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Song X, Qiao L, Dou X, Chang J, Zeng X, Deng T, Yang G, Liu P, Wang C, Xu Q, Xu C. Hypertriglyceridemia-modulated gut microbiota promotes lysophosphatidylcholine generation to aggravate acute pancreatitis in a TLR4-dependent manner. IMETA 2025; 4:e70003. [PMID: 40027483 PMCID: PMC11865321 DOI: 10.1002/imt2.70003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 03/05/2025]
Abstract
Hypertriglyceridemia (HTG) can lead to the disorder of gut microbiota in mice, resulting in the increase of endotoxin content. HTG can also aggravate the damage of intestinal barrier function and intestinal bacterial translocation in acute pancreatitis (AP) mice. Toll-like receptor 4 gene (Tlr4) knockout can significantly reduce gut permeability and endotoxin invasion in AP mice. In addition, HTG-modulated gut microbiota could up-regulate glycerophospholipid metabolism and increase lysophosphatidylcholine (LysoPC) content in a TLR4-dependent manner, thereby aggravating pancreatic injury in AP.
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Affiliation(s)
- Xiaofan Song
- School of Life SciencesNorthwestern Polytechnical UniversityXi'anChina
| | - Lei Qiao
- School of Life SciencesNorthwestern Polytechnical UniversityXi'anChina
| | - Xina Dou
- School of Life SciencesNorthwestern Polytechnical UniversityXi'anChina
| | - Jiajing Chang
- School of Life SciencesNorthwestern Polytechnical UniversityXi'anChina
| | - Xiaonan Zeng
- School of Life SciencesNorthwestern Polytechnical UniversityXi'anChina
| | - Tianjing Deng
- School of Life SciencesNorthwestern Polytechnical UniversityXi'anChina
| | - Ge Yang
- School of Life SciencesNorthwestern Polytechnical UniversityXi'anChina
| | - Peiyun Liu
- School of Life SciencesNorthwestern Polytechnical UniversityXi'anChina
| | | | - Qinhong Xu
- Department of Geriatric Surgerythe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
| | - Chunlan Xu
- School of Life SciencesNorthwestern Polytechnical UniversityXi'anChina
- Department of Geriatric Surgerythe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina
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Chen YC, Wang HY, Ogita F, Hung CH, Kuo CH, Wang JP, Wang CM, Hou CW, Wang TY. Effects of probiotic supplementation with high-intensity interval training on cardiorespiratory endurance and metabolism in Middle-Aged Obese Women. J Int Soc Sports Nutr 2024; 21:2425609. [PMID: 39618097 PMCID: PMC11613408 DOI: 10.1080/15502783.2024.2425609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 10/18/2024] [Indexed: 12/06/2024] Open
Abstract
INTRODUCTION High-intensity interval training (HIIT) has been shown to improve chronic diseases. Probiotics have been found to have similar effects. However, the additive effects of HIIT in combination with probiotics supplementation are unclear. The aim of current study was to investigate whether there were additive effects when implementing both HIIT and probiotics simultaneously. METHODS Forty-seven obese middle-aged women (Age: 44.5 ± 5.94 years, body fat percentage: 40.0 ± 4.1%) were recruited and assigned into four groups: control group (C, n = 12), probiotics group (P, n = 12), HIIT group (H, n = 11), and HIIT with probiotics group (HP, n = 12). All the participants consumed probiotics (Lactiplantibacillus plantarum TWK10, 6 × 1010 CFU/day) or placebo supplements daily. Exercise intervention groups conducted HIIT training (85-90% vVO2max for 2 min, followed by a 1-min inactive rest interval, repeated for 7 cycles) 3 sessions per week for 8 weeks. Anthropometry, cardiorespiratory endurance, blood glucose, and lipid profile were measured at baseline and after the 8-week intervention. RESULTS After the intervention, there were significant changes between groups in the variations and rates of change in waist circumference, hip circumference, and TTE. The waist circumference in group H significantly increased compared to groups C and P, while group HP did not show significant difference compared to group C. On the other hand, the hip circumference decreased significantly in group HP compared to group C, and the decreased rate in group HP was significantly greater than in groups C and P. Furthermore, the increase rates in TTE were higher in group H and HP compared to group C. CONCLUSION HIIT improves TTE but negatively affects waist circumference compared to the control group. However, when combined with probiotics, the probiotics not only help enhance TTE but also counteract the negative impact on waist circumference and further reduce hip circumference, resulting in a synergistic effect. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT06285578.
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Affiliation(s)
- Yi-Chen Chen
- University of Taipei, Laboratory of Exercise Biochemistry, Institute of Sports Sciences, Taipei, Taiwan
- National Institute of Fitness and Sports in Kanoya, Department of Sports and Life Sciences, Kanoya, Japan
| | - Hsuan-Yun Wang
- Shih Hsin University, Office of Physical Education, Taipei, Taiwan
| | - Futoshi Ogita
- National Institute of Fitness and Sports in Kanoya, Department of Sports and Life Sciences, Kanoya, Japan
| | - Chi-Hsiang Hung
- University of Taipei, Department of Ball Sports, Taipei, Taiwan
| | - Chia-Hua Kuo
- University of Taipei, Laboratory of Exercise Biochemistry, Institute of Sports Sciences, Taipei, Taiwan
| | - Jie-Ping Wang
- Hubei University, School of Physical Education, Wuhan, China
| | - Chia-Min Wang
- Soochow University, Office of Physical Education, Taipei, Taiwan
| | - Chien-Wen Hou
- University of Taipei, Laboratory of Exercise Biochemistry, Institute of Sports Sciences, Taipei, Taiwan
| | - Ting-Yao Wang
- Center of Physical Education, Tzu Chi University,Hualien, Taiwan
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Gu R, Wei H, Cui T, Wang G, Luan Y, Liu R, Yin C. Angiotensin-(1-7) improves intestinal microbiota disturbances and modulates fecal metabolic aberrations in acute pancreatitis. FASEB J 2024; 38:e70134. [PMID: 39453737 DOI: 10.1096/fj.202401565rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 10/07/2024] [Accepted: 10/15/2024] [Indexed: 10/27/2024]
Abstract
Acute pancreatitis (AP) is a serious health problem that dysregulates intestinal microbiota. Angiotensin (Ang)-(1-7) plays a protective role in the intestinal barrier in AP, but its effect on intestinal microbiota remains clear. To investigate the impact of Ang-(1-7) on AP-induced intestinal microbiota disorder and metabolites. We collected blood and fecal samples from 31 AP patients within 48 h after admission to the hospital, including 11 with mild AP (MAP), 14 with moderately severe AP (MSAP), six with severe AP (SAP). Mice were divided into four groups: control, AP, AP + Ang-(1-7) via tail vein injection, and AP + Ang-(1-7) via oral administration. The samples of mice were collected 12 h after AP. Pancreatic and intestinal histopathology scores were analyzed using the Schmidt and Chiu scores. Fecal microbiota and metabolites analysis was performed via 16S rDNA sequencing and nontargeted metabolomics analysis, respectively. In patients, the abundance of beneficial bacteria (Negativicutes) decreased and pathogenic bacteria (Clostridium bolteae and Ruminococcus gnavus) increased in SAP compared with MAP. Ang-(1-7) levels were associated with changes in the microbiota. There were differences in the intestinal microbiota between control and AP mice. Ang-(1-7) attenuated intestinal microbiota dysbiosis in AP mice, reflecting in the increase in beneficial bacteria (Odoribacter and Butyricimonas) than AP, as well as pancreatic and intestinal injuries. Oral administration of Ang-(1-7) reversing AP-induced decreases in metabolisms: secondary bile acids, emodin, and naringenin. Ang-(1-7) may improve intestinal microbiota dysbiosis and modulate fecal metabolites in AP, thereby reducing the damage of AP.
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Affiliation(s)
- Ruru Gu
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
- Department of Gastroenterology, the Second Hospital of Shandong University, Jinan, China
| | - Hongtao Wei
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Tianyu Cui
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
| | - Guoxing Wang
- Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yingyi Luan
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
| | - Ruixia Liu
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
| | - Chenghong Yin
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China
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Górski P, Swidnicka-Siergiejko A. Feeding Intolerance-A Key Factor in the Management of Acute Pancreatitis: A Review. J Clin Med 2024; 13:6361. [PMID: 39518500 PMCID: PMC11546861 DOI: 10.3390/jcm13216361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 09/23/2024] [Accepted: 10/03/2024] [Indexed: 11/16/2024] Open
Abstract
Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, which in 20% of cases can turn into a severe form, with mortality reaching up to 30%. One of the cornerstones of AP treatment is early nutritional treatment. Feeding intolerance (FI) occurs in up to 25% of patients with AP and is associated with a more severe disease course and poorer clinical outcome. Feeding intolerance can have a multifaceted clinical presentation. The early identification of FI risk factors and appropriately conducted nutritional treatment are critical to the course of the disease. In this review, we summarize the current knowledge of feeding intolerance in AP, its pathomechanisms and risk factors, and its impact on disease progression. We also present suggestions for the management of feeding intolerance.
