Abnormalities of lipid metabolism are considered risk factors for cardiovascular, metabolic, nephrologic diseases amd some malignancies, as well. Nowadays, a lot of effort is devoted to study new risk factors and surrogate markers of conditions mentioned above to improve their prognosis and decrease mortality. The aim of this thesis was to provide a comprehensive survey of lipid metabolism, characteristics of different lipid compounds in health and diseases and of possibilities of utilization of selected lipid parameters in the diagnostics of pathological conditions listed above. Selected lioid parameters were observed in several studies, focused on specific pathological conditions. Besides conventional lipid analytes, the composition of fatty acids in plasma lipid pools was studied in healthy controls, and in the patients suffering from metabolic syndrome, chronic pancreatitis, and pancreatic cancer, as well. Markers of an oxidative stress (oxidatively modified LDL particles and conjugated dienes in precipitated LDL) were assessed in healthy controls, patients with metabolic syndrome, chronic pancreatitis, pancreatic cancer, and in the patients with different concentrations of plasma apoB-48, too. LDL particles subfraction were investigated in healthy controls, in the patients with different...

Background: Chronic pancreatitis (CP) often leads to recurrent pain as well as exocrine and/or endocrine pancreatic insufficiency. This study aimed to investigate the effect of pancreatic head resections on glucose metabolism in patients with CP. Methods: Patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD), Whipple procedure (cPD), or duodenum-preserving pancreatic head resection (DPPHR) for CP between January 2011 and December 2020 were retrospectively analyzed with regard to markers of pancreatic endocrine function including steady-state beta cell function (%B), insulin resistance (IR), and insulin sensitivity (%S) according to the updated Homeostasis Model Assessment (HOMA2). Results: Out of 141 pancreatic resections for CP, 43 cases including 31 PPPD, 2 cPD and 10 DPPHR, met the inclusion criteria. Preoperatively, six patients (14%) were normoglycemic (NG), 10 patients (23.2%) had impaired glucose tolerance (IGT) and 27 patients (62.8%) had diabetes mellitus (DM). In each subgroup, no significant changes were observed for HOMA2-%B (NG: p = 0.57; IGT: p = 0.38; DM: p = 0.1), HOMA2-IR (NG: p = 0.41; IGT: p = 0.61; DM: p = 0.18) or HOMA2-%S (NG: p = 0.44; IGT: p = 0.52; DM: p = 0.51) 3 and 12 months after surgery, respectively. Conclusion: Pancreatic head resections for CP, including DPPHR and pancreatoduodenectomies, do not significantly affect glucose metabolism within a follow-up period of 12 months.

Sulfur amino acids have critical function as intracellular redox buffers and maintain homeostasis in the external milieu by combating oxidative stress. Synthesis of glutathione (GSH) is regulated at a substrate level by cysteine, which is synthesized by homocysteine via the transsulfuration pathway. Oxidative stress and diminished glutathione pools play a sustained role in the pathogenesis of acute pancreatitis. One of the aims of this study was to experimentally address the temporal relationship between plasma sulfur amino acid levels in patients suffering from acute pancreatitis. The data indicated low concentration of cysteine initially, at levels similar to those of healthy controls. Glutathione was found reduced whilst cysteinyl-glycine and ¿- glutamyl transpeptidase activity were increased in both mild and severe attacks. As the disease progressed, glutathione and cysteinyl-glycine were further increased in mild attacks and cysteine levels correlated with homocysteine and ¿-glutamyl transpeptidase activity. The progress of severe attacks was associated with glutathione depletion, reduced ¿-glutamyl transpeptidase activity and increased cysteinyl-glycine, that correlated with glutathione depletion. The corollary that ample supply of cysteine and cysteinly-glycine does not contribute towards glutathione synthesis in acute pancreatitis poses an important issue that merits resolution. Heightened oxidative stress and depletion of glutathione rationalized the progression of disease in severe attacks. An upsurge that reactive oxygen species can shift redox state of cells is determined by the ratio of the abundant redox couples reduced and oxidized glutathione (GSH: GSSG) in cell. The study reported a novel methodology for quantification of total oxidized glutathione (tGSSG) and total glutathione (tGSH) in whole blood using reverse phase high performance liquid chromatography. The novelty of the method is ascertained by the use of a mercaptan scavenger 1, methyl-2-vinyl-pyridinium trifluromethanesulfonate for the total oxidized glutathione determination. The results reported permit quantitation of tGSSG and tGSH and was applied to a control group. Finally, the study was also focussed in developing a liquid chromatography-mass spectrometric method to evaluate free and conjugated bile acids in patients suffering from various degrees of cholestatic-hepatobiliary disorders. The study reported low levels of ursodeoxycholic acid (UDCA) and slightly high levels of lithocholic acid (LCA). All the primary bile acids seem to be conjugated with glycine and taurine amino acid.

