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Pallagi P, Tóth E, Görög M, Venglovecz V, Madácsy T, Varga Á, Molnár T, Papp N, Szabó V, Kúthy-Sutus E, Molnár R, Ördög A, Borka K, Schnúr A, Kéri A, Kajner G, Csekő K, Ritter E, Csupor D, Helyes Z, Galbács G, Szentesi A, Czakó L, Rakonczay Z, Takács T, Maléth J, Hegyi P. Heavy metals in cigarette smoke strongly inhibit pancreatic ductal function and promote development of chronic pancreatitis. Clin Transl Med 2024; 14:e1733. [PMID: 38877637 PMCID: PMC11178517 DOI: 10.1002/ctm2.1733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 04/30/2024] [Accepted: 05/21/2024] [Indexed: 06/16/2024] Open
Abstract
BACKGROUND AND AIMS Smoking is recognised as an independent risk factor in the development of chronic pancreatitis (CP). Cystic fibrosis transmembrane conductance regulator (CFTR) function and ductal fluid and bicarbonate secretion are also known to be impaired in CP, so it is crucial to understand the relationships between smoking, pancreatic ductal function and the development of CP. METHODS We measured sweat chloride (Cl-) concentrations in patients with and without CP, both smokers and non-smokers, to assess CFTR activity. Serum heavy metal levels and tissue cadmium concentrations were determined by mass spectrometry in smoking and non-smoking patients. Guinea pigs were exposed to cigarette smoke, and cigarette smoke extract (CSE) was prepared to characterise its effects on pancreatic HCO3 - and fluid secretion and CFTR function. We administered cerulein to both the smoking and non-smoking groups of mice to induce pancreatitis. RESULTS Sweat samples from smokers, both with and without CP, exhibited elevated Cl- concentrations compared to those from non-smokers, indicating a decrease in CFTR activity due to smoking. Pancreatic tissues from smokers, regardless of CP status, displayed lower CFTR expression than those from non-smokers. Serum levels of cadmium and mercury, as well as pancreatic tissue cadmium, were increased in smokers. Smoking, CSE, cadmium, mercury and nicotine all hindered fluid and HCO3 - secretion and CFTR activity in pancreatic ductal cells. These effects were mediated by sustained increases in intracellular calcium ([Ca2+]i), depletion of intracellular ATP (ATPi) and mitochondrial membrane depolarisation. CONCLUSION Smoking impairs pancreatic ductal function and contributes to the development of CP. Heavy metals, notably cadmium, play a significant role in the harmful effects of smoking. KEY POINTS Smoking and cigarette smoke extract diminish pancreatic ductal fluid and HCO3 - secretion as well as the expression and function of CFTR Cd and Hg concentrations are significantly higher in the serum samples of smokers Cd accumulates in the pancreatic tissue of smokers.
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Affiliation(s)
- Petra Pallagi
- Department of Medicine, University of Szeged, Szeged, Hungary
- MTA-SZTE Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary
- HCEMM-SZTE Molecular Gastroenterology Research Group, University of Szeged, Szeged, Hungary
| | - Emese Tóth
- Department of Medicine, University of Szeged, Szeged, Hungary
- Department of Theoretical and Integrative Health Sciences, University of Debrecen, Szeged, Hungary
- Translational Pancreatology Research Group, Interdisciplinary Centre of Excellence for Research Development and Innovation, University of Szeged, Szeged, Hungary
| | - Marietta Görög
- Department of Medicine, University of Szeged, Szeged, Hungary
- MTA-SZTE Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary
| | - Viktória Venglovecz
- Translational Pancreatology Research Group, Interdisciplinary Centre of Excellence for Research Development and Innovation, University of Szeged, Szeged, Hungary
- Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
| | - Tamara Madácsy
- Department of Medicine, University of Szeged, Szeged, Hungary
- MTA-SZTE Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary
- HCEMM-SZTE Molecular Gastroenterology Research Group, University of Szeged, Szeged, Hungary
| | - Árpád Varga
- Department of Medicine, University of Szeged, Szeged, Hungary
- MTA-SZTE Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary
- HCEMM-SZTE Molecular Gastroenterology Research Group, University of Szeged, Szeged, Hungary
| | - Tünde Molnár
- MTA-SZTE Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary
- HCEMM-SZTE Molecular Gastroenterology Research Group, University of Szeged, Szeged, Hungary
| | - Noémi Papp
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Viktória Szabó
- MTA-SZTE Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary
- HCEMM-SZTE Molecular Gastroenterology Research Group, University of Szeged, Szeged, Hungary
| | - Enikő Kúthy-Sutus
- MTA-SZTE Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary
- HCEMM-SZTE Molecular Gastroenterology Research Group, University of Szeged, Szeged, Hungary
| | - Réka Molnár
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Attila Ördög
- Department of Plant Biology, University of Szeged, Szeged, Hungary
| | - Katalin Borka
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Andrea Schnúr
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Albert Kéri
- Department of Molecular and Analytical Chemistry, University of Szeged, Szeged, Hungary
| | - Gyula Kajner
- Department of Molecular and Analytical Chemistry, University of Szeged, Szeged, Hungary
| | - Kata Csekő
- Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary
- National Laboratory of Drug Research and Development (Pharmalab), Budapest, Hungary
| | - Emese Ritter
- Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary
- National Laboratory of Drug Research and Development (Pharmalab), Budapest, Hungary
| | - Dezső Csupor
- Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
- Institute for Translational Medicine, University of Pécs, Pécs, Hungary
| | - Zsuzsanna Helyes
- Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary
- National Laboratory of Drug Research and Development (Pharmalab), Budapest, Hungary
- Eötvös Loránd Research Network Chronic Pain Research Group, University of Pécs, Pécs, Hungary
| | - Gábor Galbács
- Department of Molecular and Analytical Chemistry, University of Szeged, Szeged, Hungary
| | - Andrea Szentesi
- Institute for Translational Medicine, University of Pécs, Pécs, Hungary
| | - László Czakó
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Zoltán Rakonczay
- Department of Pathophysiology, University of Szeged, Szeged, Hungary
| | - Tamás Takács
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - József Maléth
- Department of Medicine, University of Szeged, Szeged, Hungary
- MTA-SZTE Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary
- HCEMM-SZTE Molecular Gastroenterology Research Group, University of Szeged, Szeged, Hungary
| | - Péter Hegyi
- Translational Pancreatology Research Group, Interdisciplinary Centre of Excellence for Research Development and Innovation, University of Szeged, Szeged, Hungary
- Institute for Translational Medicine, University of Pécs, Pécs, Hungary
- Center of Translational Medicine and Institute of Pancreatic Disorders, Semmelweis University, Budapest, Hungary
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Tarar ZI, Farooq U, Zafar Y, Gandhi M, Raza S, Kamal F, Tarar MF, Ghouri YA. Burden of anxiety and depression among hospitalized patients with irritable bowel syndrome: a nationwide analysis. Ir J Med Sci 2023; 192:2159-2166. [PMID: 36593438 DOI: 10.1007/s11845-022-03258-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 12/20/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND AIM Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder that affects patients both physically and mentally. Our study aimed to investigate the burden of psychiatric disorders in IBS patients. METHODS We conducted a retrospective analysis of the National inpatient sample (NIS) from 2016 to 2019. We recruited patients admitted with a diagnosis of IBS and determined the prevalence of anxiety, depression, and suicide attempt/ideation. RESULTS We found a total of 1,256,325 hospitalizations with a diagnosis of IBS. Among them, 478,515 (38.1%) had anxiety and 344,165 (27.4%) had depression. The prevalence of psychiatric disorders including anxiety (38.1% vs. 15.1%), depression (38.1% vs. 15.1%), bipolar disorder (5.22% vs. 2.38%), suicidal attempt/Ideation (3.22% vs. 2.38%), and eating disorder (0.32% vs. 0.08%) was significantly higher in IBS patient population when compared to general adult population (p < 0.001). Patients with IBS had greater odds of anxiety (AOR 2.88, 95% CI 2.85-2.91, P < 0.001), depression (AOR 2.16, 95% CI 2.14-2.19, P < 0.001) and suicidal attempt/ideation (AOR 1.94, 95% CI 1.88-2.00, P < 0.001) in comparison to general population. IBS subtypes including diarrhea-predominant, constipation-predominant and mixed type were independently associated with increased odds of anxiety, depression, and suicide attempt/ideation. Patients with IBS and a co-diagnosis of anxiety or depression had increased mean length of hospital stay by 0.48 (95% CI 0.43-0.52, P < 0.001) and 0.52 (95% CI 0.06-0.97, P < 0.03) days, respectively. CONCLUSION The presence of IBS is associated with an increased associated prevalence of psychiatric disorders such as anxiety, depression, and suicide attempt/ideation.
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Affiliation(s)
- Zahid Ijaz Tarar
- Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA.
| | - Umer Farooq
- Rochester General Hospital, Rochester, NY, USA
| | - Yousaf Zafar
- University of Mississippi Medical Center, Jackson, MS, USA
| | - Mustafa Gandhi
- Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA
| | - Samina Raza
- Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA
| | - Faisal Kamal
- Department of Gastroenterology, University of California, San Francisco, USA
| | - Moosa F Tarar
- Department of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan
| | - Yezaz A Ghouri
- Division of Gastroenterology & Hepatology, School of Medicine at Columbia, University of Missouri, Columbia, MO, USA
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Talley NJ, Powell N, Walker MM, Jones MP, Ronkainen J, Forsberg A, Kjellström L, Hellström PM, Aro P, Wallner B, Agréus L, Andreasson A. Role of smoking in functional dyspepsia and irritable bowel syndrome: three random population-based studies. Aliment Pharmacol Ther 2021; 54:32-42. [PMID: 33983640 DOI: 10.1111/apt.16372] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/12/2021] [Accepted: 03/31/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND It is uncertain if functional dyspepsia (FD) or irritable bowel syndrome (IBS) are linked to smoking, and smoking cessation is not part of the routine advice provided to these patients. AIM To assess if smoking is an independent risk factor for FD and IBS. METHODS Three population-based endoscopy studies in Sweden with 2560 community individuals in total (mean age 51.5 years, 46% male). IBS (14.9%), FD (33.5%), and associated symptoms were assessed using the validated abdominal symptom questionnaire, and smoking (17.9%) was obtained from standardised questions during a clinic visit. The effect of smoking on symptom status was analysed in an individual person data meta-analysis using mixed effect logistic regression, adjusted for snuffing, age and sex. RESULTS Individuals smoking cigarettes reported significantly higher odds of postprandial distress syndrome (FD-PDS) (OR 10-19 cig/day = 1.42, 95% CI 1.04-1.98 P = 0.027, OR ≥20 cig/day = 2.16, 95% CI 1.38-3.38, P = 0.001) but not epigastric pain. Individuals smoking 20 or more cigarettes per day reported significantly higher odds of IBS-diarrhoea (OR = 2.40, 95% CI 1.12-5.16, P = 0.025), diarrhoea (OR = 2.01, 95%CI 1.28-3.16, P = 0.003), urgency (OR = 2.21, 95%CI 1.41-3.47, P = 0.001) and flatus (OR = 1.77, 95%CI 1.14-2.76, P = 0.012) than non-smokers. Smoking was not associated with IBS-constipation or IBS-mixed. CONCLUSION Smoking is an important environmental risk factor for postprandial distress syndrome, the most common FD subgroup, with over a twofold increased odds of PDS in heavy smokers. The role of smoking in IBS-diarrhoea, but not constipation, is also likely important.
