Salmonella enterica sérovar Typhi est une bactérie à Gram négatif qui cause la maladie systémique nommée fièvre typhoïde. Cette maladie affecte environ 9 millions de personnes par année et se propage par la voie fécale-orale par ingestion d’aliments ou d’eau contaminés. Ainsi, la fièvre typhoïde est particulièrement problématique dans les pays ayant des systèmes d’assainissement peu efficaces. Elle peut être traitée par des antibiotiques, mais comme pour de nombreuses bactéries, la résistance est de plus en plus commune. À la suite d’une infection aiguë, environ 5% des patients deviennent porteurs chroniques asymptomatiques grâce à la formation de biofilms dans la vésicule biliaire et excrètent la bactérie dans leurs selles continuellement. Étant le seul réservoir connu de S. Typhi, cet état constitue une source importante de persistance et de propagation de la maladie. L’état de porteur est intraitable par antibiotiques en raison de la haute tolérance aux stress des biofilms et une chirurgie pour enlever la vésicule biliaire est souvent la solution la plus efficace. Il est connu que les biofilms de Salmonella contiennent principalement de la cellulose, des fimbriae curli, de l'acide colanique et des protéines BapA. Cependant, S. Typhi a accumulé de nombreux pseudogènes au cours de son évolution humain-spécifique, dont certains sont impliqués dans la biosynthèse de composants communs de biofilm chez Salmonella, comme la cellulose et l'acide colanique. Il est également proposé que l'expression de curli soit dysfonctionnelle chez S. Typhi. La production de biofilms chez cette souche n'a jamais été caractérisée dans des conditions in vitro optimisées. Par conséquent, nous supposons que les biofilms de S. Typhi soient uniques dans leur production et leur composition. Cette étude caractérise la composition et la structure d’un biofilm de S. Typhi in vitro. Nous déterminons qu’aucun composant de biofilm communément identifié chez Salmonella ne joue un rôle majeur dans les biofilms de S. Typhi. Nous identifions un rôle important pour l’ADN extracellulaire et l’intégrité des LPS. / Salmonella enterica serovar Typhi is a Gram-negative rod-shaped bacterium that causes the systemic disease of typhoid fever. This disease affects about 9 million people per year and is spread through the fecal-oral route by ingestion of contaminated food or water. Thus, typhoid fever is particularly problematic in countries with poor sanitation systems. It is currently treatable by antibiotics but as with many other bacteria, resistance is becoming more and more common. Following acute infection, ~5% of patients become chronic asymptomatic carriers through biofilm formation in the gallbladder and continuously shed the bacteria in their feces. Being the only known reservoir of S. Typhi, this is an important source of persistence of the disease in endemic areas and propagation to new areas. The carrier state is untreatable by antibiotics due to the high stress tolerance of biofilms. Gallbladder-removal surgery is often the most efficient solution. Salmonella biofilms are known to primarily contain cellulose, curli fimbriae, colanic acid and BapA proteins. However, S. Typhi evolved to be human-specific over time and has accumulated many pseudogenes in the process, some of which are genes in the biosynthetic pathways of biofilm-related components of Salmonella, such as cellulose and colanic acid. It is also proposed that curli expression is dysfunctional in S. Typhi. Biofilm production in this strain has never been characterized in optimized in vitro conditions. Therefore, we hypothesized that S. Typhi biofilms are unique in their production and composition. This study characterizes S. Typhi biofilm composition and structure in vitro. We determine that no biofilm components commonly identified in other bacteria play a major role in S. Typhi biofilms. We identify an important role for extracellular DNA and lipopolysaccharide-layer integrity.

Title: Using of alternative therapeutic techniques to vertebrovisceral links of liver and gallbladder diseases Objectives: The aim of this thesis is to find out a sufficient amount of information on the subject of functional liver and gallbladder diseases, possibilities of conventional treatment and alternative treatment options. Another goal of this thesis is to compile an assessment protocol, based on the theoretical background, according to which it is possible to diagnose patients with functional liver and gallbladder diseases. An additional goal of this thesis is to create a treatment concept for patients with functional liver and gallbladder diseases. This treatment concept will be based on the knowledge of yoga and traditional Chinese medicine. Last goal is to compare conventional physiotherapy with the concept created. Methods: The theoretical part of this thesis focuses on the issue of functional disease of liver and gallbladder. In takes into account the current research and data found in Czech and foreign literature. The practical part looks into the effects of complex therapy methods using experiments. The therapy itself includes changes of the patients' lifestyles, which are based on traditional Chinese medicine and yoga asanas, which were compiled for the purposes of this thesis for...