Homeodynamic space (HDS) shrinks as vulnerability increases with aging and repeated damage to the cells. HDS is lost in alcoholic pancreatitis patients due to overconsumption of alcohol, smoking, and high fat diets. Etiologically relevant animal models for study of chronic pancreatitis (CP) are needed. In order to begin filling this gap a central purpose of this dissertation research was to examine relationships between the alcohol and high fat diet (AHF) and pancreatitis with attention to hypersensitivity and anxiety-like behaviors. The AHF diet induced pancreatitis described here etiologically mimics human risk factors of AHF consumption for advancement to alcoholic CP. In this study one group of mice was fed long term with a diet of high fat and alcohol for comparison with a group fed normal chow. Mice consumed a liquid diet containing 6% alcohol and a high fat supplement ad libitum over a period of five months. Each group was evaluated for heat and mechanical hypersensitivity, and histology indicative of CP. The association of pancreatitis pathology with anxiety has been understudied. Anxiety, like pain, is useful as a transient state but when anxiety is prolonged it is termed a disorder. Anxiety is often comorbid with pain and depression. Therefore, it is important to determine anxiety in mice with CP histology. This model was characterized for the interaction of pancreatitis histology, as well as persisting pain-, anxiety-, and fear-like behaviors. The AHF diet mice developed hypersensitivity, demonstrated anxiety-like behaviors, and showed concurrent histology consistent with CP. Nontransgenic mouse models where pancreatitis is induced only by a combination of ad libitum liquid food with added alcohol and lard supplementation do not currently exist, nor has an in-depth study of anxiety-like behaviors been conducted in this mouse model. This dissertation research addresses this knowledge gap.

<p>Акутни панкреатитис је ензиматско инфламаторно оболење панкреаса, са инциденцијом око 17/100000 становника. Најчешћи етиолошки чиниоци који се везују за ово стање су билијарна калкулоза (45%) и конзумација алкохолних пића (35%). Ређи узроци су одређени лекови, хипертриглицеридемија, хиперкалијемија, траума, урођени чиниоци, и идиопатски панкреатитис (20%). По међународној Атланској (Atlanta) класификацији, акутни панкреатитис се може манифестовати у умереној, умерено тешкој и тешкој форми. Умерене форме панкреатитиса се јављају у 80%, карактеришу се едемом органа и имају благ и краткотрајан клинички ток, са стопом морталитета од 1%. Основни циљ лечења болесника са акутним панкреатитисом у прва 24 сата хоспитализације јесте олакшавање тегоба, утврђивање узрока панкреатитиса и процена тежине обољења. Акутни панкреатитис билијарне етиологије узрокован је калкулозом жучне кесе и/ или жучних путева. Препоручени третман билијарне калкулозе, у циљу превенције поновног атака умерене форме билијарног панкреатитиса , подразумева уклањање жучне кесе лапароскопском холецистектомијом са интраоперативном холангиографијом. Уколико се дијагностикује калкулоза жучних канала ради се ендоскопска ретроградна холангиопанкреатографија (ЕРЦП) са ендоскопском папилотомијом (ЕПТ) и уклањем__ калкулуса и детритуса уз жучних водова, са циљем обезбеђивања нормалног протока жучи у дванаестопалачно црево. Циљ овог истраживања је оптимализација редоследа примене ЛХ и ЕРЦП са ЕПТ, идентификацијом предикционих показатеља холедохолитијазе, ради скраћења дужине хоспитализације болесника са умереном формом акутног билијарног панкреатитиса. У спроведеној проспективној анамнестичкој студији, учествовало је 100 болесника лечених од умерене форме акутног билијарног панкреатитиса, у Ургентном центру Клиничког центра Војводине, од 2011. до 2015.