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Affiliation(s)
- Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Lot 1 Kookaburra Circuit, New Lambton Heights, Australia, 2305, Australia
- NHMRC Centre for Research Excellence in Digestive Health, Australia
| | | | - Marjorie M Walker
- Faculty of Health and Medicine, University of Newcastle, Lot 1 Kookaburra Circuit, New Lambton Heights, Australia, 2305, Australia
- NHMRC Centre for Research Excellence in Digestive Health, Australia
| | - Mike P Jones
- NHMRC Centre for Research Excellence in Digestive Health, Australia
- Department of Psychology, Macquarie University, North Ryde, NSW, Australia
| | - Jukka Ronkainen
- Center for Life Course Health Research, University of Oulu, Oulu, Finland
- Primary Health Care Centre, Tornio, Finland
| | - Anna Forsberg
- Department of Medicine Solna, Karolinska Institutet, Solna, Sweden
| | | | - Per M Hellström
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | | | - Bengt Wallner
- Department of Surgical and Perioperatve Sciences, Umeå University, Umeå, Sweden
| | - Lars Agréus
- Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden
| | - Anna Andreasson
- Department of Psychology, Macquarie University, North Ryde, NSW, Australia
- Department of Medicine Solna, Karolinska Institutet, Solna, Sweden
- Stress Research Institute, Department of Psychology, Stockholm University, Stockholm, Sweden
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Yu L, Luo L, Long X, Liang X, Ji Y, Graham DY, Lu H. High-dose PPI-amoxicillin dual therapy with or without bismuth for first-line Helicobacter pylori therapy: A randomized trial. Helicobacter 2019; 24:e12596. [PMID: 31111580 DOI: 10.1111/hel.12596] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 03/23/2019] [Accepted: 04/06/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND A reliably highly effective high-dose proton-pump inhibitor plus amoxicillin (dual Helicobacter pylori therapy) has remained elusive. We compared whether the addition of bismuth to high-dose dual therapy would improve the efficacy of high-dose dual therapy as first-line treatment. METHODS This was an open-label, randomized single-center study of 160 treatment-naive patients with H. pylori infection who were randomly assigned to 14-day therapy with esomeprazole 40 mg twice a day plus amoxicillin 1 g three times a day with or without bismuth potassium citrate 600 mg (elemental bismuth 220 mg) twice a day. Antibiotic resistance was determined by agar dilution method and eradication by 13 C-urea breath test. RESULTS The per-protocol eradication rates were 96.1%; 95% CI = 88.9%-99.2% (73/76) without bismuth vs 93.3%; 95% CI = 85.1%-97.8% (70/75) with bismuth (P = 0.494). The intention-to-treat eradication rates were 92.5%; 95% CI = 84.4%-97.2% (74/80) without bismuth and 88.8%; 95% CI = 79.7%-94.7% (71/80) with bismuth (P = 0.416). Resistance to amoxicillin, clarithromycin, metronidazole, and levofloxacin was 0%, 31.7%, 81.4%, and 40.7%, respectively. Smoking reduced treatment effectiveness limited to those not receiving bismuth. The per-protocol eradication rates were 70% (7/10) vs 100% (66/66) in smokers vs non-smokers without bismuth (P = 0.002), and 100% (10/10) in smokers vs 92.3% (60/65) in non-smokers with bismuth (P = 1.0). The adverse event rates were 7.5% (6/80) without bismuth vs 11.3% (9/80) with bismuth (P = 0.416). CONCLUSIONS Fourteen-day high-dose dual therapy was both effective and safe for first-line treatment in a region of high prevalence antibiotic resistance. Adding bismuth only improved treatment effectiveness among smokers.
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Affiliation(s)
- Lou Yu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Laisheng Luo
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaohua Long
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiao Liang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yingjie Ji
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - David Y Graham
- Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas
| | - Hong Lu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Hart PA, Topazian M, Raimondo M, Cruz-Monserrate Z, Fisher WE, Lesinski GB, Steen H, Conwell DL. Endoscopic Pancreas Fluid Collection: Methods and Relevance for Clinical Care and Translational Science. Am J Gastroenterol 2016; 111:1258-66. [PMID: 27481304 PMCID: PMC5568003 DOI: 10.1038/ajg.2016.297] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Accepted: 06/01/2016] [Indexed: 02/08/2023]
Abstract
Pancreatic secretions have an important role in the regulation of a normal nutritional state but can be altered owing to a variety of pathophysiological mechanisms in the context of exocrine pancreatic disease. The development of an endoscopic technique for collection of pancreatic fluid, termed endoscopic pancreatic function testing, has led to improved understanding of these alterations and is particularly helpful to characterize chronic pancreatitis. In addition, investigators have found endoscopically collected pancreatic fluid to be a valuable biofluid for the purposes of translational science. Techniques such as proteomic, cytokine, genetic mutation, DNA methylation, and microRNA analyses, among others, can be utilized to gain a better understanding of the molecular characteristics of chronic pancreatitis and other pancreatic diseases. Endoscopic collection of pancreatic fluid is safe and relatively straightforward, permitting opportunities for longitudinal analysis of these translational markers throughout the course of disease. This manuscript summarizes our current knowledge of pancreatic fluid, with an emphasis on proper techniques for sample collection and handling, its clinical utility, and preliminary observations in translational science.
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Affiliation(s)
- Phil A. Hart
- Section of Pancreatic Disorders, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Mark Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota, USA
| | - Massimo Raimondo
- Division of Gastroenterology and Hepatology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
| | - Zobeida Cruz-Monserrate
- Section of Pancreatic Disorders, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - William E. Fisher
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Gregory B. Lesinski
- Section of Pancreatic Disorders, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Hanno Steen
- Department of Pathology, Boston Children’s Hospital and Harvard Medical School, Boston, Msaachusetts, USA
| | - Darwin L. Conwell
- Section of Pancreatic Disorders, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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High Dose Ilaprazole/Amoxicillin as First-Line Regimen for Helicobacter pylori Infection in Korea. Gastroenterol Res Pract 2016; 2016:1648047. [PMID: 27413365 PMCID: PMC4930811 DOI: 10.1155/2016/1648047] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 05/22/2016] [Accepted: 05/26/2016] [Indexed: 12/23/2022] Open
Abstract
Objective. The eradication rate of Helicobacter pylori (H. pylori) following standard triple therapy has declined over the past few decades. This study has determined whether high dose dual therapy (PPI and amoxicillin) is adequate for eradicating H. pylori in Korea. Methods. This was an open-labeled study of H. pylori infected treatment-naive patients. Subjects received dual therapy for 14 days: ilaprazole 40 mg tablets given twice a day and amoxicillin 750 mg tablets given 4 times a day. At the end of the therapy, the subjects visited the clinic to confirm compliance and monitor for any side effects. Subjects visited again after 4–6 weeks to confirm H. pylori status through a urea breath test. Results. The cure rate of H. pylori was 79.3% (23 of 29) (95% confidence interval: 61.6–90.2) in the intention-to-treat analysis and 82.1% (23 of 28) in the per-protocol analysis. Compliance rates were high (96.6%) and side effects were minimal and tolerable. Conclusion. A high dose of ilaprazole + amoxicillin was ineffective as the first-line therapy for eradicating H. pylori in Korea. Future studies should focus on intragastric pH measurements and assess amoxicillin resistance.
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Barreto SG. How does cigarette smoking cause acute pancreatitis? Pancreatology 2016; 16:157-163. [PMID: 26419886 DOI: 10.1016/j.pan.2015.09.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 08/22/2015] [Accepted: 09/03/2015] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Acute Pancreatitis (AP) is an emerging health problem world-wide and it is a major cause of admissions for gastrointestinal disease in many countries. Amongst the more common causes (alcohol and gallstones), recent evidence has emerged indicating that smoking is an independent risk factor for AP. However, the mechanisms involved in smoking-induced AP have not been completely elucidated. This review puts together all the published evidence in literature to present the clinical and laboratory evidence relating smoking to the causation of AP. DISCUSSION The two main metabolites from cigarette smoke, namely nicotine and NNK are able to induce functional and histological changes within the pancreas consistent with AP. The major mechanisms involved include their action on acinar cells and zymogen secretion through pathways involving CCK and the nicotinic preganglionic receptors. Effects on the pancreatic microvasculature may be mediated through the nitric oxide pathway. There is indirect evidence to suggest that nicotine and acrolein may lead to CFTR dysfunction thereby influencing ductal secretion. However, direct evidence for this effect is needed. The effect of cigarette smoke metabolites on stellate cells and the islets warrants further investigation in the context of pathogenesis of AP. CONCLUSION Using a step-wise approach, the review revisits the effects of the various metabolites of cigarette smoke on the constituents of the pancreas (exocrine, endocrine, neurohormonal, stellate cells, ductal system) and highlights their proven, and potential, mechanisms in triggering off an attack of AP.
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Affiliation(s)
- Savio G Barreto
- Department of Gastrointestinal Surgery, Gastrointestinal Oncology, and Bariatric Surgery, Medanta Institute of Digestive and Hepatobiliary Sciences, Medanta, The Medicity, Sector 38, Gurgaon, Haryana, India.
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Muñoz M, Coveñas R. Targeting NK-1 Receptors to Prevent and Treat Pancreatic Cancer: a New Therapeutic Approach. Cancers (Basel) 2015; 7:1215-32. [PMID: 26154566 PMCID: PMC4586765 DOI: 10.3390/cancers7030832] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2015] [Revised: 06/27/2015] [Accepted: 06/30/2015] [Indexed: 12/28/2022] Open
Abstract
Pancreatic cancer (PC) is the fourth leading cause of cancer related-deaths in both men and women, and the 1- and 5-year relative survival rates are 25% and 6%, respectively. It is known that smoking, alcoholism and psychological stress are risk factors that can promote PC and increase PC progression. To date, the prevention of PC is crucial because there is no curative treatment. After binding to the neurokinin-1 (NK-1) receptor (a receptor coupled to the stimulatory G-protein Gαs that activates adenylate cyclase), the peptide substance P (SP)-at high concentrations-is involved in many pathophysiological functions, such as depression, smoking, alcoholism, chronic inflammation and cancer. It is known that PC cells and samples express NK-1 receptors; that the NK-1 receptor is overexpressed in PC cells in comparison with non-tumor cells, and that nanomolar concentrations of SP induce PC cell proliferation. By contrast, NK-1 receptor antagonists exert antidepressive, anxiolytic and anti-inflammatory effects and anti-alcohol addiction. These antagonists also exert An antitumor action since in vitro they inhibit PC cell proliferation (PC cells death by apoptosis), and in a xenograft PC mouse model they exert both antitumor and anti-angiogenic actions. NK-1 receptor antagonists could be used for the treatment of PC and hence the NK-1 receptor could be a new promising therapeutic target in PC.
