizando como padrões a quercetina e ácido gálico. Na técnica de difusão em ágar, 100\L de suspensão bacteriana a concentração de 108 UFC/mL foram semeadas em ágar Muller Hinton e ágar Sabouraud. Discos de papel foram embebidos com 25\L das amostras vegetais e dispostos na superfície das placas de Petri. Após incubação a 37ºC por 24 horas em aerobiose foram feitas as leituras dos halos de inibição de crescimento ao redor dos discos (mm). No teste de microdiluição os orifícios das microplacas foram preenchidos com 80\L de caldo de Muller Hinton, 100\L de soluções da amostra vegetal diluída seriadamente de 1000 a 7,81\g/mL e 20\L da cultura a concentração de 107 células/mL para as bactérias e 103 células/mL para as leveduras. As microplacas foram incubadas a 37ºC durante 24 horas sob condições de aerobiose e posteriormente determinou se a CBM e CFM. Na avaliação da motilidade intestinal, foram utilizados os extratos de escapos e capítulos no solvente diclorometano e metanólicos (250mg/kg), um controle positivo (cloridrato de loperamida, 5mg/kg), controle negativo (solução fisiológica), controle do solvente (Tween 80 a 20% de metanol). Após 45 minutos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The family Eriocaulaceae is distributed over several parts of Brazil, are popularly known as "evergreen" because even after cutting and drying, retain their color and shape for many years. This work was to determine the biological potential of P. geniculatus, studying the activity antimicrobial, antioxidant and assess the motility of the extracts dichloromethanic, methanolic and hexanic. For activity determination as techniques were used antibacterial ágar diffusion and microdilution against Gram positive and Gram negative bacterium and yeasts. To determine the potential antioxidant spectrophotometric assays were performed: radical ABTS●+ , DPPH, determining the levels of phenolics and flavonoids, using standards as quercetin and gallic acid. In the diffusion technique , 100 mL of bacterial suspension concentration of 108 CFU/mL were seeded in Muller Hinton ágar and Sabouraud broth with Drigalski loop. Discs paper with 10 mm in diameter soaked with 25\L of vegetation samples were arranged on the surface of the plates. After incubation at 37 ° C for 24 hours under aerobic conditions were the readings of the inhibition of growth around the disks, measured in millimeters. In test microdilution holes of the microplate were filled with 80\L Muller Hinton broth , 100 mL of sample solutions of serially diluted plant 1000 to 7,81 \g/mL and 20\L of bacterial culture concentration of 107 cells/mL and 103 cells/mL for yeasts. The microplates were incubated at 37 ° C for 24 hours under aerobic conditions and subsequently became the technique of CBM and CFM. In the evaluation of intestinal motility, were used extracts of scapes and chapters in dichloromethane solvent and methanol (250mg/kg), a positive control (loperamide hydrochloride, 5mg/kg), negative control (saline solution), control of the solvent (Tween 80 to 20% methanol). After about 45 minutes the animals received a suspension activated... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:25:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-23Bitstream added on 2014-06-13T18:53:25Z : No. of bitstreams: 1 ocanha_jpp_me_arafcf.pdf: 7360831 bytes, checksum: 3178fcd0c169f554fd800f0b4acc8ecb (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / A família Eriocaulaceae é amplamente distribuída no Brasil, popularmente são conhecidas como “sempre viva” porque, mesmo após o corte e secagem, conservam a cor e forma por vários anos. O objetivo deste trabalho foi determinar o potencial biológico de P. geniculatus, estudando a atividade antimicrobiana, antioxidante e a motilidade intestinal dos extratos diclorometânico, metanólico e hexânico. Para determinação da atividade antimicrobiana foram utilizadas as técnicas de difusão em ágar e microdiluição. Para determinação do potencial antioxidante foram realizados os ensaios espectrofotométricos: radical ABTS●+, DPPH, determinação dos teores de fenóis e flavonóides totais, utilizando como padrões a quercetina e ácido gálico. Na técnica de difusão em ágar, 100\L de suspensão bacteriana a concentração de 108 UFC/mL foram semeadas em ágar Muller Hinton e ágar Sabouraud. Discos de papel foram embebidos com 25\L das amostras vegetais e dispostos na superfície das placas de Petri. Após incubação a 37ºC por 24 horas em aerobiose foram feitas as leituras dos halos de inibição de crescimento ao redor dos discos (mm). No teste de microdiluição os orifícios das microplacas foram preenchidos com 80\L de caldo de Muller Hinton, 100\L de soluções da amostra vegetal diluída seriadamente de 1000 a 7,81\g/mL e 20\L da cultura a concentração de 107 células/mL para as bactérias e 103 células/mL para as leveduras. As microplacas foram incubadas a 37ºC durante 24 horas sob condições de aerobiose e posteriormente determinou se a CBM e CFM. Na avaliação da motilidade intestinal, foram utilizados os extratos de escapos e capítulos no solvente diclorometano e metanólicos (250mg/kg), um controle positivo (cloridrato de loperamida, 5mg/kg), controle negativo (solução fisiológica), controle do solvente (Tween 80 a 20% de metanol). Após 45 minutos... / The family Eriocaulaceae is distributed over several parts of Brazil, are popularly known as evergreen because even after cutting and drying, retain their color and shape for many years. This