године, од којих је код 80 урађена само ЛХ, а код 20 ЛХ и ЕРЦП са ЕПТ. Анализом клиничких, ултразвучних и лабораторијских налаза, идентификовано је 5 статистички значајних предиктора холедохолитијазе; директни и укупни билирубин, алкална фосфатаза (АФ), гама глутирил транспепдидаза (гама ГТ) и це реактивни протеин (ЦРП), на основу којих је омогућено креирање математичког модела за предикцију холедохолитијазе, коришћењем теорије потпорних вектора (СВМ). Установљено је да патолошки налази ових параметара значајно указују на холедохолитијазу, те да је ЛХ препоручена као метода првог избора, код болесника код којих налази предиктора холедохолитијазе нису патолошки. Овако лечени болесници су имали значајно краће време хоспитализације. Поред тога, уколико се интраоперативном холангиографијом (ИОХ) при ЛХ установи холедохолитијаза, ЕРЦП са ЕПТ се може урадити без одлагања.</p> / <p>Akutni pankreatitis je enzimatsko inflamatorno obolenje pankreasa, sa incidencijom oko 17/100000 stanovnika. Najčešći etiološki činioci koji se vezuju za ovo stanje su bilijarna kalkuloza (45%) i konzumacija alkoholnih pića (35%). Ređi uzroci su određeni lekovi, hipertrigliceridemija, hiperkalijemija, trauma, urođeni činioci, i idiopatski pankreatitis (20%). Po međunarodnoj Atlanskoj (Atlanta) klasifikaciji, akutni pankreatitis se može manifestovati u umerenoj, umereno teškoj i teškoj formi. Umerene forme pankreatitisa se javljaju u 80%, karakterišu se edemom organa i imaju blag i kratkotrajan klinički tok, sa stopom mortaliteta od 1%. Osnovni cilj lečenja bolesnika sa akutnim pankreatitisom u prva 24 sata hospitalizacije jeste olakšavanje tegoba, utvrđivanje uzroka pankreatitisa i procena težine oboljenja. Akutni pankreatitis bilijarne etiologije uzrokovan je kalkulozom žučne kese i/ ili žučnih puteva. Preporučeni tretman bilijarne kalkuloze, u cilju prevencije ponovnog ataka umerene forme bilijarnog pankreatitisa , podrazumeva uklanjanje žučne kese laparoskopskom holecistektomijom sa intraoperativnom holangiografijom. Ukoliko se dijagnostikuje kalkuloza žučnih kanala radi se endoskopska retrogradna holangiopankreatografija (ERCP) sa endoskopskom papilotomijom (EPT) i uklanjem__ kalkulusa i detritusa uz žučnih vodova, sa ciljem obezbeđivanja normalnog protoka žuči u dvanaestopalačno crevo. Cilj ovog istraživanja je optimalizacija redosleda primene LH i ERCP sa EPT, identifikacijom predikcionih pokazatelja holedoholitijaze, radi skraćenja dužine hospitalizacije bolesnika sa umerenom formom akutnog bilijarnog pankreatitisa. U sprovedenoj prospektivnoj anamnestičkoj studiji, učestvovalo je 100 bolesnika lečenih od umerene forme akutnog bilijarnog pankreatitisa, u Urgentnom centru Kliničkog centra Vojvodine, od 2011. do 2015.godine, od kojih je kod 80 urađena samo LH, a kod 20 LH i ERCP sa EPT. Analizom kliničkih, ultrazvučnih i laboratorijskih nalaza, identifikovano je 5 statistički značajnih prediktora holedoholitijaze; direktni i ukupni bilirubin, alkalna fosfataza (AF), gama glutiril transpepdidaza (gama GT) i ce reaktivni protein (CRP), na osnovu kojih je omogućeno kreiranje matematičkog modela za predikciju holedoholitijaze, korišćenjem teorije potpornih vektora (SVM). Ustanovljeno je da patološki nalazi ovih parametara značajno ukazuju na holedoholitijazu, te da je LH preporučena kao metoda prvog izbora, kod bolesnika kod kojih nalazi prediktora holedoholitijaze nisu patološki. Ovako lečeni bolesnici su imali značajno kraće vreme hospitalizacije. Pored toga, ukoliko se intraoperativnom holangiografijom (IOH) pri LH ustanovi holedoholitijaza, ERCP sa EPT se može uraditi bez odlaganja.