Gangliosides are sialic acid-containing glycosphingolipids located on the cell surface of all animal cell types. They play a role as receptor molecules, share in cell-to-cell interaction and protect the cell against harmful environmental factors by increasing of rigidity of cell surface. This diploma thesis studies an influence of experimental cholestasis on hepatic ganglioside composition. Cholestasis was induced by bile duct ligation in Wistar rats. A significant increase of total lipid bound sialic acid and b-series gangliosides (GD1b, GT1b, event. GD3) was found in cholestatic liver when compared with controls. These results found in obstructive cholestasis correspond with the results Majer et al. Biomed. Chromatogr., 21, 446-450 (2007), described in 17α− ethinylestradiol induced cholestasis, but the increase of b-series gangliosides was milder in our study. As a second point, an effect of modulated heme-oxygenase 1 (HO-1) activity was investigated in cholestatis induced bile duct ligation (HO-1 activator- hemine, HO-1 inhibitor- Sn-mesoporphyrin). An increase of a total lipid sialic acid was found in Sn-mesoporphyrin treated animals, but a decrease of some a- and b- series gangliosides was observed. In group with activated HO-1 total sialic acid increased, but the composition of gangliosides...

Gangliosides are sialic acid-containing glycosphingolipids located on the cell surface of all animal cell types. They play a role as receptor molecules, share in cell-to-cell interaction and protect the cell against harmful environmental factors by increasing of rigidity of cell surface. This diploma thesis studies an influence of experimental cholestasis on hepatic ganglioside composition. Cholestasis was induced by bile duct ligation in Wistar rats. A significant increase of total lipid bound sialic acid and b-series gangliosides (GD1b, GT1b, event. GD3) was found in cholestatic liver when compared with controls. These results found in obstructive cholestasis correspond with the results Majer et al. Biomed. Chromatogr., 21, 446-450 (2007), described in 17ethinylestradiol induced cholestasis, but the increase of b- series gangliosides was milder in our study. As a second point, an effect of modulated heme-oxygenase 1 (HO-1) activity was investigated in cholestatic rats (HO-1 activator- hemine, HO- 1 inhibitor- Sn- mesoporphyrin). An increase of a total lipid sialic acid was found in Sn-mesoporphyrin treated animals but without significant changes in gangliosides composition. Lipid sialic acid and gangliosides were not changed in animals with hemine activated HO-1. Expression of mRNA of key...

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24499号 / 医博第4941号 / 新制||医||1064(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊藤 貴浩, 教授 中島 貴子, 教授 藤田 恭之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Introdução: O sucesso da cateterização da via biliar é de importância para o diagnóstico e terapêutica nas afecções biliopancreáticas nos procedimentos de colangiopancreatografia retrógrada endoscópica (CPRE) e está associado a complicações graves e mortalidade. O objetivo do estudo foi comparar o sucesso, perfil laboratorial e as complicações da técnica de fistulotomia papilar direta com o acesso cateter e fio-guia. Métodos: No período de julho de 2010 a maio de 2017 foram selecionados e randomizados para CPRE em dois grupos: cateterização com cateter e fioguia (Grupo I) e a fistulotomia papilar (Grupo II). As curvas de amilase, lipase e proteína C reativa (T0, 12 e 24 horas) e as complicações (pancreatite, sangramento e perfuração) foram avaliadas após CPRE. Resultados: Foram incluídos 102 pacientes (66 do sexo feminino e 36 do masculino, com idade média de 59,11±18,7 anos) e divididos em 51 pacientes para Grupo I e 51 no Grupo II. Os sucessos das cateterizações dos Grupos I e II foram de 76,47% e 100%, respectivamente (p=0,0002). Doze pacientes (23,53%) do Grupo I foram considerados pacientes de cateterização difícil e submetidos à fistulotomia papilar com sucesso no acesso biliar. Foram observadas 13,7% (2 perfurações e 5 pancreatites leves) e 2 % (1 paciente com perfuração e pancreatite) complicações nos Grupos I e II, respectivamente (p=0,062). Conclusão: A fistulotomia papilar demonstrou maior eficácia na cateterização da via biliar e com menor índice de amilasemia e lipasemia em comparação