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Affiliation(s)
- Miguel Muñoz
- Research Laboratory on Neuropeptides (IBIS), Virgen del Rocío University Hospital,41013 Sevilla, Spain.
| | - Rafael Coveñas
- Laboratory of Neuroanatomy of the Peptidergic System (Lab. 14), Institute of Neurosciences ofCastilla y León (INCYL), University of Salamanca, 37008 Salamanca, Spain.
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The noncancer effects of smoking on the gastrointestinal tract. Gastroenterol Nurs 2014; 37:366-7. [PMID: 25271830 DOI: 10.1097/sga.0000000000000069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Trang T, Chan J, Graham DY. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21 st century. World J Gastroenterol 2014; 20:11467-11485. [PMID: 25206255 PMCID: PMC4155341 DOI: 10.3748/wjg.v20.i33.11467] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 07/18/2014] [Accepted: 07/30/2014] [Indexed: 02/07/2023] Open
Abstract
Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.
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MESH Headings
- Animals
- Antacids/therapeutic use
- Chemistry, Pharmaceutical
- Drug Therapy, Combination
- Enzyme Replacement Therapy/history
- Enzyme Replacement Therapy/trends
- Exocrine Pancreatic Insufficiency/diagnosis
- Exocrine Pancreatic Insufficiency/drug therapy
- Exocrine Pancreatic Insufficiency/enzymology
- Exocrine Pancreatic Insufficiency/history
- Exocrine Pancreatic Insufficiency/physiopathology
- Gastric Emptying/drug effects
- History, 20th Century
- History, 21st Century
- Humans
- Hydrogen-Ion Concentration
- Intestinal Absorption
- Intestine, Small/drug effects
- Intestine, Small/metabolism
- Lipid Metabolism/drug effects
- Pancreas, Exocrine/drug effects
- Pancreas, Exocrine/enzymology
- Pancreas, Exocrine/physiopathology
- Tablets, Enteric-Coated
- Treatment Outcome
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12
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Li LF, Chan RLY, Lu L, Shen J, Zhang L, Wu WKK, Wang L, Hu T, Li MX, Cho CH. Cigarette smoking and gastrointestinal diseases: the causal relationship and underlying molecular mechanisms (review). Int J Mol Med 2014; 34:372-80. [PMID: 24859303 DOI: 10.3892/ijmm.2014.1786] [Citation(s) in RCA: 140] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Accepted: 05/20/2014] [Indexed: 12/16/2022] Open
Abstract
Cigarette smoking is an important risk factor for gastrointestinal (GI) disorders, including peptic ulcers, inflammatory bowel diseases, such as Crohn's disease and cancer. In this review, the relationship between smoking and GI disorders and the underlying mechanisms are discussed. It has been demonstrated that cigarette smoking is positively associated with the pathogenesis of peptic ulcers and the delay of ulcer healing. Mechanistic studies have shown that cigarette smoke and its active ingredients can cause mucosal cell death, inhibit cell renewal, decrease blood flow in the GI mucosa and interfere with the mucosal immune system. Cigarette smoking is also an independent risk factor for various types of cancer of the GI tract. In this review, we also summarize the mechanisms through which cigarette smoking induces tumorigenesis and promotes the development of cancer in various sections of the GI tract. These mechanisms include the activation of nicotinic acetylcholine receptors, the formation of DNA adducts, the stimulation of tumor angiogenesis and the modulation of immune responses in the GI mucosa. A full understanding of these pathogenic mechanisms may help us to develop more effective therapies for GI disorders in the future.
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Affiliation(s)
- L F Li
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - R L Y Chan
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - L Lu
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - J Shen
- Institute of Digestive Diseases, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - L Zhang
- Institute of Digestive Diseases, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - W K K Wu
- Institute of Digestive Diseases, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - L Wang
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - T Hu
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - M X Li
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
| | - C H Cho
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China
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13
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Attumi TA, Graham DY. High-dose extended-release lansoprazole (dexlansoprazole) and amoxicillin dual therapy for Helicobacter pylori infections. Helicobacter 2014; 19:319-22. [PMID: 24698653 PMCID: PMC4111781 DOI: 10.1111/hel.12126] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Helicobacter pylori infections have become increasingly difficult to treat. AIM To examine whether amoxicillin and high-dose dexlansoprazole would reliably achieve an H. pylori eradication rate of ≥90%. METHODS An open-label prospective pilot study of H. pylori eradication in treatment-naïve subjects with active H. pylori infection (positive by two tests). THERAPY amoxicillin 1 g and dexlansoprazole 120 mg each twice a day at approximately 12-hour intervals for 14 days. Success was accessed by urea breath test. An effective therapy was defined as a per-protocol treatment success of 90% or greater; treatment success of 80% or less was prespecified as an unacceptable result. RESULTS After 13 subjects were entered (12 men, one woman; average age of 54 years), the prespecified stopping rule of six treatment failures was achieved (i.e., the 95% confidence interval excluded achieving the required 90% success rate even if the proposed study of 50 completed patients were entered) and enrollment was stopped. Per-protocol and intention-to-treat treatment success were both 53.8%; (7/13); 95% CI = 25-80%. Compliance was 100%. Three patients (23%) reported side effects, all of which were mild and none interrupted therapy. CONCLUSION Theoretically, dual PPI plus amoxicillin should reliably eradicate H. pylori provided nearly neutral intragastric pH can be maintained. Clearly, dexlansoprazole, despite being administered at high dose and twice a day (i.e., total daily dose 240 mg), failed to achieve an intragastric milieu consistent with dual PPI plus amoxicillin therapy being an effective anti-H. pylori regimen.
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Affiliation(s)
- Taraq A Attumi
- Michael E. DeBakey Veterans Affairs Medical Center, RM 3A-320 (111D), 2002 Holcombe Boulevard and Baylor College of Medicine, Houston, TX, 77030, USA
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14
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Kadiyala V, Lee LS, Banks PA, Suleiman S, Paulo JA, Wang W, Rosenblum J, Sainani NI, Mortele K, Conwell DL. Cigarette smoking impairs pancreatic duct cell bicarbonate secretion. JOP : JOURNAL OF THE PANCREAS 2013; 14:31-8. [PMID: 23306332 DOI: 10.6092/1590-8577/1195] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 08/28/2012] [Revised: 10/24/2012] [Accepted: 11/27/2012] [Indexed: 01/08/2023]
Abstract
OBJECTIVE To compare pancreatic duct cell function in smokers (current and past) and never smokers by measurement of secretin-stimulated peak bicarbonate concentration ([HCO3-]) in endoscopic collected pancreatic fluid (PF). METHODS This retrospective study was cross-sectional in design, recording demographic information (age, gender, etc.), smoking status (former, current, never), alcohol intake, clinical data (imaging, endoscopy), and laboratory results (peak PF [HCO3-]) from subjects evaluated for pancreatic disease at a tertiary pancreas center. Univariate and multivariate statistical analysis (SAS Version 9.2, Cary, NC, USA) was performed to assess the relationship between cigarette smoking and secretin-stimulated pancreatic fluid bicarbonate concentration. RESULTS A total of 131 subjects underwent pancreatic fluid collection (endoscopic pancreatic function test, ePFT) for bicarbonate analysis: 25.2% (33 out of 131) past smokers, 31.3% (41 out of 131) current smokers, and 43.5% (57 out of 131) were never smokers. Measures of Association: The mean peak PF [HCO3-] in never smokers (81.3 ± 18.5 mEq/L) was statistically higher (indicating better duct cell function) when compared to past smokers (66.8 ± 24.7 mEq/L, P=0.005) and current smokers (70.0 ± 20.2 mEq/L, P=0.005). However, the mean peak [HCO3-] in past smokers was not statistically different from that in current smokers (P=0.575), and therefore, the two smoking groups were combined to form a single "smokers cohort". When compared to the never smokers, the smokers cohort was older (P=0.037) and had a greater proportion of subjects with definite chronic pancreatitis imaging (P=0.010), alcohol consumption ≥20 g/day (P=0.012), and abnormal peak PF [HCO3-] (P<0.001). Risk-Based Estimates: Cigarette smoking (risk ratio, RR: 2.2, 95% CI: 1.3-3.5; P<0.001), diagnosis of definite chronic pancreatitis imaging (RR: 2.2, 95% CI: 1.6-3.2; P<0.001) and alcohol consumption ≥20 g/day (RR: 1.6, 95% CI: 1.1-2.4; P=0.033) were all associated with low mean peak PF [HCO3-] (indicating duct cell secretory dysfunction). Multivariate Analysis: Smoking (odds ratio, OR: 3.8, 95% CI: 1.6-9.1; P=0.003) and definite chronic pancreatitis imaging (OR: 5.7, 95% CI: 2.2-14.8; P<0.001) were determined to be independent predictors of low peak PF [HCO3-], controlling for age, gender, and alcohol intake. Furthermore there was no interaction between smoking status and alcohol intake in predicting duct cell dysfunction (P=0.571). CONCLUSION Measurement of pancreatic fluid bicarbonate in smokers reveals that cigarette smoking (past and current) is an independent risk factor for pancreatic duct cell secretory dysfunction (low PF [HCO3-]). Furthermore, the risk of duct cell dysfunction in subjects who smoked was approximately twice the risk (RR: 2.2) in never smokers. Further in depth, translational research approaches to pancreatic fluid analysis may help unravel mechanisms of cigarette smoking induced pancreatic duct cell injury.
