Jueves 21 de Febrero de 2008; 12:04hrs.

Hepatitis E Virus and Chronic Hepatitis in Organ-Transplant Recipients

 

• Nassim Kamar, Janick Selves, Jean-Michel Mansuy et al. Engl J Med. 2008 Feb 21; 358(8):811-817
  
• Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.....Más...

 

Jueves 14 de Febrero de 2008; 12:40 hrs.

 

Tumor-Node-Metastasis Staging of Pancreatic Adenocarcinoma

 

• Matthew H. G. Katz, MD, Rosa Hwang, MD, Jason B. Fleming, MD and Douglas B. Evans, MD. Published online before print February 13, 2008. CA Cancer J Clin 2008 doi: 10.3322/CA.2007.0012

• Accurate disease staging of patients with pancreatic cancer is essential to divide patients into prognostic subgroups, to allow delivery of stage-specific therapies, and to facilitate meaningful discussions between physicians and patients regarding management and expected outcomes. The tumor-node-metastasis staging system of the American Joint Commission on Cancer has undergone significant revisions over the past 2 decades. In its current form, the system places an emphasis on preoperative clinical staging and facilitates division of patients with pancreatic cancer into 4 groups based on a determination of local resectability and the presence or absence of distant disease as determined on high-quality cross-sectional imaging. A modern understanding of local tumor factors that influence technical resectability is incorporated into the algorithm. In this review, we examine the American Joint Commission on Cancer staging system, describe the rationale for its use, and demonstrate how it is a clinically relevant tool for the staging and management of patients with pancreatic cancer....Más.

 

Martes 12 de Febrero de 2008; 10:13 hrs.

Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells

• Fabián Arenas, Isabel Hervias, Miriam Úriz, Ruth Joplin, Jesús Prieto and Juan F. Medina. J. Clin. Invest. 118(2): 695-709 (2008). doi:10.1172/JCI33156.

• Primary biliary cirrhosis (PBC) is a cholestatic disease associated with autoimmune phenomena and alterations in both biliary bicarbonate excretion and expression of the bicarbonate carrier AE2. The bile acid ursodeoxycholic acid (UCDA) is currently used in treatment of cholestatic liver diseases and is the treatment of choice in PBC; however, a subset of PBC patients respond poorly to UDCA monotherapy. In these patients, a combination of UDCA and glucocorticoid therapy appears to be beneficial. To address the mechanism of this benefit, we analyzed the effects of UDCA and dexamethasone on AE2 gene expression in human liver cells from hepatocyte and cholangiocyte lineages. The combination of UDCA and dexamethasone, but not UDCA or dexamethasone alone, increased the expression of liver-enriched alternative mRNA isoforms AE2b1 and AE2b2 and enhanced AE2 activity. Similar effects were obtained after replacing UDCA with UDCA conjugates. In in vitro and in vivo reporter assays, we found that a UDCA/dexamethasone combination upregulated human AE2 alternate overlapping promoter sequences from which AE2b1 and AE2b2 are expressed. In chromatin immunoprecipitation assays, we demonstrated that combination UCDA/dexamethasone treatment induced...Más.

 

Miércoles 09 Enero 2008; 09:30 hrs.

Celiac Disease: Discovery Of Enzyme's Structure May Lead To New Treatments

ScienceDaily (Jan. 9, 2008) — Researchers have discovered a new structure for a key enzyme associated with celiac disease, a finding that could lead to the design of new medications for the common digestive disorder, according to an article scheduled for the Jan. 7 issue of Chemical & Engineering News. Celiac disease is a condition in which the stomach cannot properly digest wheat and other gluten-containing foods. The disease afflicts an estimated 2 million people in the United States alone.

In the article, C&EN Deputy Assistant Managing Editor Stu Borman notes that the disease is believed to occur when the protein gluten interacts with an enzyme called transglutaminase 2 (TG2), triggering an autoimmune reaction that damages the small intestine and causes diarrhea, abdominal pain and other symptoms. As a result, people with the disease are urged to follow a strict gluten-free diet.

Although scientists have previously obtained the X-ray crystal structure of human TG2, they have only revealed its "closed" or inactive form, the article points out. Now, Chaitan Khosla and colleagues at Stanford University report the first-ever determination of the "open" structure of the enzyme, in which its active site is accessible to substrates.

The finding that could help scientists design inhibitors of the enzyme that could serve as medications for celiac disease and other related conditions, according to the article.

Journal article: "Enzyme opens for business"

Adapted from materials provided by American Chemical Society.

Martes 08 Enero 2008; 09:56 hrs.

Genetic Background of Celiac Disease and Its Clinical Implications

Victorien M. Wolters, M.D.  and Cisca Wijmenga, Ph.D. Am J Gastroenterol 2007;102:1–6 Celiac disease (CD) is a complex genetic disorder with multiple contributing genes. Linkage studies have identified several genomic regions that probably contain CD susceptibility genes. The most important genetic factors identified are HLA-DQ2 and HLA-DQ8, which are necessary but not sufficient to predispose to CD. The associations found in non-HLA genomewide linkage and association studies are much weaker. This might be because a large number of non-HLA genes contributes to the pathogenesis of CD. Hence, the contribution of a single predisposing non-HLA gene might be quite modest. Practically all CD patients carry HLA-DQ2 or HLA-DQ8, while the absence of these molecules has a negative predictive value for CD close to 100%. Genetic risk profiles for CD would be helpful in clinical practice for predicting disease susceptibility and progression.Más.

Lunes 07 Enero 2008; 23:17 hrs.

Crohn Disease: Gene Decreases Intestinal Inflammation

ScienceDaily (Jan. 7, 2008) — There are two major types of inflammatory bowel disease (IBD), Crohn disease (CD) and ulcerative colitis (UC). Conflicting reports have indicated that the soluble factor IL-22 can have both IBD promoting and IBD controlling effects.

But now, Atsushi Mizoguchi and colleagues at Massachusetts General Hospital, Boston, have established that IL-22 ameliorates disease in a mouse model of UC.

Expression of IL-22 is much higher in the intestines of individuals with CD than UC. To investigate the role of IL-22 in IBD, the authors used a new microinjection-based strategy to deliver the gene that makes IL-22 to the walls of the intestine of mice who suffer from an intestinal disease that models UC.

Delivery of the Il-22 gene ameliorated local intestinal inflammation through enhanced mucus production. Consistent with this, when the same strategy was used to deliver a gene that makes a protein that neutralizes IL-22, IL-22--binding protein, to the walls of the intestines of normal mice it enhanced chemical-induced intestinal inflammation.

The authors therefore suggest that individuals with UC might benefit from local delivery of the IL-22 gene to their intestines.

Journal article:  IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. Journal of Clinical Investigation. January 3, 2008.