work was to determine the biological potential of P. geniculatus, studying the activity antimicrobial, antioxidant and assess the motility of the extracts dichloromethanic, methanolic and hexanic. For activity determination as techniques were used antibacterial ágar diffusion and microdilution against Gram positive and Gram negative bacterium and yeasts. To determine the potential antioxidant spectrophotometric assays were performed: radical ABTS●+ , DPPH, determining the levels of phenolics and flavonoids, using standards as quercetin and gallic acid. In the diffusion technique , 100 mL of bacterial suspension concentration of 108 CFU/mL were seeded in Muller Hinton ágar and Sabouraud broth with Drigalski loop. Discs paper with 10 mm in diameter soaked with 25\L of vegetation samples were arranged on the surface of the plates. After incubation at 37 ° C for 24 hours under aerobic conditions were the readings of the inhibition of growth around the disks, measured in millimeters. In test microdilution holes of the microplate were filled with 80\L Muller Hinton broth , 100 mL of sample solutions of serially diluted plant 1000 to 7,81 \g/mL and 20\L of bacterial culture concentration of 107 cells/mL and 103 cells/mL for yeasts. The microplates were incubated at 37 ° C for 24 hours under aerobic conditions and subsequently became the technique of CBM and CFM. In the evaluation of intestinal motility, were used extracts of scapes and chapters in dichloromethane solvent and methanol (250mg/kg), a positive control (loperamide hydrochloride, 5mg/kg), negative control (saline solution), control of the solvent (Tween 80 to 20% methanol). After about 45 minutes the animals received a suspension activated... (Complete abstract click electronic access below)

Submitted by Tiago José Caparica Módolo (tiago.vet10@gmail.com) on 2018-06-12T17:22:24Z No. of bitstreams: 1 TiagoModoloTESE.pdf: 1069308 bytes, checksum: ec33fab464148f69f2639d9206f39612 (MD5) / Approved for entry into archive by Alexandra Maria Donadon Lusser Segali null (alexmar@fcav.unesp.br) on 2018-06-12T17:52:27Z (GMT) No. of bitstreams: 1 modolo_tjc_dr_jabo.pdf: 1069308 bytes, checksum: ec33fab464148f69f2639d9206f39612 (MD5) / Made available in DSpace on 2018-06-12T17:52:27Z (GMT). No. of bitstreams: 1 modolo_tjc_dr_jabo.pdf: 1069308 bytes, checksum: ec33fab464148f69f2639d9206f39612 (MD5) Previous issue date: 2018-05-18 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / A detomidina é um dos fármacos mais utilizados para a sedação de muares, porém não há dose estabelecida para esta espécie sendo indicado utilizar uma dose 50% maior que a indicada para equinos. Assim, o objetivo deste estudo foi avaliar a eficácia e os efeitos cardiovasculares da detomidina em muares comparando duas doses diferentes, a utilizada em equinos ( G1 - 0,02 mg/kg) e a dose 50% maior (G2 – 0,03 mg/kg). Para isso, foram utiizados 6 muares (2 machos e 4 fêmeas), adultos (339±27 kg), os animais receberam as duas doses com espaçamento mínimo de 7 dias, formando assim dois grupos experimentais com 6 animais cada. Antes da aplicação (M0) da detomidina pela via intravenosa e 5, 15, 30, 45 e 60 minutos após a aplicação (M5; M15; M30; M45; M60, respectivamente) foram avaliados frequência cardíaca, frequência respiratória, motilidade intestinal, altura da cabeça, além dos parâmetros ecocardiográficos: diâmetro interno do ventrículo esquerdo ao final da sístole e da diástole, fração de encurtamento, fração de ejeção, volume do ventrículo esquerdo ao final da sístole e da diástole, volume sistólico e débito cardíaco. A altura da cabeça do G2 permaneceu significativamente menor até o M60 quando comparado ao M0 do mesmo grupo, já do G1 ficou significativamente menor até o M45 quando comparado ao basal. O débito cardíaco do G1 foi significativamente menor nos M5, M15, M30 quando comparado ao M0 doG1, já do G2 permaneceu significativamente menor, quando compardo ao M0 do G2, do M5 ao M45. Concluiu-se que os muares que receberam dose 50% maior de detomidina permaneceram sedados por um período maior, porém os efeitos cardiovasculares também foram mais prolongados. / Detomidine is the drugs most used for sedation of mules, but there is no established dose for this species being indicated to use a dose 50% greater than indicated for horses. Thus, the objective of this study was to evaluate the efficacy and cardiovascular effects of detomidine in mules comparing two different doses, the used in horses (G1 - 0.02 mg / kg) and the 50% higher dose (G2 - 0.03 mg / kg). For this, 6 muares (2 males and 4 females), adults (339 ± 27 kg) were used, the animals received the two doses with a minimum spacing of 7 days, thus forming two experimental groups with 6 animals each. Before the application (M0) of detomidine intravenously and 5, 15, 30, 45 and 60 minutes after the application (M5, M15, M30, M45, M60, M60, respectively) were evaluated heart rate, respiratory rate, intestinal motility, height of the head, in addition to the echocardiographic parameters: internal left ventricular diameter at the end of systole and diastole, fraction of shortening, ejection fraction, left ventricular volume at the end of systole and diastole, systolic volume and cardiac output. The head height of G2 remained significantly lower until M60, whereas G1 was significantly lower up to M45, cardiac output of G1 was significantly lower in M5, M15, M30, whereas G2 remained smaller than M5 at M45. Concluding that mules receiving a 50% higher dose of detomidine remained sedated for a longer period, but the cardiovascular effects were also longer. / 140230/2014-9