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Affiliation(s)
- Vivek Kadiyala
- Center for Pancreatic Disease, Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
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15
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Wittel UA, Momi N, Seifert G, Wiech T, Hopt UT, Batra SK. The pathobiological impact of cigarette smoke on pancreatic cancer development (review). Int J Oncol 2012; 41:5-14. [PMID: 22446714 PMCID: PMC3589138 DOI: 10.3892/ijo.2012.1414] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Accepted: 01/25/2012] [Indexed: 12/13/2022] Open
Abstract
Despite extensive efforts, pancreatic cancer remains incurable. Most risk factors, such as genetic disposition, metabolic diseases or chronic pancreatitis cannot be influenced. By contrast, cigarette smoking, an important risk factor for pancreatic cancer, can be controlled. Despite the epidemiological evidence of the detrimental effects of cigarette smoking with regard to pancreatic cancer development and its unique property of being influenceable, our understanding of cigarette smoke-induced pancreatic carcinogenesis is limited. Current data on cigarette smoke-induced pancreatic carcinogenesis indicate multifactorial events that are triggered by nicotine, which is the major pharmacologically active constituent of tobacco smoke. In addition to nicotine, a vast number of carcinogens have the potential to reach the pancreatic gland, where they are metabolized, in some instances to even more toxic compounds. These metabolic events are not restricted to pancreatic ductal cells. Several studies show that acinar cells are also greatly affected. Furthermore, pancreatic cancer progenitor cells do not only derive from the ductal epithelial lineage, but also from acinar cells. This sheds new light on cigarette smoke-induced acinar cell damage. On this background, our objective is to outline a multifactorial model of tobacco smoke-induced pancreatic carcinogenesis.
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Affiliation(s)
- Uwe A Wittel
- Department of General- and Visceral Surgery, Universitätsklinik Freiburg, Freiburg, Germany.
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16
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DiMagno MJ, Dimagno EP. Pancreas divisum does not cause pancreatitis, but associates with CFTR mutations. Am J Gastroenterol 2012; 107:318-20. [PMID: 22306946 PMCID: PMC3458421 DOI: 10.1038/ajg.2011.430] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Bertin et al. partially dispel arguments that pancreas divisum (PD) causes pancreatitis, but fascinatingly indicate that PD associates with CFTR gene mutations predisposing to pancreatitis. This association, however, does not definitely confer a pathophysiological role for PD in pancreatitis but may denote that PD co-mingles with CFTR mutations without influencing pancreatitis or CFTR mutations influence pancreatic duct embryogenesis. We advise "idiopathic pancreatitis" patients with PD to undergo genetic testing. In lieu of CFTR mutations undertake no endoscopic/surgical procedure; if CFTR mutations are found, then refer patients for genetic counseling and withhold endoscopic/surgical therapy unless randomized studies show benefit.
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17
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Long-term nicotine exposure causes increased concentrations of trypsinogens and amylase in pancreatic extracts in the rat. Pancreas 2008; 37:288-94. [PMID: 18815551 DOI: 10.1097/mpa.0b013e31816a7744] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
UNLABELLED To develop radioimmunoassays (RIAs) for rat trypsinogens 1 and 2 and to investigate the effect of nicotine exposure on concentration and production of pancreatic zymogens in the rat. METHODS Male Sprague-Dawley rats were supplied with either normal or nicotine-containing (0.77 mM) water for 28 days and were then killed. Rabbit antibodies for the activation peptides of trypsinogens 1 and 2 were obtained for use in the RIAs. Concentrations of the both trypsinogens in pancreatic extracts were measured by the RIAs after activation by enterokinase. DNA and amylase were measured using commercial kits. mRNA for trypsinogens 1 and 2, procolipase, and cholecystokinin receptor was measured by in situ hybridization. RESULTS The specificity of the RIA for the trypsinogen 1 activation peptide was satisfactory. The RIA for the trypsinogen 2 activation peptide showed a limited cross-reaction toward the synthetic trypsinogen 1 activation peptide, but the importance of this cross-reaction was moderate when investigated in samples of activated trypsinogens. Weight gain was reduced in nicotine-treated animals. Concentrations of amylase, trypsinogen 1, trypsinogen 2, and the ratio of trypsinogen 2 to 1 were all increased in pancreatic extracts of nicotine-fed animals. Total DNA and mRNA for the trypsinogens, procolipase, and cholecystokinin receptor were not affected by nicotine exposure. CONCLUSIONS The combination of increased proenzyme concentrations and unaffected mRNA levels suggests that nicotine impairs secretion rather than production of pancreatic zymogens.
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18
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Lindkvist B, Appelros S, Manjer J, Berglund G, Borgstrom A. A prospective cohort study of smoking in acute pancreatitis. Pancreatology 2008; 8:63-70. [PMID: 18235217 DOI: 10.1159/000114868] [Citation(s) in RCA: 82] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2006] [Accepted: 06/21/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS Little is known about risk factors for acute pancreatitis other than gallstones and alcohol consumption. The aim of this study was to investigate if smoking or body mass index (BMI) are associated with acute pancreatitis and to determine relative risks (RR) for acute pancreatitis related to smoking, BMI, and alcohol consumption. METHODS From 1974 to 1992, selected birth-year cohorts of residents in Malmo, Sweden (born 1921-1949) were invited to a health-screening investigation including physical examination, blood sampling and a questionnaire. In total, 33,346 individuals participated. Cases of acute pancreatitis were identified from diagnosis registries (n = 179). Incidence rates were calculated in different risk factor categories. A Cox's analysis revealed RR. RESULTS Current versus never smoking at baseline was associated with acute pancreatitis (RR 2.14, 95% confidence interval (CI) 1.48-3.09) after adjustment for age, sex, BMI and alcohol consumption. This association was stronger in heavy smokers (20-30 cigarettes/day) (RR 3.19, 95% CI 2.03-5.00). Smoking was associated with a RR of 3.57 (95% CI 0.98-13.0) for acute pancreatitis in subjects who reported no alcohol consumption. An increased risk for acute pancreatitis was also found for high versus low risk, self-reported alcohol consumption (RR 2.55, 95% CI 1.59-4.08) and for gamma-GT levels in the highest versus the lowest quartile (RR 2.14, 95% CI 1.32-3.49). There was also a weak correlation between BMI and acute pancreatitis. CONCLUSIONS Smoking is associated with the incidence of acute pancreatitis in a dose-response manner. and IAP.
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Affiliation(s)
- Bjorn Lindkvist
- Department of Clinical Sciences, Malmo University Hospital, Lund University, Malmo, Sweden.
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19
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Cigarette smoke-induced pancreatic damage: experimental data. Langenbecks Arch Surg 2008; 393:581-8. [PMID: 18193450 DOI: 10.1007/s00423-007-0273-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2007] [Accepted: 12/30/2007] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS Epidemiological data clearly indicate that cigarette smoking is associated with an increased risk for developing chronic pancreatitis and pancreatic cancer. Despite of this clear epidemiological correlation, cigarette smoke-induced pancreatic damage has only been investigated in a small number of experimental studies. METHODS Experimental studies examining the effect of cigarette smoke or cigarette smoke constituents on the pancreas were reviewed. RESULTS Recent data indicate that smoking also induces chronic pancreatic inflammation in rodents within a period of 12 weeks upon exposure with environmental cigarette smoke. Supported by the finding that morphologic pancreatic damage is also induced by nicotine treatment, cigarette smoke-induced pancreatic damage is likely to be caused by a disturbance of regulation of exocrine pancreas. The morphological alterations, however, induced by nicotine, are less pronounced and therefore, other substances and pathophysiologic mechanisms, such as carcinogen action or cigarette smoke-induced reduction of anti-protease activity, are likely to aggravate pancreatic damage upon cigarette smoke inhalation. CONCLUSION These data indicate that several constituents of cigarette smoke induce a disturbance of pancreatic function. This multifactorial event induces morphologic pancreatic damage upon cigarette smoke exposure in rodents.
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Abstract
In Japan, the number of patients with both chronic pancreatitis (CP) and pancreatic cancer (PC) is increasing. A nationwide survey on CP revealed that the total number of patients treated for CP in Japan in 2002 was estimated as 45,200 (95% confidence interval, 35,600-54,700), and 20,137 patients died of PC in 2002. Alcoholic pancreatitis was the most common type of pancreatitis (67.5 %). Cigarette smoking was an independent and significant risk factor for CP. The risks of pancreatic and nonpancreatic cancers increased in the course of CP. While alcohol consumption may increase the risk of PC via CP, smoking was important as a risk factor for both CP and PC. The increasing incidence of PC was closely related to the increasing intake of animal fat. Lifestyle in patients with CP appeared to be the same as that in patients with PC. Environmental factors such as lifestyle in combination with genetic factors may increase the risk for both CP and PC. Therefore, changing and improving lifestyle habits such as drinking, smoking and nutrition may reduce the risks for both CP and PC.
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Affiliation(s)
- Makoto Otsuki
- The Third Department of Internal Medicine (Gastroenterology and Metabolism), University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu.
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Abstract
Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence, addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. In addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However, there is a large degree of between-study variability that demonstrates the need for larger, well-controlled case-control studies to identify target genes and deduce mechanisms that account for the genetic basis of inter-individual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.
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Affiliation(s)
- Stewart L MacLeod
- Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Arkansas Center for Birth Defects Research and Prevention, 1120 Marshall St. Mail Slot 512-40, Little Rock, AR 72202, United States.
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Abstract
Tobacco smoke, with its complexity of constituents, damages the pancreatic organ in multiple ways. Smoke not only affects pancreatic secretion patterns via its nicotine content but induces inflammatory reactions and exerts carcinogenic effects by several other constituents. Smoke enhances ethanol-induced pancreatic injury and accelerates the development and progression of chronic pancreatitis independent of etiology. Through the process of inflammation, smoking contributes to pancreatic carcinogenesis. The experiment of Wittel and colleagues published in this issue of the American Journal of Gastroenterology sheds further light on this topic by reporting in great detail two different kinds of pancreatic damage in rats exposed to high doses of smoke.
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Affiliation(s)
- P Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von Guericke-University Magdeburg, Magdeburg, Germany
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23
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Affiliation(s)
- M V Apte
- South Western Sydney Clinical School, The University of New South Wales, Level 2, Thomas and Rachel Moore Education Centre, Liverpool Hospital, Liverpool, NSW 2170, Australia
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Delhaye M, Arvanitakis M, Verset G, Cremer M, Devière J. Long-term clinical outcome after endoscopic pancreatic ductal drainage for patients with painful chronic pancreatitis. Clin Gastroenterol Hepatol 2004; 2:1096-106. [PMID: 15625655 DOI: 10.1016/s1542-3565(04)00544-0] [Citation(s) in RCA: 125] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Endotherapy for patients with painful chronic pancreatitis (CP) gives early and midterm clinical results comparable with those of conventional surgery. The authors evaluated long-term clinical outcome after endoscopic pancreatic ductal drainage, focusing on pain and pancreatic endocrine/exocrine functions. METHODS Of 110 patients with painful CP endoscopically treated between October 1987 and December 1989, 56 long-surviving patients were followed-up for 14.4 years (SD, .6 y); 40 patients died and 14 patients were lost to follow-up evaluation. Technical results included decreased ductal dilation and stone clearance. Clinical results included the rate of hospitalizations for pain before and after endotherapy, the need for surgery, the course of endocrine/exocrine insufficiencies, and late mortality. RESULTS Complete or partial technical success initially was obtained in 48 of 56 long-surviving patients. Long-term clinical success (< or =5 hospitalizations for pain during follow-up evaluation, without surgery) was obtained for 37 of 56 patients. At a mean follow-up time of 14.4 years, 44 patients had avoided surgery and the annual rate of hospitalizations for pain decreased significantly (before endotherapy: 0.98 [+/-1.36] vs 0.40 [+/-0.51] for the 3 years thereafter vs 0.14 [+/-0.22] for the last 11 years of follow-up evaluation; P < .001). Short duration of disease before initial therapy and absence of smoking at the last follow-up evaluation were associated with long-term clinical success. CONCLUSIONS Endotherapy provides long-term benefits for about two thirds of patients with painful CP. Good clinical outcome was associated with cessation or absence of smoking, whereas alcohol abuse increased the risks for diabetes mellitus, steatorrhea, and mortality.