Background The gallstone prevalence in the western world is 10-20%. Most gallstones are silent, but symptoms and complications appear in 20-40%. The incidence of symptom development in patients with silent gallstones is 2-4% per year. The indication for surgical (including endoscopic) treatment of gallstones is symptoms of certain magnitude, and no contraindications. During the past three decades an intense technical development in imaging (ultrasound, computerised tomography and magnetic resonance imaging), endoscopic therapy, and surgery has taken place. The aim of this thesis is to scrutinize changes in management of complicated gallstone disease on a population-based level, using national register data. Have the new methods improved the treatment of acute pancreatitis, common bile duct stones and acute gallbladder disease? Methods Data is collected from National Patient Register (NPR) run by The Swedish National Board of Health and Welfare. NPR collects discharge data from every admission from every Swedish hospital. Mortality is calculated as standardised mortality ratio (SMR) using age-, gender-, and calendar year specific survival estimates. We have studied both general trends in admissions and treatment alternatives and outcomes in defined patient cohorts. Length of hospital stay, readmission, and mortality has been used as proxy indicators of the effectiveness of treatment strategies used. Results During the study period mortality in acute pancreatitis (SMR within 90 days of admission) improved and hospital stay for all patients with acute pancreatitis decreased. Cholecystectomy rate at or shortly after index stay for mild acute biliary pancreatitis increased from 14.5 % to 22.7 %. Of all patients with acute pancreatitis 68.4 % of the patients had no aetiological diagnosis in the register. The incidence of bile duct interventions increased 27.8% from 1988 through 2006. The favoured treatment of bile duct stones changed from open choledocholithectomy to endoscopic sphincterotomy with stone extraction during the same period. However, in 2006, still 19.6% of bile duct interventions for stones were performed as choledochotomy and in the great majority of these cases as open surgery. This indicates a continuing need of education in open bile duct surgery. Mean hospital stay for treatment of common bile duct stones decreased significantly (4.5 days) during the period studied. The mortality (SMR) diminished although without statistical significance during the time period, and there was no significant difference in SMR between choledochotomy and endoscopic sphincterotomy. For acute gallbladder disease a moderate increase of admissions occurred from 1988 through 2006. The relation between acute cholecystectomies versus all cholecystectomies did not change during this period. Of all patients admitted with acute gallbladder disease 32.3 % were cholecystectomised during their first hospital stay, whereas 20.3 % underwent elective cholecystectomy and 6.1 % emergency cholecystectomy within two years of first admission. 41.4 % of patients were not operated on for gallbladder disease within two years of first admission with this diagnosis. Mortality from first admission and 90 days onwards was elevated three-fold during the entire period without time trend, without statistical difference between age groups, and between patients who had cholecystectomy at first admission or later. Conclusion During the audit period treatment of acute pancreatitis improved. However, etiological classification and timing of cholecystectomy in mild acute biliary pancreatitis fell below accepted guidelines. Interventions on the common bile duct for gallstone disease increased significantly. Common bile duct clearance has been separated from cholecystectomy, and cholecystectomy often not done. Only one third of all patients with acute gallbladder disease underwent cholecystectomy at first admission. There is room for improvement in treatment of complicatedgallstone disease, and, gallstone surgeons still need good knowledge in open biliary surgery.