Submitted by PAULO SÉRGIO MARINELLI (professor.marinelli@gmail.com) on 2016-07-22T17:54:29Z No. of bitstreams: 1 TesePAULOSERGIOMARINELLIFINAL2016.pdf: 927674 bytes, checksum: beb1c758b76a3f632022e11378f2bcab (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-07-22T19:40:11Z (GMT) No. of bitstreams: 1 marinelli_ps_dr_bauru.pdf: 927674 bytes, checksum: beb1c758b76a3f632022e11378f2bcab (MD5) / Made available in DSpace on 2016-07-22T19:40:11Z (GMT). No. of bitstreams: 1 marinelli_ps_dr_bauru.pdf: 927674 bytes, checksum: beb1c758b76a3f632022e11378f2bcab (MD5) Previous issue date: 2016-07-11 / As hortaliças não-convencionais como ora-pro-nóbis (Pereskia aculeata Mill.) e moringa (Moringa oleifera Lam.) são uma alternativa alimentar com excelente valor nutricional, de fácil cultivo e baixo custo. Têm sido descritas como importantes fontes de proteínas de composição equilibrada de aminoácidos, alto teor de fibras e de lipídios, principalmente ácidos graxos insaturados. Assim, este trabalho teve como objetivo a elaboração e caracterização das farinhas das folhas de Pereskia aculeata Mill. e Moringa oleifera Lam., além da avaliação sobre ratos Wistar de parâmetros bioquímicos e motilidade intestinal dos efeitos da administração destas farinhas. A caracterização química das farinhas foi feita por meio da determinação de umidade, cinzas, lipídios, composição de ácidos graxos, proteínas, aminograma, carboidratos, fibras, sódio, cálcio, e potássio. Os dados obtidos foram submetidos à análise de variância (ANOVA) complementada com o teste de Tukey. As farinhas estudadas apresentaram valores de umidade considerados seguros pela legislação brasileira. O alto teor de carboidratos das farinhas é indicativo de uma planta potencialmente energética. Verificou-se ainda que as farinhas apresentaram altos teores de proteína, fibras, cálcio e na composição de ácidos graxos, destacou-se o α-linolênico. Com relação aos estudos bioquímicos e antropométricos, observou-se que a utilização das farinhas melhorou o perfil lipídico, evitou ganho de peso e não apresentou efeitos adversos significativos. O uso das farinhas também influenciou positivamente a motilidade intestinal. Pelos resultados obtidos nas análises, pode-se explorar o uso dessas farinhas em produtos alimentícios com a finalidade de agregar valor nutricional e produzir alimentos que contribuam para o bem-estar e a saúde do consumidor. / Unconventional vegetables like ora-pro-nobis (Pereskia aculeata Mill.) and moringa (Moringa oleifera Lam.) are an alternative food with excellent nutritional value, easy to grow and low cost. They have been described as important sources of protein balanced amino acid composition, high fiber content and lipids, especially unsaturated fatty acids. Thus, this study aimed to the preparation and characterization of flour leaves of Pereskia aculeata Mill. Moringa oleifera Lam, apart from review of biochemical parameters of Wistar rats and intestinal motility effects of administration of these flour. The chemical characterization of flour was made by the moisture determination, ash, lipids, fatty acid composition, protein, aminogram, carbohydrates, fiber, sodium, calcium, and potassium. The data were submitted to analysis of variance (ANOVA) complemented by the Tukey test. Flours studied showed humidity values considered safe by Brazilian law. The high carbohydrate content of the flours is indicative of a potentially energy plant. It was also found that the meal had high levels of protein, fiber, calcium and fatty acid composition, the highlight was the α-linolenic. With regard to the anthropometric and biochemical studies it was observed that the use of flour has improved lipid profile avoided weight gain and has no significant adverse effects. The use of flours also positively influenced the intestinal motility. The results obtained in the analysis, one can explore the use of these flours in food products in order to add nutritional value and produce foods that contribute to the welfare and consumer health.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-04-04T12:38:24Z No. of bitstreams: 1 lyviaguarizenogueira.pdf: 1164256 bytes, checksum: 7749eec9de6c8874889e02d34d03dada (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-04-04T15:35:59Z (GMT) No. of bitstreams: 1 lyviaguarizenogueira.pdf: 1164256 bytes, checksum: 7749eec9de6c8874889e02d34d03dada (MD5) / Made available in DSpace on 2017-04-04T15:35:59Z (GMT). No. of bitstreams: 1 lyviaguarizenogueira.pdf: 1164256 bytes, checksum: 7749eec9de6c8874889e02d34d03dada (MD5) Previous issue date: 2009-04-03 / Várias espécies de Senna são bastante conhecidas por suas propriedades terapêuticas, sendo utilizadas na medicina popular para o tratamento de inflamação na garganta e constipação. Neste estudo, foram avaliadas algumas propriedades biológicas e farmacológicas das folhas de Senna macranthera como as atividades anti-inflamatória, laxativa, sobre motilidade intestinal, antimicrobiana e antioxidante. A triagem fitoquímica do seu extrato metanólico e partições permitiu a identificação de compostos fenólicos como flavonoides, taninos e cumarinas na maioria das amostras, com exceção da partição em hexano, que apresentou antronas, triterpenos e esteroides em sua composição. O perfil cromatofráfico obtido por CLAE mostrou a presença da