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Affiliation(s)
- Myriam Delhaye
- Medicosurgical Department of Gastroenterology, Erasme University Hospital, 1070 Brussels, Belgium.
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25
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Stevens T, Conwell DL, Zuccaro G. Pathogenesis of chronic pancreatitis: an evidence-based review of past theories and recent developments. Am J Gastroenterol 2004; 99:2256-70. [PMID: 15555009 DOI: 10.1111/j.1572-0241.2004.40694.x] [Citation(s) in RCA: 136] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
In the past several decades, four prominent theories of chronic pancreatitis pathogenesis have emerged: the toxic-metabolic theory, the oxidative stress hypothesis, the stone and duct obstruction theory, and the necrosis-fibrosis hypothesis. Although these traditional theories are formulated based on compelling scientific observations, substantial contradictory data also exist for each. Furthermore, the basic premises of some of these theories are directly contradictory. Because of the recent scientific progress in the underlying genetic, cellular, and molecular pathophysiology, there have been substantial advances in the understanding of chronic pancreatitis pathogenesis. This paper will provide an evidence-based review and critique of the traditional pathogenic theories, followed by a discussion of the new advances in pancreatic fibrogenesis. Moreover, we will discuss plausible pathogenic sequences applied to each of the known etiologies.
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Affiliation(s)
- Tyler Stevens
- The Pancreas Clinic, Section of Endoscopy and Pancreaticobiliary Disease, Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio 44118, USA
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Lindkvist B, Appelros S, Manjer J, Borgström A. Trends in incidence of acute pancreatitis in a Swedish population: is there really an increase? Clin Gastroenterol Hepatol 2004; 2:831-7. [PMID: 15354285 DOI: 10.1016/s1542-3565(04)00355-6] [Citation(s) in RCA: 94] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Recent reports have suggested an increasing incidence of acute pancreatitis, and changing patterns of risk factors, over the past decades. The aim of this study was to investigate trends in the incidence of acute pancreatitis, and risk factors related to the disease, in a general population over a 15-year period. METHODS Clinical, autopsy, and forensic records for all patients with a first attack of acute pancreatitis in Malmö, Sweden, from 1985 to 1999, were validated retrospectively. Evidence for diagnosis was reconsidered and plausible cause was assessed. The incidence of gallstone disease, lung cancer, and alcohol-related conditions in the background population were retrieved from hospital diagnosis records and cancer and cause-of-death registries. RESULTS A total of 929 first attacks of acute pancreatitis were identified. The total incidence of acute pancreatitis increased by 3.9% per year (95% confidence interval [CI], 2.1-5.8). The incidence of gallstone-related pancreatitis increased by 7.6% per year (95% CI, 4.0-11.4), and this correlated with an increase in the incidence of other gallstone-related conditions ( r = 0.68; P = 0.005). Alcohol-related pancreatitis decreased by -5.1% per year (95% CI, -7.4 to -2.8), and this correlated with a decrease in the incidence of delirium tremens ( r = 0.75; P = 0.001), mortality from cirrhosis ( r = 0.81; P < 0.001), and incidence of lung cancer ( r = 0.57; P = 0.026). CONCLUSIONS There was a statistically significant increase in the incidence of acute pancreatitis. Gallstone-related pancreatitis increased, and alcohol-related pancreatitis decreased. Both of these trends were statistically significant and correlated with trends in the incidence of other conditions associated with either gallstone disease or alcohol abuse.
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Affiliation(s)
- Björn Lindkvist
- Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
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Abstract
Although the majority of patients with chronic pancreatitis present a history of excessive alcohol consumption, the pathophysiology underlying chronic alcoholic pancreatitis remains poorly defined. Since experimental animal models represent helpful tools in understanding human disease, numerous laboratory studies have been designed to study the effects of alcohol on the pancreas. In the present article we summarize the existing animal models that have been used to investigate the effects of acute and chronic alcohol application on the development of morphological alterations and pancreatic injury. Despite considerable experimental effort, acute or chronic ethanol feeding alone failed to cause acute or chronic pancreatitis in animals. However, ethanol-feeding and the combination with other procedures has demonstrated several mechanisms that play a role in ethanol-induced pancreatic injury. Among these ethanol-induced alterations and mechanisms are the reduction of pancreatic blood-flow and microcirculation, damaging effects of ethanol metabolites, increased pancreatic acinar cell expression of digestive and lysosomal enzymes, increased glandular enzyme content, additional nutritional factors, pancreatic duct obstruction, and limitations of pancreatic regeneration. Although no satisfactory animal model for alcoholic pancreatitis has been developed, these animal models have provided insights in several factors that predispose the pancreas to development of pancreatic injury and contribute to alcoholic pancreatitis.
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Affiliation(s)
- Alexander Schneider
- Department of Medicine, Division of Gastroenterology and Hepatology, Human Genetics, Cell Biology and Physiology, University of Pittsburgh, Pa., USA
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28
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Abstract
The utilization of recent advances in molecular and genomic technologies and progress in pancreatic imaging techniques provided remarkable insight into genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis. Translation of these advances into clinical practice demands a reassessment of current approaches to diagnosis, classification, and staging. We conclude that an adequate pancreatic biopsy must be the gold standard against which all diagnostic approaches are judged. Although computed tomography remains the initial test of choice for the diagnosis of chronic pancreatitis, the roles of endoscopic retrograde pancreatography, endoscopic ultrasonography, and magnetic resonance imaging are considered. Once chronic pancreatitis is diagnosed, proper classification becomes important. Major predisposing risk factors to chronic pancreatitis may be categorized as either (1) toxic-metabolic, (2) idiopathic, (3) genetic, (4) autoimmune, (5) recurrent and severe acute pancreatitis, or (6) obstructive (TIGAR-O system). After classification, staging of pancreatic function, injury, and fibrosis becomes the next major concern. Further research is needed to determine the clinical and natural history of chronic pancreatitis developing in the context of various risk factors. New methods are needed for early diagnosis of chronic pancreatitis, and new therapies are needed to determine whether interventions will delay or prevent the progression of the irreversible damage characterizing end-stage chronic pancreatitis.
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Affiliation(s)
- B Etemad
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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29
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Imoto M, DiMagno EP. Cigarette smoking increases the risk of pancreatic calcification in late-onset but not early-onset idiopathic chronic pancreatitis. Pancreas 2000; 21:115-9. [PMID: 10975703 DOI: 10.1097/00006676-200008000-00002] [Citation(s) in RCA: 79] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
An association exists between cigarette smoking and pancreatitis owing to alcohol. We determined whether cigarette smoking affected the course of pancreatic calcification and insufficiency in idiopathic chronic pancreatitis. Medical records were analyzed of 24 persons with early- and 42 with late-onset idiopathic chronic pancreatitis who were diagnosed between 1976 and 1982 and then followed prospectively until 1985. Smoking equaled >5 pack-years before calcification or insufficiency or last follow-up. Mean follow-up after onset of chronic pancreatitis was 27 and 13 years in early- and late-onset idiopathic chronic pancreatitis, respectively. Incidence of calcification in the two groups was 58 and 43%, respectively. In early-onset idiopathic chronic pancreatitis, smokers and nonsmokers developed calcification at a similar rate and frequency (58%). In late-onset idiopathic chronic pancreatitis, smokers developed pancreatic calcifications faster (p < 0.001) and more frequently (83 vs. 13%, p < 0.001) than nonsmokers. The association between smoking and pancreatic calcification was independent of gender, body mass index, and exocrine or endocrine insufficiency. Smoking did not affect development of exocrine or endocrine insufficiency. Cigarette smoking increases the risk of pancreatic calcification of late- but not of early-onset idiopathic chronic pancreatitis. These data support encouraging cessation of smoking in chronic pancreatitis.
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Affiliation(s)
- M Imoto
- Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA
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30
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Graham DY, Osato MS. H. pylori in the pathogenesis of duodenal ulcer: interaction between duodenal acid load, bile, and H. pylori. Am J Gastroenterol 2000; 95:87-91. [PMID: 10638564 DOI: 10.1111/j.1572-0241.2000.01704.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Helicobacter pylori (H. pylori) growth is inhibited by bile yet it can grow in the duodenal bulb and cause ulcer disease. The aim of this study was to test the effect of bile on H. pylori viability and growth and to determine whether acidification of bile reduces its inhibitory activity. METHODS Fresh human bile was collected at laparotomy and tested for inhibitory activity of H. pylori using broth dilution assays. Six clinical isolates of H. pylori obtained from patients with duodenal ulcer were used for each experiment. The bile was diluted from 1:3 to 1:192; its inhibitory effect on H. pylori was tested before and after acidification, treatment with cholestyramine, or chloroform. Bile was acidified to a pH of 2-6, centrifuged at 8000 rpm for 20 min to remove precipitated bile acids, and the supernatant pH readjusted. Controls included BHI broth without bile (positive control) and bile that was acidified to pH 2 and neutralized without centrifugation. RESULTS Human bile inhibited H. pylori growth in a dose dependent manner. Growth of all strains was supported for all strains only at a dilution of 1:192. In contrast, after acidification to pH < or =5 and centrifugation to remove precipitated bile acids, all strains grew at a bile dilution of 1:12. Neither chloroform extraction of lipids, nor acidification without centrifugation removed the inhibitory action of bile. In contrast, cholestyramine sequestration of bile acids completely removed all inhibitory activity. CONCLUSIONS The duodenal acid load may be the critical factor to explain the ability of H. pylori to colonize the duodenal bulb by precipitating glycine-conjugated bile salts. The combination of a high duodenal acid load and H. pylori infection is likely the critical event in the pathogenesis of H. pylori-related duodenal ulcer disease.