a cateterização com papilótomo e fio guia. As complicações foram semelhantes entre as duas técnicas / Background: The success of biliary tract cannulation is important for the diagnosis and treatment of biliopancreatic diseases in endoscopic retrograde cholangiopancreatography (ERCP) procedures. ERCP is associated with severe complications and mortality. The aim of the study was to compare the success, laboratory profile and complications of the direct papillary fistulotomy technique with standard catheter and guidewire access. Methods: In the period from July 2010 to May 2017, two groups were selected and randomized for ERCP: cannulation with catheter and guidewire (Group I) and papillary fistulotomy (Group II). The curves of amylase, lipase and C-reactive protein (T0, 12 and 24 hours) and complications (pancreatitis, bleeding and perforation) were evaluated after ERCP. Results: A total of 102 patients (66 females and 36 males, mean age 59.11 ± 18.7 years) were divided into 51 patients for Group I and 51 for Group II. The success of cannulation was 76.47% and 100%, in Groups I and II, respectively (p = 0.0002). Twelve patients (23.53%) of Group I were considered to have difficult cannulation and were submitted to fistulotomy with successful biliary access. There were 13.73% (2 perforations and 5 mild pancreatitis) and 2% (1 patient with perforation and pancreatitis) complications in Groups I and II, respectively (p=0,062). Conclusion: Papillary fistulotomy demonstrated greater efficacy in the bile duct cannulation and presented lower serum amylase and lipase compared with standard catheter and guidewire cannulation. Complications were similar in the two techniques

Introdução: O sucesso da cateterização da via biliar é de importância para o diagnóstico e terapêutica nas afecções biliopancreáticas nos procedimentos de colangiopancreatografia retrógrada endoscópica (CPRE) e está associado a complicações graves e mortalidade. O objetivo do estudo foi comparar o sucesso, perfil laboratorial e as complicações da técnica de fistulotomia papilar direta com o acesso cateter e fio-guia. Métodos: No período de julho de 2010 a maio de 2017 foram selecionados e randomizados para CPRE em dois grupos: cateterização com cateter e fioguia (Grupo I) e a fistulotomia papilar (Grupo II). As curvas de amilase, lipase e proteína C reativa (T0, 12 e 24 horas) e as complicações (pancreatite, sangramento e perfuração) foram avaliadas após CPRE. Resultados: Foram incluídos 102 pacientes (66 do sexo feminino e 36 do masculino, com idade média de 59,11±18,7 anos) e divididos em 51 pacientes para Grupo I e 51 no Grupo II. Os sucessos das cateterizações dos Grupos I e II foram de 76,47% e 100%, respectivamente (p=0,0002). Doze pacientes (23,53%) do Grupo I foram considerados pacientes de cateterização difícil e submetidos à fistulotomia papilar com sucesso no acesso biliar. Foram observadas 13,7% (2 perfurações e 5 pancreatites leves) e 2 % (1 paciente com perfuração e pancreatite) complicações nos Grupos I e II, respectivamente (p=0,062). Conclusão: A fistulotomia papilar demonstrou maior eficácia na cateterização da via biliar e com menor índice de amilasemia e lipasemia em comparação a cateterização com papilótomo e fio guia. As complicações foram semelhantes entre as duas técnicas / Background: The success of biliary tract cannulation is important for the diagnosis and treatment of biliopancreatic diseases in endoscopic retrograde cholangiopancreatography (ERCP) procedures. ERCP is associated with severe complications and mortality. The aim of the study was to compare the success, laboratory profile and complications of the direct papillary fistulotomy technique with standard catheter and guidewire access. Methods: In the period from July 2010 to May 2017, two groups were selected and randomized for ERCP: cannulation with catheter and guidewire (Group I) and papillary fistulotomy (Group II). The curves of amylase, lipase and C-reactive protein (T0, 12 and 24 hours) and complications (pancreatitis, bleeding and perforation) were evaluated after ERCP. Results: A total of 102 patients (66 females and 36 males, mean age 59.11 ± 18.7 years) were divided into 51 patients for Group I and 51 for Group II. The success of cannulation was 76.47% and 100%, in Groups I and II, respectively (p = 0.0002). Twelve patients (23.53%) of Group I were considered to have difficult cannulation and were submitted to fistulotomy with successful biliary access. There were 13.73% (2 perforations and 5 mild pancreatitis) and 2% (1 patient with perforation and pancreatitis) complications in Groups I and II, respectively (p=0,062). Conclusion: Papillary fistulotomy demonstrated greater efficacy in the bile duct cannulation and presented lower serum amylase and lipase compared with standard catheter and guidewire cannulation. Complications were similar in the two techniques