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Affiliation(s)
- Piotr Górski
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, ul. M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
| | - Agnieszka Swidnicka-Siergiejko
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, ul. M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland
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Bukowski JS, Jamer T, Kowalska-Duplaga K, Marczuk M, Stelmaszczyk-Emmel A, Banasiuk M, Banaszkiewicz A. Very early and early nutrition in children with pancreatitis-A randomised trial. J Pediatr Gastroenterol Nutr 2024; 79:343-351. [PMID: 38938000 DOI: 10.1002/jpn3.12301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 06/03/2024] [Accepted: 06/17/2024] [Indexed: 06/29/2024]
Abstract
OBJECTIVES The aim of our study was to assess the impact of the very early introduction of refeeding on the course of acute pancreatitis (AP) in children. Additionally, we evaluated the effect of nutrition on inflammatory markers, including cytokines. METHODS This prospective randomised study was conducted in three university hospitals in Poland. Patients, aged 1-18 years with AP, were randomised into two groups: A-refeeding within 24 h of hospital admission (very early), and B-refeeding at least 24 h after admission (early nutrition). The severity of AP was assessed after 48 h. The serum concentrations of four cytokines (tumour necrosis factor α [TNFα], interleukin-1β [IL-1β], interleukin-6 [IL-6] and interleukin-8 [IL-8]) and C-reactive protein, as well as the activity of amylase, lipase and aminotransferases, were measured during the first 3 days of hospitalisation. RESULTS A total of 94 children were recruited to participate in the study. The statistical analysis included 75 patients with mild pancreatitis: 42-group A and 33-group B. The two groups did not differ in the length of hospitalisation (p = 0.22), AP symptoms or results of laboratory tests. Analysis of cytokine levels was conducted for 64 children: 38-group A and 26-group B. We did not find a difference in concentrations of the measured cytokines, except for IL-1β on the third day of hospitalisation (p = 0.01). CONCLUSIONS The time of initiation of oral nutrition within 24 h (very early) or after 24 h (early) from the beginning of hospitalisation had no impact on the length of hospitalisation, concentrations of TNF-α, IL-1β, IL-6 and IL-8, activity of amylase and lipase or occurrence of symptoms in children with mild AP.
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Affiliation(s)
- Jan S Bukowski
- Department of Paediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland
| | - Tatiana Jamer
- Department of Paediatrics, Gastroenterology and Nutrition, Wroclaw Medical University, Wroclaw, Poland
| | - Kinga Kowalska-Duplaga
- Department of Paediatrics, Gastroenterology and Nutrition, Jagiellonian University Medical College, Cracow, Poland
| | - Martyna Marczuk
- Department of Paediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland
| | - Anna Stelmaszczyk-Emmel
- Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland
| | - Marcin Banasiuk
- Department of Paediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland
| | - Aleksandra Banaszkiewicz
- Department of Paediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland
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6
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Tsomidis I, Voumvouraki A, Kouroumalis E. The Pathogenesis of Pancreatitis and the Role of Autophagy. GASTROENTEROLOGY INSIGHTS 2024; 15:303-341. [DOI: 10.3390/gastroent15020022] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
The pathogenesis of acute and chronic pancreatitis has recently evolved as new findings demonstrate a complex mechanism operating through various pathways. In this review, the current evidence indicating that several mechanisms act in concert to induce and perpetuate pancreatitis were presented. As autophagy is now considered a fundamental mechanism in the pathophysiology of both acute and chronic pancreatitis, the fundamentals of the autophagy pathway were discussed to allow for a better understanding of the pathophysiological mechanisms of pancreatitis. The various aspects of pathogenesis, including trypsinogen activation, ER stress and mitochondrial dysfunction, the implications of inflammation, and macrophage involvement in innate immunity, as well as the significance of pancreatic stellate cells in the development of fibrosis, were also analyzed. Recent findings on exosomes and the miRNA regulatory role were also presented. Finally, the role of autophagy in the protection and aggravation of pancreatitis and possible therapeutic implications were reviewed.
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Affiliation(s)
- Ioannis Tsomidis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Crete, Greece
| | - Argyro Voumvouraki
- 1st Department of Internal Medicine, AHEPA University Hospital, 54621 Thessaloniki, Greece
| | - Elias Kouroumalis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Crete, Greece
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Tomaszewska E, Świątkiewicz M, Muszyński S, Donaldson J, Ropka-Molik K, Arciszewski MB, Murawski M, Schwarz T, Dobrowolski P, Szymańczyk S, Dresler S, Bonior J. Repetitive Cerulein-Induced Chronic Pancreatitis in Growing Pigs-A Pilot Study. Int J Mol Sci 2023; 24:ijms24097715. [PMID: 37175426 PMCID: PMC10177971 DOI: 10.3390/ijms24097715] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/20/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
Chronic pancreatitis (CP) is an irreversible and progressive inflammatory disease. Knowledge on the development and progression of CP is limited. The goal of the study was to define the serum profile of pro-inflammatory cytokines and the cell antioxidant defense system (superoxidase dismutase-SOD, and reduced glutathione-GSH) over time in a cerulein-induced CP model and explore the impact of these changes on selected cytokines in the intestinal mucosa and pancreatic tissue, as well as on selected serum biochemical parameters. The mRNA expression of CLDN1 and CDH1 genes, and levels of Claudin-1 and E-cadherin, proteins of gut barrier, in the intestinal mucosa were determined via western blot analysis. The study showed moderate pathomorphological changes in the pigs' pancreas 43 days after the last cerulein injection. Blood serum levels of interleukin (IL)-1-beta, IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGTP), SOD and GSH were increased following cerulein injections. IL-1-beta, IL-6, TNF-alpha and GSH were also increased in jejunal mucosa and pancreatic tissue. In duodenum, decreased mRNA expression of CDH1 and level of E-cadherin and increased D-lactate, an indicator of leaky gut, indicating an inflammatory state, were observed. Based on the current results, we can conclude that repetitive cerulein injections in growing pigs not only led to CP over time, but also induced inflammation in the intestine. As a result of the inflammation, the intestinal barrier was impaired.
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Affiliation(s)
- Ewa Tomaszewska
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Małgorzata Świątkiewicz
- Department of Animal Nutrition and Feed Science, National Research Institute of Animal Production, 32-083 Balice, Poland
| | - Siemowit Muszyński
- Department of Biophysics, Faculty of Environmental Biology, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Janine Donaldson
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg 2193, South Africa
| | - Katarzyna Ropka-Molik
- Department of Animal Molecular Biology, National Research Institute of Animal Production, 32-083 Balice, Poland
| | - Marcin B Arciszewski
- Department of Animal Anatomy and Histology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Maciej Murawski
- Department of Animal Nutrition, Biotechnology and Fisheries, Faculty of Animal Science, University of Agriculture in Kraków, 30-059 Kraków, Poland
| | - Tomasz Schwarz
- Department of Animal Genetics, Breeding and Ethology, Faculty of Animal Science, University of Agriculture in Kraków, 30-059 Kraków, Poland
| | - Piotr Dobrowolski
- Department of Functional Anatomy and Cytobiology, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, 20-033 Lublin, Poland
| | - Sylwia Szymańczyk
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland
| | - Sławomir Dresler
- Department of Analytical Chemistry, Medical University of Lublin, 20-059 Lublin, Poland
- Department of Plant Physiology and Biophysics, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, 20-033 Lublin, Poland
| | - Joanna Bonior
- Department of Medical Physiology, Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-126 Kraków, Poland
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Venkatesh K, Glenn H, Delaney A, Andersen CR, Sasson SC. Fire in the belly: A scoping review of the immunopathological mechanisms of acute pancreatitis. Front Immunol 2023; 13:1077414. [PMID: 36713404 PMCID: PMC9874226 DOI: 10.3389/fimmu.2022.1077414] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 12/21/2022] [Indexed: 01/13/2023] Open
Abstract
Introduction Acute pancreatitis (AP) is characterised by an inflammatory response that in its most severe form can cause a systemic dysregulated immune response and progression to acute multi-organ dysfunction. The pathobiology of the disease is unclear and as a result no targeted, disease-modifying therapies exist. We performed a scoping review of data pertaining to the human immunology of AP to summarise the current field and to identify future research opportunities. Methods A scoping review of all clinical studies of AP immunology was performed across multiple databases. Studies were included if they were human studies of AP with an immunological outcome or intervention. Results 205 studies met the inclusion criteria for the review. Severe AP is characterised by significant immune dysregulation compared to the milder form of the disease. Broadly, this immune dysfunction was categorised into: innate immune responses (including profound release of damage-associated molecular patterns and heightened activity of pattern recognition receptors), cytokine profile dysregulation (particularly IL-1, 6, 10 and TNF-α), lymphocyte abnormalities, paradoxical immunosuppression (including HLA-DR suppression and increased co-inhibitory molecule expression), and failure of the intestinal barrier function. Studies including interventions were also included. Several limitations in the existing literature have been identified; consolidation and consistency across studies is required if progress is to be made in our understanding of this disease. Conclusions AP, particularly the more severe spectrum of the disease, is characterised by a multifaceted immune response that drives tissue injury and contributes to the associated morbidity and mortality. Significant work is required to develop our understanding of the immunopathology of this disease if disease-modifying therapies are to be established.
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Affiliation(s)
- Karthik Venkatesh
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
- The Kirby Institute, The University of New South Wales, Kensington, NSW, Australia
| | - Hannah Glenn
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
| | - Anthony Delaney
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
- Division of Critical Care, The George Institute for Global Health, Newtown, NSW, Australia
| | - Christopher R. Andersen
- Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia
- The Kirby Institute, The University of New South Wales, Kensington, NSW, Australia
- Division of Critical Care, The George Institute for Global Health, Newtown, NSW, Australia
| | - Sarah C. Sasson
- The Kirby Institute, The University of New South Wales, Kensington, NSW, Australia
- Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia
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Liu D, Wen L, Wang Z, Hai Y, Yang D, Zhang Y, Bai M, Song B, Wang Y. The Mechanism of Lung and Intestinal Injury in Acute Pancreatitis: A Review. Front Med (Lausanne) 2022; 9:904078. [PMID: 35872761 PMCID: PMC9301017 DOI: 10.3389/fmed.2022.904078] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 05/10/2022] [Indexed: 12/12/2022] Open
Abstract
Acute pancreatitis (AP), as a common cause of clinical acute abdomen, often leads to multi-organ damage. In the process of severe AP, the lungs and intestines are the most easily affected organs aside the pancreas. These organ damages occur in succession. Notably, lung and intestinal injuries are closely linked. Damage to ML, which transports immune cells, intestinal fluid, chyle, and toxic components (including toxins, trypsin, and activated cytokines to the systemic circulation in AP) may be connected to AP. This process can lead to the pathological changes of hyperosmotic edema of the lung, an increase in alveolar fluid level, destruction of the intestinal mucosal structure, and impairment of intestinal mucosal permeability. The underlying mechanisms of the correlation between lung and intestinal injuries are inflammatory response, oxidative stress, and endocrine hormone secretion disorders. The main signaling pathways of lung and intestinal injuries are TNF-α, HMGB1-mediated inflammation amplification effect of NF-κB signal pathway, Nrf2/ARE oxidative stress response signaling pathway, and IL-6-mediated JAK2/STAT3 signaling pathway. These pathways exert anti-inflammatory response and anti-oxidative stress, inhibit cell proliferation, and promote apoptosis. The interaction is consistent with the traditional Chinese medicine theory of the lung being connected with the large intestine (fei yu da chang xiang biao li in Chinese). This review sought to explore intersecting mechanisms of lung and intestinal injuries in AP to develop new treatment strategies.