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Affiliation(s)
- D Y Graham
- Department of Medicine, Veterans Affairs Medical Center, Houston, Texas 77030, USA
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31
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Liede KE, Haukka JK, Hietanen JH, Mattila MH, Rönkä H, Sorsa T. The association between smoking cessation and periodontal status and salivary proteinase levels. J Periodontol 1999; 70:1361-8. [PMID: 10588500 DOI: 10.1902/jop.1999.70.11.1361] [Citation(s) in RCA: 45] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Little information is available about the effects of the cessation of cigarette smoking on oral health, although cigarette smoking has been shown to be associated with a variety of oral diseases. The aim of this study was to compare periodontal status, salivary proteolytic activity, especially collagenase-2 (MMP-8) levels, and oral mucosal status in individuals who had quit smoking for at least 6 months (mean 3.5, SD 1.3 years) and in regular smokers. METHODS The subjects were 409 white male smokers aged 55 to 74 years with 15 or more remaining teeth. They had participated in a major cancer prevention study (ATBC Study). Eighty-two of the men had given up smoking and 327 were smokers. The subjects were examined clinically to determine the prevalence of periodontal pockets, gingival bleeding (BOP) and suppuration, and prevalence of keratotic oral mucosal lesions. The loss of alveolar bone was determined radiographically. Candida albicans was cultivated, and lesions showing leukoplakia were examined histopathologically. General proteolytic activity and collagenase-2 or matrix metalloproteinase-8 (MMP-8) levels in saliva, salivary pH, and buffering capacity were measured. Linear regression, logistic regression, or Fisher's exact test were used in statistical analysis. RESULTS Salivary general proteolytic activity and MMP-8 levels were lower in current smokers than in ex-smokers (P <0.05 and P <0.05, respectively). The prevalence of > or = 4 mm deep pockets, gingival suppuration, and loss of crestal bone were statistically significantly lower (P = 0.003, P<0.001, and P<0.05, respectively) and salivary buffering capacity higher (P <0.05) in those who had quit smoking compared to current smokers; there was no difference in BOP. The prevalence of oral leukoplakia did not differ significantly between smokers and quitters, but was higher in those who smoked >15 cigarettes per day compared to quitters (odds ratio 3.5, 95% CI, 0.8 to 15.3). CONCLUSIONS These data suggest that periodontal status and oral mucosal health are better in those who have quit cigarette smoking compared to current smokers. However, the data further suggest that smoking may significantly lower both general proteolytic enzyme activity and MMP-8 levels in saliva. Thus, care should be taken in interpreting results revealing salivary/mouthrinse proteinases as diagnostic markers for oral/periodontal disease activity.
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Affiliation(s)
- K E Liede
- University of Helsinki, Institute of Dentistry, Finland.
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32
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Abstract
The pathogenesis of peptic ulcer disease is multifactorial, including the effects of Helicobacter pylori, gastric acid, pepsin, gastroduodenal motility, smoking and nicotine, and the complex interaction of an array of other so-called aggressive and protective factors. Since the discovery and acceptance of H. pylori as a major etiologic agent in peptic ulcer disease, the role of smoking has received less attention. Smokers are more likely to develop ulcers, ulcers in smokers are more difficult to heal, and ulcer relapse is more likely in smokers. These clinical observations may be explained by the adverse effects that smoking has on mucosal aggressive and protective factors. Of the aggressive factors, smoking appears to have no consistent effect on acid secretion. However, smoking impairs the therapeutic effects of histamine-2 antagonists, may stimulate pepsin secretion, promotes reflux of duodenal contents into the stomach, increases the risk for and harmful effects of H. pylori, and increases production of free radicals, vasopressin, secretion by the pituitary, secretion of endothelin by the gastric mucosa, and production of platelet activating factor. Smoking also affects the mucosal protective mechanisms. It decreases gastric mucosal blood flow and inhibits gastric mucous secretion, gastric prostaglandin generation, salivary epidermal growth factor secretion, duodenal mucosal bicarbonate secretion, and pancreatic bicarbonate secretion. These adverse effects of smoking on aggressive and protective factors quality it as an important contributor to the pathogenesis of peptic ulcer disease and indicate that smoking plays a significant facilitative role in the development and maintenance of peptic ulcer disease.
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Affiliation(s)
- G L Eastwood
- State University of New York Health Science Center, Syracuse 13210-2399, USA
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33
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Murthy S, Dinoso VP, Natrajan R. Neurohormonal mechanisms of cigarette smoke-induced duodenal mucosal bicarbonate secretion in the rat. Peptides 1997; 18:1061-6. [PMID: 9357067 DOI: 10.1016/s0196-9781(97)00030-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The effect of cigarette smoke and nicotine on duodenal mucosal bicarbonate secretion (DMBS) was studied in rats. Cigarette smoke but not intravenous nicotine administered acutely to anesthetized rats via a tracheostomy tube stimulated DMBS by 47 +/- 6%. The increase was neurally mediated via atropine-sensitive postganglionic cholinergic neurons. Introduction of cigarette smoke after the infusion of vasoactive intestinal peptide and porcine histidine isoleucine (PHI) also caused a delayed increase in DMBS. However, the magnitude of this increase was similar to that seen in control non-peptide-infused rats. The increase in bicarbonate secretion predominantly involved Brunner's glands. Rats exposed to cigarette smoke for 4 and 8 days before direct instillation of smoke via tracheostomy tube did not show any increase in their DMBS. These studies indicate that in the rat, cigarette smoke increases DMBS, most likely secreted by the Brunner's glands. The increase is neurally mediated via atropine-sensitive postganglionic cholinergic neurons. Gastroenteric neuropeptides do not exert any influence on cigarette smoke-mediated DMBS secretion in the rat. Unlike acute exposure to cigarette smoke, chronic exposure (4 and 8 days) of rats to cigarette smoke abolishes increase in DMBS induced by subsequent exposure to cigarette smoke. This last observation may, in part, may explain the tendency of chronic smokers who have duodenal bulb ulcers to show greater propensity to higher rate of recurrence and protracted healing.
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Affiliation(s)
- S Murthy
- Division of Gastroenterology and Hepatology, Allegheny University of the Health Sciences University, Philadelphia, PA 19102-1192, USA.
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34
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Affiliation(s)
- T Kamada
- First Department of Medicine, Osaka University School of Medicine, Suita, 565, Japan
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35
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Hunt RH, Cederberg C, Dent J, Halter F, Howden C, Marks IN, Rune S, Walt RP. Optimizing acid suppression for treatment of acid-related diseases. Dig Dis Sci 1995; 40:24S-49S. [PMID: 7859582 DOI: 10.1007/bf02214870] [Citation(s) in RCA: 58] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gastric acid is of central importance in the pathogenesis of duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Pharmacological reduction of acid secretion is, therefore, the mainstay of current treatment, but the optimal degree of acid suppression remains incompletely understood. This paper considers the ideal ways of assessing and reporting the pharmacological effectiveness of acid-inhibiting drugs and relating such data to clinical efficacy. Twenty-four-hour intragastric pH measurements are widely used for this purpose, although this technique cannot measure secretion quantitatively. Data on suppression of 24-hr intragastric acidity for groups of subjects have been successfully correlated with healing rates for duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Three primary determinants of healing have been derived from antisecretory data. These are the degree of suppression of acidity, the duration of suppression of acidity, and the duration of treatment. The order of importance of these determinants varies depending on the disease. Data on 24-hr intragastric acidity should be accompanied whenever possible by data on 24-hr plasma gastrin levels, as the relationship between suppression of acidity and a rise in gastrin varies widely between individuals. It is not possible to predict the plasma gastrin level from the intragastric pH or any other measurement of intragastric acidity. Comparative data sets in groups of subjects may provide useful information. Proton pump inhibitors produce a greater and longer-lasting degree of suppression of acidity than conventional doses of H2-receptor antagonists. For this reason, they are more effective in healing duodenal ulcer and gastric ulcer. However, in view of the importance of duration of treatment, healing rates with the H2-receptor antagonists approach those obtained with proton pump inhibitors if treatment is continued for a longer time. In gastroesophageal reflux disease in particular, although the optimal degree of acid suppression is not yet defined, the consistently superior performance of proton pump inhibitors demonstrates that increased suppression of acidity is clinically beneficial.
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Affiliation(s)
- R H Hunt
- Division of Gastroenterology, McMaster University Medical Center, Hamilton, Ontario, Canada
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36
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Scott AM, Kellow JE, Shuter B, Nolan JM, Hoschl R, Jones MP. Effects of cigarette smoking on solid and liquid intragastric distribution and gastric emptying. Gastroenterology 1993; 104:410-6. [PMID: 8425683 DOI: 10.1016/0016-5085(93)90408-5] [Citation(s) in RCA: 58] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The acute effects of cigarette smoking on gastric emptying are controversial, whereas its effects on the intragastric distribution of solids and liquids are not established. METHODS Dual isotope gastric scintigraphy was performed in 15 habitual smokers (studied twice, either sham smoking or actively smoking) and in 15 age- and sex-matched nonsmokers. RESULTS Acute smoking was associated with an increased prevalence of episodes of retrograde intragastric movement of solids (3 of 15 sham subjects vs. 12 of 15 actively smoking subjects; P < 0.01) and of liquids (0 of 15 vs. 7 of 15; P < 0.01) from distal to proximal stomach. Fundal half-emptying time (T1/2) for liquids was also prolonged by smoking (43 +/- 19 minutes sham vs. 125 +/- 216 minutes active; P < 0.05). Acute smoking delayed solid lag time (13 +/- 6 minutes sham vs. 32 +/- 18 active; P < 0.05) and liquid T1/2 (46 +/- 21 vs. 90 +/- 50 minutes; P < 0.05). In the nonsmokers, such episodes of proximal intragastric redistribution did not occur, and intragastric and overall emptying parameters did not differ significantly from those of habitual sham smokers. CONCLUSIONS Acute cigarette smoking produces excessive antrofundal redistribution of both solid and liquid contents and delays solid and liquid gastric emptying.
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Affiliation(s)
- A M Scott
- Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, Australia
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37
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Scott AM, Kellow JE, Eckersley GM, Nolan JM, Jones MP. Cigarette smoking and nicotine delay postprandial mouth-cecum transit time. Dig Dis Sci 1992; 37:1544-7. [PMID: 1396001 DOI: 10.1007/bf01296500] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The acute effects of both cigarette smoking and nicotine on postprandial mouth-cecum transit were studied in 20 habitual smokers, 10 males and 10 females. Mouth-cecum transit time was measured by the breath hydrogen technique, following ingestion of a standard mixed liquid meal. Each subject was studied on four separate occasions, either (1) sham or actively smoking two standard cigarettes, commencing 20 min after the meal, or (2) chewing two placebo or nicotine tablets over a 60-min period, commencing immediately after the meal. The time of administration of these stimuli was designed to minimize the effects on mouth-cecum transit time of alterations in gastric emptying. Mouth-cecum transit time was prolonged in response to both smoking [median and interquartile range: 120 (95, 150) min vs 100 (75, 140) min, P = 0.01] and nicotine [120 (80, 170) min vs 100 (70, 140) min, P = 0.002]. No difference was observed between sexes with respect to nicotine; the effect of smoking on mouth-cecum transit time, however, was less pronounced in females compared to males [difference active-placebo: 10 (10, 20) min vs 35 (20, 60) min, P = 0.01]. We conclude that acute cigarette smoking delays mouth-cecum transit time, an effect most likely due to nicotine.
