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Environmental and lifestyle factors play an important role in the natural history of Crohn's disease and ulcerative colitis. A group of international experts from the International Organization for the Study of Inflammatory Bowel Diseases voted on a series of consensus statements to inform the management of inflammatory bowel disease (IBD). The recommendations include avoiding traditional cigarette smoking in patients with Crohn's disease or ulcerative colitis, screening for symptoms of depression, anxiety, and psychosocial stressors at diagnosis and during flares (with referral to mental health professionals when appropriate), and encouraging regular physical activity as tolerated. Patients using dietary approaches for treatment of their IBD should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation. We recommend formal assessment for obesity and nutritional deficiencies, and patients should be encouraged to maintain a normal body-mass index. A shared decision-making approach to contraception should include the consideration of IBD-related factors, and risk factors for venous thromboembolism. Long-term or frequent use of high-dose non-steroidal anti-inflammatory drugs should be avoided. For primary prevention of disease in the offspring of patients with IBD, we recommend avoiding passive exposure to tobacco, using antibiotics judiciously, and considering breastfeeding when able.

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Consultable des del TDX, Títol obtingut de la portada digitalitzada, En la enfermedad por hígado graso no alcohólico (NAFLD), la alteración en el metabolismo de lípidos, estrés oxidativo y alteración en la producción de citocinas en un hígado graso causan inflamación y fibrosis hepáticas. La obesidad y diabetes se asocian a cambios histológicos desde esteatosis simple hasta necroinflamación y fibrosis (esteatohepatitis no alcohólica o NASH), una de las manifestaciones de NAFLD. La NASH es precursora de cirrosis. La prevalencia de NAFLD y NASH es de 20 y 2-3%, respectivamente. En la actualidad no se ha destacado la efectividad de un tratamiento en particular. Sin embargo, el conocimiento de su fisiopatología (resistencia a la insulina, seguida de una lipoperoxidación hepática con afectación del parénquima) sugiere el uso de hipoglucemiantes y antioxidantes, además de la pérdida de peso. La obesidad y resistencia a la insulina, mediada por TNF-, aumentan la liberación de ácidos grasos libres (FFA) de los adipocitos, aumentando su concentración en hígado. Los FFA inducen estrés oxidativo y favorecen la lipoperoxidación, estimulando la expresión de TNF- en hepatocitos y adipocitos e induciendo así la resistencia a la insulina y fibrogénesis. No existen modelos animales que definan los cambios moleculares y fisiológicos en la transición entre esteatosis y esteatohepatitis debido a la falta de un modelo que presente todas las características clave de la NAFLD. Los modelos de animales para NASH han identificado la deficiencia de leptina y estrés oxidativo como los principales factores patogénicos de la esteatosis y esteatohepatitis. Los modelos más ilustrativos de esteatohepatitis se fundamentan en la hipótesis del "hit" múltiple, que sugiere que el hígado graso es especialmente vulnerable a oxidantes y a desarrollar esteatohepatitis cuando factores agresores generan suficientes oxidantes como para causar muerte de hepatocitos e inflamación. Así, la esteatohepatitis incrementa la sensibilidad a otros factores agresores que inducen fibrosis, In non-alcoholic fatty liver disease (NAFLD), lipid metabolism alteration, oxidative stress and alteration on cytokine production lead to liver inflammation and fibrosis. Obesity and diabetes are associated to hystological changes ranging from simple steatosis to necroinflammation and fibrosis (non-alcoholic steatohepatitis, NASH), one of the manifestations of NAFLD. NASH precedes cirrhosis. The prevalence of NAFLD and NASH is of 20 and 2-3%, respectively. At the present time, there is no single, effective treatment. However, the knowledge of its physiopathology (insulin resistance, followed by hepatic lipid peroxidation affecting the parenchima) suggests the use of hypoglicemiants and antioxidants, along with weight loss. Obesity and insulin resistance mediated by TNF- increase the liberation of free fatty acids (FFA) from adipocytes, therefore increasing their concentration in the liver. FFA induce oxidative stress, followed by lipoperoxidation, which in turn stimulates TNF- expression in hepatocytes and adipocytes and induces insulin resistance and fibrogenesis. There are no animal models that define the molecular and physiological changes occurring during the transition of steatosis to steatohepatitis due to the lack of a model that presents every feature key for the development of NAFLD. NASH animal models have identified leptin and oxidative stress as the main pathogenic factors of steatosis and esteatohepatitis. The most illustrative models of steatohepatitis are based on the multiple "hit" hypothesis, which suggests that fatty liver is particularly vulnerable to oxidants and to develop steatohepatitis when aggressive factors generate enough oxidants as to cause hepatocyte death and inflammation. Steatohepatitis increases liver sensibility to other aggresive factors inducing liver fibrosis, therefore favouring the evolution to cirrhosis. The model induced by a choline and methionine-deficient diet (CMD) underscores the importance of the increased hepatocyte C