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Affiliation(s)
- Dongling Liu
- School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China
| | - Linlin Wen
- School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
- County People’s Hospital, Pingliang, China
| | - Zhandong Wang
- School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
| | - Yang Hai
- Gansu University of Chinese Medicine/Scientific Research and Experimental Center, Lanzhou, China
| | - Dan Yang
- School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
| | - Yanying Zhang
- Gansu University of Chinese Medicine/Scientific Research and Experimental Center, Lanzhou, China
- Gansu Provincial Engineering Laboratory for Research and Promotion of Quality Standardization of Authentic Medicinal Materials in Gansu Province/Provincial Key Laboratory of Pharmaceutical Chemistry and Quality Research in Colleges and Universities in Gansu Province/Gansu Provincial Laboratory Animal Industry Technology Center, Lanzhou, China
| | - Min Bai
- Gansu Provincial Engineering Laboratory for Research and Promotion of Quality Standardization of Authentic Medicinal Materials in Gansu Province/Provincial Key Laboratory of Pharmaceutical Chemistry and Quality Research in Colleges and Universities in Gansu Province/Gansu Provincial Laboratory Animal Industry Technology Center, Lanzhou, China
| | - Bing Song
- Gansu University of Chinese Medicine/Scientific Research and Experimental Center, Lanzhou, China
- Gansu Provincial Engineering Laboratory for Research and Promotion of Quality Standardization of Authentic Medicinal Materials in Gansu Province/Provincial Key Laboratory of Pharmaceutical Chemistry and Quality Research in Colleges and Universities in Gansu Province/Gansu Provincial Laboratory Animal Industry Technology Center, Lanzhou, China
| | - Yongfeng Wang
- Gansu Provincial Engineering Laboratory for Research and Promotion of Quality Standardization of Authentic Medicinal Materials in Gansu Province/Provincial Key Laboratory of Pharmaceutical Chemistry and Quality Research in Colleges and Universities in Gansu Province/Gansu Provincial Laboratory Animal Industry Technology Center, Lanzhou, China
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Yin C, Lu S, Wei D, Xiong J, Zhu L, Yan S, Meng R. Effects of nutritional support combined with insulin therapy on serum proteins, inflammatory factors, pentraxin-3, and serum amylase levels in patients with diabetic ketoacidosis complicated with acute pancreatitis. Medicine (Baltimore) 2021; 100:e27920. [PMID: 34941035 PMCID: PMC8702117 DOI: 10.1097/md.0000000000027920] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 11/06/2021] [Indexed: 01/05/2023] Open
Abstract
To explore the effects of nutritional support combined with insulin therapy on serum protein, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), pentraxin-3 (PTX-3), and serum amylase (AMS) levels in patients with diabetic ketoacidosis complicated with acute pancreatitis.A total of 64 patients with diabetic ketoacidosis complicated with acute pancreatitis admitted to our hospital from January 2018 to February 2019 were enrolled in this prospective study. They were divided into the study group and the control group according to the random number table method, with 32 patients in each group. Patients in the study group were given nutritional support combined with insulin therapy, and patients in the control group were given insulin therapy.There were no significant differences in general data including age, gender, body mass index, course and type of diabetes, acute physiology and chronic health evaluation II, RANSON, CT grades between the 2 groups before treatment (all P > .05). After 7 days of treatment, the clinical efficacy of the study group was significantly higher than that of the control group (study group vs control group, 94.44% vs 75.00%, P < .05). After 7 days of treatment, the levels of prealbumin and albumin in the study group were significantly higher than those in the control group (P < .05). After 7 days of treatment, the levels of PCT, CRP, TNF-α, PTX-3, and AMS in the 2 groups were significantly lower than those before treatment (P < .05), and the levels of PCT, CRP, TNF-α, PTX-3, and AMS in the study group were significantly lower than those in the control group. After 7 days of treatment, the levels of IgG, IgM, and IgA in the 2 groups were significantly higher than those before treatment, and the levels of IgG, IgM, and IgA in the study group were significantly higher than those in the control group (P < .05).Nutritional support combined with insulin is obviously effective in the treatment of diabetic ketoacidosis complicated with acute pancreatitis, which can improve serum protein levels, reduce inflammatory response, improve immune function, and is worthy of clinical application.
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Affiliation(s)
- Chao Yin
- Department of Geriatrics, Tangshan Worker Hospital, Tangshan, China
| | - Songtao Lu
- Department of Geriatrics, Tangshan Worker Hospital, Tangshan, China
| | - Dongmei Wei
- Department of Geriatrics, Tangshan Worker Hospital, Tangshan, China
| | - Juwen Xiong
- Department of Emergency, Tangshan 120 Emergency Command Center, Tangshan, China
| | - Lishuang Zhu
- Department of Rehabilitation, Tangshan Worker Hospital, Tangshan, China
| | - Shaoru Yan
- Department of Orthopaedics, Tangshan People's Hospital, Tangshan, China
| | - Rui Meng
- Department of Rheumatology and Immunology, Tangshan Worker Hospital, Tangshan, China
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11
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Patel BK, Patel KH, Bhatia M, Iyer SG, Madhavan K, Moochhala SM. Gut microbiome in acute pancreatitis: A review based on current literature. World J Gastroenterol 2021; 27:5019-5036. [PMID: 34497432 PMCID: PMC8384740 DOI: 10.3748/wjg.v27.i30.5019] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/04/2021] [Accepted: 06/23/2021] [Indexed: 02/06/2023] Open
Abstract
The gut microbiome is a complex microbial community, recognized for its potential role in physiology, health, and disease. The available evidence supports the role of gut dysbiosis in pancreatic disorders, including acute pancreatitis (AP). In AP, the presence of gut barrier damage resulting in increased mucosal permeability may lead to translocation of intestinal bacteria, necrosis of pancreatic and peripancreatic tissue, and infection, often accompanied by multiple organ dysfunction syndrome. Preserving gut microbial homeostasis may reduce the systemic effects of AP. A growing body of evidence suggests the possible involvement of the gut microbiome in various pancreatic diseases, including AP. This review discusses the possible role of the gut microbiome in AP. It highlights AP treatment and supplementation with prebiotics, synbiotics, and probiotics to maintain gastrointestinal microbial balance and effectively reduce hospitalization, morbidity and mortality in an early phase. It also addresses novel therapeutic areas in the gut microbiome, personalized treatment, and provides a roadmap of human microbial contributions to AP that have potential clinical benefit.
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Affiliation(s)
- Bharati Kadamb Patel
- Department of Surgery, National University of Singapore, Singapore 119228, Singapore
| | - Kadamb H Patel
- School of Applied Sciences, Temasek Polytechnic, Singapore 529757, Singapore
| | - Madhav Bhatia
- Department of Pathology, University of Otago, Christchurch 8140, New Zealand
| | - Shridhar Ganpati Iyer
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- National University Hospital, National University of Singapore, Singapore 119228, Singapore
| | - Krishnakumar Madhavan
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- National University Hospital, National University of Singapore, Singapore 119228, Singapore
| | - Shabbir M Moochhala
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
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12
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Gut microbiota in pancreatic diseases: possible new therapeutic strategies. Acta Pharmacol Sin 2021; 42:1027-1039. [PMID: 33093569 DOI: 10.1038/s41401-020-00532-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 09/08/2020] [Indexed: 12/13/2022]
Abstract
Pancreatic diseases such as pancreatitis, type 1 diabetes and pancreatic cancer impose substantial health-care costs and contribute to marked morbidity and mortality. Recent studies have suggested a link between gut microbiota dysbiosis and pancreatic diseases; however, the potential roles and mechanisms of action of gut microbiota in pancreatic diseases remain to be fully elucidated. In this review, we summarize the evidence that supports relationship between alterations of gut microbiota and development of pancreatic diseases, and discuss the potential molecular mechanisms of gut microbiota dysbiosis in the pathogenesis of pancreatic diseases. We also propose current strategies toward gut microbiota to advance a developing research field that has clinical potential to reduce the cost of pancreatic diseases.
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13
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He L, Sun Y. Advances in research of early use of prophylactic antibiotics in severe acute pancreatitis. Shijie Huaren Xiaohua Zazhi 2021; 29:609-614. [DOI: 10.11569/wcjd.v29.i11.609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Severe acute pancreatitis (SAP) is a common critical digestive system disease with high mortality, which can lead to multiple organ failure. SAP is often accompanied by massive necrosis of the pancreas, which is prone to secondary infection. Infected pancreatic necrosis is associated with an increased mortality of SAP. Whether early prophylactic use of antibiotics in the treatment of SAP can reduce the incidence of secondary infection is still controversial. This paper reviews the research progress of prophylactic use of antibiotics in the treatment of secondary infection of SAP in recent years.
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Affiliation(s)
- Lin He
- Department of Critical Care Medicine, the Second Affiliated Hospital, Hefei 230601, Anhui Province, China
| | - Yun Sun
- Department of Critical Care Medicine, the Second Affiliated Hospital, Hefei 230601, Anhui Province, China
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14
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Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives. J Clin Med 2020; 9:jcm9113535. [PMID: 33139601 PMCID: PMC7692447 DOI: 10.3390/jcm9113535] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 10/28/2020] [Accepted: 10/30/2020] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.
