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| 1 | Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases显示文摘Inflammatory bowel diseases(IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor(TNF)-α, interleukin(IL)-1b, IL-8, and IL-17A], anti-inflammatory cytokines(IL-4 and IL-13), and immunoregulatory cytokines(IL-10 and transforming growth factors b) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide(NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase(iN OS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iN OS. A positive correlation between NO production and increased pro-inflammatory cytokine levels(TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD. | Imene Soufli Ryma Toumi Hayet Rafa Chafia Touil-Boukoffa | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，3： | 30 |
| 2 | Esophageal motility abnormalities in gastroesophageal reflux disease显示文摘Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophagealmotility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from nonerosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted. | Irene Martinucci Nicola de Bortoli Maria Giacchino Giorgia Bodini Elisa Marabotto Santino Marchi Vincenzo Savarino Edoardo Savarino | 2014 | World Journal of Gastrointestinal Pharmacology and Therapeutics2014，5，2： | 24 |
| 3 | Eosinophilic gastroenteritis:Approach to diagnosis and management显示文摘Eosinophilic gastroenteritis(EGE) is a rare and benign inflammatory disorder that predominantly affects the stomach and the small intestine.The disease is divided into three subtypes(mucosal,muscular and serosal) according to klein's classification,and its manifestations are protean,depending on the involved intestinal seg-ments and layers.Hence,accurate diagnosis of EGE poses a significant challenge to clinicians,with evidence of the following three criteria required:Suspicious clinical symptoms,histologic evidence of eosinophilic infiltration in the bowel and exclusion of other pathologies with similar findings.In this review,we designed and applied an algorithm to clarify the steps to follow for diagnosis of EGE in clinical practice.The management of EGE represents another area of debate.Prednisone remains the mainstay of treatment;however the disease is recognized as a chronic disorder and one that most frequently follows a relapsing course that requires maintenance therapy.Since prolonged steroid treatment carries of risk of serious adverse effects,other options with better safety profiles have been proposed;these include budesonide,dietary restrictions and steroid-sparing agents,such as leukotriene inhibitors,azathioprine,anti-histamines and mast-cell stabilizers.Single cases or small case series have been reported in the literature for all of these options,and we provide in this review a summary of these various therapeutic modalities,placing them within the context of our novel algorithm for EGE management according to disease severity upon presentation. | Antoine Abou Rached Weam El Hajj | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，4： | 24 |
| 4 | Understanding and treating refractory constipation显示文摘Chronic constipation is a frequently encountered disorder in clinical practice. Most constipated patients benefit from standard medical approaches. However, current therapies may fail in a proportion of patients. These patients deserve better evaluation and thorough investigations before their labeling as refractory to treatment. Indeed, several cases of apparent refractoriness are actually due to misconceptions about constipation, poor basal evaluation (inability to recognize secondary causes of constipation, use of constipating drugs) or inadequate therapeutic regimens. After a careful reevaluation that takes into account the above factors, a certain percentage of patients can be defined as being actually resistant to first-line medical treatments. These subjects should firstly undergo specific diagnostic examination to ascertain the subtype of constipation. The subsequent therapeutic approach should be then tailored according to their underlying dysfunction. Slow transit patients could benefit from a more robust medical treatment, based on stimulant laxatives (or their combination with osmotic laxatives, particularly over the short-term), enterokinetics (such as prucalopride) or secretagogues (such as lubiprostone or linaclotide). Patients complaining of obstructed defecation are less likely to show a response to medical treatment and might benefit from biofeedback, when available. When all medical treatments prove to be unsatisfactory, other approaches may be attempted in selected patients (sacral neuromodulation, local injection of botulinum toxin, anterograde continence enemas), although with largely unpredictable outcomes. A further although irreversible step is surgery (subtotal colectomy with ileorectal anastomosis or stapled transanal rectal resection), which may confer some benefit to a few patients with refractoriness to medical treatments. | Gabrio Bassotti Corrado Blandizzi | 2014 | World Journal of Gastrointestinal Pharmacology and Therapeutics2014，5，2： | 23 |
