Performance of Serum-Based Scores for Identification of Mild Hepatic Steatosis in HBV Mono-infected and HBV–HIV Co-infected Adults

Digestive Diseases and Sciences - There are limited data on noninvasive methods to identify hepatic steatosis in coexisting hepatitis B virus (HBV) infection. To evaluate the diagnostic performance...     

Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis

The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn’s disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD4⁺CD45RB^hi T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of Vdr-deficient IECs with the hVDR transgene completely rescued Vdr-null mice from severe colitis and death, even though the mice still maintained a hyperresponsive Vdr-deficient immune system. Mechanistically, VDR signaling attenuated PUMA induction in IECs by blocking NF-κB activation, leading to a reduction in IEC apoptosis. Together, these results demonstrate that gut epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this anticolitic activity is independent of nonepithelial immune VDR actions.     

Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice

BACKGROUND & AIMS: Eosinophilic esophagitis (EE) is frequently associated with atopic disease, including dermatitis and asthma. Data are emerging that atopic skin may provide an early entry point for antigen sensitization. We aimed to test the hypothesis that epicutaneous exposure to antigen primes for subsequent respiratory antigen-induced EE. METHODS: Wild-type and genetically engineered mice were subjected to epicutaneous antigen sensitization and the development of experimental EE, and immune responses were examined. RESULTS: We show that exposure to antigen via the epicutaneous route primes for marked eosinophilic inflammation in the esophagus triggered by a single airway antigen challenge. The development of experimental EE is associated with significant skin eosinophilia, accelerated bone marrow eosinophilopoiesis, blood eosinophilia, and large increases in serum antigen-specific immunoglobulin G1/immunoglobulin E using ovalbumin or Aspergillus fumigatus as the epicutaneous antigen. Mechanistic analysis with gene-targeted mice showed that interleukin-5 was required for esophageal eosinophilia and that interleukin-4, interleukin-13, and STAT6 contributed to a lesser extent. CONCLUSIONS: These findings provide the first evidence that epicutaneous exposure to allergens potently primes for EE via a Th2-dependent mechanism.     

Hematologic,immunologic reconstitution,and outcome of 342 autologous peripheral blood stem cell transplantations after cryopreservation in a −80°C mechanical freezer and preserved less than 6 months

BACKGROUND: Controlled‐rate freezing and storage in nitrogen is the standard technique for cryopreservation of peripheral hematopoietic progenitor cells (PHPCs) but presents high cost and dimethyl sulfoxide (DMSO) toxicity. Cryopreservation at ?80°C, by uncontrolled rate freezing with only 3.5% DMSO, preserves the functional capacities of PHPCs, produces successful engraftment, and reduces toxicity during infusion. STUDY DESIGN AND METHODS: Long‐term hematopoietic and immunologic reconstitution for 342 autografts (311 adults, 31 children) after PHPCs were cryopreserved at ?80°C was studied at 3, 6, and 12 months. The median (range) storage time of PHPCs cryopreserved was 1.7 (0.1‐5.99) months. RESULTS: Hemoglobin (Hb), white blood cells, and platelets (PLTs) reach normal values to trilineage at 12 months for 39% patients. Multivariate analysis shows a significant impact on CD34+ infused and on conditioning regimen for PLTs. Hb was influenced by growth factor administration at 3 months. Long‐term recovery is also highly dependent on blood counts (Hb, PLT, and neutrophil) at start of high‐dose chemotherapy. Only 43% of patients had reached normal lymphocyte values at 12 months after transplant, and a profound CD4+ T‐lymphocyte deficit remained, as others reported. CONCLUSION: Transplantation with PHPCs cryopreserved at ?80°C for no more than 6 months is satisfactory for long‐term hematopoietic and immunologic reconstitution, even if a profound CD4+ T lymphocyte deficit persists at 1 year. This easier and cheaper cryopreservation method also leads to successful engraftment.     

CD4+ T cells that enter the draining lymph nodes after antigen injection participate in the primary response and become central-memory cells

We explored the relationship between the time of naive CD4+ T cell exposure to antigen in the primary immune response and the quality of the memory cells produced. Naive CD4+ T cells that migrated into the skin-draining lymph nodes after subcutaneous antigen injection accounted for about half of the antigen-specific population present at the peak of clonal expansion. These late-arriving T cells divided less and more retained the central-memory marker CD62L than the T cells that resided in the draining lymph nodes at the time of antigen injection. The fewer cell divisions were related to competition with resident T cells that expanded earlier in the response and a reduction in the number of dendritic cells displaying peptide-major histocompatibility complex (MHC) II complexes at later times after antigen injection. The progeny of late-arriving T cells possessed the phenotype of central-memory cells, and proliferated more extensively during the secondary response than the progeny of the resident T cells. The results suggest that late arrival into lymph nodes and exposure to antigen-presenting cells displaying lower numbers of peptide-MHC II complexes in the presence of competing T cells ensures that some antigen-specific CD4+ T cells divide less in the primary response and become central-memory cells.     

Endoscopic ultrasound-guided endoscopic transmural drainage of pancreatic pseudocysts

BACKGROUND: Surgery is the traditional treatment for symptomatic pancreatic pseudocysts, but the morbidity is still too high. Minimally invasive endoscopic approaches have been encouraged. AIMS: To evaluate the efficacy of endoscopic ultrasound-guided endoscopic transmural drainage of pancreatic pseudocysts. METHODS: From January, 2003 to August, 2006, 31 consecutive symptomatic patients submitted to 37 procedures at the same endoscopic unit were retrospectively analysed. Chronic and acute pancreatitis were found in, respectively, 17 (54.8%) and 10 (32.3%) cases. Bulging was present in 14 (37.8%) cases. Cystogastrostomy or cystoduodenostomy were created with an interventional linear echoendoscope under endosonographic and fluoroscopic control. By protocol, only a single plastic stent, without nasocystic drain, was used. Straight or double pigtail stents were used in, respectively, 22 (59.5%) and 15 (40.5%) procedures. RESULTS: Endoscopic ultrasound-guided transmural drainage was successful in 29 (93.5%) patients. Two cases needed surgery, both due to procedure-related complications. There was no mortality related to the procedure. Twenty-four patients were followed-up longer than 4 weeks. During a mean follow-up of 12.6 months, there were six (25%) symptomatic recurrences due to stent clogging or migration, with two secondary infections. Median time for developing complications and recurrence of the collections was 3 weeks. These cases were successfully managed with new stents. Complications were more frequent in patients treated with straight stents and in those with a recent episode of acute pancreatitis. CONCLUSIONS: Endoscopic transmural drainage provides an effective approach to the management of pancreatic pseudocysts.