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15
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Extrapancreatic infections are common in acute pancreatitis and they are related to organ failure: a population-based study. Eur J Gastroenterol Hepatol 2020; 32:1293-1300. [PMID: 32675778 DOI: 10.1097/meg.0000000000001847] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Although the impact of pancreatic infections in acute pancreatitis has been studied extensively, there are no population-based data on extrapancreatic infections and their potential relation to organ failure. We aimed to study the occurrence of pancreatic and extrapancreatic bacterial infections in acute pancreatitis and their relation to patient outcome. PATIENTS AND METHODS All patients with first-time acute pancreatitis from 2003 to 2012 in a defined area in Sweden were retrospectively evaluated. Data on acute pancreatitis severity, organ failure, infections, and in-hospital mortality were collected. RESULTS Overall, 304 bacterial infections occurred in 248/1457 patients (17%). Fifteen percent had extrapancreatic and 2% had pancreatic infections. The lungs (35%), the urinary tract (24%), and the bile ducts (18%) were the most common sites of extrapancreatic infections. Organ failure, severe acute pancreatitis, and in-hospital mortality were more common in patients with vs those without (pancreatic/extrapancreatic) infections (P < 0.05). Organ failure and severe acute pancreatitis occurred more frequently in pancreatic vs extrapancreatic infections (70% vs 34%, P < 0.001 and 67% vs 28%, P < 0.001), but in-hospital mortality did not differ between the two groups (7.4% vs 6.8%, P = 1.0). Both pancreatic and extrapancreatic infections were independent predictors of organ failure (P < 0.05). Out of culture-positive infections, 18% were due to antibiotic-resistant bacteria, without any significant difference between extrapancreatic vs pancreatic infections (P > 0.05). About two out of five infections were of nosocomial origin. CONCLUSION Extrapancreatic infections occurred in 15% and pancreatic infections in 2% of patients with first-time acute pancreatitis. Both pancreatic and extrapancreatic infections were independent predictors of organ failure, leading to increased mortality.
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16
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Gastrointestinal Failure Is a Predictor of Poor Outcome in Patients with Acute Pancreatitis. Dig Dis Sci 2020; 65:2419-2426. [PMID: 31722056 DOI: 10.1007/s10620-019-05952-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 11/08/2019] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Although gastrointestinal dysfunction is common in patients with acute pancreatitis, its impact on the outcome of disease has not been adequately studied. The present study was conducted to study the frequency of gastrointestinal failure (GIF) as well as its effect on outcome in patients with acute pancreatitis. METHODS Patients with acute pancreatitis admitted in our unit were prospectively studied. Gastrointestinal dysfunction and intra-abdominal pressures were measured daily till their resolution, and gastrointestinal failure score was calculated. Baseline parameters including various severity scores were noted. The patients were followed till clinical recovery or death. RESULTS Sixty-four patients (mean age 41.52 ± 16.28 years; 45 (70.3%) males) were prospectively studied. Forty-five (70.3%) patients had severe disease, and 18 (28.1%) patients succumbed to illness. GIF was present in 31 (48.4%) patients. The median duration of GIF was 5 (range 1-20) days. The presence of GIF was significantly associated with mortality (p value < 0.05). On multivariate analysis, the presence of GIF [OR 10.6 (95% CI 1.97-57.04)] and duration of ICU stay [OR 1.08 (95% CI 1.015-1.15)] were found to be independent predictors of mortality. CONCLUSION Gastrointestinal failure is an important organ failure in patients with acute pancreatitis and is an independent predictor of mortality. Incorporation of gastrointestinal failure scores in dynamic assessment of patients with acute pancreatitis could help us in better stratifying severity of patients and predicting outcome.
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17
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Ryu KH. [Gut Microbiota and Pancreatobiliary System]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2020; 75:231-239. [PMID: 32448854 DOI: 10.4166/kjg.2020.75.5.231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/01/2020] [Accepted: 05/01/2020] [Indexed: 11/03/2022]
Abstract
The gut microbiota is part of the human body that is involved in body metabolism and the occurrence of various diseases. Detecting and analyzing their genetic information (microbiome) is as important as analyzing human genes. The core microbiome, the key functional genes shared by all humans, helps better understand the physiology of the human body. Information on the gut microbiome of a diseased person can help diagnose and treat disease. The pancreatobiliary system releases functional antimicrobial substances, such as bile acids and antimicrobial peptides, which affect the gut microbiota directly. In response, the gut microbiota influences pancreatobiliary secretion by controlling the generation and emission of substances through indirect signaling. This crosstalk maintains homeostasis of the pancreatobiliary system secretion and microbiota. Dysbiosis and disease can occur if this fails to work properly. Bile acid therapy has been used widely and may affect the microbial environment in the intestine. An association of the gut microbiota has been reported in many cases of pancreatobiliary diseases, including malignant tumors. Traditionally, most pancreatobiliary diseases are accompanied by infections from the gut microbiota, which is an important target for treatment. The pancreatobiliary system can control its function through physical and drug therapy. This may be a new pioneering field in the study or treatment of the gut microbiota.
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Affiliation(s)
- Ki-Hyun Ryu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
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18
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Ding L, Yang Y, Li H, Wang H, Gao P. Circulating Lymphocyte Subsets Induce Secondary Infection in Acute Pancreatitis. Front Cell Infect Microbiol 2020; 10:128. [PMID: 32296650 PMCID: PMC7136471 DOI: 10.3389/fcimb.2020.00128] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 03/09/2020] [Indexed: 12/13/2022] Open
Abstract
Acute pancreatitis (AP) is considered a cascade of immune responses triggered by acinar cell necrosis. AP involves two main processes of systemic inflammatory response syndrome and subsequent compensatory anti-inflammatory response syndrome. Although great efforts have been made regarding AP therapy, the mortality rate of AP remains high. Secondary infection acts a lethal factor in AP. Lymphocytes act as major immune mediators in immune responses in the course of this disease. However, the relationship between lymphocytes and secondary infection in AP is unclear. This review summarizes the variation of lymphocytes and infection in AP. Knowledge of the characterization of circulating lymphocyte abnormalities is relevant for understanding the pathophysiology of AP.
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Affiliation(s)
- Lili Ding
- Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, China
| | - Yimin Yang
- Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, China
| | - Hongxiang Li
- Department of Intensive Care Unit, The First Hospital of Jilin University, Changchun, China
| | - Haijiao Wang
- Department of Gynecology Oncology, The First Hospital of Jilin University, Changchun, China
| | - Pujun Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, China
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19
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Thomas RM, Jobin C. Microbiota in pancreatic health and disease: the next frontier in microbiome research. Nat Rev Gastroenterol Hepatol 2020; 17:53-64. [PMID: 31811279 DOI: 10.1038/s41575-019-0242-7] [Citation(s) in RCA: 208] [Impact Index Per Article: 41.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/11/2019] [Indexed: 12/12/2022]
Abstract
Diseases intrinsic to the pancreas such as pancreatitis, pancreatic cancer and type 1 diabetes mellitus impart substantial health and financial burdens on society but identification of novel mechanisms contributing to these pathologies are slow to emerge. A novel area of research suggests that pancreatic-specific disorders might be modulated by the gut microbiota, either through a local (direct pancreatic influence) or in a remote (nonpancreatic) fashion. In this Perspectives, we examine literature implicating microorganisms in diseases of the pancreas, specifically pancreatitis, type 1 diabetes mellitus and pancreatic ductal adenocarcinoma. We also discuss evidence of an inherent pancreatic microbiota and the influence of the intestinal microbiota as it relates to disease association and development. In doing so, we address pitfalls in the current literature and areas of investigation that are needed to advance a developing field of research that has clinical potential to reduce the societal burden of pancreatic diseases.
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Affiliation(s)
- Ryan M Thomas
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.,Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA
| | - Christian Jobin
- Department of Medicine, Division of Gastroenterology, University of Florida College of Medicine, Gainesville, FL, USA.
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20
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Abstract
Bacterial translocation is a phenomenon in which live bacteria or their products cross the intestinal barrier to other organs or the circulatory system. Gut translocation of bacteria has been reported in both animal models, and clinical trials often accompany acute pancreatitis and are believed to be linked to patient outcome, especially in severe acute pancreatitis. Therefore, the mechanisms of intestinal bacterial translocation in acute pancreatitis have become a topic of interest in recent years. This review discusses Bacterial translocation in acute pancreatitis, identifies possible mechanisms of action, and provides an overview of the methods used to detect Bacterial translocation in acute pancreatitis. This review also highlights areas that require further research.
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Affiliation(s)
- Jinbo Liu
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, P.R. China.,Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou,Sichuan, P.R. China
| | - Lin Huang
- Department of Paediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, P.R. China
| | - Ming Luo
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, P.R. China
| | - Xianming Xia
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, P.R. China.,Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou,Sichuan, P.R. China
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21
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Singh N, Sonika U, Moka P, Sharma B, Sachdev V, Mishra SK, Upadhyay AD, Saraya A. Association of endotoxaemia & gut permeability with complications of acute pancreatitis: Secondary analysis of data. Indian J Med Res 2019; 149:763-770. [PMID: 31496529 PMCID: PMC6755773 DOI: 10.4103/ijmr.ijmr_763_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Background & objectives: In acute pancreatitis (AP) gut barrier dysfunction is considered as an important predisposing factor leading to increased intestinal permeability (IP). In this study a pooled analysis of data published in our previous four studies on various aspects of gut permeability and endotoxaemia in patients with AP was attempted to find an association between increased IP and severity of disease and associated complications. Methods: This study was a pooled analysis of data of four previously published prospective studies on AP. Gut permeability, assessed by lactulose/mannitol excretion in urine and endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM) were measured on days zero and seven (D0 and D7) of admission. All patients received standard treatment of AP. We studied whether IgG and IgM anti-endotoxin titres and lactulose-mannitol ratio (LMR) at admission and D7 were associated with organ failure, infection and mortality. Results: The titres of anti-endotoxin IgG and IgM were lower in all patients of AP (n=204), both in mild AP (n=24) and severe AP (n=180) in the first week, compared to controls (n=15). There was no significant difference in serum IgG and IgM anti-endotoxin levels and LMR at baseline and at D7 among patients with organ failure, infection and mortality. Interpretation & conclusions: Our findings showed that serum IgG and IgM anti-endotoxin titres and LMR at admission and at day 7 were not associated with organ failure, infection, and death of patients with AP.