Es wurden 44 Hunde mit einem kongenitalen Portosystemischen Shunt präoperativ hinsichtlich ihrer Leberzellintegrität (ALT, AP, GLDH, GGT) und ihrer hepatischen Synthese- (Harnstoff, Cholesterin, Albumin) bzw. Metabolisierungsrate (Ammoniak) untersucht. Die hepatische Durchblutungs- und Resorptionsrate wurde anhand des Verlaufs der Serumgallensäuren im Gallensäuren-Stimulationstest mit Ceruletid (0,3µg/kg KM i.v.)vor und 30 min nach Stimulation (FSBA; PSBA) beurteilt. Eine Verlaufsuntersuchung erfolgte bei den Hunden, bei denen das Shuntgefäß in zwei Operationen verschlossen worden war. Die Untersuchungen wurden jeweils prae operationem, am zweiten, vierten und siebten Tag post operationem sowie abschließend mindestens 120 Tage nach vollständigem Verschluss des Shuntgefäßes durchgeführt. Es wurden die Ergebnisse der einzelnen Untersuchungstage untereinander mit Hilfe des gepaarten t-Tests sowie mit einer Kontrollgruppe (63 lebergesunde Hunde)unter Anwendung des unpaaren t-Tests verglichen. / The hepatic enzymes: alanine aminotransferase (ALT), alkaline phosphatase (AP), glutamat dehydrogenase (GLDH), gamma-glutamyl transferase (GGT); the hepatic synthetic (urea, cholesterol, albumin) and metabolic activity (ammonia) and the hepatic blood flow (serum bile acid stimulation test) were determined in 44 dogs with congeintal portosystemic shunt and in 63 healthy dogs. After determination of fasting serum bile acids (FSBA), the gallbladder contraction was induced by administration of 0,3µg/kg iv ceruletide (Takus). Blood samples of the poststimulatin serum bile acids (PSBA) were taken 30 minutes post administration. The portosystemic shunt was first attenuated (surgery 1) and 4 weeks later completely ligated (surgery 2). All dogs treated with this surgical procedure were examined with the described laboratory design before surgery, the second, the fourth, the seventh day after surgery and approxiamtely 120 days after complete ligation in a follow up study. To compare the developmentof the biochemical and hepatic alterations the paired and unpaired t-test were used.

A cirurgia geral tem experimentado após a década de noventa, com o desenvolvimento da laparoscopia, espetacular melhoria em todos os resultados. Uma menor morbimortalidade se deve ao menor trauma cirúrgico causado pelas cirurgias feitas por pequenos orifícios. O desenvolvimento tecnológico de endoscópios rígidos e flexíveis, propiciou aos médicos um acesso direto às patologias abdominais sem a necessidade de grandes aberturas da cavidade celômica. Assim, houve grande melhoria não somente dos resultados estéticos, mas principalmente na redução de morbidade. Nas cirurgias das vias biliares isso não foi diferente. Com o aprimoramento da técnica cirúrgica laparoscópica, a via de acesso cirúrgico endoscópica passou a ser preferida. Entretanto, a realidade da laparoscopia em muitos locais não se faz presente no tratamento da coledocolitíase, principalmente quando tal patologia é tratada em centros com menor aporte de recursos financeiros. A retirada de cálculos da via biliar principal exige o uso de fibroscópios de alto custo, bem como dispositivos descartáveis de alto valor, forçando o cirurgião desprovido de tais recursos muitas vezes a realizar a cirurgia de maneira convencional ou, no mínimo, aumentado a dificuldade do procedimento por via laparoscópica. Com o intuito de equacionar tal dificuldade, propõe-se com este dispositivo, mais um conceito de abordagem para este problema, inédito, testado em macroambiente, com utilização de cateter contendo balão com polímero autoexpansivo capaz de apreender os cálculos da via biliar principal por meio de inclusão. Utilizando os preceitos da colangiografia per operatória, o novo método propõe a retirada dos cálculos da via biliar principal de maneira indireta com auxílio de métodos de imagem comuns à maioria dos hospitais de média complexidade. / General surgery has experienced after the nineties, with the development of laparoscopy, spectacular improvement in outcomes. Lower morbidity and mortality is due to less surgical trauma caused by surgeries performed by small orifices. The technological development of rigid and flexible endoscopes gave doctors direct access to abdominal pathologies without the need for large openings in the coelomic cavity. Thus, there was a great improvement not only in the aesthetic results, but mainly in the reduction of morbidity. In biliary surgeries this was not different. With the improvement of the laparoscopic surgical technique, the endoscopic cirurgical approach was favored. However, the reality of laparoscopy in many places is not present in the treatment of choledocholithiasis, especially when such pathology is treated in centers with lower financial resources. Removal of stones from the main biliary tract requires the use of high-cost fibroscopes as well as high-value disposable devices, forcing the surgeon devoid of such resources, many times undergoing conventional surgery or at a minimum, increasing the difficulty of the procedure by laparoscopic approach. With the purpose of equating this difficulty, it is proposed with this device, another concept of approach to this problem, novel, tested in macro environment, with the use of balloon catheter containing self expanding polymer capable of grasping the calculi of the common bile duct by inclusion. Using the trans-operative cholangiography precepts, the new method proposes to extract the principal biliary tract calculi indirectly with the help of imaging methods common to the most hospitals.