ABSTRACT
Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) has emerged as an alternative drainage technique for patients with malignant biliary obstruction. However, few reports have discussed the occurrence of late-onset rupture of hepatic artery pseudoaneurysms following EUS-HGS. A recently available drill dilator equipped with a long screw segment was used in the dilation step of EUS-HGS. We highlight the potential concern that this long screw segment may increase the risk of damage to the hepatic artery, leading to late-onset life-threatening rupture of a pseudoaneurysm.
ABSTRACT
Monotherapy with a selective Janus kinase (JAK) inhibitor or intensive granulocyte and monocyte adsorptive apheresis (GMA) has been limited to patients with intractable ulcerative colitis (UC). No previous reports have described the efficacy including histopathological evaluations and the safety of combination therapy with upadacitinib (UPA) plus intensive GMA (two sessions per week) for intractable UC showing resistance to conventional agents and adalimumab. This retrospective study evaluated the 10-week clinical and histopathological efficacy of induction combination therapy with UPA plus intensive GMA in patients with intractable UC. Among eight patients (moderate UC, n = 1; severe UC, n = 7) who received combination therapy with UPA plus intensive GMA, 50.0% had achieved clinical remission by 10 weeks. Percentages of patients with histological-endoscopic mucosal improvement and mucosal healing at 10 weeks were 62.5% and 12.5%, respectively. After excluding one patient who discontinued treatment by week 10 because of intolerance for UPA, mean full Mayo score, endoscopic subscore and C-reactive protein concentration at baseline were 11.43 ± 0.37, 3 ± 0 and 1.29 ± 0.70 mg/dL, respectively. Corresponding values at 10 weeks were 2.28 ± 0.77 (P < 0.03), 1.14 ± 0.34 (P < 0.03) and 0.03 ± 0.008 mg/dL (P < 0.05), respectively. Adverse events of herpes zoster, temporary increase in creatinine phosphokinase and anemia were observed in one patient each. One patient discontinued combination therapy at week 4 because of temporary taste abnormality due to UPA. Combination comprising UPA plus intensive GMA appears likely to achieve satisfactory induction of clinical remission and histopathological improvement for patients with intractable UC for whom conventional agents and anti-tumor necrosis factor-α antibody have failed.
ABSTRACT
Crohn's disease is a chronic, debilitating, inflammatory bowel disease. Here, we report a critical role of phospholipase C-ß3 (PLC-ß3) in intestinal homeostasis. In PLC-ß3-deficient mice, exposure to oral dextran sodium sulfate induced lethality and severe inflammation in the small intestine. The lethality was due to PLC-ß3 deficiency in multiple non-hematopoietic cell types. PLC-ß3 deficiency resulted in reduced Wnt/ß-catenin signaling, which is essential for homeostasis and the regeneration of the intestinal epithelium. PLC-ß3 regulated the Wnt/ß-catenin pathway in small intestinal epithelial cells (IECs) at transcriptional, epigenetic, and, potentially, protein-protein interaction levels. PLC-ß3-deficient IECs were unable to respond to stimulation by R-spondin 1, an enhancer of Wnt/ß-catenin signaling. Reduced expression of PLC-ß3 and its signature genes was found in biopsies of patients with ileal Crohn's disease. PLC-ß regulation of Wnt signaling was evolutionally conserved in Drosophila. Our data indicate that a reduction in PLC-ß3-mediated Wnt/ß-catenin signaling contributes to the pathogenesis of ileal Crohn's disease.
Subject(s)
Crohn Disease , Phospholipase C beta , Wnt Signaling Pathway , Crohn Disease/pathology , Crohn Disease/metabolism , Crohn Disease/genetics , Phospholipase C beta/metabolism , Phospholipase C beta/genetics , Animals , Humans , Mice , beta Catenin/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Ileum/pathology , Ileum/metabolism , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
Allergic rhinitis (AR) is caused by type I hypersensitivity reaction in the nasal tissues. The interaction between CD300f and its ligand ceramide suppresses immunoglobulin E (IgE)-mediated mast cell activation. However, whether CD300f inhibits the development of allergic rhinitis (AR) remains elusive. We aimed to investigate the roles of CD300f in the development of AR and the effectiveness of intranasal administration of ceramide liposomes on AR in murine models. We used ragweed pollen-induced AR models in mice. Notably, CD300f deficiency did not significantly influence the ragweed-specific IgE production, but increased the frequency of mast cell-dependent sneezing as well as the numbers of degranulated mast cells and eosinophils in the nasal tissues in our models. Similar results were also obtained for MCPT5-exprssing mast cell-specific loss of CD300f. Importantly, intranasal administration of ceramide liposomes reduced the frequency of sneezing as well as the numbers of degranulated mast cells and eosinophils in the nasal tissues in AR models. Thus, CD300f-ceramide interaction, predominantly in mast cells, alleviates the symptoms and progression of AR. Therefore, intranasal administration of ceramide liposomes may be a promising therapeutic approach against AR by targeting CD300f.
Subject(s)
Liposomes , Rhinitis, Allergic , Animals , Mice , Administration, Intranasal , Sneezing , Ceramides , Disease Models, Animal , Rhinitis, Allergic/drug therapy , Immunoglobulin E , Nasal Mucosa , Mice, Inbred BALB C , OvalbuminABSTRACT
A 44-year-old woman who had been diagnosed with ulcerative colitis (UC) at 22 years old was diagnosed with severe flare-up of UC based on endoscopic findings associated with new-onset active pyoderma gangrenosum (PG) on both lower legs after she decided to discontinue UC treatment. Systemic treatment with intravenous prednisolone at 30 mg/day had achieved insufficient response to UC and PG, resulting in a diagnosis of corticosteroid-refractory UC and PG. Combination therapy with upadacitinib at 45 mg/day plus intensive granulocyte and monocyte adsorptive apheresis (GMA) was started to achieve clinical remission of UC. Ten weeks after starting this combination therapy, clinical improvement of UC was achieved with PG ulcer healing on both lower legs. A combination of upadacitinib plus intensive GMA may offer an effective therapeutic option for patients with active PG in addition to UC but has yet to be approved for induction or maintenance treatment of PG worldwide. PG is a dermatological involvement in UC patients that requires attention.
ABSTRACT
Liquefaction-induced ground deformations in reclaimed lands generated by the 1995 Hanshin-Awaji earthquake are described. Some typical examples of large ground displacements which were measured by aerial survey are introduced and their caused damage to buried pipes, foundation piles and storage tanks are presented. Characteristics of ground displacements and strains in the filled areas are investigated.(AU)