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Affiliation(s)
- Namrata Singh
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Ujjwal Sonika
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Praneeth Moka
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Brij Sharma
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vikas Sachdev
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Sushil Kumar Mishra
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Datt Upadhyay
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Anoop Saraya
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
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22
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Liu L, Guo Y, Zheng J, Lu Y, Shen Y, Huang C, Zeng Y, Wang X. Paneth cell ablation increases the small intestinal injury during acute necrotizing pancreatitis in rats. Mol Med Rep 2019; 20:473-484. [PMID: 31180547 PMCID: PMC6579996 DOI: 10.3892/mmr.2019.10274] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 03/29/2019] [Indexed: 01/11/2023] Open
Abstract
The present work aimed to investigate the role of Paneth cells in small intestinal injury during acute necrotizing pancreatitis (ANP) using rat models established by injection of dithizone, a metal chelator of zinc with the ability to selectively ablate Paneth cells. Sprague‑Dawley rats were randomly divided into four groups: Sham‑operated group, ANP group (3.5% sodium taurocholate solution, 1 ml/kg body weight), dithizone group (100 mg/kg of body weight) and ANP + dithizone group (sodium taurocholate solution was administered 6 h after dithizone injection). Each group was further divided into five subgroups (6, 12, 24, 36 and 48 h) based on the time period between induction of the model and sample collection. The present results suggested the number of Paneth cells was gradually decreased in the ANP group in a time‑dependent manner. Most of the Paneth cells were ablated in the ANP + dithizone group at 6 h, but a subset of Paneth cells recovered after 24‑48 h. Compared with the ANP group, combination of dithizone and ANP significantly induced more severe histopathological injuries in the pancreas and distal ileum, with higher Schmidt and Chiu's scores, respectively. Additionally, increased expression levels of tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑1β and IL‑17A were detected in the ileum, causing an increase in intestinal permeability, as assessed by a decrease in the expression level of the intestinal tight junction protein occludin and high plasma levels of diamine oxidase and D‑lactate. The increase in intestinal permeability led to the translocation of bacteria to the bloodstream, triggering systemic inflammation, as assessed by the increased plasma levels of TNF‑α, IL‑1β and IL‑17A, reducing the survival rates of rats, which was 66.7% and 83.3% in the ANP + dithizone and the ANP group, respectively. The increase in intestinal endoplasmic reticulum stress, as assessed by high expression levels of binding‑immunoglobulin protein and activating transcription factor 6, may be one mechanism associated with Paneth cells loss and intestinal barrier impairment during ANP. Collectively, the present study suggested that the absence of Paneth cells may be an important factor involved in intestinal injury, promoting the progression of ANP.
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Affiliation(s)
- Liyan Liu
- International Medical Care Center, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, P.R. China
| | - Yuecheng Guo
- Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, P.R. China
| | - Junyuan Zheng
- Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, P.R. China
| | - Yingying Lu
- Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, P.R. China
| | - Yucui Shen
- Department of Gastroenterology, Shanghai Fourth People's Hospital, Shanghai 200080, P.R. China
| | - Chunlan Huang
- Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, P.R. China
| | - Yue Zeng
- Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, P.R. China
| | - Xingpeng Wang
- Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 201620, P.R. China
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23
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Zhao G, Zhuo YZ, Cui LH, Li CX, Chen SY, Li D, Liu JH, Li DH, Cui NQ, Zhang SK. Modified Da-chai-hu Decoction regulates the expression of occludin and NF-κB to alleviate organ injury in severe acute pancreatitis rats. Chin J Nat Med 2019; 17:355-362. [PMID: 31171270 DOI: 10.1016/s1875-5364(19)30041-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Indexed: 02/07/2023]
Abstract
Modified Da-chai-hu Decoction (MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis (SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD (23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase (DAO), pulmonary surfactant protein-A (SP-A), and C-reactive protein (CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase (MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB (NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4 ± 585.5) U·L-1vs (5626.4 ± 795.1)U·L-1], DAO [(1100.1 ± 334.3) U·L-1vs (1666.4 ± 525.3) U·L-1] and CRP [(7.6 ± 1.2) μg·mL-1vs (17.8 ± 3.8) μg·mL-1]. However, the serum SP-A concentration [(106.1 ± 16.6) pg·mL-1vs (90.1 ± 14.9) pg·mL-1] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.
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Affiliation(s)
- Guang Zhao
- Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China; Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China
| | - Yu-Zhen Zhuo
- Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China; Institute of Integrated Traditional Chinese and Western medicine, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China
| | - Li-Hua Cui
- Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China; Institute of Integrated Traditional Chinese and Western medicine, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China
| | - Cai-Xia Li
- Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China; Institute of Integrated Traditional Chinese and Western medicine, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China
| | - Sha-Yan Chen
- Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China; Department of Clinical Laboratory, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China
| | - Dan Li
- Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China; Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China
| | - Jun-Hong Liu
- Institute of Integrated Traditional Chinese and Western medicine, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China
| | - Di-Hua Li
- Institute of Integrated Traditional Chinese and Western medicine, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China
| | - Nai-Qiang Cui
- Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China; Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China
| | - Shu-Kun Zhang
- Nankai Clinical College, Tianjin Medical University, Tianjin 300107, China; Institute of Integrated Traditional Chinese and Western medicine, Tianjin Nankai Hospital, Tianjin Hospital of Integrated Traditional Chinese and Western medicine, Tianjin 300100, China.
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24
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Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice. J Gastroenterol 2019; 54:347-358. [PMID: 30519748 DOI: 10.1007/s00535-018-1529-0] [Citation(s) in RCA: 153] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Accepted: 11/08/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND The gut is implicated in the pathogenesis of acute pancreatitis (AP) and the infectious complications of AP are commonly associated with enteric bacteria, yet whether gut microbiota dysbiosis participants in AP severity remains largely unknown. METHODS We collected clinical information and fecal samples from 165 adult participants, including 41 with mild AP (MAP), 59 with moderately severe AP (MSAP), 30 with severe AP (SAP) and 35 healthy controls (HC). The serum inflammatory cytokines and gut barrier indexes were detected. Male C57BL/6 mice with AP were established and injuries of pancreas were evaluated in antibiotic-treated mice, germ-free mice as well as those transplanted with fecal microbiota. The gut microbiota was analyzed by 16S rRNA gene sequencing. RESULTS The structure of gut microbiota was significantly different between AP and HC, and the disturbed microbiota was closely correlated with systematic inflammation and gut barrier dysfunction. Notably, the microbial composition changed further with the worsening of AP and the abundance of beneficial bacteria such as Blautia was decreased in SAP compared with MAP and MSAP. The increased capacity for the inferred pathway, bacterial invasion of epithelial cells in AP, highly correlated with the abundance of Escherichia-Shigella. Furthermore, the antibiotic-treated mice and germ-free mice exhibited alleviated pancreatic injury after AP induction and subsequent fecal microbiota transplantation in turn exacerbated the disease. CONCLUSIONS This study identifies the gut microbiota as an important mediator during AP and its dysbiosis is associated with AP severity, which suggests its role as potential therapeutic target.
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Sun L, Yue M, Dai Y, Yu C, Chen C. Confocal laser endomicroscopy reveals alterations in duodenal permeability in patients with acute pancreatitis. J Int Med Res 2019; 47:1279-1287. [PMID: 32516018 PMCID: PMC6421367 DOI: 10.1177/0300060518820430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 11/29/2018] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE Intestinal permeability increases during the course of acute pancreatitis (AP). We assessed duodenal permeability alterations in patients with AP by confocal laser endomicroscopy (CLE). METHODS Thirty patients with AP underwent CLE evaluation of the antral and duodenal mucosa. Images were graded based on the appearance of capillaries and the degree of fluorescein leakage. RESULTS Patients with AP had increased duodenal mucosal permeability that could be detected by CLE. The mucosal permeability progressively increased in the gastric antrum, duodenal bulb, and descending duodenum. The CLE parameters in the antrum and duodenal bulb were not significantly different between patients with mild and severe AP. The CLE grades in the descending duodenum were higher in patients with severe than mild AP. The C-reactive protein level in AP was positively correlated with the permeability in the duodenal bulb and descending duodenum, while the computed tomography severity index score was positively correlated with the mucosal permeability in the duodenal bulb and descending duodenum. CONCLUSION CLE revealed increased duodenal permeability in patients with AP. Higher permeability in the descending duodenum was observed in severe than mild AP. Further large-scale studies are needed to confirm the relationship between altered duodenal permeability and the severity of AP.