Estudos recentes estimam que a maioria das estenoses benignas é de natureza iatrogênica podendo ser evitada. A incidência de lesões graves dos ductos biliares durante a colecistectomia é de aproximadamente 1/300 a 1/500 procedimentos (0,2 a 0,3%). Estas lesões podem resultar em coleperitôneo, fístula biliar, estenose de via biliar ou associação dessas complicações. O objetivo deste trabalho foi de relatar os casos de lesões de vias biliares tratados no Serviço de Cirurgia da Faculdade de Medicina da Universidade Federal de Goiás. Foram estudados retrospectivamente 31 pacientes, de 1990 a 2002, com diagnóstico de lesões de vias biliares pós colecistectomia. 29 pacientes (93,5%) eram do sexo feminino e 2 (6,5%) eram do sexo masculino. A idade variou de 21 a 80 anos com média de 46,6 anos. Pacientes provenientes da capital do Estado de Goiás eram em número de 12 (38,7%) enquanto 19 (61,2%) eram provenientes de outras regiões do país. A colecistectomia foi realizada eletivamente em 24 pacientes (77,4%) enquanto em 7 pacientes (22,5%) foi realizada cirurgia de urgência. A via de acesso através de incisão subcostal foi empregada em 70,9% dos pacientes e a via longitudinal (mediana e paramediana direita) em 29,1%. As principais manifestações clínicas foram icterícia em 87,9% dos pacientes, fístula biliocutânea em 29%, peritonite em 29,0%, colangite em 29% e sepse em 6,4% dos pacientes. A Colangiografia Retrógrada Endoscópica foi o exame mais empregado para o diagnóstico da lesão de via biliar. As lesões dos ductos biliares foram classificadas segundo a classificação proposta por Strasberg. Aproximadamente metade (54,8%) das lesões de vias biliares foram classificadas como Strasberg E3 e E4. A técnica cirúrgica mais utilizada para o tratamento das lesões de vias biliares foi a Hepaticojejunoanastomose, com alça jejunal exclusa em Y de Roux, em 20 (64,5%) pacientes. Os 4 óbitos foram em lesões totais proximais. As lesões parciais evoluíram melhor a longo prazo / Recent studies have estimated that most of the benign biliary stenosis are iatrogenic in nature, and can thus be prevent. The incidence of severe injury to the biliary ducts during a cholecystectomy is of approximately 1/300 to 1/500 procedures (0.2-0.3%). These lesions can result in choleperitoneum, biliary fistula, stenosis of the biliary tract or an association of these complications. The objective of this paper was to report on biliary tract injuries treated at the Surgical Unit of the School of Medicine of the Federal University of Goias. Thirty-one patients with a diagnosis of biliary tract lesions, post cholecistectomy, were studied, retrospectively, from 1990 to 2002. Twenty-nine individuals (93.5%) were female, and two (6.4%), males. Their age ranged from 21 to 80 years (average of 46.6 years).Twelve (38.7%) individuals came from the capital of State of Goias and 19 (61.2%), from other regions. Cholecystectomy was performed as an elective procedure in 24 (77.4%) patients, and 7 (22.5%) underwent emergency surgery. A subcostal incision was used in 70.9% of the cases, while the longitudinal approach was used in 29.1%. The main clinical manifestations were jaundice in 87.9%, cutaneous fistula in 29%, peritonitis in 29%, cholangitis in 29% and sepsis in 6.4% of the patients. The Endoscopic Retrograde Cholangiography was the diagnostic test most frequently ordered. Biliary duct injuries were classified according to the criteria proposed by Strasberg. Aproximately half (54.8%) of the injuries were classified as Strasberg E3 and E4. The most common surgical technique used in the treatment of this condition was a Roux-en-Y hepaticojejunostomy in twenty (64.5%). Four patients with proximal injuries died. Long term followup disclosed better results with partial injuries

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.