antraquinona emodina em todas as amostras. A partição em hexano reduziu significativamente o edema de pata induzido pela carragenina em ratos, de maneira similar ao diclofenaco de sódio. Atividade laxativa comparável ao padrão bisacodil foi observada para o extrato em metanol e partição em hexano, porém somente o último aumentou a motilidade intestinal. Além disso, o extrato metanólico e partições foram avaliados quanto a sua atividade antioxidante e a partição em acetato de etila apresentou pronunciada atividade, comparável ao padrão rutina. Significativa atividade antibacteriana sobre Pseudomonas aeruginosa também foi encontrada para o extrato em metanol e partição em hexano. Não foi observada citotoxidade para Artemia salina ou espécies de Leishmania para nenhuma amostra. / Several species of Senna are well known for their therapeutic properties, being used in the folk medicine to treat throat inflammation and constipation. In this study, an attempt was made to evaluate some biological and pharmacological properties of Senna macranthera leaves. In this regard, the anti-inflammatory, the laxative and the intestinal motility effects, and also the antimicrobial and antioxidant activities of its methanolic extract and partitions were determined. The phytochemical screening allowed the identification of phenolic compounds like flavonoids, tannins and coumarins in the majority of the extracts except for the hexane one which presented anthrones, triterpenes and steroids in its composition. The HPLC profile showed the presence of the anthraquinone emodine in all samples. The hexane partition significantly reduced carrageenan-induced paw edema in rats in a manner similar to that of sodium diclofenac. Laxative effect was observed for the methanolic extract and hexane partition comparative to the standard drug bisacodyl, however only the later increased the intestinal motility. Moreover, the samples were evaluated for their antioxidant activity and ethyl acetate partition presented a pronounced activity comparable to the standard rutin. Antibacterial activity against Pseudomonas aeruginosa was also found for metanolic extratct and hexane partition. No cytotoxicity against Artemia salina and Leishmania species were detected for any extracts.

In order to investigate the effect of food restriction on fat mobilization in horses with impaction in left ventral colon during treatment, serum triglycerides, NEFA and total bilirubine (TB) were measured before and after treatment. On another side, the determination of alcohol dehydrogenase (ADH) activity in serum could facilitate the distinguishing of the non-strangulating intestinal obstruction from the potential fatal strangulation obstruction and could submit a new prognostic biochemical parameter for intestinal strangulation. With the intention of giving a highlight over the analgesic effect of Buscopan® compositum in horses with colic, it was attempted to investigate the effect of Buscopan® compositum on the intestinal motility of healthy conscious horses in different regions of intestine. A significant elevation of NEFA and TB was observed in horses with impaction in left ventral colon at admission. By relieving the impaction, there was a significant elevation of triglycerides in comparison to its level at admission. There was a significant increase in ADH activity in all horses with acute intestinal obstruction. ADH activity was significantly higher in horses with strangulation in comparison to non-strangulation obstruction. There was only a significant correlation between ADH and lactate in horses with non-strangulation obstruction and colon torsion. Only AST and GLDH were significantly increased in horses with colon torsion. ADH activity > 20 U/l had 80.56% specificity and 80.49% sensitivity for discriminating horses with intestinal strangulation from non-strangulation obstruction. ADH activity < 80 U/l had 94.44% specificity and 66.67% sensitivity for survival. Buscopan® compositum had an immediate, rapid and significant (p< 0.05) reduction of duodenal, cecal and left ventral colon contractions after application. Cecal and left ventral colon contractions restored rapidly their normal contractions after 30 min, while duodenal contractions returned to the normal rate after 120 min of Buscopan® compositum administration. The horses with impaction in left ventral colon are susceptible to fat mobilization during the period of treatment as a result of food restriction. It was characterized by a revisable hypertri-glyceridemia and hyperbililrubinemia. Serum ADH activity could have a useful clinical value in detecting the intestinal strangulation and predicting the prognosis in horses with intestinal strangulation. Buscopan® compositum at its therapeutic dosage has an immediate, potent, short-lived reductive effect on cecum and left ventral colon contractions but a minor, longer effect on the duodenal contractions. Therefore, it is thought to be more effective in treatment of spasmodic colic than in large colon impaction. / Um den Effekt der Nahrungskarenz auf die Fettmobilisation bei Pferden mit Verstopfung der linken ventralen Längslagen des Kolons während der Behandlung zu untersuchen, wurden Triglyceride (TG), freie Fettsäuren (FFS) und Gesamtbilirubin (GB) bestimmt. Andererseits ermöglicht die Bestimmung der Aktivität der Alkoholdehydrogenase (ADH) im Serum die Unterscheidung zwischen einer nichtstrangulierenden intestinalen Obstruktion und einer potentiell