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Affiliation(s)
- A M Scott
- Department of Medicine, Royal North Shore Hospital, Sydney, Australia
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38
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Gomita Y, Eto K, Furuno K, Mimaki Y, Araki Y. Influences of exposure to cigarette smoke on concentration of nicorandil in plasma of rats. J Pharm Sci 1992; 81:228-31. [PMID: 1386384 DOI: 10.1002/jps.2600810308] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Influences of acute exposure to cigarette smoke on plasma concentrations of nicorandil administered orally and parenterally were investigated in rats by HPLC. The animals were exposed to tobacco smoke of two kinds of cigarettes using a smoking machine (i.e., the cigarette smoke contained either low or high nicotine and tar). The plasma concentration of nicorandil administered orally at a dose of 10 mg/kg had a lower absorption phase in two cigarette smoke-exposed groups, particularly in the high nicotine and tar-containing cigarette smoke-exposed group, compared with the nonsmoking control group. The AUC and MRT values in a high nicotine and tar-containing cigarette smoke-exposed group were lower and higher, respectively, than in the nonsmoking control group. However, there was no marked difference in nicorandil plasma concentrations between the cigarette smoke-exposed group and the nonsmoking control group when nicorandil was administered ip or iv at a dose of 5 mg/kg. These results suggest that cigarette smoke exposure causes the suppression or delay of absorption of nicorandil from the gastrointestinal tract.
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Affiliation(s)
- Y Gomita
- Department of Hospital Pharmacy, Okayama University Medical School, Japan
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39
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Bynum TE. Clinical aspects of gastroduodenal ulcer recurrence: an overview. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1992; 191:1-3. [PMID: 1357739 DOI: 10.3109/00365529209093221] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Duodenal ulcer is a disease characterized by very high rates of recurrence: up to 80% at 1 year, 95% at 2 years. Maintenance therapy will reduce relapse rates. However, when therapy directed against gastric acid is stopped, the slope of the recurrence curve is identical whether therapy is stopped after 6 weeks, 8 weeks, 3 months, 6 months, 1 year, or 2 years. This suggests that therapy directed against acid does nothing to change the natural history of ulcer disease. Cytoprotective therapy is equally successful as H2-blockers at healing ulcer or reducing relapse rates, but the time to recurrence is significantly prolonged after either acute or maintenance cytoprotective therapy is stopped. This suggests that cytoprotective therapy has a beneficial effect that does improve the natural history of ulcer disease. The mechanism by which maintenance therapy reduces ulcer relapse could be masking symptoms (analgesic), accelerated healing, or true prevention of ulcer recurrence. By using frequent endoscopic assessment combined with complex statistical evaluation (calculating traditional ulcer prevalence, point prevalence, and maximal ulcer prevalence), we showed that sucralfate cytoprotection genuinely prevents ulcer recurrence. The incidence of asymptomatic ulcer recurrence after sucralfate is 10% but is up to 40% after H2-blocker therapy.
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Affiliation(s)
- T E Bynum
- Harvard Medical School, Boston, Massachusetts
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40
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Eto K, Gomita Y, Furuno K, Mimaki Y, Okazaki M, Araki Y. Influences of long-term cigarette smoke exposure on pharmacokinetics of theophylline, and on liver microsomal enzymes in rats. DRUG METABOLISM AND DRUG INTERACTIONS 1992; 10:265-77. [PMID: 1304445 DOI: 10.1515/dmdi.1992.10.4.265] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The influences of long-term cigarette smoke exposure on pharmacokinetics of oral theophylline (20 mg/kg), and on liver microsomal enzymes which metabolize drugs were studied in rats. Animals were exposed to cigarette smoke for 20 min each in the morning and evening every day for 26 days in the pharmacokinetic study, and 27 days for the enzyme assays. Theophylline was administered 13 h after the last exposure to smoke, and plasma concentrations were measured using HPLC. Plasma concentrations of theophylline during the absorption phase and 6 h after oral administration were lower in the long-term cigarette smoke-exposed group than in the control group. In the smoke-exposed group, the AUC and Ka were lower, and the Ke was slightly higher than in the control group. Liver weight and the ratio of liver weight to body weight were lower in the smoke-exposed group, and cytochrome b5 content and NADPH-cytochrome P-450 reductase activity were higher, but cytochrome P-450 content did not differ from the control group. These results indicate that long-term exposure to cigarette smoke suppresses theophylline absorption from the gastrointestinal tract, accelerates its elimination, and affects liver microsomal enzymes which metabolize drugs.
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Affiliation(s)
- K Eto
- Department of Hospital Pharmacy, Okayama University Medical School, Japan
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41
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Abstract
The maxim "once an ulcer, always an ulcer" is still an appropriate description for the chronic nature of peptic ulcer disease. The goals for treating patients with ulcer disease are to relieve symptoms, heal the acute ulcer, reduce the risk of ulcer recurrence and complications, and decrease the economic impact of this chronic disease while maintaining the patient's quality of life. Patients with documented peptic ulcer disease should be carefully evaluated and a treatment plan devised that takes into account the possible need for maintenance therapy. Risk factors that seem to reflect a high likelihood of ulcer recurrence should be identified early in all ulcer patients and attempts made to minimize or correct them in the future. Assuming that a diagnosis of peptic ulcer disease has been firmly established and an adequate period of drug treatment makes complete ulcer healing likely, a reasonable way to proceed is outlined in Figure 4. If the patient is young and generally healthy, has an uncomplicated ulcer and few risk factors favoring ulcer relapse, either no treatment or symptomatic selfcare would be reasonable. If one chooses the latter course, the patient can be given a prescription for 3 to 6 months of medication and told to take full therapy for any recurrent symptoms, continuing the treatment until symptoms are relieved. The failure of such treatment to relieve symptoms after 2 to 3 weeks, the onset of alarming symptoms such as intense pain, vomiting, or melena, or possibly the exhaustion of the 6-month supply of medication with continued mild symptoms should lead to reevaluation. Alternatively, such a patient could be managed with no therapy and seen again if ulcer symptoms recur and reevaluated for further diagnosis and treatment. Obviously, patients who are candidates for these approaches to postulcer healing management are those with a low risk for ulcer recurrence and who are likely to be compliant with follow-up advice. Accordingly, careful patient selection seems most important in prescribing symptomatic self-care or intermittent full-dose maintenance treatment. On the other hand, if the patient has had a complicated course of ulcer disease, such as bleeding, or has a significant number of risk factors that would make early ulcer relapse highly likely, it would be prudent to institute continuous maintenance therapy while working to reduce or eliminate the adverse risk factors. Any relapse of symptomatic ulcer disease during noncontinuous maintenance therapy should indicate the need for return to a continuous dosing program.(ABSTRACT TRUNCATED AT 400 WORDS)
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Affiliation(s)
- D L Earnest
- Section of Gastroenterology, University of Arizona Health Sciences Center, Tucson
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42
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Abstract
Despite extensive research, the etiology of peptic ulcer disease remains unclear. Given the multiple processes that control acid and pepsin secretion and defense and repair of the gastroduodenal mucosa, it is likely that the cause of ulceration differs between individuals. Acid and pepsin appear to be necessary but not sufficient ingredients in the ulcerative process. It is clear that the majority of gastric ulcers and a substantial number of duodenal ulcers do not have increased gastric acid secretion. Recent research has focused more on protection and repair of the stomach and duodenum. NSAIDs cause a significant number of gastric and duodenal ulcers; this is probably due to inhibition of prostaglandin production with loss of its protective effects. In the absence of NSAIDs and gastrinoma, it appears that most gastric ulcers and all duodenal ulcers occur in the setting of H. pylori infection. Evidence is mounting in support of H. pylori as a necessary ingredient in the ulcerative process, similar to acid and pepsin. It is not known whether the bacteria or the accompanying inflammation is the more important factor in the pathophysiology. Although the pathophysiology of gastric ulcer and duodenal ulcer is similar, there are clearly differences between the two groups. Duodenal ulcer is typified by H. pylori infection and duodenitis and in many cases impaired duodenal bicarbonate secretion in the face of moderate increases in acid and peptic activity. These facts suggest the following process: increased peptic activity coupled with decreased duodenal buffering capacity may lead to increased mucosal injury and result in gastric metaplasia. In the presence of antral H. pylori, the gastric metaplasia can become colonized and inflamed. The inflammation or the infection itself then disrupts the process of mucosal defense or regeneration resulting in ulceration. A cycle of further injury and increased inflammation with loss of the framework for regeneration may then cause a chronic ulcer. Gastric ulcer often occurs with decreased acid-peptic activity, suggesting that mucosal defensive impairments are more important. The combination of inflammation, protective deficiencies, and moderate amounts of acid and pepsin may be enough to induce ulceration. Many questions remain in understanding the pathophysiology of peptic ulcer disease. The physiology and pathophysiology of mucosal regeneration and the mechanisms by which H. pylori and inflammation disrupt normal gastroduodenal function will be fruitful areas of future investigation.
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Affiliation(s)
- H R Mertz
- Department of Medicine, University of California, School of Medicine, Los Angeles
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43
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Burman P, Mårdh S, Lööf L, Naesdal J, Karlsson FA. Peptic ulcer disease: absence of antibodies stimulating the histamine sensitive adenylate cyclase of gastric mucosal cells. Gut 1991; 32:620-3. [PMID: 1648024 PMCID: PMC1378875 DOI: 10.1136/gut.32.6.620] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The possible presence of parietal cell stimulating antibodies was examined in sera from 57 patients with relapsing ulcer disease. The sera were obtained at the time of symptomatic relapse and all patients had ulcers confirmed by endoscopy. A sensitive assay based on adenosine 3':5' cyclic monophosphate (cAMP) production in isolated porcine gastric mucosal cells was used as a measure. cAMP production increased up to four hours of incubation and was histamine responsive; an approximately 20-fold increase was found with histamine 10(-4) mol/l. Sera from both patients and healthy control subjects showed some inhibitory effect on basal cAMP production compared with incubation in medium only, whereas immunoglobulin preparations had a weaker non-specific effect. No stimulation was found when the patients' sera and immunoglobulins (up to a concentration of 6 mg/ml) were examined. These results suggest that gastric acid hypersecretion in duodenal ulcer disease is not an effect of histamine receptor stimulating antibodies. The data thus argue against a recent hypothesis that severe chronic ulcer disease in some patients has an autoimmune origin.