Η ηπατική εγκεφαλοπάθεια είναι ένα πολύπλοκο νευροψυχιατρικό σύνδρομο που έχει συσχετισθεί με οξείες και χρόνιες ηπατοπάθειες. Τα τελευταία χρόνια συσσωρεύονται πληροφορίες που εμπλέκουν το οξειδωτικό στρες (φορτίο) ως παράγοντα-κλειδί στην παθογένεση της ηπατικής εγκεφαλοπάθειας σε μελέτες που χρησιμοποιούν ως μετρούμενους δείκτες την υπεροξείδωση λιπιδίων και το οξειδοαναγωγικό ζεύγος της γλουταθειόνης (GSH/GSSG). Στην παρούσα μελέτη χρησιμοποιήθηκε ένα μοντέλο πειραματικού αποφρακτικού ίκτερου με απολίνωση του χοληδόχου πόρου. Αρσενικοί αρουραίοι χωρίστηκαν σε ομάδες ελέγχου, ψευδώς χειρουργημένων, και σε ομάδες απολίνωσης χοληδόχου πόρου που είτε θυσιάστηκαν την 5η ημέρα, είτε τη 10η ημέρα, ή τους χορηγήθηκαν αντιοξειδωτικοί παράγοντες (NAC, ALP, Vit-E). Στη συνέχεια, μελετήθηκε η θειολική οξειδοαναγωγική κατάσταση στον εγκέφαλο των αρουραίων, και μάλιστα ανά περιοχές (εγκεφαλικός φλοιός, στέλεχος, παρεγκεφαλίδα), καθώς και η επίδραση των επιλεγμένων αντιοξειδωτικών παραγόντων σε αυτήν. Χρησιμοποιήθηκε για πρώτη φορά μια πιο αντιπροσωπευτική εκτίμηση του οξειδωτικού στρες, καθώς ποσοτικοποιήθηκαν συγκεκριμένοι δείκτες υψηλού (GSSG, NPSSR, NPSSC, PSSR, PSSC, PSSP, υπεροξείδια λιπιδίων) και χαμηλού (GSH, CSH, PSH) οξειδωτικού στρες. Τα αποτελέσματά μας δείχνουν αύξηση των πρώτων και μείωση των τελευταίων σε όλες τις εγκεφαλικές περιοχές καταδεικνύοντας έτσι την παρουσία αυξημένου οξειδωτικού φορτίου στον αποφρακτικό ίκτερο. Το σημαντικότερο αποτέλεσμα αυτής της μελέτης είναι ότι κατέδειξε πρώιμα σημεία οξειδωτικού στρες στον εγκέφαλο ήδη από την 5η ημέρα μετά την απολίνωση του χοληδόχου πόρου. Οι μεταβολές των βιοχημικών δεικτών, και αυτό αφορά σε όλους τους δείκτες και σε όλες τις εγκεφαλικές περιοχές, αρχίζουν να φαίνονται από την 5η ημέρα και γίνονται στατιστικά σημαντικές τη 10η ημέρα από την απολίνωση του χοληδόχου πόρου. Διαπιστώσαμε επιπλέον ότι η GSH είχε περίπου διπλάσιες τιμές στον εγκεφαλικό φλοιό από ό, τι στο στέλεχος και την παρεγκεφαλίδα, και ότι στο στέλεχος παρατηρήθηκε μια δραματική αύξηση των επιπέδων των NPSSR τη 10η ημέρα μετά την απολίνωση του χοληδόχου πόρου, τα οποία όμως παρέμειναν χαμηλά στις άλλες δύο περιοχές. Καθώς είναι γνωστό πως το οξειδωτικό στρες έχει ενοχοποιηθεί στην παθογένεση διαφόρων νευροεκφυλιστικών παθήσεων στον άνθρωπο, τα ευρήματα αυτά θα μπορούσαν να συσχετισθούν με διαφορές στη φυσιολογία και τη βιοχημεία των περιοχών αυτών και ενδεχομένως να σχετίζονται με τον τρόπο που το οξειδωτικό στρες εκφράζεται στην παθοφυσιολογία και άλλων νοσολογικών καταστάσεων όπως η πλάγια αμυοτροφική σκλήρυνση, η νόσος Parkinson, και η νόσος Alzheimer. Έχει ενδιαφέρον το γεγονός ότι τα βασικά γάγγλια και οι πυρήνες του στελέχους είναι θέσεις εκλεκτικής βλάβης στην εγκεφαλοπάθεια από χολερυθρίνη στο νεογνικό ίκτερο. Στη δεύτερη πειραματική φάση, στους ικτερικούς αρουραίους