</p> / <p>Acute pancreatitis is an enzymatic inflammatory disease of the pancreas, with an incidence of around 17/100000 inhabitants. The most common etiological factors that are associated with this condition are biliary calculi (45%) and consumption of alcoholic beverages (35%). Less common causes include certain medications, hypertriglyceridemia, hyperkalemia, trauma, congenital factors and idiopathic pancreatitis (20%). According to the Atlanta International classification, acute pancreatitis can be manifested in a moderate, moderately severe and severe forms. Moderate forms of pancreatitis occur in 80%, characterized by pancreatic edema and have mild and short clinical course, with a mortality rate of 1%. The main goal of treatment of patients with acute pancreatitis in the first 24 hours of hospitalization is to facilitate complaints, determining the cause of pancreatitis and assessment of severity of the disease. Acute biliary pancreatitis is caused by calculosis of the gallbladder and / or bile ducts. The recommended treatment of biliary calculi, in order to prevent repeated attacks of moderate biliary pancreatitis, involves the removal of the gallbladder thru laparoscopic cholecystectomy with intraoperative cholangiography. If presence of bile duct calculi is established, an endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic papillotomy (EPT) and removes stones and detritus along the bile ducts is indicated, with the aim of ensuring the normal flow of bile into the duodenum. The aim of this study is the optimization of the order of application LH and ERCP with EPT, the identification of predictable indicators of choledocholithiasis, in order to shorten the length of hospitalization of patients with a moderate form of acute biliary pancreatitis. We conducted prospective case control study, with 100 patients involved, treated for moderate forms of acute biliary pancreatitis in the Emergency Center of the Clinical Center of Vojvodina, from 2011 to 2015, of which 80 made only with LH and 20 with LH at and ERCP with EPT . The analysis of clinical, ultrasound and laboratory findings identified 5 significant predictors of choledocholithiasis; direct and total bilirubin, alkaline phosphatase (AF), gamma glutiril transpepdidase (gamma GT) and C reactive protein (CRP), under which enabled the creation of a mathematical model for predicting choledocholithiasis, using the Support vector machines (SVM). It was found that pathological findings of these parameters indicate a significant choledocholithiasis, and LH is recommended as the first choice in patients in whom there are not present pathological predictors of choledocholithiasis. Thus treated patients had a significantly shorter hospital stay. In addition, if the intraoperative cholangiography (IOH) during LH show choledocholithiasis, ERCP with the EPT can be done without delay.</p>

L’hyperchylomicronémie familiale est un trait monogénique caractérisé par un taux de triglycérides plasmatiques à jeun supérieur à 10 mmol/L (la normale étant de 1,7 mmol/L). L’hyperchylomicronémie familiale est le plus souvent causée par une déficience dans le gène LPL (pour lipoprotéine lipase). La déficience en lipoprotéine lipase (LPLD) est aussi associée à un risque élevé de pancréatite. La pancréatite en soi est reconnue comme un trait complexe génétique dont plusieurs gènes sont associés à sa susceptibilité. Étant donné l’expression variable de la pancréatite chez les patients LPLD, les résultats de ce mémoire présentent certains facteurs génétiques pouvant être responsables du risque de l’expression de la pancréatite aigüe récurrente chez les sujets LPLD. L’analyse par séquençage des régions codantes et promotrices des gènes CTRC (pour « Chymotrypsin C ») et SPINK1 (pour « Serine protease inhibitor Kazal type 1 ») a été effectuée chez 38 patients LPLD et 100 témoins. Ces deux gènes codent pour des protéines impliquées dans le métabolisme des protéases