Consultable des del TDX, Títol obtingut de la portada digitalitzada, La Enfermedad inflamatoria intestinal engloba una serie de enfermedades, siendo las más frecuentes la Colitis Ulcerosa y la Enfermedad de Crohn. Estas enfermedades de etiología desconocida y sin tratamiento curativo cursan crónicamente con periodos de remisión. Epidemiológicamente afectan a países industrializados lo que indica la influencia del factor ambiental siendo la dieta un factor clave. La evolución epidemiológica de esta enfermedad y de los hábitos alimenticios de las poblaciones con mayores índices de incidencia muestran una relación entre el aumento del consumo de grasas, especialmente de la familia n6. Los primeros datos genéticos quedaron patentes en estudios con gemelos y con familiares de enfermos. En la actualidad algunas alteraciones genéticas se asocian a distintos fenotipos de la enfermedad. Para el correcto funcionamiento del colon la mucosa intestinal compartimentaliza sus elementos de manera que se beneficia de los elementos positivos (nutrientes y flora comensal) a la vez que se protege de los posibles agentes tóxicos o patológicos del medio extraintestinal. En primera línea de interacción una monocapa epitelial constituye una barrera selectiva. Formada por células especializadas en la secreción de factores protectores y agentes antimicrobianos, y provistas de distintos receptores, el epitelio intestinal está implicado en la adquisición de la tolerancia frente a nutrientes y flora comensal mediante la información captada por estos receptores y que es transferida al compartimiento que se encuentra por debajo de esta monocapa epitelial, la lámina propia. En la lámina propia distintos tipos celulares inmunocompetentes instauran tolerancia frente a los nutrientes y a la flora comensal y estructuran una respuesta efectora frente a patógenos. La teoría más consolidada de las causas de la enfermedad inflamatoria intestinal es el reconocimiento anómalo de la flora comensal por parte del sistema inmune de la mucosa intestinal, provocando una inflamació, Inflammatory bowel disease (IBD) (Crohn's disease, ulcerative colitis and indeterminate colitis) is a chronic condition of unknown etiology with no curative treatment. It alternates periods of inflammatory activity with those of remission. This disease affects more frequently the developed countries, pointing out that there might be an environmental influence. One of the most important environmental factors that have been related to IBD is diet. There has been shown a relationship between a high fat intake (specially n6 fatty acids) with a greater IBD incidence. Another factor that is needed for this disease development is genetic susceptibility. The first associations between genetics and IBD were discovered when studies of twins and other close relatives of IBD patients were performed. Nowadays there is evidence of specific genetic alterations associated to different disease phenotypes. For a proper colonic physiology, the intestinal mucosa has developed an efficient background in order to obtain benefits from positive elements such as nutrients and commensal bacteria, and, at the same time, protecting itself from extraintestinal toxic and pathologic agents. The first line acts as a selective barrier and is constituted of an epithelial monolayer. Different specialized cells constitute the epithelial barrier. These cells secrete protective factors such as antimicrobial agents. This epithelial barrier works in tolerance acquisition to nutrients and commensal bacteria. The extraepitelial information is transferred to lamina propria situated under epithelial layer through epithelial receptors. Different immunological cells constitute the lamina propia. This compartment acts tolerating nutrients and comensal flora, and is implicated in the effector response to pathogens. Although disease causes are unknown, the implicated factors seem to be clear. The consolidated theory about causes of IBD is the abnormal recognition of commensal flora by the intestinal immunological

OBJECTIVES: Inflammatory bowel disease (IBD), e. g., Crohns disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD. METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied. RESULTS: The previously reported "high-risk" haplotype (A) was associated with IBD (P = 0.001) (OR = 1.25 (1.05-1.50)) and CD (P = 0.02) (OR = 1.31 (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A. CONCLUSIONS: This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.