χορηγήσαμε αντιοξειδωτικούς παράγοντες, που έχουν επανειλημμένα μελετηθεί τόσο in vitro όσο και σε ζωικά μοντέλα, σε μια προσπάθεια να αναστρέψουμε τις διαταραχές που είχαν παρατηρηθεί. Ένα πρώτο εύρημα ήταν η ευεργετική δράση στην υπεροξείδωση των λιπιδίων, που ποσοτικοποιήθηκε με τον υπολογισμό της MDA, στις ομάδες και των τριών αντιοξειδωτών αλλά κυρίως στις ALP και Vit-E. Και στις τρεις ομάδες που έλαβαν αντιοξειδωτικά, αντίθετα με την ομάδα απολίνωσης χοληδόχου πόρου, δεν παρατηρήθηκε εξάντληση του συνολικού κυτταρικού περιεχόμενου γλουταθειόνης. Επιπλέον, και στις τρεις ομάδες αντιοξειδωτικών δεν παρατηρήθηκε αύξηση των NPSSR στο εγκεφαλικό στέλεχος, γεγονός που υποδηλώνει ότι η συσσώρευση των μη-πρωτεϊνικών δισουλφιδίων στο στέλεχος εμποδίστηκε από τους αντιοξειδωτικούς παράγοντες. Η ανισορροπία των πρωτεϊνικών θειολών, όπως αυτή φάνηκε από τη μείωση της PSH και την αύξηση του PSSP, αναστράφηκε σημαντικά μόνο στην ομάδα NAC στην οποία η PSH αυξήθηκε στα φυσιολογικά επίπεδα. Εν συντομία, η παρούσα μελέτη είναι η πρώτη που καταδεικνύει με σαφήνεια το οξειδωτικό στρες στον εγκέφαλο στο μοντέλο του αποφρακτικού ίκτερου και μάλιστα αρκετά πρώιμα. Χρησιμοποιεί μια συστοιχία βιοχημικών δεικτών που περιγράφουν την θειολική αναγωγική κατάσταση και την υπεροξείδωση των λιπιδίων και μελετά τις ευεργετικές επιδράσεις γνωστών αντιοξειδωτικών παραγόντων στον πειραματικό αποφρακτικό ίκτερο. Τα αποτελέσματά της θα μπορούσαν να προσφέρουν κάποια βοήθεια στην κατανόηση ορισμένων μηχανισμών της ηπατικής εγκεφαλοπάθειας στους ανθρώπους. Μελλοντικές έρευνες θα απαντήσουν ερωτήματα σχετικά με τα γενεσιουργά αίτια του οξειδωτικού στρες, την ίδια την παρουσία των ελευθέρων ριζών και την παθοφυσιολογία του φαινομένου. / Hepatic encephalopathy is a complex neuropsychiatric syndrome that has been associated with acute and chronic liver diseases. Accumulated evidence over the last several years has implicated oxidative stress a key factor in the pathogenesis of hepatic encephalopathy. These studies utilize measurements of lipid peroxidation products and glutathione (GSH) and its oxidized disulfide GSSG. A model of experimental obstructive jaundice after ligation of the biliary duct has been used in the present study. Male Wistar rats were divided into control, sham operated and bile duct ligated groups that were sacrificed either on the 5th or the 10th day, or they have been treated with antioxidant agents (NAC, ALP, Vit-E). Subsequently, the thiol redox state of various areas (cortex, midbrain and cerebellum) of the rat brain and the effect of selected antioxidants were studied. For the first time specific markers of high oxidative stress (GSSG, NPSSR, NPSSC, PSSR, PSSC, PSSP, lipid peroxides) and low oxidative stress (GSH, CSH, PSH) were quantified providing a more detailed assessment of the phenomenon. Our results