au niveau du pancréas et ont déjà été associés avec la pancréatite dans la littérature. Notre étude a permis d’identifier une combinaison de deux polymorphismes (CTRC-rs545634 et SPINK1-rs11319) associée significativement avec la récidive d’hospitalisations pour douleur abdominale sévère ou pour pancréatite aigüe récurrente chez les patients LPLD (p<0,001). Ces résultats suggèrent que le risque de récidive de pancréatite chez les patients LPLD peut être influencé par des variants dans des gènes de susceptibilité à la pancréatite. L’identification de biomarqueurs génétiques améliore la compréhension des mécanismes physiopathologiques de la pancréatite chez les patients LPLD ce qui, par conséquent, permet de mieux évaluer et caractériser les risques de pancréatite afin d'adapter un plan d'intervention préventif pour ces patients. / Familial hyperchylomicronemia is a monogenic trait characterized by an increased fasting plasma triglyceride levels ≥ 10 mmol/L (normal is 1.7 mmol/L). Familial hyperchylomicronemia is most often caused by a deficiency in the LPL gene. Lipoprotein lipase deficiency (LPLD) is also associated with an increased risk of pancreatitis. Pancreatitis is recognized as a complex genetic trait and several genes are associated with its susceptibility. Considering the variable expression of pancreatitis in LPLD patients, results of this manuscript demonstrate that genetic factors may be responsible of the increased risk of recurrent acute pancreatitis episodes in LPLD subjects. The sequencing analysis of the coding and promoters regions of CTRC gene (for Chymotrypsin C) and SPINK1 gene (for Serine protease inhibitor Kazal type 1) was performed. These two genes encode proteins involved in the metabolism of the pancreas proteases and have been associated with pancreatitis in literature. A combination of two polymorphisms (CTRC-rs545634 and SPINK1-rs11319) have been identified and associated with recurrent hospitalizations for severe abdominal pain or recurrent acute pancreatitis in LPLD patients (p <0.001). These results suggest that the risk of recurrent episodes of pancreatitis in LPLD patients may be influenced by variants in susceptibility genes. The identification of genetic biomarkers improves the understanding of the pathophysiological mechanisms of pancreatitis in LPLD patients which therefore helps to assess and characterize the risk of pancreatitis to adapt preventive intervention plan for these patients.

Pancreatic cancer (PC) is extremely severe malignant disease with a five-year survival of less than 5%. Currently there is no reliable tool for the diagnosis of PC in its early stages. At the time of clinical symptoms most patients are in an advanced stage of the disease and the treatment does not usually have a significant effect. For these reasons emphasis is gradually shifting to the search for the suitable molecular markers for improvement of the diagnosis and assessment of the survival prognosis with respect to a possibility of surgical treatment. MiRNA represent one of the most promising markers, although, their examination in pancreatic tissue is a complicated process. One of the reasons is the very small amount of the source material coming from a fine needle biopsy. A second cause of problems is the subtle character of the pancreatic tissue resulting in significantly lower yields of molecular genetic analysis when compared to other epithelial tissues. An additional negative factor is heterogeneity of the tissue resulting in disproportionate representation of tumor cells within the sample. A suitable choice of procedures for isolation of nucleic acids (NA) and subsequent analysis including quantification of tumor cells is critical for accurate evaluation of the miRNA levels. This work is...