tödlichen Strangulation. ADH kann somit als ein neuer prognostischer biochemischer Parameter für die intestinale Strangulation eingesetzt werden. Um den spasmolytischen Effekt von Buscopan compositum bei Pferden mit Kolik zu untersuchen, wurde der Effekt von Buscopan compositum auf die intestinale Kontraktion von gesunden Pferden in verschiedenen Regionen des Darmes getestet. Eine signifikante Erhöhung der FFS und des GB wurde bei Aufnahme von Pferden mit einer Verstopfung in der linken ventralen Längslagen festgestellt. Nach der Behandlung der Verstopfung konnte eine signifikante Erhöhung der Konzentration von TG, bezogen auf die TG Konzentration bei Aufnahme in die Klinik, festgestellt werden. Bei Pferden mit akuter intestinaler Obstruktion wurde eine signifikante Erhöhung der Aktivität der ADH beobachtet. Die Aktivität der ADH war bei Pferden mit einer Strangulation signifikant höher als bei Pferden, die eine nichtstrangulierende Obstruktion des Darmes hatten. Bei Pferden mit einer nichtstrangulierenden Obstruktion oder einer Kolontorsion wurde eine positive Korrelation zwischen der ADH-Aktivität und der Laktatkonzentration im Serum festgestellt. Nur bei Pferden mit Kolontorsion waren die Aktivitäten von AST und GLDH signifikant erhöht. Für die Unterscheidung zwischen Pferden mit einer intestinalen Strangulation oder einer nichtstrangulierenden Obstruktion wurde für die ADH- Aktivität größer als 20 U/l eine Spezifität von 80,56% und eine Sensitivität von 80,49% ermittelt. Eine ADH-Aktivität kleiner 80 U/l zeigt, mit einer Spezifität von 94,44% und einer Sensitivität von 66,67%, eine günstige Prognose für das Überleben des Pferdes an. Nach Gabe von Buscopan® compositum trat eine sofortige schnelle und signifikante (p<0,05) Reduktion der Kontraktionen im Duodenum, Zäkum und den linken ventralen Längslagen ein. Die Kontraktionen des Zäkums und der linken ventralen Längslagen normalisierten sich schnell innerhalb von 30 min, wogegen die Kontraktionen des Duodenums erst 120 min nach der Applikation von Buscopan® compositum den Normalzustand erreichten. Pferde mit einer Verstopfung in der linken ventralen Längslagen des Kolons sind während der medizinischen Behandlung anfällig für Fettmobilisation aufgrund der reduzierten Futter-aufnahme. Dies ist gekennzeichnet durch eine reversible Hypertriglyceridämie und eine Hyperbilirubinämie. Die Aktivität von ADH im Serum kann ein nützlicher klinischer Parameter sein, um eine intestinale Strangulation zu identifizieren und bietet sich auch als prognostischer Marker bei intestinaler Strangulation an. Die Applikation von Buscopan® compositum in der therapeutischen Dosierung hat eine sofortige, potente und kurzzeitige Reduktion der Kontraktionen des Zäkums und der linken ventralen Längslage aber einen geringen und länger anhaltenden Effekt auf die duodenalen Kontraktionen zur Folge. Daraus folgt, dass Buscopan® compositum bei der Behandlung von Krampfkoliken effektiver ist als bei Verstopfungen des großen Kolons.

In order to investigate the effect of food restriction on fat mobilization in horses with impaction in left ventral colon during treatment, serum triglycerides, NEFA and total bilirubine (TB) were measured before and after treatment. On another side, the determination of alcohol dehydrogenase (ADH) activity in serum could facilitate the distinguishing of the non-strangulating intestinal obstruction from the potential fatal strangulation obstruction and could submit a new prognostic biochemical parameter for intestinal strangulation. With the intention of giving a highlight over the analgesic effect of Buscopan® compositum in horses with colic, it was attempted to investigate the effect of Buscopan® compositum on the intestinal motility of healthy conscious horses in different regions of intestine. A significant elevation of NEFA and TB was observed in horses with impaction in left ventral colon at admission. By relieving the impaction, there was a significant elevation of triglycerides in comparison to its level at admission. There was a significant increase in ADH activity in all horses with acute intestinal obstruction. ADH activity was significantly higher in horses with strangulation in comparison to non-strangulation obstruction. There was only a significant correlation between ADH and lactate in horses with non-strangulation obstruction and colon torsion. Only AST and GLDH were significantly increased in horses with colon torsion. ADH activity > 20 U/l had 80.56% specificity and 80.49% sensitivity for discriminating horses with intestinal strangulation from non-strangulation obstruction. ADH activity < 80 U/l had 94.44% specificity and 66.67% sensitivity for survival. Buscopan® compositum had an immediate, rapid and significant (p< 0.05) reduction of duodenal, cecal and left ventral colon contractions after application. Cecal and left ventral colon contractions restored rapidly their normal contractions after 30 min, while duodenal contractions returned to the normal rate after 120 min of Buscopan® compositum administration. The horses with impaction in left ventral colon are susceptible to fat mobilization during the period of treatment as a result of food restriction. It was characterized by a revisable hypertri-glyceridemia and hyperbililrubinemia. Serum ADH activity could have a useful clinical value in detecting the intestinal strangulation and predicting the prognosis in horses with intestinal strangulation. Buscopan® compositum at its