Consultable des del TDX, Títol obtingut de la portada digitalitzada, Introducció: El càncer colorectal és un dels càncers més freqüentes del nostre país així com en la majoria de societats occidentals. Els factors mebiambientals juguen un paper determinant en el seu desenvolupament. Els nutrients i específicament els greixos, estarien entre els factors més destacats. Tot i que a Groenlàndia, Finlàndia i algunes zones mediterrànies, les dietes tenen un alt contingut en greix, la incidència de càncer colorrectal és relativament baixa en comparació amb la resta de països occidentals. Una important diferència dietètica és l'elevat consum de peix i oli de peix (ric en els àcids grassos n-3, eicosapentaeonic (EPA) i docosahexaenoic (DHA)) en el cas del països nòrdics i l'oli de oliva (ric en àcid oleic C18:1, n-9) a la conca mediterrània. La tesi es basa en la hipòtesi que «l'oli de peix i el d'oliva són capaços de modular el desenvolupament del càncer colorrectal. Objectius: L'objectiu de l'estudi va ser avaluar els mecanismes pels quals aquests olis realitzaven aquesta modulació i la implicació dels àcids grassos presents en aquests. Resultats: Per respondre els objectius plantejats es van utilitzar dues estratègies d'estudi. La primera es basa en estudis in vitro amb línies cel·lulars d'adenocarcinoma colorectal, Caco-2 i Ht-29. L'altra es basa en l'estudi de l'efecte dels diferents nutrients en un model animal d'inducció de la carcinogènesi colorectal. L'oli de peix i l'oli d'oliva indueixen la diferenciació en cèl·lules Caco-2. Com a resultat de la diferenciació aquestes cèl·lules comencen a expressar els enzims Sucrasa-Isomaltasa i la Dipeptidilpeptidasa IV. La regulació de l'homeòstasi del teixit colònic depèn d'una estreta relació entre la proliferació cel·lular i l'apoptosi o mort cel·lular programada Mitjançant estudis d'incorporació de timidina tritiada, hem demostrat que l'oli de peix té un important efecte inhibidor de la proliferació de les cèl·lules Caco-2 i HT-29. Sembla ser, que aquests efectes són deguts als àcids grassos, Introduction: Colorectal cancer is one of the most frequent cancers in our country as well as in most of the occidental societies. Environmental factors play a crucial role on its development. Nutrients and in concrete fat seems to be one of the most determinant components. Although relatively high fat diets are consumed in Greenland, Finland and some Mediterranean areas, colorectal cancer incidence remains relatively low there. An important difference between these regions and the rest of the western countries is the much higher consumption of fish and fish oil (rich in the n-3 fatty acids eicosapentaenoic, C20:5 and docosahexaenoic, C22:6) in the case of the Northern countries, and fish and olive oil (containing mostly oleic acid, C18:1, n-9) down in the Mediterranean basin. The hypothesis of our study was if «fish oil and olive oil are able to modulate the colorectal cancer development». Aims: The objectives of this study were to evaluate the mechanisms implicated in the modulation of cancer by these oils and determine the implications of its fatty acids. Results: In order to answer the objectives mentioned above we followed two study strategies. First, we performed: in vitro studies using adenocarcinoma cell lines, Caco-2 and Ht-29. The other one is the study of the effects of several nutrients in an animal model of carcinogenesis induction . Fish oil and olive oil induced the differentiation of Caco-2 cells. As a result of this differentiation, the cells began to express Sucrase-Isomaltase and Dipeptydilpeptidase IV enzymes. Homeostasis regulation of colonic tissue depends on a tightly relationship between cell proliferation and cell loss, through apoptosis. With [3H] thymidine incorporation studies, we demonstrated that fish oil has an important inhibitor effect on the proliferation of Caco-2 and HT-29 cells. It seems that this effect is caused by EPA i DHA (n-3 fatty acids present in fish oil). The most important effect on the development of colorectal cancer