INTRODUÇÃO: Relatos conflitantes têm dificultado para se estabelecer o potencial benefício da glutamina (GLN) no tratamento de condições inflamatórias agudas. Nós avaliamos o efeito da infusão parenteral de GLN, prévia à pancreatite aguda (PA) experimental, nos mediadores inflamatórios, morbidade e mortalidade. MÉTODOS: Ratos Lewis (n = 131) receberam glutamina parenteral (grupo GG), solução salina (grupo SS ou controle), ou permaneceram sem infusão parenteral (grupo Sham) por 48h. Após este período, foi induzida PA por meio da injecção retrógrada de taurocolato de sódio no ducto pancreático. Sangue, amostras de pulmão, fígado, pâncreas e líquido ascítico foram colhidos a partir de 2, 12 e 24 horas após PA para avaliação das variáveis propostas (citocinas, hsp, histologia, amilase). Sessenta animais permaneceram vivos após PA para a análise da mortalidade em sete dias. RESULTADOS: A análise entre grupos não mostrou diferenças significativas nos níveis de citocinas (p > 0,05). Análise cinética dentro de cada grupo ao longo do tempo mostrou maior INF-y no grupo Sham e SS às 2h do que em 12h e 24h, maior IL-2 e inferior IL-10 no Sham, às 24h do que em 2h e 12h, e menor IL-10 no SS e GG em 24 h do que no tempo de 2h (p <= 0.05). O grupo GG exibiu maior expressão de HSP 90 no pulmão e no fígado do que no grupo Sham nos tempos de 2h e 12h, respectivamente; e maior expressão no fígado de HSP90 e HSP70 no grupo SS no tempo 12 horas (p < 0,01). O grupo Sham apresentou maior expressão de HSP 70 no pulmão e HSP 90 no fígado do que os outros grupos no tempo de 24h. Não ocorreram alterações na taxa de mortalidade. CONCLUSÕES: Em modelo de PA experimental induzida por taurocolato de sódio, o pré-tratamento com GLN parenteral melhorou o perfil dos mediadores inflamatórios, sem afetar a mortalidade / INTRODUCTION: Conflicting reports have hindered establish the potential glutamine (GLN) benefit in treating acute inflammatory conditions. We evaluated the effect of parenteral GLN infusion before experimental acute pancreatitis (AP), as systemic inflammation-reproducing model, on inflammatory mediators and mortality. METHODS: Lewis rats (n=131) received parenteral glutamine (GG group), saline (SS or Control group), or remained without parenteral infusion ( Sham group) for 48h. Thereafter, AP was induced by retrograde injection of sodium taurocholate into pancreatic duct. Blood, lung, liver and pancreas samples were collected from 2, 12 and 24h post-AP to assess serum cytokines levels, tissue HSP expression, histology and amylase. Sixty animals remained alive post-PA for seven-day mortality analysis. RESULTS: Punctual between-groups analysis did not show differences in cytokine levels (p > 0.05). Intragroup analysis over time showed higher INF-y in Sham and SS at 2h than at 12h and 24h, higher IL-2 and lower IL-10 in Sham at 24h than at 2h and 12h, and lower IL-10 in SS and GG at 24h than at 2h timepoint (p <= 0.05). GG group exhibited higher lung and liver HSP90 than Sham at 2h and 12h timepoints, respectively; and higher liver HSP90 and HSP70 than SS at 12h timepoint (p < 0.01). Sham group presented higher lung HSP70 and liver HSP90 than the others at 24h timepoint (p < 0.02). No changes occurred on mortality rate. CONCLUSIONS: In sodium taurocholate-induced PA model, pretreatment with parenteral GLN improved inflammatory mediator\'s profile, without affecting mortality

A pancreatite crônica alcoólica (PCA) tem o álcool como seu principal fator etiológico, a relação entre ingestão de álcool e estado nutricional é complexa e as características nutricionais dos portadores de PCA são pouco conhecidas. Neste trabalho, foram avaliados três grupos de pacientes do sexo masculino, o primeiro (A) com 20 pacientes com PCA, o segundo (B) com 12 etlistas crônicos não pancreatopatas e não hepatopatas e o terceiro (C) com 16 indivíduos não etlistas, não pancreatopatas e não hepatopatas. Para analisar os três grupos utilizaram-se a avaliação antropométrica, a quantificação da