therapeutic dosage has an immediate, potent, short-lived reductive effect on cecum and left ventral colon contractions but a minor, longer effect on the duodenal contractions. Therefore, it is thought to be more effective in treatment of spasmodic colic than in large colon impaction.:Contents I List of Abbreviations II 1 Introduction and Literature 1 2 Results 4 2.1 Publication 1: Triglyceride, free fatty acids and total bilirubin in horses with left ventral large colon impaction 4 2.2 Publication 2: Clinical evaluation of serum alcohol dehydrogenase activity in horses with acute intestinal obstruction 9 2.3 Publication 3: Effect of Buscopan® compositum on the motility of the duodenum, cecum and left ventral colon in healthy conscious horses 43 3 Discussion 60 4 Summary 68 5 Zusammenfassung 70 6 References 72 7 Acknowledgement 81 / Um den Effekt der Nahrungskarenz auf die Fettmobilisation bei Pferden mit Verstopfung der linken ventralen Längslagen des Kolons während der Behandlung zu untersuchen, wurden Triglyceride (TG), freie Fettsäuren (FFS) und Gesamtbilirubin (GB) bestimmt. Andererseits ermöglicht die Bestimmung der Aktivität der Alkoholdehydrogenase (ADH) im Serum die Unterscheidung zwischen einer nichtstrangulierenden intestinalen Obstruktion und einer potentiell tödlichen Strangulation. ADH kann somit als ein neuer prognostischer biochemischer Parameter für die intestinale Strangulation eingesetzt werden. Um den spasmolytischen Effekt von Buscopan compositum bei Pferden mit Kolik zu untersuchen, wurde der Effekt von Buscopan compositum auf die intestinale Kontraktion von gesunden Pferden in verschiedenen Regionen des Darmes getestet. Eine signifikante Erhöhung der FFS und des GB wurde bei Aufnahme von Pferden mit einer Verstopfung in der linken ventralen Längslagen festgestellt. Nach der Behandlung der Verstopfung konnte eine signifikante Erhöhung der Konzentration von TG, bezogen auf die TG Konzentration bei Aufnahme in die Klinik, festgestellt werden. Bei Pferden mit akuter intestinaler Obstruktion wurde eine signifikante Erhöhung der Aktivität der ADH beobachtet. Die Aktivität der ADH war bei Pferden mit einer Strangulation signifikant höher als bei Pferden, die eine nichtstrangulierende Obstruktion des Darmes hatten. Bei Pferden mit einer nichtstrangulierenden Obstruktion oder einer Kolontorsion wurde eine positive Korrelation zwischen der ADH-Aktivität und der Laktatkonzentration im Serum festgestellt. Nur bei Pferden mit Kolontorsion waren die Aktivitäten von AST und GLDH signifikant erhöht. Für die Unterscheidung zwischen Pferden mit einer intestinalen Strangulation oder einer nichtstrangulierenden Obstruktion wurde für die ADH- Aktivität größer als 20 U/l eine Spezifität von 80,56% und eine Sensitivität von 80,49% ermittelt. Eine ADH-Aktivität kleiner 80 U/l zeigt, mit einer Spezifität von 94,44% und einer Sensitivität von 66,67%, eine günstige Prognose für das Überleben des Pferdes an. Nach Gabe von Buscopan® compositum trat eine sofortige schnelle und signifikante (p<0,05) Reduktion der Kontraktionen im Duodenum, Zäkum und den linken ventralen Längslagen ein. Die Kontraktionen des Zäkums und der linken ventralen Längslagen normalisierten sich schnell innerhalb von 30 min, wogegen die Kontraktionen des Duodenums erst 120 min nach der Applikation von Buscopan® compositum den Normalzustand erreichten. Pferde mit einer Verstopfung in der linken ventralen Längslagen des Kolons sind während der medizinischen Behandlung anfällig für Fettmobilisation aufgrund der reduzierten Futter-aufnahme. Dies ist gekennzeichnet durch eine reversible Hypertriglyceridämie und eine Hyperbilirubinämie. Die Aktivität von ADH im Serum kann ein nützlicher klinischer Parameter sein, um eine intestinale Strangulation zu identifizieren und bietet sich auch als prognostischer Marker bei intestinaler Strangulation an. Die Applikation von Buscopan® compositum in der therapeutischen Dosierung hat eine sofortige, potente und kurzzeitige Reduktion der Kontraktionen des Zäkums und der linken ventralen Längslage aber einen geringen und länger anhaltenden Effekt auf die duodenalen Kontraktionen zur Folge. Daraus folgt, dass Buscopan® compositum bei der Behandlung von Krampfkoliken effektiver ist als bei Verstopfungen des großen Kolons.:Contents I List of Abbreviations II 1 Introduction and Literature 1 2 Results 4 2.1 Publication 1: Triglyceride, free fatty acids and total bilirubin in horses with left ventral large colon impaction 4 2.2 Publication 2: Clinical evaluation of serum alcohol dehydrogenase activity in horses with acute intestinal obstruction 9 2.3 Publication 3: Effect of Buscopan® compositum on the motility of the duodenum, cecum and left ventral colon in healthy conscious horses 43 3 Discussion 60 4 Summary 68 5 Zusammenfassung 70 6 References 72 7 Acknowledgement 81