show increase in the first and decrease in the latter group of markers in all studied brain areas, therefore demonstrating high oxidative stress in the obstructive jaundice. The major impact of the present study is the demonstration of early signs of oxidative stress in the brain. Using this battery of biochemical markers, deviations from control and sham animals occurred as early as 5 days following bile duct ligation; by the 10th day the majority of these changes became statistically significant. It was also observed that GSH values in cerebral cortex were twice as high as those in midbrain and cerebellum and a dramatic increase in the levels of NPSSR on the 10th day after bile duct ligation in midbrain that was not observed in the other brain areas. These findings could be attributed to specificities of metabolic or biochemical status of neurons and astrocytes and alterations of blood-brain barrier permeability in different brain areas and probably should be taken into account in further studies, since, as we know, oxidative stress has been implicated in the pathogenesis of many human diseases like Parkinson’s , Alzheimer’s and Amyotrophic Lateral Sclerosis (ALS). It is of interest that basal ganglia and brainstem nuclei are, as well, the sites of selective damage in bilirubin encephalopathy in jaundiced neonates. Jaundiced rats were treated with agents that have frequently been used in vitro and in vivo for their antioxidant effects, in an effort to reverse the observed alterations in redox state. In the treated groups, there was no decrease in the total cell glutathione content unlike the bile duct ligated rats. There was also no significant difference in the levels of lipid peroxidation as compared with control and sham groups. The imbalance of protein thiols demonstrated by the decrease of PSH and the increase of PSSP was considerably reversed only in the NAC group. In all treated groups, no NPSSR increase was found suggesting that the antioxidant agents suppressed the accumulation of non-protein disulfides in the midbrain. In brief, this experimental study demonstrates the oxidative profile of the brain associated with obstructive jaundice at an early and later stage. A battery of biochemical markers that define the thiol redox state is utilized and the beneficial effects of known antioxidants are examined. The evidence presented supports the concept that oxidative stress is neither a uniform matter affecting brain in a general way nor that any antioxidant agent could prevent damage by enhancing equally well different defence system. It is also likely that oxidative stress is one of the important mechanisms of jaundice-induced encephalopathy. Further studies could provide with more evidence on the pathogenetic mechanisms and generative causes of the oxidative stress in obstructive jaundice.