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Affiliation(s)
- P Burman
- Department of Internal Medicine, Uppsala University, Sweden
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44
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Eto K, Gomita Y, Furuno K, Yao K, Moriyama M, Araki Y. Influences of cigarette smoke inhalation on pharmacokinetics of cimetidine in rats. DRUG METABOLISM AND DRUG INTERACTIONS 1991; 9:103-14. [PMID: 1800017 DOI: 10.1515/dmdi.1991.9.2.103] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The influences of cigarette smoke inhalation on the pharmacokinetics of cimetidine administered orally and parenterally were investigated in rats using a smoking machine. The animals were exposed to two kinds of cigarette smoke, low- or high-nicotine.tar, inhaled for 10 min immediately after oral (50 mg/kg), intraperitoneal (25 mg/kg) or intravenous (10 mg/kg) administration of cimetidine. The plasma level after cimetidine was administered orally was lower in the absorption phase in the two cigarette smoke inhaling groups than in the non-smoking control group, and was particularly marked in the high-nicotine.tar cigarette smoke inhaling group. In contrast, no significant difference was found in cimetidine plasma level between the cigarette smoke inhaling groups and the non-smoking control group when administered intraperitoneally or intravenously. These results suggest that cigarette smoke inhalation may cause a suppression or a delay in cimetidine absorption from the gastrointestinal tract, and that the degree of influence is dependent upon the content of nicotine.tar in the cigarette smoke.
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Affiliation(s)
- K Eto
- Department of Hospital Pharmacy, Okayama University Dental School, Japan
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45
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Kaufmann D, Wilder-Smith CH, Kempf M, Neumann J, Schmolls H, Witzel L, Walt RP, Röhmel J, Merki HS. Cigarette smoking, gastric acidity and peptic ulceration. What are the relationships? Dig Dis Sci 1990; 35:1482-7. [PMID: 2253533 DOI: 10.1007/bf01540565] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The influence of cigarette smoking on intragastric acidity was assessed in duodenal ulcer patients in symptomatic remission and in healthy volunteers in a retrospective study. Continuous 24-hr pH recordings in 150 nonsmokers and 174 smokers receiving placebo treatment were compared. Daytime intragastric acidity was higher in smokers with a median pH (interquartile range) of 1.56 (1.34-1.80) than in nonsmokers, who had a median pH of 1.70 (1.45-1.97) (P less than 0.001). There was no difference in 24-hr and nighttime median pH between the two groups. The small difference in daytime intragastric acidity in smokers and nonsmokers is unlikely to account for the increased prevalence of peptic ulcer disease in smokers. The analysis of smoking status in duodenal ulcer patients and healthy controls and males and females supports the general trend towards higher daytime acidity in smokers. Again, no differences in pH during the 24-hr or night period were found between the groups. The epidemiological and clinical correlation between smoking and duodenal ulcer disease is not adequately explained by increased intragastric acidity.
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Affiliation(s)
- D Kaufmann
- Department of Medicine, Inselspital, University of Berne, Switzerland
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46
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Lau PP, Dubick MA, Yu GS, Morrill PR, Geokas MC. Dynamic changes of pancreatic structure and function in rats treated chronically with nicotine. Toxicol Appl Pharmacol 1990; 104:457-65. [PMID: 1696755 DOI: 10.1016/0041-008x(90)90167-s] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Adult, male Sprague-Dawley rats weighing initially 185-225 g, were treated with 5, 15, or 50 mg nicotine or placebo 3-week-release pellets by sc implantation, for 1.5, 3, 6 and 12 weeks. These doses of nicotine correspond to infusion rates of 9.9, 29.8, and 99.2 micrograms/h, respectively. At the highest nicotine dose trypsin and chymotrypsin activities were markedly higher in pancreas from 12-week nicotine-treated rats compared with controls. This was associated with a fourfold increase in steady-state amylase mRNA levels in comparison to placebo controls. In addition, secretagogue-stimulated enzyme release from pancreatic acini isolated from rats treated with 50 mg nicotine pellets was significantly higher than controls at 1.5 and 3 weeks and declined below control levels after 12 weeks of treatment. In rats treated with 15-mg nicotine pellets, maximal secretagogue-stimulated enzyme release from isolated acini occurred at 1.5 weeks, declining thereafter to control levels. Electron microscopy of pancreas from rats treated with the 50 mg nicotine dose revealed intracytoplasmic vaculoes appearing after 3 weeks of treatment, and persisting throughout the remaining experimental period. It is concluded that 12-week nicotine treatment results in increased pancreatic enzyme biosynthesis and accumulation of digestive enzymes within the pancreas. This is associated with altered responsiveness to secretagogues and evidence of morphological damage.
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Affiliation(s)
- P P Lau
- Department of Medicine, Department of Veterans Affairs Medical Center, Martinez, California 94553
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47
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Glise H. Epidemiology in peptic ulcer disease. Current status and future aspects. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1990; 175:13-8. [PMID: 2237275 DOI: 10.3109/00365529009093122] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Peptic ulcer incidence is declining. A decreased prevalence of smokers together with other factors have contributed to this change. The widespread use of non-steroidal anti-inflammatory drugs (NSAID) has increased the incidence of ulcer in the older population and serious complications, such as perforation and bleeding, have been observed especially in older women. Helicobacter pylori infection is virtually always present in duodenal and gastric ulcer and active chronic gastritis, but not prepyloric ulcer. The fact that this organism is not eradicated with the use of most drugs for peptic ulcer may explain the high rate of recurrence in ulcer disease since relapse rates are reported to be considerably lower when H. pylori is eradicated. In a substantial number of patients peptic ulcers are silent. These fall into two categories: the regular ulcer patient with relapses that heal spontaneously and rarely cause problems, and older patients without prior ulcer disease receiving NSAID treatment, presenting with a life-threatening complication as the first indication of ulcer disease. Despite all the new knowledge of peptic ulcer disease presented, the questions still outnumber the answers; it is therefore suggested that future research focus on the role of NSAIDs and H. pylori.
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Affiliation(s)
- H Glise
- Dept. of Surgery, NAL, Trollhättan, Sweden
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48
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Hosotani R, Chowdhury P, McKay D, Rayford PL. Mechanism of action of nicotine on amylase release by isolated pancreatic acini. Pharmacol Biochem Behav 1989; 33:663-6. [PMID: 2479952 DOI: 10.1016/0091-3057(89)90405-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The effects of nicotine on the pH of acinar suspension, amylase release and on amylase response stimulated by carbachol were examined in isolated rat pancreatic acini. Additions of nicotine at concentrations ranging from 10 microM to 30 mM caused dose-dependent increases in pH of acinar suspension with simultaneous amylase release (p less than 0.05). There was no increase in amylase release when acinar cells were incubated with nicotine adjusted to pH 7.40. Carbachol alone released amylase whereas nicotine (pH 7.40) at a concentration of 10 mM caused a significant and nonparallel inhibition of amylase release in response to graded doses of carbachol. At concentrations ranges between 3 microM and 10 mM, nicotine at pH 7.40 inhibited amylase release stimulated by 1 microM carbachol, with a half maximal inhibition at 0.8 +/- 0.2 mM. These results indicate that in isolated rat pancreatic acini nicotine at pH 7.40 has no effect on basal nonstimulated amylase release but it inhibits carbachol-stimulated amylase response in a noncompetitive manner. These observations may have direct implications in underlying mechanism of pancreatic disorders.
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Affiliation(s)
- R Hosotani
- Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock 72205
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Kawano S, Sato N, Tsuji S, Ogihara T, Tanimura H, Ito T, Tsujii M, Hayashi N, Sakura H, Kamada T. Effect of cigarette smoking on the gastric mucosal blood volume index and hemoglobin oxygenation in man. GASTROENTEROLOGIA JAPONICA 1989; 24:1-7. [PMID: 2707547 DOI: 10.1007/bf02774862] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The acute effect of cigarette smoking on the gastric mucosal blood volume index and the oxygen saturation of hemoglobin (SO2) in the gastric mucosa was investigated in 12 young male volunteers using reflectance spectrophotometry during endoscopy. Six of these volunteers were habitual smokers who had smoked more than 20 cigarettes a day for more than five years. The others were non-habitual smokers who smoked less than 20 cigarettes a year. The indices of mucosal blood volume and the mucosal blood SO2 level were calculated from the spectra obtained at the lesser curvature of the lower corpus of the stomach before and after cigarette smoking. The indices of mucosal blood volume and mucosal blood SO2 decreased significantly after one to three puffs of cigarette smoking in all subjects as compared to the value before smoking, and the degree of decrease in these parameters was significantly greater in the non-habitual smokers than in the habitual smokers. These results suggest that only one to three puffs of cigarette smoking causes a decrease in the mucosal blood volume and the mucosal blood SO2 which might be related to weakening of mucosal defensive factors.
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Affiliation(s)
- S Kawano
- First Department of Internal Medicine, Osaka University Medical School, Japan
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50
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Chowdhury P, Hosotani R, Rayford PL. Inhibition of CCK or carbachol-stimulated amylase release by nicotine. Life Sci 1989; 45:2163-8. [PMID: 2481202 DOI: 10.1016/0024-3205(89)90083-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
This study was undertaken to investigate the mechanisms of action of nicotine on receptor mediated enzyme secretion in isolated rat pancreatic acini. Acinar cells were isolated from untreated and nicotine treated rats by collagenase digestion and differential centrifugation. Cells from the untreated animals were incubated with either varying concentrations of nicotine (range 10 microM to 30 mM) or with a fixed dose of 10 mM nicotine with varying concentrations of carbachol(10nM to 100 microM). Cells from the nicotine treated animals(16 weeks in drinking water) were incubated with either a fixed dose of CCK-8(10(-10) M) or carbachol(10(-5) M). All incubations were conducted at 37 C for 30 min. Amylase released in the media was measured by spectrophotometry. In pancreatic acinar cells isolated from control rats, amylase release stimulated by carbachol was inhibited by nicotine. Acinar cells isolated from rats treated with nicotine at nicotine concentrations of 1.23 mM also showed significant inhibition of amylase release in response to CCK-8 and carbachol compared to their identical controls. Nicotine induced inhibition curves of amylase release stimulated by carbachol were non-parallel suggesting that the effect of nicotine on acinar cells is regulated by mechanisms other than carbachol receptors. Nicotine may have a direct inhibitory effect on the intracellular mechanisms of pancreatic enzyme secretion. We conclude that the mechanism by which nicotine inhibits pancreatic enzyme secretion is complex.
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Affiliation(s)
- P Chowdhury
- Department of Physiology and Biophysics, University of Arkansas For Medical Sciences, Little Rock 72205
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