[ES] La endoscopia capsular (CE) es una ampliamente utilizada alternativa mínimamente invasiva a la endoscopia tradicional, que permite la visualización de todo el intestino delgado, mientras no es posible hacerlo fácilmente con los procedimientos más invasivos. Sin embargo, esos métodos tradicionales aún suelen ser la primera opción de tratamiento, ya que todavía existen desafíos importantes en el campo de la CE, incluyendo el tiempo necesario para el diagnóstico por vídeo después del procedimiento, el hecho de que la cápsula no se puede controlar activamente, la falta de consenso sobre una buena preparación del paciente y el coste alto. En esta tesis doctoral, nuestro objetivo es extraer más información de los procedimientos de endoscopía por cápsula para ayudar a aliviar estos problemas desde una perspectiva que parece estar subrepresentada en la investigación actual. Primero, como el objetivo principal en esta tesis, pretendemos desarrollar un método de evaluación de la limpieza en procedimientos de CE automático y objetivo para asistir la investigación médica en métodos de preparación de los pacientes. Específicamente, a pesar de que una preparación adecuada del paciente pueda ayudar a obtener una mejor visibilidad, los estudios sobre el método más efectivo son contradictorios debido a la ausencia de tal método. Por lo tanto, pretendemos proporcionar un método de ese tipo, capaz de presentar la limpieza en una escala intuitiva, con una novedosa arquitectura relativamente ligera de una red neuronal convolucional en su núcleo. Entrenamos este modelo en un conjunto de datos extensivo de más de 50,000 parches de imágenes, obtenidos de 35 procedimientos CE diferentes, y lo comparamos con métodos de clasificación del estado del arte. A partir de la clasificación, desarrollamos un método para automáticamente estimar las probabilidades a nivel de píxel y deducir los puntos en la escala de la evaluación de la limpieza a través de umbrales aprendidos. Después, validamos nuestro método en un entorno clínico en 30 videos de CE obtenidos nuevamente, comparando las puntuaciones resultantes con las asignadas de forma independiente por especialistas humanos. Obtuvimos la mayor precisión de clasificación para el método propuesto (95,23%), con tiempos de predicción promedios significativamente más bajos que para el segundo mejor método. En la validación, encontramos un acuerdo aceptable con dos especialistas humanos en comparación con el acuerdo interhumano, mostrando su validez como método de evaluación objetivo. Adicionalmente, otro objetivo de este trabajo es detectar automáticamente el túnel y ubicar el túnel en cada fotograma. Para este objetivo, entrenamos un modelo basado en R-CNN, concretamente el detector ligero YOLOv3, en un total de 1385 fotogramas, extraídos de procedimientos de CE de 10 pacientes diferentes. De tal manera, alcanzamos una precisión del 86,55% y una recuperación del 88,79% en nuestro conjunto de datos de test. Ampliando este objetivo, también pretendemos visualizar la motilidad intestinal de una manera análoga a una manometría intestinal tradicional, basada únicamente en la técnica mínimamente invasiva de CE. Para esto, alineamos los fotogramas con similar orientación y derivamos los parámetros adecuados para nuestro método de segmentación de las propiedades del rectángulo delimitador del túnel. Finalmente, calculamos el tamaño relativo del túnel para construir un equivalente de una manometría intestinal a partir de información visual. Desde que concluimos nuestro trabajo, nuestro método para la evaluación automática de la limpieza se ha utilizado en un estudio a gran escala aún en curso, en el que participamos activamente. Mientras gran parte de la investigación se centra en la detección automática de patologías, como tumores, pólipos y hemorragias, esperamos que nuestro trabajo pueda hacer una contribución significativa para extraer más información de la CE también en otras áreas frecuentemente subestimadas. / [CA] L'endoscòpia capsular (CE) és una àmpliament utilitzada alternativa mínimament invasiva a l'endoscòpia tradicional, que permet la visualització de tot l'intestí prim, mentre no és possible fer-lo fàcilment amb els procediments més invasius. No obstant això, aqueixos mètodes tradicionals encara solen ser la primera opció de tractament, ja que encara existeixen desafiaments importants en el camp de la CE, incloent el temps necessari per al diagnòstic per vídeo després del procediment, el fet que la càpsula no es pot controlar activament, la falta de consens sobre una bona preparació del pacient i el cost alt. En aquesta tesi doctoral, el nostre objectiu és extraure més informació dels procediments de endoscopía per càpsula per a ajudar a alleujar aquests problemes des d'una perspectiva que sembla estar subrepresentada en la investigació actual. Primer, com l'objectiu principal en aquesta tesi, pretenem desenvolupar un mètode d'avaluació de la neteja en procediments de CE automàtic i objectiu per a assistir la investigació mèdica en mètodes de preparació dels pacients. Específicament, a pesar que una preparació adequada del pacient puga ajudar a obtindre una millor visibilitat, els estudis sobre el mètode més efectiu són contradictoris a causa de l'absència de tal mètode. Per tant, pretenem proporcionar un mètode d'aqueix tipus, capaç de presentar la neteja en una escala intuïtiva, amb una nova arquitectura relativament lleugera d'una xarxa neuronal convolucional en el seu nucli. Entrenem aquest model en un conjunt de dades extensiu de més de 50,000 pegats d'imatges, obtinguts de 35 procediments CE diferents, i el comparem amb mètodes de classificació de l'estat de l'art. A partir de la classificació, desenvolupem un mètode per a automàticament estimar les probabilitats a nivell de píxel i deduir els punts en l'escala de l'avaluació de la neteja a través de llindars apresos. Després, validem el nostre mètode en un entorn clínic en 30 vídeos de CE obtinguts novament, comparant les puntuacions resultants amb les assignades de manera independent per especialistes humans. Vam obtindre la major precisió de