ingestão alcoólica, quando existente, o inquérito dietético obtido por Recordatório de 24 horas, a composição corpórea, obtida por bioimpedância elétrica, exames séricos relacionados à avaliação hepática e pancreática, dosagem de vitaminas e de sais minerais, além de marcadores inflamatórios, como proteína C reativa, seroamiloide A e leptina, além de exames de imagem, como ultrassonografia abdominal e/ou tomografia computadorizada de abdômen. A PCA (Grupo A) não se associou à queda da ingestão dietética, porém houve redução da massa magra, evidenciando desnutrição protéica; os etilistas sem pancreatite (Grupo B) apresentaram menor massa magra em relação aos pacientes do grupo C e foi possível demonstrar que a composição corpórea e o perfil inflamatório são distintos e relevantes, não apenas na PCA (Grupo A), mas também nos etilistas sem lesão pancreática (Grupo B), que também devem ser melhor estudados e acompanhados ao longo do seu curso clínico. Em síntese, encontraram-se evidências de subnutrição e aberrações metabólicas tanto nos casos de alcoolismo com lesão pancreática quanto nos etilistas aparentemente sem lesão pancreática ou hepática. Achado até o momento não relatado pela literatura / Alcoholic pancreatitis has alcohol as the primary etiologic factor. The relationship between alcohol intake and nutritional status is complex and the nutritional characteristics of patients with this disease are unknown. In this study, we evaluated three groups of male patients, one (A) with 20 patients with alcoholic pancreatitis, another (B) with 12 alcoholics without pancreatic or liver disease and the last (C) with 16 non - alcoholics , free from any systemic disease or organ insufficiency. To analyze the three groups, we used anthropometric assessment, quantification of alcohol intake, dietary recall, body composition estimated by bioimpedance analysis, biochemical tests related to liver and pancreatic function, dosage of vitamins and minerals, inflammatory markers namely C-reactive protein, leptin and serum amyloid A, in addition to imaging studies such as abdominal ultrasonography and computed tomography of the abdomen whenever required. Group A was not associated with decrease in food intake, but there was a reduction in lean body mass, indicating undernutrition. Alcoholics without pancreatitis (group B) also showed lower lean mass compared to patients in group C, demonstring that changes in body composition and inflammatory status are distinct and relevant also in alcoholics without pancreatic injury (Group B). They should be better studied and monitored throughout their clinical course. In synthesis evidence of undernutrition and metabolic aberrations were demonstrated in both alcoholism with pancreatic damage and in nominally healthy alcoholics, a finding not hitherto reported in the literature

Pancreatite aguda é uma das principais causas de síndrome da resposta inflamatória sistêmica (SRIS). Complicações sistêmicas são os principais fatores responsáveis pela ocorrência de falência de múltiplos órgãos e sistemas e morte durante a primeira etapa da doença. Os níveis de mediadores inflamatórios possuem uma relação com a gravidade da pancreatite. O TNF-alfa tem sido descrito como o agente iniciador da resposta inflamatória da pancreatite aguda. Estudos prévios usando a pentoxifilina para bloquear a produção de TNF-alfa têm demonstrado efeitos benéficos quando usada em modelos experimentais de sepse ou choque. A infecção pancreática é a mais grave complicação da pancreatite aguda com índices de mortalidade que podem chegar a 80%. Os mecanismos que determinam a ocorrência da infecção pancreática não são bem esclarecidos. Objetivo: Determinar o efeito da inibição da produção de TNF-alfa na pancreatite aguda com a administração de pentoxifilina. Métodos: Foi utilizado um modelo experimental de pancreatite aguda grave através da injeção intraductal de taurocolato de sódio a 2,5%. Cento e vinte e quatro ratos Wistar machos foram divididos em três grupos: Controle (animais submetidos ao procedimento cirúrgico sem a administração de taurocolato de sódio), Pancreatite (animais submetidos à indução da pancreatite aguda) e Pentoxifilina (animais submetidos à indução da pancreatite aguda seguida da administração intraperitoneal de 25 mg/Kg de pentoxifilina). Foi realizada a dosagem sérica das interleucinas 6 e 10 e TNF-alfa duas horas após a indução da pancreatite. Foram analisadas a ocorrência de translocação bacteriana e a incidência de infecção pancreática, através de culturas realizadas 24 horas após a indução da pancreatite aguda e a mortalidade global. A ocorrência de infecção pancreática foi considerada como positiva quando a concentração de bactérias expressa em UFC/g foi maior que 105. Resultados: Quando comparado ao grupo Pancreatite, o grupo Pentoxifilina apresentou redução significativa da lesão histológica pancreática, dos níveis de IL-6, IL-10 e TNF-alfa e da ocorrência de infecção pancreática (p < 0,05), tais alterações se associam a redução significativa da mortalidade no grupo Pentoxifilina. Conclusão: A inibição da produção de TNF-alfa através da administração de pentoxifilina foi capaz de reduzir o processo inflamatório local e sistêmico, reduzir a translocação bacteriana e infecção pancreática e melhorar a sobrevida com redução dos índices de mortalidade desta grave doença / Acute pancreatitis (AP) is considered one of the typical conditions causing systemic inflammatory response (SIRS). Systemic complications are the most important contributors to multiple organ failure and death during the first stages of severe acute pancreatitis. Levels of pro-inflammatory cytokines increase during the course of AP, and these levels appear to be correlated with the severity of pancreatic inflammation. TNF-alfa may be an initiator of inflammatory process in AP. Previous studies using pentoxifylline to block TNF-alfa production have showed beneficial effects in experimental models of sepsis and shock. The gut is a target organ of the SIRS causing gut barrier dysfunction allowing bacteria and toxin translocation. Bacterial translocation has been implicated in the development of multiple organ failure and is one of the major causes of pancreatic infection in patients with pancreatic necrosis. Aim: To determinate the effects of inhibition of TNF-? on the pancreatic and systemic inflammatory response, pancreatic infection, and mortality rate in necrotizing acute pancreatitis in rats. Methods: An experimental model of severe AP by injection of 0.5ml of 2.5% sodium taurocholate into the pancreatic duct was utilized. A hundred and twenty four male Wistar rats were divided in 3 groups: Sham (surgical procedure without AP induction), Pancreatitis (AP Induction), and Pentoxifylline (AP induction plus administration of 25 mg/kg pentoxifylline). Pancreatic inflammatory response was measured by histological studies and systemic inflammatory response was analyzed measuring the production of inflammatory cytokines (IL-6, IL-10, and TNF-alfa). Pancreatic infection was evaluated with bacterial cultures performed 24 h after the AP induction. The numbers of organisms were expressed as colony forming units (CFU) per gram. The occurrence of pancreatic infection was also analyzed and considered positive when the CFU/g was > 105. A parallel survival study was also performed. Results: Inhibition of TNF-alfa by pentoxifylline shows beneficial effects in this experimental model. The Pentoxifylline group had a statistically significant reduction of histological damage in the pancreas, inflammatory cytokines levels (IL-6, IL-10, and TNF-?), and occurrence of pancreatic infection (p < 0.05). These changes were associated with a significant reduction of mortality rate. Conclusions: Inhibition of TNF-alfa reduced local and systemic inflammatory response, reduced systemic complication as pancreatic infection, and decrease mortality rate in this model. Pentoxifylline may provide a useful therapy in the treatment of acute pancreatitis