Acute pancreatitis is an inflammatory process that initiates with the damage of the pancreatic acinar cells and can also involve other organs and peripancreatic tissues. Vascular alterations are proposed as factors that contribute significantly to the morbidity of patients with pancreatitis. However, few studies were directed to understand these alterations and the underlying mechanisms. In this way, the objective of this study was to investigate vascular changes caused by acute pancreatitis induced by common bile duct obstruction (CBDO) on the vascular reactivity of rat mesenteric artery, in order to generate scientific knowledge about the mechanisms involved in this condition and enable future approaches that lead to a better treatment of this disease in humans. For this purpose, adult male Wistar rats were used (220-300 g) and divided into two groups: (i) sham animals, which were submitted to surgery procedure without obstruction of the duct and (ii) CBDO animals which were submitted to surgery procedure and obstruction of the common bile duct. After 24 or 48 h of this surgery, animals were anesthetized and the superior mesenteric artery was removed. Serum samples were also obtained for amylase determination. Mesentery artery rings were obtained (1-2 mm) and used for in vitro reactivity experiments and measurement of nitric oxide (NO) and superoxide anion (O2 -). For the reactivity experiments, the rings were mounted in isolated organ chambers and cumulative concentration-response curves to acetylcholine or phenylephrine were obtained. For evaluating the production of NO and O2 -, rings were incubated with specific fluorescent dyes. Levels of serum amylase were augmented in animals with CBDO after 24 (p<0.05) or 48 h (p<0.001) of obstruction, when compared with sham group, confirming the induction of pancreatitis. Mesenteric rings from CBDO animals showed decreased relaxing response for acetylcholine or contractile response to phenylephrine after 24 or 48 h of induction of pancreatitis, when compared with sham group. Our data also showed an increase in NO (p<0,05) and O2 - (p<0,05) production in the rings collected after 48 h of the surgical procedure, but not after 24 h. These findings showed that acute pancreatitis induction by CBDO impaired relaxation and contractile response, possibly by mechanisms that are triggered by increased NO and O2 - production, probably associated with the inflammatory process. Additional studies are needed to identify the mechanisms underlying these vascular effects of acute pancreatitis. / A pancreatite aguda é um processo inflamatório que se desenvolve a partir de lesão dos ácinos pancreáticos e também pode envolver tecidos peripancreáticos e outros órgãos. Alterações na função vascular são propostas como fatores que contribuem sobremaneira para a morbidade dos pacientes com pancreatite, entretanto poucos estudos foram direcionados para entender estas alterações e os mecanismos subjacentes. Com base nessas premissas, o objetivo do presente estudo foi investigar as alterações vasculares provocadas pela pancreatite aguda induzida por obstrução do ducto biliopancreático (ODBP) sobre a reatividade de artéria mesentérica de ratos, com o intuito de gerar conhecimento científico sobre os mecanismos envolvidos nesta condição e permitir abordagens futuras que levem ao melhor tratamento desta doença em humanos. Para tanto, foram utilizados ratos machos adultos Wistar (220-300 g) que foram divididos em grupos falso operado (Sham), no qual somente houve a cirurgia, sem obstrução do ducto, ou ODBP, o qual foi submetido a cirurgia e obstrução do ducto biliopancreático. Em seguida, os animais dos diferentes grupos foram eutanasiados após 24 ou 48 h e a artéria mesentérica superior foi removida, bem como soro foi separado para dosagem de amilase. Desta artéria foram obtidos anéis com endotélio (1-2 mm) que foram utilizados para a realização dos experimentos de reatividade in vitro e mensuração de óxido nítrico (NO) e ânion superóxido (O2 -). Para os experimentos de reatividade, os anéis foram montados em sistema de banho de órgão isolado e foi testada sua resposta relaxante ou contrátil, mediante estimulação com acetilcolina (ACh) ou fenilefrina (Fen) respectivamente. Para avaliar a produção de NO e O2 -nos anéis dos animais dos diferentes grupos, foram utilizadas sondas fluorescentes específicas para estes radicais livres. Nos animais com ODBP foram encontradas concentrações séricas de amilase elevadas após 24 (p<0,05) ou 48 h (p<0,001), quando comparados ao grupo sham, confirmando a indução da pancreatite. Os anéis dos animais com ODBP demonstraram uma diminuição da resposta relaxante à acetilcolina ou contrátil à fenilefrina após 24 ou 48 h da indução da pancreatite, quando comparados aos animais do grupo sham. Também foi observado aumento na produção de NO (p<0,05) e de O2 - (p<0,05) nos anéis coletados após 48 h, mas não 24 h da indução da pancreatite. Estes achados mostraram que a indução da pancreatite aguda por ODBP prejudica tanto a resposta relaxante quanto a contrátil de anéis de artéria mesentérica, por mecanismos que possivelmente são desencadeados pelo aumento na produção de NO e O2 -, provavelmente associado com o processo inflamatório. Entretanto, experimentos adicionais são necessários para identificar os mecanismos pelos quais a pancreatite aguda causa estes efeitos.

