Introdução: A infecção crônica pelo vírus da hepatite C (VHC) está associada à presença da resistência insulínica e da esteatose hepática, independentemente dos fatores metabólicos do hospedeiro. A alteração na enzima MTHFR resulta em hiperhomocisteinemia, que altera o metabolismo intracelular dos lipídios e pode estar relacionada à esteatose hepática e à fibrose, em portadores do VHC. A redução da atividade hepática da MTP resulta em acúmulo de gordura nos hepatócitos, contribuindo para a severidade da esteatose hepática e da fibrose em portadores do VHC. Como objetivos foram estudados os polimorfismos 677 C/T do gene da MTHFR e -493 G/T do gene da MTP e sua relação com as variáveis clínicas, bioquímicas e histológicas em pacientes com infecção crônica pelo VHC. Métodos: 174 pacientes sem tratamento prévio com RNA do VHC positivo e com biópsia hepática foram genotipados para o polimorfismo 677C/T da MTHFR por Restriction Fragment Length Polymorfism-Polimerase Chain (PCRRFLP) e para -493G/T da MTP, por sequenciamento. Todos os pacientes tinham marcadores negativos para doença de Wilson, hemocromatose e doença autoimune, e também tinham baixa ingesta alcoólica, com menos de 100g/semana. Variáveis bioquímicas foram analisadas no momento da realização da biópsia hepática. Resultados: A frequência do genótipo TT do gene MTHFR foi de 9,8% nos pacientes com genótipo não 1 do VHC. No entanto, foi encontrada associação entre o genótipo TT x CT /CC do polimorfismo do gene MTHFR, com o grau de esteatose e fibrose em ambos os genótipos da hepatite C (p < 0,05). Uma diferença significativa foi encontrada em níveis plasmáticos de homocisteína em pacientes com esteatose (p = 0,03). A frequência do genótipo GG+GT do gene MTP foi de 56,8% nos pacientes com genótipo 1 do VHC com fibrose hepática grau 3+4 (OR 1,8, IC 95% 1,3-2,3). Foi observada uma associação direta entre a presença da esteatose hepática nos pacientes com VHC com o genótipo GG+GT do polimorfismo -493G/T do gene da MTP independentemente do genótipo do VHC (OR = 0,4, IC 95% 0,2-0,8, p = 0,01). Conclusões: o genótipo TT do polimorfismo C677T do gene da MTHFR foi mais frequente no genótipo não 1 do VHC, independentemente da classificação histopatológica, assim como a frequência do genótipo CT + TT na presença de fibrose grau 1+ 2 e da esteatose hepática. A hiperhomocisteinemia foi altamente prevalente em indivíduos com esteatose. Por outro lado, a presença do alelo G do do polimorfismo -493G/T do gene da MTP está associada a uma menor expressão da MTP hepática, protegendo contra a esteatose em pacientes com VHC do Nordeste do Brasil. Estudos adicionais em outras populações são necessários para avaliar melhor o papel desses polimorfismos em indivíduos infectados pelo VHC / Background: Chronic hepatitis C (CHC) infection has been shown to promote insulin resistance and hepatic steatosis independent of host metabolic factors. A lower MTHFR activity is associated to hiperhomocysteinemia and also may be related to steatosis and fibrosis in CHC. Futhermore a reduction on hepatic MTP activity resulting in fatty liver and could contribute to the severity of hepatic steatosis and fibrosis in CHC. The aim was to investigate this this polymorphism in the 677 C/T MTHFR and -493G/T MTP genes and there relation with metabolic and histological variables in patients with CHC. Methods: One hundred seven-four untreated patients with viral RNA and liver biopsy were genotyped for the 677C/T MTHFR and 493G/T MTP polymorphisms. The 677C/T polymorphism of the MTHFR gene was identified by Restriction Fragment Length Polymorfism- Polimerase Chain (PCRRFLP) and the 493 G/T polymorphism of the MTP gene was determined by direct sequencing of the polymerase chain reaction products. All patients were negative for markers of Wilsons disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake less than 100g/week. A set of metabolic markers were also measured at the time of liver biopsies. Results: Among subjects infected with CHC genotype non-1 the frequency of MTHFR genotypes TT was 9.8%. Nevertheless, association was found between the MTHFR genotype TT x CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A significant difference was found on plasma homocysteine levels in patients with steatosis (p=0.03). Among subjects infected with CHC genotype 1 with fibrosis grade 3+4 the frequency of MTP genotypes GG+GT was 56.8% (OR 1.8; CI 95% 1.3-2.3). Observed an association with steatosis as dependent variable identified in genotypes GG+GT as independent protective factors against steatosis (OR=0.4, CI 95% 0.2-0.8, p = 0.01). Conclusion: The presence of genotype TT of MTHFR C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype CT+TT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis. On the other hand the presence of the G allele of MTP 493G/T, which is possibly associated with a lower MTP hepatic expression, protects against steatosis in CHC patients from northeast of Brazil. Additional studies in other populations are needed to further assess the role of this polimorphysm in CHC