classificació per al mètode proposat (95,23%), amb temps de predicció mitjanes significativament més baixos que per al segon millor mètode. En la validació, trobem un acord acceptable amb dos especialistes humans en comparació amb l'acord interhumà, mostrant la seua validesa com a mètode d'avaluació objectiu. Addicionalment, un altre objectiu d'aquest treball és detectar automàticament el túnel i situar el túnel en cada fotograma. Per a aquest objectiu, entrenem un model basat en R-CNN, concretament el detector lleuger YOLOv3, en un total de 1385 fotogrames, extrets de procediments de CE de 10 pacients diferents. De tal manera, aconseguim una precisió del 86,55% i una recuperació del 88,79% en el nostre conjunt de dades de test. Ampliant aquest objectiu, també pretenem visualitzar la motilitat intestinal d'una manera anàloga a una manometría intestinal tradicional, basada únicament en la tècnica mínimament invasiva de CE. Per a això, alineem els fotogrames amb similar orientació i derivem els paràmetres adequats per al nostre mètode de segmentació de les propietats del rectangle delimitador del túnel. Finalment, calculem la grandària relativa del túnel per a construir un equivalent d'una manometría intestinal a partir d'informació visual. Des que concloem el nostre treball, el nostre mètode per a l'avaluació automàtica de la neteja s'ha utilitzat en un estudi a gran escala encara en curs, en el qual participem activament. Mentre gran part de la investigació se centra en la detecció automàtica de patologies, com a tumors, pòlips i hemorràgies, esperem que el nostre treball puga fer una contribució significativa per a extraure més informació de la CE també en altres àrees sovint subestimades. / [EN] Capsule endoscopy (CE) is a widely used, minimally invasive alternative to traditional endoscopy that allows visualisation of the entire small intestine, whereas more invasive procedures cannot easily do this. However, those traditional methods are still commonly the first choice of treatment for gastroenterologists as there are still important challenges surrounding the field of CE. Among others, these include the time consuming video diagnosis following the procedure, the fact that the capsule cannot be actively controlled, lack of consensus on good patient preparation and the high cost. In this doctoral thesis, we aim to extract more information from capsule endoscopy procedures to aid in alleviating these issues from a perspective that appears to be under-represented in current research. First, and as the main objective in this thesis, we aim to develop an objective, automatic cleanliness evaluation method in CE procedures to aid medical research in patient preparation methods. Namely, even though adequate patient preparation can help to obtain a cleaner intestine and thus better visibility in the resulting videos, studies on the most effective preparation method are conflicting due to the absence of such a method. Therefore, we aim to provide such a method, capable of presenting results on an intuitive scale, with a relatively light-weight novel convolutional neural network architecture at its core. We trained this model on an extensive data set of over 50,000 image patches, collected from 35 different CE procedures, and compared it with state-of-the-art classification methods. From the patch classification results, we developed a method to automatically estimate pixel-level probabilities and deduce cleanliness evaluation scores through automatically learnt thresholds. We then validated our method in a clinical setting on 30 newly collected CE videos, comparing the resulting scores to those independently assigned by human specialists. We obtained the highest classification accuracy for the proposed method (95.23%), with significantly lower average prediction times than for the second-best method. In the validation of our method, we found acceptable agreement with two human specialists compared to interhuman agreement, showing its validity as an objective evaluation method. Additionally, we aim to automatically detect and localise the tunnel in each frame, in order to help determine the capsule orientation at any given time. For this purpose, we trained an R-CNN based model, namely the light-weight YOLOv3 detector, on a total of 1385 frames, extracted from CE procedures of 10 different patients, achieving a precision of 86.55% combined with a recall of 88.79% on our test set. Extending on this, we additionally aim to visualise intestinal motility in a manner analogous to a traditional intestinal manometry, solely based on the minimally invasive technique of CE, through aligning the frames with similar orientation and using the bounding box parameters to derive adequate parameters for our tunnel segmentation method. Finally, we calculate the relative tunnel size to construct an equivalent of an intestinal manometry from visual information. Since we concluded our work, our method for automatic cleanliness evaluation has been used in a still on-going, large-scale study, with in which we actively participate. While much research focuses on automatic detection of pathologies, such as tumors, polyps and bleedings, we hope our work can make a significant contribution to extract more information from CE also in other areas that are often overlooked. / Noorda, RA. (2022). Clearing the Way in Capsule Endoscopy with Deep Learning and Computer Vision [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/183752