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(2011)Journal ArticleSignificance : Prominent fibrosis is a major histological feature of chronic pancreatitis, a progressive necroinflammatory condition of the pancreas, most commonly associated with alcohol abuse. Patients with this disease often develop exocrine and endocrine insufficiency characterised by maldigestion and diabetes. Up until just over a decade ago, there was little understanding of the pathogenesis of pancreatic fibrosis in chronic pancreatitis. Recent Studies : In recent times, significant progress has been made in this area, mostly due to the identification, isolation and characterisation of the cells, namely pancreatic stellate cells (PSCs) that are now established as key players in pancreatic fibrogenesis. In health, PSCs maintain normal tissue architecture via regulation of the synthesis and degradation of extracellular matrix (ECM) proteins. During pancreatic injury, PSCs transform into an activated phenotype that secretes excessive amounts of the ECM proteins that comprise fibrous tissue. Critical Issues : This Review summarises current knowledge and critical aspects of PSC biology which have been increasingly well characterised over the past few years, particularly with respect to the response of PSCs to factors that stimulate or inhibit their activation and the intracellular signalling pathways governing these processes. Based on this knowledge, several therapeutic strategies have been examined in experimental models of pancreatic fibrosis, demonstrating that pancreatic fibrosis is a potentially reversible condition, at least in early stages. Future Directions : These will involve translation of the laboratory findings into effective clinical approaches to prevent/inhibit PSC activation so as to prevent, retard or reverse the fibrotic process in pancreatitis.
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(2012)Journal ArticleWhile the morphology and function of cells of the exocrine and endocrine pancreas have been studied over several centuries, one important cell type in the gland, the pancreatic stellate cell (PSC), had remained undiscovered until as recently as twenty years ago. Even after its first description in 1982, it was to be another 16 years before its biology could begin to be studied, because it was only in 1998 that methods were developed to isolate and culture PSCs from rodent and human pancreas. PSCs are now known to play a critical role in pancreatic fibrosis, a consistent histological feature of two major diseases of the pancreas - chronic pancreatitis and pancreatic cancer. In health, PSCs maintain normal tissue architecture via regulation of the synthesis and degradation of extracellular matrix (ECM) proteins. Recent studies have also implied other additional functions for PSCs as progenitor cells, immune cells or intermediaries in exocrine pancreatic secretion in humans. During pancreatic injury, PSCs transform from their quiescent phase into an activated, myofibroblast-like phenotype that secretes excessive amounts of ECM proteins leading to the fibrosis of chronic pancreatitis and pancreatic cancer. An ever increasing number of factors that stimulate and/or inhibit PSC activation via paracrine and autocrine pathways are being identified and characterized. It is also now established that PSCs interact closely with pancreatic cancer cells to facilitate cancer progression. Based on these findings, several therapeutic strategies have been examined in experimental models of chronic pancreatitis as well as pancreatic cancer, in a bid to inhibit/retard PSC activation and thereby alleviate chronic pancreatitis or reduce tumour growth in pancreatic cancer. The challenge that remains is to translate these pre-clinical developments into clinically applicable treatments for patients with chronic pancreatitis and pancreatic cancer.
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(2008)Journal ArticleA process evaluation was applied to the development and implementation of a receptive music therapy tool, with a view to promoting evidence-based practice via clear linkage from theory to practice. This music tool was required for a research project in the noisy emergency department (ED) of a large urban hospital. The process evaluation focuses on questions about the suitability, planning, application, and effectiveness of this tool used within the research project protocol. The music tool intervention was applied to fifteen selected patients who received a choice of four genre-based relaxation playlists (GRP) over a two-hour period via headphones and MP3 players. The process evaluation method utilized data sources including key informant interactive interviews, observational data, reflective practices, patient feedback and an independent music review. Responses from patients (aged 23-91 years) indicated that most patients listened to multiple genres and most patients (n=14) indicated that the music made them feel better, thereby indicating suitability and effectiveness. Independent music reviewers confirmed that the music playlists contained relaxing musical elements, based on established music therapy criteria. This project was innovative in clearly documenting a music tool development process (GRP) and in turn applying a process evaluation to systematically review both the development and implementation of the tool. In doing so, linkage from theory to practice was established, contributing to understandings about music for relaxation in healthcare.
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(2010)Journal ArticleAlcoholic pancreatitis is a major complication of alcohol abuse. The risk of developing pancreatitis increases with increasing doses of alcohol, suggesting that alcohol exerts dose-related toxic effects on the pancreas. However, it is also clear that only a minority of alcoholics develop the disease, indicating that an additional trigger may be required to initiate clinically evident pancreatic injury. It is now well established that alcohol is metabolised by the pancreas via both oxidative and non-oxidative metabolites. Alcohol and its metabolites produce changes in the acinar cells which may promote premature intracellular digestive enzyme activation thereby predisposing the gland to autodigestive injury. Pancreatic stellate cells (PSCs) are activated directly by alcohol and its metabolites and also by cytokines and growth factors released during alcohol-induced pancreatic necroinflammation. Activated PSCs are the key cells responsible for producing the fibrosis of alcoholic chronic pancreatitis. Efforts to identify clinically relevant factors that may explain the susceptibility of some alcoholics to pancreatitis have been underway for several years. An unequivocal, functionally characterised, association is yet to be identified in clinical studies, although in the experimental setting, endotoxin has been shown to trigger overt pancreatic injury and to promote disease progression in alcohol-fed animals. Thus, while the molecular effects of alcohol on the pancreas have been increasingly clarified in recent years, identification of predisposing or triggering factors remains a challenge.