Consultable des del TDX, Títol obtingut de la portada digitalitzada, Es requereix la Interleucina 6 (IL-6) per a la regeneració normal del fetge però la font específica d'aquest factor de creixement roman desconeguda. En aquest estudi s'ha investigat si el senyal s'origina del macròfag resident al fetge, la cèl.lula de Kupffer. Per a dur a terme aquesta recerca, s'ha utilitzat un model animal de trasplantament de moll d'os en ratolins. Específicament, s'han remplaçat les cèl.lules derivades del moll d'os del receptor que inclouen, per tant, les cèl.lules de Kupffer, per les del donant amb les seves corresponents característiques genotípiques. Els receptors, en aquest cas, eren ratolins deficients genèticament en la seva capacitat de producció d'IL-6, ratolins knockout IL-6 (KO IL-6), i dels que havia quedat abastament demostrat a la literatura que eren incapaços de tenir una regeneració hepàtica normal. Aquests ratolins s'irradiaven amb una dosi coneguda letal de 1000 RADs i se'ls rescatava amb el trasplantament del moll d'os de ratolins de la mateixa soca però genèticament normals (IL-6 +/+), és a dir amb capacitat de producció d'IL-6. D'aquesta manera, es pretén la creació d'un animal quimera, en el que l'única font d'IL-6 provingués de les seves cèl.lules derivades del moll d'os. Es trasplantaven un total de 107 cèl.lules. Inversament, es feia el mateix procediment amb el trasplantament de cèl.lules d'animals KO a animals genotípicament normals. L'èxit de l'empeltament es demostrava inicialment amb la supervivència de l'animal més enllà de 6 setmanes. La comprovació experimental d'aquest empeltament es feia inicialment amb la demostració del fragment SRY del cromosoma Y en els fetges d'animals femella als que s'havien trasplantat cèl.lules d'animals mascle. Posteriorment, s'objectivava l'expressió in situ d'IL-6 per part de les cèl.lules de Kupffer en els animals receptors KO i la producció d'IL-6 per part dels esplenòcits d'aquest animals després de l'estimulació amb lipopolisacàrid. L'aïllament de les cèl.lules de Kupffer en ani, Interleukin-6 (IL-6) is required for normal liver regeneration, but the specific cellular source of this growth factor is unknown. We investigated whether this signal originates from the resident macrophage, the Kupffer cell. Using a murine model of bone marrow transplantation, we replaced recipient bone marrow-derived cells, including Kupffer cells, with cells of donor genetic phenotype. Recipients deficient in IL-6 (IL-6(-/-)) were lethally irradiated, then rescued with 107donor bone marrow cells capable of expressing IL-6 (IL-6(+/+)). Conversely, IL-6(+/+) recipients received IL-6(-/-) marrow. Successful engraftment was measured by the presence of the Y chromosome SRY locus in the livers of female recipients receiving male marrow, in situ IL-6 expression by Kupffer cells, and up-regulation of IL-6 in splenocytes after activation with lipopolysaccharide (LPS). Kupffer cell isolation in IL-6(-/-) females receiving IL-6(+/+) male marrow clearly showed the presence of the SRY locus and IL-6 allele, whereas males receiving female marrow demonstrated IL-6 disrupted gene and no SRY, confirming the extent of replacement. Replacement of these cells in IL-6(-/-) mice with IL-6(+/+) bone marrow successfully restored the regenerative response after partial hepatectomy (PHx) as indicated by signal transduction and activator of transcription 3 (STAT3) activation and hepatocyte DNA replication. Alternatively, complete replacement of Kupffer cells in IL-6(+/+) mice by transplantation with IL-6(-/-) cells significantly inhibited liver regeneration and was partially restored by administration of IL-6. In order to demonstrate that the only bone-marrow-derived cells needed to support a normal hepatic regeneration are the ones from macrophage origin, the regenerative response in some immunodeficient animals was assessed. Previously, the presence of the intrahepatic extrathymic population of immune cells called T Natural Killer lymphocytes was ruled out by flux citometry. A partial he