Estudos recentes estimam que a maioria das estenoses benignas é de natureza iatrogênica podendo ser evitada. A incidência de lesões graves dos ductos biliares durante a colecistectomia é de aproximadamente 1/300 a 1/500 procedimentos (0,2 a 0,3%). Estas lesões podem resultar em coleperitôneo, fístula biliar, estenose de via biliar ou associação dessas complicações. O objetivo deste trabalho foi de relatar os casos de lesões de vias biliares tratados no Serviço de Cirurgia da Faculdade de Medicina da Universidade Federal de Goiás. Foram estudados retrospectivamente 31 pacientes, de 1990 a 2002, com diagnóstico de lesões de vias biliares pós colecistectomia. 29 pacientes (93,5%) eram do sexo feminino e 2 (6,5%) eram do sexo masculino. A idade variou de 21 a 80 anos com média de 46,6 anos. Pacientes provenientes da capital do Estado de Goiás eram em número de 12 (38,7%) enquanto 19 (61,2%) eram provenientes de outras regiões do país. A colecistectomia foi realizada eletivamente em 24 pacientes (77,4%) enquanto em 7 pacientes (22,5%) foi realizada cirurgia de urgência. A via de acesso através de incisão subcostal foi empregada em 70,9% dos pacientes e a via longitudinal (mediana e paramediana direita) em 29,1%. As principais manifestações clínicas foram icterícia em 87,9% dos pacientes, fístula biliocutânea em 29%, peritonite em 29,0%, colangite em 29% e sepse em 6,4% dos pacientes. A Colangiografia Retrógrada Endoscópica foi o exame mais empregado para o diagnóstico da lesão de via biliar. As lesões dos ductos biliares foram classificadas segundo a classificação proposta por Strasberg. Aproximadamente metade (54,8%) das lesões de vias biliares foram classificadas como Strasberg E3 e E4. A técnica cirúrgica mais utilizada para o tratamento das lesões de vias biliares foi a Hepaticojejunoanastomose, com alça jejunal exclusa em Y de Roux, em 20 (64,5%) pacientes. Os 4 óbitos foram em lesões totais proximais. As lesões parciais evoluíram melhor a longo prazo / Recent studies have estimated that most of the benign biliary stenosis are iatrogenic in nature, and can thus be prevent. The incidence of severe injury to the biliary ducts during a cholecystectomy is of approximately 1/300 to 1/500 procedures (0.2-0.3%). These lesions can result in choleperitoneum, biliary fistula, stenosis of the biliary tract or an association of these complications. The objective of this paper was to report on biliary tract injuries treated at the Surgical Unit of the School of Medicine of the Federal University of Goias. Thirty-one patients with a diagnosis of biliary tract lesions, post cholecistectomy, were studied, retrospectively, from 1990 to 2002. Twenty-nine individuals (93.5%) were female, and two (6.4%), males. Their age ranged from 21 to 80 years (average of 46.6 years).Twelve (38.7%) individuals came from the capital of State of Goias and 19 (61.2%), from other regions. Cholecystectomy was performed as an elective procedure in 24 (77.4%) patients, and 7 (22.5%) underwent emergency surgery. A subcostal incision was used in 70.9% of the cases, while the longitudinal approach was used in 29.1%. The main clinical manifestations were jaundice in 87.9%, cutaneous fistula in 29%, peritonitis in 29%, cholangitis in 29% and sepsis in 6.4% of the patients. The Endoscopic Retrograde Cholangiography was the diagnostic test most frequently ordered. Biliary duct injuries were classified according to the criteria proposed by Strasberg. Aproximately half (54.8%) of the injuries were classified as Strasberg E3 and E4. The most common surgical technique used in the treatment of this condition was a Roux-en-Y hepaticojejunostomy in twenty (64.5%). Four patients with proximal injuries died. Long term followup disclosed better results with partial injuries