| 5 | Local ablative treatments for hepatocellular carcinoma:An updated review显示文摘Ablative treatments currently represent the first-line option for the treatment of early stage unresectable hepatocellular carcinoma(HCC).Furthermore,they are effective as bridging/downstaging therapies before orthotopic liver transplantation.Contraindications based on size,number,and location of nodules are quite variable in literature and strictly dependent on local expertise.Among ablative therapies,radiofrequency ablation(RFA) has gained a pivotal role due to its efficacy,with a reported 5-year survival rate of 40%-70%,and safety.Although survival outcomes are similar to percutaneous ethanol injection,the lower local recurrence rate stands for a wider application of RFA in hepato-oncology.Moreover,RFA seems to be even more cost-effective than liver resection for very early HCC(single nodule ≤ 2 cm) and in the presence of two or three nodules ≤ 3 cm.There is increasing evidence that combining RFA to transarterial chemoembolization may increase the therapeutic benefit in larger HCCs without increasing the major complication rate,but more robust prospective data is still needed to validate these pivotal findings.Among other thermal treatments,microwave ablation(MWA) uses high frequency electromagnetic energy to induce tissue death via coagulation necrosis.In comparison to RFA,MWA has several theoretical advantages such as a broader zone of active heating,higher temperatures within the targeted area in a shorter treatment time and the lack of heatsink effect.The safety concerns raised on the risks of this procedure,due to the broader and less predictable necrosis areas,have been recently overcome.However,whether MWA ability to generate a larger ablation zone will translate into a survival gain remains unknown.Other treatments,such as high-intensity focused ultrasound ablation,laser ablation,and cryoablation,are less investigated but showed promising results in early HCC patients and could be a valuable therapeutic option in the next future. | Antonio Facciorusso Gaetano Serviddio Nicola Muscatiello | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，4： | 23 |
| 6 | Therapy of gallstone disease:What it was,what it is,what it will be显示文摘Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones.The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol gallstones.In this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis. | Piero Portincasa Agostino Di Ciaula Leonilde Bonfrate David QH Wang | 2012 | World Journal of Gastrointestinal Pharmacology and Therapeutics2012，3，2： | 21 |
| 7 | Pathogenic mechanisms of pancreatitis显示文摘Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pan-creatitis characterized by marked stroma formation with a high number of infiltrating granulocytes(such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells(PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in pro-moting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways(i.e., Transforming growth factor-β/SMAD, mitogen--activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin(IL)-1, IL-1β, IL-6, IL--8 IL-10, IL-18, IL--33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for pancreatic pathogenesis. | Murli Manohar Alok Kumar Verma Sathisha Upparahalli Venkateshaiah Nathan L Sanders Anil Mishra | 2017 | World Journal of Gastrointestinal Pharmacology and Therapeutics2017，8，1： | 21 |
| 8 | Phage therapy: An alternative to antibiotics in the age of multi-drug resistance显示文摘The practice of phage therapy, which uses bacterial viruses(phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins against multidrug-resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage-or antibiotic-based, each have relative advantages and disadvantages; accordingly, many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infection. Although much about phages and human health is still being discovered, the time to take phage therapy serious again seems to be rapidly approaching. | Derek M Lin Britt Koskella Henry C Lin | 2017 | World Journal of Gastrointestinal Pharmacology and Therapeutics2017，8，3： | 20 |
