1,720,998 research outputs found

    Infliximab in Crohn's disease: a look at the (not so distant) future.

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    Although infliximab has brought about a major advance in the treatment of Crohn’s disease (CD), several questions remain unanswered. In particular, there is no consensus regarding the best timing to use it in the ideal therapeutic algorithm. Another controversial issue is whether this medication should be given or not for life once proven effective in the individual patient. Therapy with infliximab has also been associated to the development of intestinal strictures in CD: hence, some authors have discouraged its use in their presence. Finally, given its powerful antiinflammatory action, infliximab could in theory be effective in preventing postsurgical recurrence of CD, an as yet almost inescapable consequence of “curative” surgery. This review will focus on and discuss the relevant recent literature related to these issues with special regard to the efficacy and safety of infliximab in the presence of intestinal strictures and the potential role of this medication in preventing recurrence after surgery

    Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis

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    Hyaluronic acid (HA) is a glycosaminoglycan of extracellular matrix related to cell surface which interacts with various cell types. To understand the role of HA during hepatocarcinogenesis, we assessed the effect of the inhibition of HA deposition and its association with heterogeneous hepatocellular carcinoma (HCC) cells. In this study, we used transgenic mice C57BL/6J-Tg(Alb1HBV)44Bri/J (HBV-TG) and normal C57BL/6 J (WT) for in vivo study, while HCC cells Huh7 and JHH6 as in vitro models. Both models were treated with an HA inhibitor 4-methylumbelliferone (4MU). We observed that 4MU treatments in animal model down-regulated the mRNA expressions of HA-related genes Has3 and Hyal2 only in HBV-TG but not in normal WT. As observed in vivo, in HCC cell lines, the HAS2 mRNA expression was down-regulated in Huh7 while HAS3 in JHH6, both with or without the presence of extrinsic HA. Interestingly, in both models, the expressions of various cancer stem cells (CD44, CD90, CD133, and EpCAM) were also decreased. Further, histological analysis showed that 4MU treatment with dose 25 mg/kg/day reduced fibrosis, inflammation, and steatosis in vivo, in addition to be pro-apoptotic. We concluded that the inhibition of HA reduced the expressions of HA-related genes and stem cells markers in both models, indicating a possible modulation of cells-to-cells and cells-to-matrix interaction.Fil: Sukowati, Caecilia H. C.. Università di Udine; ItaliaFil: Anfuso, Beatrice. No especifíca;Fil: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Ie, Susan I.. Eijkman Institute For Molecular Biology; IndonesiaFil: Raseni, Alan. Institute for Research and Health Care Burlo Garofolo; ItaliaFil: Vascotto, Fulvia. Institute for Research and Health Care Burlo Garofolo; ItaliaFil: Avellini, Claudio. University Hospital Santa Maria della Misericordia; ItaliaFil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tiribelli, Claudio. No especifíca

    Mesenchymal chondrosarcoma of the spleen: report of a case.

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    BACKGROUND: Chondrosarcoma is a malignant tumor of chondrogenic origin and the mesenchymal type is a very rare finding. Mesenchymal chondrosarcoma tends to develop mostly in the skeleton but may also occur as a primary tumor in periosteal nervous and muscular tissues, the anterior cerebral falx, meninges, brain, maxillary sinus, eyelid, thyroid, pleura and mediastinum, while in the abdomen the most frequent locations are the kidney, retroperitoneum and even the perineum and the anogenital area. Apparently, the only splenic mesenchymal chondrosarcoma in the literature occurred in a dog. METHODS AND STUDY DESIGN: Our paper reports the case of a patient who had a diagnosis of mesenchymal chondrosarcoma of the spleen. Results. We adopted surgery as the main therapeutic procedure without achieving complete recovery but preserving a good quality of life for our patient, minimizing the repercussions of the disease on her working and relational life. CONCLUSIONS: The absence of important or invalidating symptoms and the persistence of good general conditions before and after each surgical operation encouraged us to adopt the surgical option as the most rational

    Prevention of post-surgical recurrence of Crohn's disease. A perspective [La prevenzione della recidiva post-chirurgica nel morbo di Crohn: Uno sguardo al futuro]

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    La malattia di Crohn intestinale conduce spesso a stenosi, occlusione e intervento chirurgico. Peraltro, la malattia recidiva di frequente. I farmaci tradizionali sono assai poco efficaci nel prevenire questa complicanza. I farmaci biologici sembrano invece assai promettenti e potenzialmente in grado di cambiare la gestione globale di questa malattia

    Evaluation of donor hepatic iron concentration as a factor of early fibrotic progression after liver transplantation

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    BACKGROUND/AIMS: Hepatic iron may act as an important co-morbid factor in non-hemochromatotic liver diseases, but whether it may favour fibrogenesis after liver transplantation is not known. To verify whether the hepatic iron concentration of the graft might play a role in the rapid fibrotic progression frequently observed after liver transplantation for chronic hepatitis C. METHODS: The hepatic iron concentration, measured at the time of the donor operation, was retrospectively related to the histological follow-up data of 68 recipients (49 males, 19 females), of whom 38 were hepatitis C virus positive. RESULTS: The hepatic iron concentration in donor liver biopsies ranged from 25 to 7,100 microg/gdw. After a median follow-up of 19 months, nine patients (five HCV positive) had a staging score >3. There was a significant association between a higher frequency of increasing staging and donor age >50 years. In female HCV-positive recipients, a graft hepatic iron concentration >1,200 microg/gdw was associated with fibrosis progression >0.15 fibrosis units per month (4/4 vs. 1/7, p<0.01). CONCLUSIONS: The graft hepatic iron concentration may be one of the factors involved in early fibrosis progression due to recurrent hepatitis C in female recipients

    Selective effect of infliximab on the inflammatory component of a colonic stricture in Crohn's disease

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    Although infliximab has been shown to improve the clinical course of Crohn’s disease, its effect on intestinal strictures is controversial. We describe the case of a woman with steroid-resistant colonic Crohn’s disease presenting with intermittent obstruction because of a tight stricture in the splenic flexure. Compared with uninvolved areas, biopsies showed intense edema and inflammatory cell infiltration and immunohistochemistry revealed an excess of TNF-α. Her symptoms responded promptly (CDAI went from 444 to 168) to an infliximab infusion (10 mg kg−1 BW), which also had a dramatic effect on the stricture, now presenting radiologically as a moderate residual, apparently fibrotic, narrowing of the lumen. Endoscopy and histology confirmed the resolution of inflammation and TNF-α virtually disappeared. The patient refused additional infusions and after a few months the disease recurred with features identical to the pre-treatment phase. She then opted for surgery. Histology of the resected strictured colon revealed edema, inflammation, and fibrosis, with TNF-α back to pretreatment levels. This case indicates that, in the colon, infliximab specifically relieves the TNF-α-mediated inflammatory component of the stricture while having no effect on fibrosis and suggests that the response to infliximab treatment may depend on the nature of the, stricture itself
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