Dyslipidemia can be a comorbidity of both insulin-resistance and atherosclerosis. Hypertriglyceridemia is common in hyperglycemia and is associated with hypoalphalipoproteinemia (low HDL) and with altered nucleotide or purinergic signaling. We therefore hypothesized that extracellular nucleotides may affect hepatic lipoprotein metabolism. Our studies confirm this view and show that nucleotides regulate cellular proteolytic pathways in liver cells and thereby control lipoprotein secretion and their metabolism by hepatic lipase (HL). Treatment of liver cells with the nucleotide, adenosine diphosphate (ADP), stimulates VLDL-apoB100 and apoE secretion, but blocks HDL-apoA-I and HL secretion. ADP functions like a proteasomal inhibitor to block proteasomal degradation and stimulate apoB100 secretion. Blocking the proteosome is known to activate autophagic pathways. The nucleotide consequently stimulates autophagic degradation in liver cells and increases cellular levels of the autophagic proteins, LC3 and p62. Confocal studies show that ADP increases cellular LC3 levels and promotes co-localization of LC3 and apoA-I in an autophagosomal degradation compartment. ADP acts through the G-protein coupled receptor, P2Y13, to stimulate autophagy and block both HDL and HL secretion. Overexpression of P2Y13 increases cellular LC3 levels and blocks the induction of both HDL and HL secretion, while P2Y13 siRNA reduce LC3 protein levels and cause up to a ten-fold stimulation in HDL and HL secretion. P2Y13 gene expression regulates autophagy through the insulin receptor (IR-β). A reduction in P2Y13 expression increases the phosphorylation of IR-β and protein kinase B (Akt) >3-fold, while increasing P2Y13 expression inhibits the activation of IR-β and Akt. Experiments with epitope-labeled apoA-I and HL show that activation of purinergic pathways has no effect on the internalization and degradation of extracellular apoA-I and HL, which confirms the view that nucleotides primarily impact intracellular protein transport and degradation. In conclusion, elevated blood glucose levels may promote dyslipidemia by stimulating purinergic signaling through P2Y13 and IR-β and perturbing the intracellular degradation and secretion of both HDL and VLDL.

Le projet de cette thèse porte sur la graisse ectopique cardiaque et son lien avec les pathologies cardiovasculaires. Dans un premier travail, nous avons mis au point la technique de mesure du volume de graisse épicardique, et du contenu en triglycérides intramyocardique chez le patient obèse morbide en imagerie de résonance magnétique à 3T, et spectroscopie proton. Nous avons montré que les deux dépôts de graisse ectopique augmentent avec l’obésité, mais sans continuum avec la prise de poids. Alors que la graisse épicardique est liée aux paramètres de la tolérance glucidique, la graisse intramyocardique est liée à la fonction cardiaque. Dans un second travail, nous avons montré qu’une perte de poids induite par une chirurgie bariatrique induit une diminution significative de la graisse épicardique, sans modifier la graisse intramyocardique, suggérant une différence de flexibilité de ces graisses avec la perte de poids. Nous avons également exploré le lien entre graisse épicardique et athérosclérose. Sur une cohorte de volontaires sains, nous avons montré que l’accumulation de graisse épicardique était inversement corrélée à la vasoréactivité de la microcirculation coronaire, suggérant que la graisse épicardique pourrait influer de manière précoce la fonction endothéliale. Enfin, en utilisant une approche transcriptomique, nous avons montré une signature spécifique du TAE humain en fonction de sa localisation anatomique. Ces travaux ouvrent de nouvelles pistes dans la compréhension du développement de la graisse ectopique cardiaque. / Cardiac ectopic fat deposition and its link with cardiovascular pathophysiology was the aim of this PhD project. We first developed 3T cardiovascular magnetic resonance imaging assessment of epicardial fat volume, and proton spectroscopy measurement of myocardial triglyceride content in a cohort of morbid obese subjects. We demonstrated that the two cardiac depots increased with obesity, but not continuously with gain weight. While epicardial fat was related to glucose tolerance parameters, myocardial fat was related to cardiac function. We then studied the effect of bariatric surgery induced weight loss on epicardial and myocardial fat, and found a significant decrease in epicardial fat, but no change in myocardial fat, highlighting differences in the dynamics and flexibility of these two fat pads with weight loss. Focusing on epicardial fat and its potential role in atherosclerosis, we evaluated the effect of epicardial fat volume on endothelium dependent vasoreactivity of the coronary microcirculation, in highly selected healthy volunteers. We found that a high epicardial fat amount was associated with a lower coronary microvascular response, suggesting that epicardial fat could early influence endothelial function. Finally, we identified a specific signature of three anatomically distinct human epicardial adipose tissues, using a transcriptomic approach. All together, our data bring new insights in the comprehension of specific partitioning of cardiac ectopic lipid deposition.