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Affiliation(s)
- Lingjia Sun
- Department of Gastroenterology, Ningbo No. 2 Hospital, Ningbo,
China
| | - Min Yue
- Department of Gastroenterology, The First Affiliated Hospital,
Zhejiang University, Hangzhou, China
| | - Yining Dai
- Department of Infectious Diseases, Zhejiang Provincial People’s
Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital,
Zhejiang University, Hangzhou, China
| | - Chunxiao Chen
- Department of Gastroenterology, The First Affiliated Hospital,
Zhejiang University, Hangzhou, China
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Breakdown of the Gut Barrier in Patients with Multiple Organ Dysfunction Syndrome is Attenuated by Continuous Blood Purification: Effects on Tight Junction Structural Proteins. Int J Artif Organs 2018. [DOI: 10.1177/039139881003300102] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background Breakdown of the gut barrier increases intestinal permeability and allows movement of intraluminal contents across the mucosa, which can lead to distant organ injury and multiple organ dysfunction syndrome (MODS). Intestinal permeability is associated with alterations in cellular tight junctions involving the structural proteins occludin and zonula occludens-1 (ZO-1). The aim of this study was to investigate the effect of continuous blood purification (CBP) on gut barrier function in patients with MODS. Method Serum diamine oxidase (DAO) and endotoxin, epithelial monolayer permeability, and transepithelial electrical resistance (TER) were used as markers for the assessment of gut barrier function in 22 patients with MODS who underwent continuous venovenous hemofiltration (CVVH) for 24 hours. Blood samples were taken from patients at 0, 6, 12, and 24 hours during CVVH therapy. Serum DAO and endotoxin were determined by spectrophotography. Permeability and TER were assessed using Caco-2 cell monolayers. Occludin and ZO-1 protein levels were analyzed by immunoblotting and immunofluorescence staining. And inducible nitric oxide synthase (iNOS) mRNA levels and nitric oxide (NO) production were determined by real-time PCR and spectrophotography, respectively. Result Gut barrier dysfunction was evident in patients with MODS compared with normal controls. Serum DAO, endotoxin levels, and epithelial permeability were elevated, while TER was decreased in patients with MODS, and this change was more pronounced in nonsurvivors. Breakdown and reorganization of occludin and ZO-1 away from tight junctions was found in all MODS patients. After CBP treatment, APACHE II and MODS scores improved significantly. Serum DAO and endotoxin levels and epithelial permeability also diminished, while TER increased in all patients; CBP significantly attenuated breakdown and reorganization of tight junction proteins, and also attenuated the inflammation-induced increase in iNOS mRNA expression and NO production. Conclusion Breakdown of gut barrier function is present in patients with MODS and may be correlated with poor outcomes in the disease. CBP can not only improve the general conditions, as measured by the APACHE II score, but also improve gut barrier dysfunction by attenuating the breakdown and reorganization of occludin and ZO-1. This beneficial effect of CBP on gut barrier dysfunction is associated with down-regulation of iNOS.
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Zhang J, Yuan C, Hua G, Tong R, Luo X, Ying Z. Early Gut Barrier Dysfunction in Patients with Severe Acute Pancreatitis: Attenuated by Continuous Blood Purification Treatment. Int J Artif Organs 2018. [DOI: 10.1177/039139881003301003] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Objectives The aim of this study was to investigate the effect of continuous blood purification (CBP) on early gut mucosal dysfunction in patients with severe acute pancreatitis (SAP). Methods Patients with SAP were randomized to receive 24 hours of continuous veno-venous hemofiltration (CVVH; n=33) or no CVVH (n=30). Blood samples were taken from the patients at 0, 6, 12, and 24 hours during CVVH therapy. Serum diamine oxidase (DAO) and endotoxin, epithelial permeability, transepithelial electrical resistance (TER) and F-actin rearrangement of the epithelial monolayer were used as the markers for the assessment of gut barrier function and the effect of CBP therapy in patients with SAP. Results Patients with SAP had increased levels of serum DAO, endotoxin, and epithelial permeability when compared with normal controls, and the increase was more pronounced in patients with organ dysfunction (p<0.01). F-actin rearrangement, loose cell-cell junction, and iNOS mRNA upregulation were found in all patients. After CBP treatment, Acute Physiology and Chronic Health Evaluation II score and SOFA score improved significantly; levels of serum DAO, endotoxin, and epithelial permeability decreased (p<0.05). CBP also significantly attenuated reorganization of actin and downregulated iNOS mRNA expression and NO production (p<0.05). Conclusions CBP can not only improve the general conditions but also effectively improve gut barrier dysfunction. The beneficial effect of CBP on gut barrier dysfunction is associated with the improvement of cytoskeletal instability, by downregulating iNOS through the removal of excess proinflammatory factors.
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Affiliation(s)
- JianBin Zhang
- Departments of Nephrology Diseases, The Third Affiliated Hospital of Nanchang University, Nanchang, JiangXi - China
| | - Chen Yuan
- Departments of Nephrology Diseases, The Third Affiliated Hospital of Nanchang University, Nanchang, JiangXi - China
| | - Gan Hua
- Departments of Nephrology Diseases, First Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing - China
| | - RuYan Tong
- Departments of Nephrology Diseases, The Third Affiliated Hospital of Nanchang University, Nanchang, JiangXi - China
| | - XiangFeng Luo
- Departments of Nephrology Diseases, The Third Affiliated Hospital of Nanchang University, Nanchang, JiangXi - China
| | - Zhou Ying
- Departments of Nephrology Diseases, The Third Affiliated Hospital of Nanchang University, Nanchang, JiangXi - China
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Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:5264592. [PMID: 29686719 PMCID: PMC5857302 DOI: 10.1155/2018/5264592] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 11/29/2017] [Accepted: 12/20/2017] [Indexed: 12/11/2022]
Abstract
Despite recent advances in understanding the complex pathogenesis of pancreatitis, the management of the disease remains suboptimal. The use of phytoceuticals (plant-derived pleiotropic multitarget molecules) represents a new research trend in pancreatology. The purpose of this review is to discuss the phytoceuticals with pancreatoprotective potential in acute pancreatitis and whose efficacy is based, at least in part, on their capacity to modulate the acinar cell death. The phytochemicals selected, belonging to such diverse classes as polyphenols, flavonoids, lignans, anthraquinones, sesquiterpene lactones, nitriles, and alkaloids, target the balance between apoptosis and necrosis. Activation of apoptosis via various mechanisms (e.g., inhibition of X-linked inhibitor of apoptosis proteins by embelin, upregulation of FasL gene expression by resveratrol) and/or inhibition of necrosis seem to represent the essential key for decreasing the severity of the disease. Apart from targeting the apoptosis/necrosis balance, the phytochemicals displayed other specific protective activities: inhibition of inflammasome (e.g., rutin), suppression of neutrophil infiltration (e.g., ligustrazine, resveratrol), and antioxidant activity. Even though many of the selected phytoceuticals represent a promising therapeutic alternative, there is a shortage of human evidence, and further studies are required to provide solid basis to justify their use in the treatment of pancreatitis.
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Effect of Endotoxemia in Suckling Rats on Pancreatic Integrity and Exocrine Function in Adults: A Review Report. Gastroenterol Res Pract 2018; 2018:6915059. [PMID: 29576768 PMCID: PMC5821989 DOI: 10.1155/2018/6915059] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 11/29/2017] [Accepted: 12/10/2017] [Indexed: 02/07/2023] Open
Abstract
Background. Endotoxin (LPS), the component of Gram-negative bacteria, is responsible for sepsis and neonatal mortality, but low concentrations of LPS produced tissue protection in experimental studies. The effects of LPS applied to the suckling rats on the pancreas of adult animals have not been previously explored. We present the impact of neonatal endotoxemia on the pancreatic exocrine function and on the acute pancreatitis which has been investigated in the adult animals. Endotoxemia was induced in suckling rats by intraperitoneal application of LPS from Escherichia coli or Salmonella typhi. In the adult rats, pretreated in the early period of life with LPS, histological manifestations of acute pancreatitis have been reduced. Pancreatic weight and plasma lipase activity were decreased, and SOD concentration was reversed and accompanied by a significant reduction of lipid peroxidation products (MDA + 4 HNE) in the pancreatic tissue. In the pancreatic acini, the significant increases in protein signals for toll-like receptor 4 and for heat shock protein 60 were found. Signal for the CCK1 receptor was reduced and pancreatic secretory responses to caerulein were diminished, whereas basal enzyme secretion was unaffected. These pioneer studies have shown that exposition of suckling rats to endotoxin has an impact on the pancreas in the adult organism.
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Management of Acute Pancreatitis in the Pediatric Population: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas Committee. J Pediatr Gastroenterol Nutr 2018; 66:159-176. [PMID: 29280782 PMCID: PMC5755713 DOI: 10.1097/mpg.0000000000001715] [Citation(s) in RCA: 149] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. METHODS The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. RESULTS The diagnosis of pediatric AP should follow the published INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values ≥3 times upper limits of normal, (3) imaging findings consistent with AP). Adequate fluid resuscitation with crystalloid appears key especially within the first 24 hours. Analgesia may include opioid medications when opioid-sparing measures are inadequate. Pulmonary, cardiovascular, and renal status should be closely monitored particularly within the first 48 hours. Enteral nutrition should be started as early as tolerated, whether through oral, gastric, or jejunal route. Little evidence supports the use of prophylactic antibiotics, antioxidants, probiotics, and protease inhibitors. Esophago-gastro-duodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography have limited roles in diagnosis and management. Children should be carefully followed for development of early or late complications and recurrent attacks of AP. CONCLUSIONS This clinical report represents the first English-language recommendations for the management of pediatric AP. Future aims should include prospective multicenter pediatric studies to further validate these recommendations and optimize care for children with AP.
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Zhang M, Zhu HM, He F, Li BY, Li XC. Association between acute pancreatitis and small intestinal bacterial overgrowth assessed by hydrogen breath test. World J Gastroenterol 2017; 23:8591-8596. [PMID: 29358867 PMCID: PMC5752719 DOI: 10.3748/wjg.v23.i48.8591] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 12/12/2017] [Accepted: 12/13/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To elucidate the effects of small intestinal bacterial overgrowth (SIBO) on the severity and complications of acute pancreatitis (AP). METHODS In total, 208 patients with AP as defined by the revised Atlanta classification were admitted to Xuanwu Hospital of Capital Medical University from 2013 to 2016. All patients were admitted within 72 h of AP onset. The hydrogen breath test was performed 7 d after AP onset to detect hydrogen production and evaluate the development of SIBO. The incidence of SIBO was analyzed in patients with AP of three different severity grades. The association between SIBO and complications of AP was also assessed. RESULTS Of the 27 patients with severe AP (SAP), seven (25.92%) developed SIBO. Of the 86 patients with moderately severe AP (MSAP), 22 (25.58%) developed SIBO. Of the 95 patients with mild AP (MAP), eight (8.42%) developed SIBO. There were significant differences in the rates of SIBO among patients with AP of different severities. Additionally, more severe AP was associated with higher rates of SIBO positivity (P < 0.05). SIBO in patients with AP mainly occurred within 72 h of the onset of AP. The incidence of organ failure was significantly higher in patients with SIBO than in those without (P < 0.05). CONCLUSION SIBO occurs more frequently in patients with MSAP or SAP than in those with MAP, usually ≤ 72 h after AP onset. Additionally, SIBO is associated with organ failure.