| 9 | Ocular drug delivery systems:An overview显示文摘The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration,especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal,dynamic and static ocular barriers. Also,therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades,ocular drug delivery research acceleratedly advanced towards developing a novel,safe and patient compliant formulation and drug delivery devices/techniques,which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also,it includes development of conventional topical formulations such as suspensions,emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand,for posterior ocular delivery,research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreo-retinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topicaldrops. Also,these novel devices and/or formulations are easy to formulate,no/negligibly irritating,possess high precorneal residence time,sustain the drug release,and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also,recent developments with other ocular drug delivery strategies employing in situ gels,implants,contact lens and microneedles have been discussed. | Ashaben Patel Kishore Cholkar Vibhuti Agrahari Ashim K Mitra | 2013 | World Journal of Pharmacology2013，2，2： | 18 |
| 10 | Update on the management of gastrointestinal varices显示文摘Cirrhosis of liver is a major problem in the western world. Portal hypertension is a complication of cirrhosis and can lead to a myriad of pathology of which include the development of porto-systemic collaterals. Gastrointestinal varices are dilated submucosal veins, which often develop at sites near the formation of gastroesophageal collateral circulation. The incidence of varices is on the rise due to alcohol and obesity. The most significant complication of portal hypertension is life-threatening bleeding from gastrointestinal varices, which is associated with substantial morbidity and mortality. In addition, this can cause a significant burden on the health care facility. Gastrointestinal varices can happen in esophagus, stomach or ectopic varices. There has been considerable progress made in the understanding of the natural history, pathophysiology and etiology of portal hypertension. Despite the development of endoscopic and medical treatments, early mortality due to variceal bleeding remains high due to significant illness of the patient. Recurrent variceal bleed is common and in some cases, there is refractory variceal bleed. This article aims to provide a comprehensive review of the management of gastrointestinal varices with an emphasis on endoscopic interventions, strategies to handle refractory variceal bleed and newer endoscopic treatment modalities. Early treatment and improved endoscopic techniques can help in improving morbidity and mortality. | Umesha Boregowda Chandraprakash Umapathy Nasir Halim Madhav Desai Arpitha Nanjappa Subramanyeswara Arekapudi Thimmaiah Theethira Helen Wong Marina Roytman Shreyas Saligram | 2019 | World Journal of Gastrointestinal Pharmacology and Therapeutics2019，10，1： | 18 |
| 11 | Diagnosis and therapy of non-variceal upper gastrointestinal bleeding显示文摘Non-variceal upper gastrointestinal bleeding(UGIB) is defined as bleeding proximal to the ligament of Treitz in the absence of oesophageal, gastric or duodenal varices. The clinical presentation varies according to the intensity of bleeding from occult bleeding to melena or haematemesis and haemorrhagic shock. Causes of UGIB are peptic ulcers, Mallory-Weiss lesions,erosive gastritis, reflux oesophagitis, Dieulafoy lesions or angiodysplasia. After admission to the hospital a structured approach to the patient with acute UGIB that includes haemodynamic resuscitation and stabilization as well as pre-endoscopic risk stratification has to be done. Endoscopy offers not only the localisation of the bleeding site but also a variety of therapeutic measures like injection therapy, thermocoagulation or endoclips. Endoscopic therapy is facilitated by acid suppression with proton pump inhibitor(PPI) therapy. These drugs are highly effective but the best route of application(oral vs intravenous) and the adequate dosage are still subjects of discussion. Patients with ulcer disease are tested for Helicobacter pylori and eradication therapy should be given if it is present. Non-steroidal antiinflammatory drugs have to be discontinued if possible. If discontinuation is not possible, cyclooxygenase-2 inhibitors in combination with PPI have the lowest bleeding risk but the incidence of cardiovascular events is increased. | Erwin Biecker | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 17 |
| 12 | Role of macrophages in the progression of acute pancreatitis显示文摘In addition to pancreatic cells,other inflammatory cell populations contribute to the generation of inflammatory mediators during acute pancreatitis.In particular,macrophages could be activated by mediators released during pancreatitis by a damaged pancreas.It has been reported that peritoneal macrophages,alveolar macrophages and Kupffer cells become activated in different stages of severe acute pancreatitis.However,macrophages display remarkable plasticity and can change their physiology in response to environmental cues.Depending on their microenvironmental stimulation,macrophages could follow different activation pathways resulting in marked phenotypic heterogeneity.This ability has made these cells interesting therapeutical targets and several approaches have been assayed to modulate the progression of inflammatory response secondary to acute pancreatitis.However,despite the recent advances in the modulation of macrophage function in vivo,the therapeutical applications of these strategies require a better understanding of the regulation of gene expression in these cells. | Sabrina Gea-Sorlí Daniel Closa | 2010 | World Journal of Gastrointestinal Pharmacology and Therapeutics2010，1，5： | 16 |