Objetivo: Sintetizar el efecto de la suplementación con ácidos grasos omega-3 sobre los componentes del Síndrome Metabólico (SM) en adultos con infección por el Virus de la Inmunodeficiencia Humana (VIH) en Tratamiento Antirretroviral de Gran Actividad (TARGA). Métodos: Llevamos a cabo una revisión sistemática y metaanálisis de ensayos clínicos aleatorizados. Definimos el SM según los criterios del ATP III basado en cinco componentes: triglicéridos, HDL, glucosa, circunferencia abdominal y presión arterial. Nuestra búsqueda primaria fue realizada en PubMed-MEDLINE, EMBASE, SCOPUS, Web of Science, CENTRAL, LILACS, SciELO hasta diciembre del 2019. Evaluamos el riesgo de sesgo con la herramienta Cochrane para ensayos clínicos. Estimamos el efecto conjunto mediante metaanálisis de efectos fijos y aleatorios en función a la heterogeneidad estadística. Calculamos diferencias de medias no estandarizadas (ΔMNE) y diferencia de medias estandarizadas (ΔME) con el estadístico d de Cohen (d-Cohen) para estimar el tamaño de efecto. Registramos el estudio en PROSPERO (CRD42019115749). Resultados: Encontramos un total de 13125 registros, a partir de los cuales incluimos 15 artículos en nuestro análisis: triglicéridos (15), HDL (5), glucosa (4), circunferencia abdominal (2) y presión arterial (1). Ocho artículos tuvieron alto riesgo de sesgo. Realizamos metaanálisis con nueve estudios para triglicéridos, observamos reducción significativa de los niveles [ΔMNE: -77,50 mg/dL (IC95% -117,72 a -37,28; I2: 27,2%)] con un efecto pequeño [Cohen-d: -0,43 (IC95% -0,62 a -0,25; I2:0,0%)]. Este efecto se acentúa cuando se acompaña de dieta y ejercicio [Cohen-d: -0,62 (IC95% -1,17 a -0,06; I2:0,0%)] o cuando se utiliza dosis mayores a 4 gr al día [Cohen-d: -0,58 (IC95% -0,93 a -0,23; I2:0,0%)]. No encontramos variación de acuerdo con los niveles basales de triglicéridos [Cohen-d: -0,43 (IC95% -0,62 a -0,25; I2:0,0%)]. Asimismo, efectuamos metaanálisis con cinco estudios para HDL, notamos que no hubo incremento significativo [ΔMNE:1,01 mg/dL (IC95% -1,35 a 3,37; I2: 0,0%)] con Cohen-d: 0,11 (IC95% -0,11 a 0,32; I2:0,0%). Al evaluar los otros componentes del SM detectamos alta heterogeneidad clínica y metodológica, por lo que no realizamos metaanálisis; no obstante, la totalidad de los estudios reportaron que no había efecto significativo de la suplementación sobre los niveles de glucosa sérica, circunferencia abdominal y presión arterial. Del mismo modo, no realizamos síntesis cuantitativa de los eventos adversos por la heterogeneidad y falta de reporte en los artículos individuales; sin embargo, la mayoría de los estudios informaron baja frecuencia de eventos adversos y sin diferencias con los producidos en los grupos de control. Conclusiones: En pacientes con infección por el VIH en TARGA la suplementación con ácidos grasos omega-3 reduce los niveles séricos de triglicéridos. No se observa efecto sobre los niveles séricos de HDL. La evidencia referente a los otros componentes del SM es escasa y apunta a que no habría efecto. Hubo baja frecuencia de eventos adversos fundamentalmente leves. / Objective: To synthesize the efficacy of omega-3 fatty acid supplementation on Metabolic Syndrome (MS) in adult with Human Immunodeficiency Virus (HIV) infection receiving Highly Active Antiretroviral Therapy (HAART). Methods: We carried out a systematic review and meta-analysis of randomized clinical trials. We used ATP III criteria to define MS based on five components: triglycerides, HDL, glucose, waist circumference and blood pressure. We performed a literature search in PubMed-Medline, Scopus, Web of Science, CENTRAL, LILACS, SciELO and EMBASE until December 2019. We assessed the risk of bias using the Cochrane tool for clinical trials. We calculated combined effect using random and fixed effects meta-analysis according the statistical heterogeneity. We calculated non-standardized means (ΔNSM) and standardized means (ΔSM) with Cohen’s d (Cohen-d) to estimate effect size. We registered this study in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42019115749). Results: From 13,125 records, we included 15 in our analysis: triglycerides (15), HDL (5), glucose (4), waist circumference (2) and blood pressure (1). Eight studies had high risk of bias. We performed a quantitative synthesis with nine studies for triglycerides. We observed a significant reduction in serum levels [ΔNSM: 77,50 mg/dL (CI95% -117,72 to -37,28; I2: 27,2%)] with a small effect [Cohen-d: -0,43 (CI95% -0,62 to -0,25; I2:0,0%)]. This effect was higher when omega-3 supplementation included diet and exercise [Cohen-d: -0,62 (CI95% -1,17 to -0,06; I2:0,0%)] or when the doses was greater than 4 g per day [Cohen-d: -0,58 (CI95% -0,93 to -0,23; I2:0,0%)]. We did not find variation according to basal triglyceride levels [Cohen-d: -0,43 (CI95% -0,62 to -0,25; I2:0,0%)]. For HDL, we made a meta-analysis with five studies. No significant effect was found [ΔNSM: 1,01 mg/dL (CI95% -1,35 to 3,37; I2: 0,0%)] with Cohen-d: 0,11 (CI95% -0,11 to 0,32; I2:0,0%). We found high clinical and methodological heterogeneity when evaluating the other components of MS and therefore no meta-analysis was made. Nonetheless, all the studies indicated that there was no significant effect of supplementation on serum glucose, waist circumference and blood pressure levels. Likewise, we did not perform a quantitative synthesis of adverse events by heterogeneity and lack of reporting of these on individual articles. Nevertheless, most studies reported mild adverse events in some patients compared to the placebo control group. Conclusions: The supplementation of omega-3 fatty acid in adult patients with HIV in HAART reduces the serum triglyceride levels. Furthermore, the serum levels of HDL are not affected. The evidence regarding to the other components of MS is insufficient and suggests that there would be no effect. The adverse events found were mild. / Tesis