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Affiliation(s)
- Mei Zhang
- Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Hong-Ming Zhu
- Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Fang He
- Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Bang-Yi Li
- Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
| | - Xiao-Cui Li
- Department of Gastroenterology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
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Nighot M, Al-Sadi R, Guo S, Rawat M, Nighot P, Watterson MD, Ma TY. Lipopolysaccharide-Induced Increase in Intestinal Epithelial Tight Permeability Is Mediated by Toll-Like Receptor 4/Myeloid Differentiation Primary Response 88 (MyD88) Activation of Myosin Light Chain Kinase Expression. THE AMERICAN JOURNAL OF PATHOLOGY 2017; 187:2698-2710. [PMID: 29157665 PMCID: PMC5718096 DOI: 10.1016/j.ajpath.2017.08.005] [Citation(s) in RCA: 152] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 08/07/2017] [Accepted: 08/22/2017] [Indexed: 12/15/2022]
Abstract
Lipopolysaccharides (LPSs) are a major component of the Gram-negative bacterial cell wall and play an important role in mediating intestinal inflammatory responses in inflammatory bowel disease. Although recent studies suggested that physiologically relevant concentrations of LPS (0 to 1 ng/mL) cause an increase in intestinal epithelial tight junction (TJ) permeability, the mechanisms that mediate an LPS-induced increase in intestinal TJ permeability remain unclear. Herein, we show that myosin light chain kinase (MLCK) plays a central role in the LPS-induced increase in TJ permeability. Filter-grown Caco-2 intestinal epithelial monolayers and C57BL/6 mice were used as an in vitro and in vivo intestinal epithelial model system, respectively. LPS caused a dose- and time-dependent increase in MLCK expression and kinase activity in Caco-2 monolayers. The pharmacologic MLCK inhibition and siRNA-induced knock-down of MLCK inhibited the LPS-induced increase in Caco-2 TJ permeability. The LPS increase in TJ permeability was mediated by toll-like receptor 4 (TLR-4)/MyD88 signal-transduction pathway up-regulation of MLCK expression. The LPS-induced increase in mouse intestinal permeability also required an increase in MLCK expression. The LPS-induced increase in intestinal permeability was inhibited in MLCK-/- and TLR-4-/- mice. These data show, for the first time, that the LPS-induced increase in intestinal permeability was mediated by TLR-4/MyD88 signal-transduction pathway up-regulation of MLCK. Therapeutic targeting of these pathways can prevent an LPS-induced increase in intestinal permeability.
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Affiliation(s)
- Meghali Nighot
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico; Albuquerque Veterans Affairs Medical Center, Albuquerque, New Mexico
| | - Rana Al-Sadi
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico
| | - Shuhong Guo
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico
| | - Manmeet Rawat
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico; Albuquerque Veterans Affairs Medical Center, Albuquerque, New Mexico
| | - Prashant Nighot
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico
| | | | - Thomas Y Ma
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico; Albuquerque Veterans Affairs Medical Center, Albuquerque, New Mexico.
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Ji YF, Zhang XM, Mitchell DG, Li XH, Chen TW, Li Y, Bao ZG, Tang W, Xiao B, Huang XH, Yang L. Gastrointestinal tract involvement in acute pancreatitis: initial findings and follow-up by magnetic resonance imaging. Quant Imaging Med Surg 2017; 7:641-653. [PMID: 29312869 PMCID: PMC5756785 DOI: 10.21037/qims.2017.12.03] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Accepted: 12/08/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND To study the initial and follow up patterns of gastrointestinal tract involvement in acute pancreatitis (AP) using magnetic resonance imaging (MRI). METHODS A total of 209 patients with AP undergoing abdominal MRI on 1.5 T MRI were compared to 100 control patients selected from our daily clinical caseload who underwent MRI over the same recruitment period and had no other disease which can cause abnormality of gastrointestinal tract. Initial and follow up MRI examinations of gastrointestinal tract abnormalities were noted for AP patients. The severity of AP was graded by the MRSI and APACHE II. Spearman correlation of gastrointestinal tract involvement with MRSI and APACHE II was analyzed. RESULTS In 209 patients with AP, 63% of the AP patients on their initial MRI exams and 5% of control subjects had at least one gastrointestinal tract abnormality (P<0.05). In the control group, thirty-seven patients were normal on MRI, 24 patients with renal cysts, eighteen patients with liver cysts, eleven patients with liver hemangiomas, and ten patients with splenomegaly. The abnormalities of gastrointestinal tract observed in AP patients included thickened stomach wall (20%), thickened duodenum wall (27%), thickened ascending colon wall (11%), thickened transverse colon wall (15%), and thickened descending colon wall (26%), among others. Gastrointestinal tract abnormalities were correlated with the MRSI score (r=0.46, P<0.05) and APACHE II score (r=0.19, P<0.05). Among 62 patients who had follow up examinations, 26% of patients had gastrointestinal tract abnormality, which was significantly lower than that in the initial exams (P<0.05). Resolution of gastrointestinal tract abnormal MRI findings coincided with symptom alleviation in AP patients. CONCLUSIONS Gastrointestinal tract abnormalities on MRI are common in AP and they are positively correlated with the severity of AP. It may add value for determining the severity of AP.
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Affiliation(s)
- Yi-Fan Ji
- Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Xiao-Ming Zhang
- Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Don G. Mitchell
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Xing-Hui Li
- Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Tian-Wu Chen
- Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Yong Li
- Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Zhi-Guo Bao
- Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Wei Tang
- Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Bo Xiao
- Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Xiao-Hua Huang
- Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
| | - Lin Yang
- Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
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Leccioli V, Oliveri M, Romeo M, Berretta M, Rossi P. A New Proposal for the Pathogenic Mechanism of Non-Coeliac/Non-Allergic Gluten/Wheat Sensitivity: Piecing Together the Puzzle of Recent Scientific Evidence. Nutrients 2017; 9:nu9111203. [PMID: 29099090 PMCID: PMC5707675 DOI: 10.3390/nu9111203] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Revised: 10/27/2017] [Accepted: 10/31/2017] [Indexed: 12/12/2022] Open
Abstract
Non-coeliac/non-allergic gluten/wheat sensitivity (NCG/WS) is a gluten-related disorder, the pathogenesis of which remains unclear. Recently, the involvement of an increased intestinal permeability has been recognized in the onset of this clinical condition. However, mechanisms through which it takes place are still unclear. In this review, we attempt to uncover these mechanisms by providing, for the first time, an integrated vision of recent scientific literature, resulting in a new hypothesis about the pathogenic mechanisms involved in NCG/WS. According to this, the root cause of NCG/WS is a particular dysbiotic profile characterized by decreased butyrate-producing-Firmicutes and/or Bifidobacteria, leading to low levels of intestinal butyrate. Beyond a critical threshold of the latter, a chain reaction of events and vicious circles occurs, involving other protagonists such as microbial lipopolysaccharide (LPS), intestinal alkaline phosphatase (IAP) and wheat α-amylase trypsin inhibitors (ATIs). NCG/WS is likely to be a multi-factor-onset disorder, probably transient and preventable, related to quality and balance of the diet, and not to the presence of gluten in itself. If future studies confirm our proposal, this would have important implications both for the definition of the disease, as well as for the prevention and therapeutic-nutritional management of individuals with NCG/WS.
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Affiliation(s)
- Valentina Leccioli
- Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, via Ferrata 1, 27100 Pavia, Italy.
| | - Mara Oliveri
- Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, via Ferrata 1, 27100 Pavia, Italy.
| | - Marcello Romeo
- C.E.R.H.M. Center for Experimental Research for Human Microbiome Ludes H.E.I., Pietro Stiges Palace, Strait Street, 1436 Valletta, Malta.
| | - Massimiliano Berretta
- Department of Medical Oncology, CRO-Aviano, National Cancer Institute, Via Franco Gallini 2, 33081 Aviano, Italy.
| | - Paola Rossi
- Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, via Ferrata 1, 27100 Pavia, Italy.
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Jinhong Tablet Reduces Damage of Intestinal Mucosal Barrier in Rats with Acute Biliary Infection via Bcl-2/Bax mRNA and Protein Regulation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:4985926. [PMID: 29234407 PMCID: PMC5646335 DOI: 10.1155/2017/4985926] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/17/2017] [Accepted: 08/23/2017] [Indexed: 12/22/2022]
Abstract
Objective To explore the effects and mechanism of Jinhong Tablet on intestinal mucosal barrier function and SIRS in rats with acute biliary infection. Methods 36 SD male rats were divided into three groups: sham operation (control), acute biliary infection (ABI) model, and Jinhong Tablet (Jinhong) group. Jinhong group were force-fed with Jinhong Tablet, while the other two groups received oral saline. At days 3 and 5, morphological changes of intestinal mucosa were assessed. Serum diamine oxidase (DAO), D-lactate, and endotoxin levels were measured. And the genes bcl-2 and bax in intestinal tissues were tested by real-time PCR and Western blotting. Results Intestinal damage was significantly less severe in Jinhong group compared with ABI group, as indicated by Chiu's scoring, TUNEL analysis, and serum DAO, D-lactic acid, and endotoxin levels. Additionally, the expression of bax mRNA and protein was decreased and the ratio of bcl-2/bax mRNA and protein was increased compared with ABI group. Conclusion Jinhong Tablet had a positive intervention on acute biliary infection through improving inflammation and intestinal mucosal barrier, inhibiting excessive apoptosis of intestinal epithelial cells via bax and bcl-2 gene, and protein regulation.