| 13 | Visceral hypersensitivity and electromechanical dysfunction as therapeutic targets in pediatric functional dyspepsia显示文摘Functional gastrointestinal disorders(FGID) are common clinical syndromes diagnosed in the absence of biochemical,structural,or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age,geography,and culture. Etiology of abdominal pain associated FGIDs,including functional dyspepsia(FD),remains incompletely understood,but growing evidence implicates the importance of visceral hypersensitivity and electromechanical dysfunction. This manuscript explores data supporting the role of visceral hypersensitivity and electromechanical dysfunction in FD,with focus on pediatric data when available,and provides a summary of potential therapeutic targets. | John M Rosen Jose T Cocjin Jennifer V Schurman Jennifer M Colombo Craig A Friesen | 2014 | World Journal of Gastrointestinal Pharmacology and Therapeutics2014，5，3： | 16 |
| 14 | Influence of environmental factors in the development of inflammatory bowel diseases显示文摘Idiopathic inflammatory bowel diseases(IBD), Crohn's disease(CD) and ulcerative colitis(UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its intestinal microflora through an environmental stimulus. Urbanization and industrialization are associated with IBD. Epidemiological data, clinical observations and family/immigrants studies indicate the significance of environmental influence in the development of IBD. Some environmental factors have a different effect on the subtypes of IBD. Smoking and appendectomy is negatively associated with UC, but they are aggravating factors for CD. A westernized high fat diet, full of refined carbohydrates is strongly associated with the development of IBD, contrary to a high in fruit, vegetables and polyunsaturated fatty acid-3 diet that is protective against these diseases. High intake of nonsteroidal antiinflammatory drug and oral contraceptive pills as well as the inadequacy of vitamin D leads to an increased risk for IBD and a more malignant course of disease. Moreover, other factors such as air pollution, psychological factors, sleep disturbances and exercise influence the development and the course of IBD. Epigenetic mechanism like DNA methylation, histone modification and altered expression of miR NAS could explain the connection between genes and environmental factors in triggering the development of IBD. | Evangelia Legaki Maria Gazouli | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，1： | 15 |
| 15 | Diagnosis and treatment of gastroesophageal reflux disease显示文摘Gastroesophageal reflux disease(GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical,atypi-cal and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms,these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations,further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis,peptic stricture,Barrett's esophagus,esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification,medical therapy and surgical therapy. Life-style modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids,histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy,others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gas-troesophageal reflux disease. | Raul Badillo Dawn Francis | 2014 | World Journal of Gastrointestinal Pharmacology and Therapeutics2014，5，3： | 14 |
| 16 | Mesalazine preparations for the treatment of ulcerative colitis: Are all created equal?显示文摘Oral mesalazine(also known as mesalamine) is a 5-aminosalicylic acid compound used in the treatment of mild to moderate ulcerative colitis, with high rates of efficacy in induction and maintenance of remission.The therapeutic effect of mesalazine occurs topically at the site of diseased colonic mucosa. A myriad of oral mesalazine preparations have been formulated with various drug delivery methods to minimize systemic absorption and maximise drug availability at the inflamed colonic epithelium. It remains unclear whether different oral mesalazine formulations are bioequivalent. This review aims to evaluate the differences between mesalazine formulations based on the currently available literature and explore factors which may influence the selection of one agent above another. | Bei Ye Daniel R van Langenberg | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 14 |