Se plantea la ejecución de un modelo de negocio especializado en el sector alimentación, en el rubro de comida elaborada, dirigida al segmento de nivel socioeconómico A de Lima Metropolitana con restricciones dietéticas de carácter médico, cuya propuesta de valor reúna elementos como: libertad, seguridad, simplicidad, diversidad, calidad, exclusividad y garantía certificadas, resumidas en una sola frase: “Todo lo que sí puedes comer”, especialmente dirigido a personas con sobrepeso u obesidad, diabetes, problemas en los niveles de triglicéridos y/o colesterol e intolerancia al gluten o enfermedad celíaca. Los resultados positivos de la validación de la propuesta, se ven alentados aún más por el contexto post pandémico o la nueva normalidad, que favorece el comercio electrónico, y que además ha puesto en evidencia el riesgo para la salud y la vida que representan algunas de las dolencias mencionadas antes, incluso el sobrepeso u obesidad, ampliamente extendida y hasta validada o empoderada socialmente. En el aspecto financiero, se confirma que la proyección inicial de la propuesta es muy interesante, en la medida que confluyen dos condiciones favorables. La primera de ellas es que en el mercado no existe un proveedor exacto de este tipo de producto para los consumidores de comida dietética de índole clínica, y la segunda se deriva del carácter obligatorio de la restricción médica que le confiere a la demanda el carácter inelástico. Estos factores son los que permiten calificarla como viable. / The execution of a business model specialized in the food sector is proposed in the area of food, to the target at the A socioeconomic level segment of Metropolitan Lima with dietary restrictions of a medical reasons, whose value proposition gathers elements such as: freedom, security , simplicity, diversity, quality, exclusivity and certified guarantee, summarized in one sentence: "Everything you can eat", especially thought for people with overweight or obese, diabetes, problems with triglyceride and/or cholesterol levels and gluten intolerance or celiac disease. The positive results of the validation of the proposal are further encouraged by the post-pandemic context or the new normality, which promote electronic commerce, and which has also highlighted the risk to health and life that some of the aforementioned ailments, including overweight or obesity, widely spread and even socially validated or empowered In the financial aspect, it is confirmed that the initial projection of the proposal is very interesting, to the extent that two favorable conditions converge. The first is that there is no exact supplier of this type of product on the market for consumers of clinical dietary foods, and the second is derived from the mandatory nature of the medical restriction that makes demand inelastic. These factors are what allow it to be classified as viable. / Trabajo de investigación

No description available.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

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

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