Trypsin activity governs increased susceptibility to pancreatitis in mice expressing human PRSS1R122H
Currently, an effective targeted therapy for pancreatitis is lacking. Hereditary pancreatitis (HP) is a heritable, autosomal-dominant disorder with recurrent acute pancreatitis (AP) progressing to chronic pancreatitis (CP) and a markedly increased risk of pancreatic cancer. In 1996, mutations in PRSS1 were linked to the development of HP. Here, we developed a mouse model by inserting a full-length human PRSS1R122H gene, the most commonly mutated gene in human HP, into mice. Expression of PRSS1R122H protein in the pancreas markedly increased stress signaling pathways and exacerbated AP. After the attack of AP, all PRSS1R122H mice had disease progression to CP, with similar histologic features as those observed in human HP. By comparing PRSS1R122H mice with PRSS1WT mice as well as enzymatically inactivated Dead-PRSS1R122H mice, we unraveled that increased trypsin activity is the mechanism for R122H mutation to sensitize mice to the development of pancreatitis. We further discovered that trypsin inhibition, in combination with anticoagulation therapy, synergistically prevented progression to CP in PRSS1R122H mice. These animal models help us better understand the complex nature of this disease and provide powerful tools for developing and testing novel therapeutics for human pancreatitis.
Nature Reviews Gastroenterology &Hepatology, Published online: 06 December 2019; doi:10.1038/s41575-019-0242-7An area of research suggests a role for microbiota in the pathogenesis of pancreatic diseases, such as pancreatitis, pancreatic cancer and type 1 diabetes mellitus. In this Perspectives, the authors examine the literature implicating microorganisms in diseases of the pancreas as well as the evidence of an inherent pancreatic microbiota.
ConclusionsPancreatic cancer patients with acute pancreatitis diagnosed up to 90 days before cancer diagnosis had earlier stage at diagnosis and better survival than patients without acute pancreatitis.
ConclusionsKnowledge of pancreatic surgery and management of possible complications ought to be present in the oncologic-gynecologic armamentarium. All patients should be referred to specialized, dedicated, tertiary centers in order to reduce, promptly recognize and optimally manage complications.
AbstractDipeptidyl peptidase (DPP) ‐4 inhibitors, a class of oral hypoglycemic agents, are widely used, especially in Asian populations, as they have been shown to be well‐tolerated and to cause relatively few hypoglycemic events despite exerting a potent glucose‐lowering effect by promoting endogenous insulin secretion, beside s also having extra‐pancreatic effects. Meanwhile, use of DPP‐4 inhibitors has been reported to be associated with the development of bullous pemphigoid (BP), a rare autoimmune blistering skin disease1, even though the absolute increase in the risk of development of BP is relatively low.
Conclusions: The predictive value of FiCE for pancreatic cancer prevalence was 47%. Histological confirmation with pancreatic juice cytology is necessary before surgical resection. PMID: 31744269 [PubMed - as supplied by publisher]
Pancreatic exocrine insufficiency occurs when there is insufficient production or delivery of pancreatic enzymes required for the digestion and absorption of food. It is associated with relatively poor outcomes, including reduced quality of life and survival.1 Common causes are cancer of the head/body of the pancreas, chronic pancreatitis, pancreatic resection and cystic fibrosis. It can occur following duodenectomy, gastrectomy or untreated coeliac disease via a reduction in cholecystokinin and thereby post-prandial pancreatic stimulation.
Authors: Brennan GT, Saif MW Abstract Pancreatic enzyme replacement therapy is safe and effective at treating pancreatic exocrine insufficiency. There are multiple causes of pancreatic exocrine insufficiency including chronic pancreatitis, cystic fibrosis and pancreatic cancer. Testing fecal elastase-1 level is useful for the diagnosis of pancreatic exocrine insufficiency. Starting doses of pancreatic enzyme replacement therapy should be at least 30-40,000 IU with each meal and 15-20,000 IU with snacks. pancreatic enzyme replacement therapy should be taken in divided doses throughout meals. Patients who do not resp...
Abdominal pain is common and is associated with high disease burden and health care costs in pediatric acute recurrent and chronic pancreatitis (ARP/CP). Despite the strong central component of pain in ARP/CP and the efficacy of psychological therapies for other centralized pain syndromes, no studies have evaluated psychological pain interventions in children with ARP/CP. The current trial seeks to 1) evaluate the efficacy of a psychological pain intervention for pediatric ARP/CP, and 2) examine baseline patient-specific genetic, clinical, and psychosocial characteristics that may predict or moderate treatment response.
Publication date: Available online 14 November 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Puvanesswaray Ramakrishnan, Wei Mee Loh, Subash C.B. Gopinath, Srinivasa Reddy Bonam, Ismail M. Fareez, Rhanye Mac Guad, Maw Shin Sim, Yuan Seng WuAbstractActivated pancreatic stellate cells (PSCs) have been widely accepted as a key precursor of excessive pancreatic fibrosis, which is a crucial hallmark of chronic pancreatitis (CP) and its formidable associated disease, pancreatic cancer (PC). Hence, anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs. Most of the a...
Abstract Differentiating pancreatitis from pancreatic cancer would improve diagnostic specificity, and prognosticating pancreatitis that progresses to pancreatic cancer would also improve diagnoses of pancreas pathology. The high glycolytic metabolism of pancreatic cancer can cause tumor acidosis, and different levels of pancreatitis may also have different levels of acidosis, so that extracellular acidosis may be a diagnostic biomarker for these pathologies. AcidoCEST MRI can noninvasively measure extracellular pH (pHe) in the pancreas and pancreatic tissue. We used acidoCEST MRI to measure pHe in a KC model trea...