| 17 | Bilirubin in coronary artery disease:Cytotoxic or protective?显示文摘Bilirubin has traditionally been considered a cytotoxic waste product.However,recent studies have shown bilirubin to have anti-oxidant,anti-inflammatory,vasodilatory,anti-apoptotic and anti-proliferative functions.These properties potentially confer bilirubin a new role of protection especially in coronary artery disease(CAD),which is a low grade inflammatory process exacerbated by oxidative stress.In fact,recent literature reports an inverse relationship between serum concentration of bilirubin and the presence of CAD.In this article,we review the current literature exploring the association between levels of bilirubin and risk of CAD.We conclude that current evidence is inconclusive regarding the protective effect of bilirubin on CAD.A causal relationship between low serum bilirubin level and increased risk of CAD is not currently established. | Nancy Gupta Tavankit Singh Rahul Chaudhary Sushil K Garg Gurprataap Singh Sandhu Varun Mittal Rahul Gupta Roxana Bodin Sachin Sule | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，4： | 14 |
| 18 | Proton pump inhibitor-associated pneumonia:Not a breath of fresh air after all?显示文摘Over the past two decades,proton pump inhibitors (PPIs)have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders.Unfortunately,this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings.While generally well-tolerated,research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired(CAP)and hospital-acquired pneumonias(HAP).The mechanism behind PPI-associated pneumonia may be multifactorial,but is thought to stem from compromising the stomach's'acid mantle'against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated.A secondary postulate is that PPIs,through their inhibition of extra-gastric H+/K+ATPase enzymes,may reduce the acidity of the upper aerodigestive tract,thus resulting in increased bacterial colonization of the larynx,esophagus and lungs.To date,several retrospective case control studies have been published looking at the association between PPI use and CAP.Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia,but only two could define a dose-response re-lationship.Furthermore,other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP,we reviewed two retrospective cohort studies and one prospective study.One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy,while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H2RAs.The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H2RAs.In conclusion,the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H2RAs,but the findings are not consistent across all studies.Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP.Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations.In the interim,it appears prudent to limit the use of PPIs to situations where they are clinically indicated and,in such cases,use them at the lowest effective dose.In the case of prescribing for stress ulcer prophylaxis in ICU patients,perhaps H2RAs should be used as the preferred agents over PPIs. | Alexander L Fohl Randolph E Regal | 2011 | World Journal of Gastrointestinal Pharmacology and Therapeutics2011，2，3： | 12 |
| 19 | Inflammatory role of the acinar cells during acute pancreatitis显示文摘Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and f inally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the f inal balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/ phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the f irst inflammatory signals which can mediate the activation and recruitment of circulating inflammatorycells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis. | Isabel De Dios | 2010 | World Journal of Gastrointestinal Pharmacology and Therapeutics2010，1，1： | 11 |
| 20 | Stress ulcer prophylaxis guidelines:Are they being implemented in Lebanese health care centers?显示文摘AIM:To evaluate the current practice of stress ulcer prophylaxis (SUP) in Lebanese Health care centers.METHODS:A multi-center prospective chart review study was conducted over 8 mo.A questionnaire was distributed to pharmacy students who collected data on demographics,SUP medications,dose,route,duration and associated risk factors.The appropriateness of SUP use was determined as per American Society of Health-System Pharmacists guidelines.Institutional review board approval was obtained from each hospital center.RESULTS:A total of 1004 patients were included.67% of the patients who received prophylaxis did not have an indication for SUP.The majority (71.6%) of the patients who were administered parenteral drugs can tolerate oral medications.Overall,the regimen of acid-suppressant drugs was suboptimal in 87.6% of the sample.This misuse was mainly observed in non-teaching hospitals.CONCLUSION:This study highlighted the need,in Lebanese hospitals,to establish clinical practice guidelines for the use of SUP;mainly in non-critical care settings. | Abeer Zeitoun Maya Zeineddine Hani Dimassi | 2011 | World Journal of Gastrointestinal Pharmacology and Therapeutics2011，2，4： | 10 |
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