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Shen Q, Li Z, Huang S, Li L, Gan H, Du XG. Intestinal mucosal barrier dysfunction in SAP patients with MODS ameliorated by continuous blood purification. Int J Artif Organs 2017; 41:0. [PMID: 28967086 DOI: 10.5301/ijao.5000644] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/28/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND Dysfunction of the intestinal mucosal barrier plays an important role in the pathophysiology of severe acute pancreatitis (SAP). Continuous blood purification (CBP) has been shown to improve the prognosis of SAP patients. In order to investigate the effect of CBP on intestinal mucosal barrier dysfunction in SAP patients with MODS, we conducted in vivo and in vitro experiments to explore the underlying mechanisms. METHODS The markers for the assessment of intestinal mucosal barrier function including serum diamine oxidase (DAO), endotoxin and intestinal epithelial monolayer permeability were detected during CBP therapy. The distribution and expression of cytoskeleton protein F-actin and tight junction proteins claudin-1 were observed. In addition, Rho kinase (ROCK) mRNA expression and serum tumor necrosis factor-alpha (TNF-α) levels during CBP were determined. RESULTS SAP patients with MODS had increased levels of serum DAO, endotoxin and intestinal epithelial monolayer permeability when compared with normal controls. While the distribution of F-actin and claudin-1 was rearranged, and the expression of claudin-1 significantly decreased, but F-actin had no change. Meanwhile, ROCK mRNA expression and serum TNF-α level were increased. However, after CBP treatment, levels of serum DAO, endotoxin and intestinal epithelial monolayer permeability decreased. The F-actin and claudin-1 reorganization attenuated and the expression of claudin-1 increased. At the same time, ROCK mRNA expression and serum TNF-α level were decreased. CONCLUSIONS CBP can effectively improve intestinal mucosal barrier dysfunction. The beneficial effect is associated with the improvement of cytoskeleton and tight junction proteins in stability by downregulation of ROCK mRNA expression through the removal of excess proinflammatory factors.
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Affiliation(s)
- Qing Shen
- Department of Nephrology, First Affiliated Hospital of Chongqing Medical University, Chongqing - China
| | - Zhengrong Li
- Department of Nephrology, First Affiliated Hospital of Chongqing Medical University, Chongqing - China
| | - Shanshan Huang
- Department of Nephrology, First Affiliated Hospital of Chongqing Medical University, Chongqing - China
| | - Liman Li
- Department of Nephrology, First Affiliated Hospital of Chongqing Medical University, Chongqing - China
| | - Hua Gan
- Department of Nephrology, First Affiliated Hospital of Chongqing Medical University, Chongqing - China
| | - Xiao-Gang Du
- Department of Nephrology, First Affiliated Hospital of Chongqing Medical University, Chongqing - China
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李 雪, 杨 文, 周 谊. 集束化护理在重症急性胰腺患者胃肠功能恢复中的应用. Shijie Huaren Xiaohua Zazhi 2017; 25:2071-2079. [DOI: 10.11569/wcjd.v25.i23.2071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
重症急性胰腺炎(severe acute pancreatitis, SAP)是临床中常见的发病率高、并发症多、死亡率较高的疾病, 其死亡的主要原因是并发了不同程度的多器官功能障碍综合征(multiple organ dysfunction syndrome, MODS), 全身炎症反应综合征(systemic inflammatory response syndrome, SIRS)是导致MODS的重要基础, 而胃肠功能障碍又是激发SIRS的源头. 因此, 胃肠功能障碍在该病的发生发展过程中起重要作用, 早期胃肠功能恢复有助于疾病的恢复和并发症的预防. 集束化护理的运用, 可以使每一位患者在有限的时间内, 得到最有效的治疗, 这是集束化护理最突出的特点. 文章就集束化护理在SAP患者的胃肠功能恢复中的应用进行简要综述, 为临床工作提供循证参考.
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Chai-Qin-Cheng-Qi Decoction and Carbachol Improve Intestinal Motility by Regulating Protein Kinase C-Mediated Ca 2+ Release in Colonic Smooth Muscle Cells in Rats with Acute Necrotising Pancreatitis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:5864945. [PMID: 28529530 PMCID: PMC5424168 DOI: 10.1155/2017/5864945] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 02/06/2017] [Accepted: 03/01/2017] [Indexed: 02/05/2023]
Abstract
Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 μg/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all P < 0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-β1) mRNA and PLC protein (both P < 0.05), while both treatments upregulated protein kinase C-alpha (PKC-α) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all P < 0.05). Neither treatment significantly altered L-arginine-induced PKC-β1 and PKC-ε mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca2+]i (3563.5 and 3046.9 versus 1086.9, both P < 0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca2+]i in colonic SMCs via upregulating PLC, PKC and downregulating AC.
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Moran RA, Jalaly NY, Kamal A, Rao S, Klapheke R, James TW, Thiruvengadam SK, Makary MA, Hirose K, Kumbhari V, Stein EM, Khashab MA, Lennon AM, Kalloo AN, Zaheer A, Hernaez R, Singh VK. Ileus is a predictor of local infection in patients with acute necrotizing pancreatitis. Pancreatology 2016; 16:966-972. [PMID: 27727097 DOI: 10.1016/j.pan.2016.10.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2016] [Revised: 09/08/2016] [Accepted: 10/03/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND & OBJECTIVES Infected pancreatic necrosis (IPN) is associated with increased morbidity and mortality. Gut barrier dysfunction has been shown to increase the risk of bacterial translocation from the gut into the pancreatic bed. The primary aim of the study is to evaluate if ileus, a clinical marker of gut barrier dysfunction, can predict the development of IPN. METHODS A retrospective cohort study of patients with necrotizing pancreatitis (NP) was conducted from 2000 to 2014. Ileus was defined as ≥2 of the following criteria: nausea/vomiting; inability to tolerate a diet, absence of flatus, abdominal distension and features of ileus on imaging. Extensive necrosis was defined as >30% nonenhancing pancreatic parenchyma on contrast-enhanced CT. Multivariable cox proportional hazard analysis was used to evaluate known and potential predictors of IPN. RESULTS 142 patients were identified with NP, 61 with IPN and 81 with sterile necrosis. In comparison to a diagnosis of ileus documented in the medical chart, the ileus criteria had a sensitivity, specificity and positive and negative predictive value of 100%, 93%, 78% and 100%, respectively. On multivariate cox proportional hazard analysis, ileus [HR:2.6; 95%CI:1.4-4.9] and extensive necrosis [HR:2.8; 95%CI:1.3-5.8] were independently associated with the development of IPN while there was no association with bacteremia [HR:1.09; 95%CI:0.6-2.1]. CONCLUSION Ileus in NP can be accurately defined using surgical criteria. Ileus is independently associated with the future development of IPN. Further studies will be needed to determine if ileus can serve as a clinical marker to direct therapeutic interventions aimed at reducing the incidence of IPN.
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Affiliation(s)
- Robert A Moran
- Pancreatitis Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Niloofar Y Jalaly
- Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ayesha Kamal
- Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sandesh Rao
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Robert Klapheke
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Theodore W James
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Martin A Makary
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medical, Baltimore, MD, USA
| | - Kenzo Hirose
- Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medical, Baltimore, MD, USA
| | - Vivek Kumbhari
- Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ellen M Stein
- Pancreatitis Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mouen A Khashab
- Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Anne Marie Lennon
- Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Anthony N Kalloo
- Pancreatitis Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Atif Zaheer
- Pancreatitis Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Abdominal Imaging, Department of Radiology, Johns Hopkins University School of Medical, Baltimore, MD, USA
| | - Ruben Hernaez
- Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Vikesh K Singh
- Pancreatitis Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Fukui H. Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation? Inflamm Intest Dis 2016. [PMID: 29922669 DOI: 10.1159/000447252.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/28/2022] Open
Abstract
Background Increased intestinal permeability due to barrier dysfunction is supposed to cause microbial translocation which may induce low-grade inflammation in various diseases. However, this series of events has not been comprehensively evaluated yet. Summary Intestinal epithelial barrier dysfunction and increased permeability have been described in patients with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), alcoholic liver disease, nonalcoholic steatohepatitis (NASH), liver cirrhosis, acute pancreatitis, primary biliary cholangitis (PBC), type 1 and type 2 diabetes, chronic kidney disease, chronic heart failure (CHF), depression, and other diseases. Most clinical reports used either permeability assays of challenge tests or measurement of circulating bacterial markers like endotoxin for assessment of 'the leaky gut'. The intestinal permeability assessed by the challenge tests has often been related to the changes of tight junction proteins in the epithelium or circulating endotoxin levels. In patients with IBD, alcoholic liver disease, NASH, liver cirrhosis, PBC, obstructive jaundice, severe acute pancreatitis, and CHF, endotoxemia and proinflammatory cytokinemia have been found in addition to increased permeability. In the serum of patients with IBS and depression, antiflagellin antibodies and antilipid A antibodies were detected, respectively, together with increased permeability and proinflammatory cytokinemia. The site of infection, which is localized to the intestine in IBD and IBS, includes various extraintestinal organs in other diseases. The relation of gut dysbiosis to intestinal barrier dysfunction has gradually been clarified. Key Messages Although no direct cause-and-effect relationship has been confirmed, all clinical and experimental data suggest the importance of intestinal hyperpermeability in the inflammatory changes of various diseases. Increased intestinal permeability is a new target for disease prevention and therapy. Considering the close relationship of 'the leaky gut' and gut dysbiosis to the major diseases, we can conclude that meticulous dietetic and probiotic approaches to recover healthy microbiota have the potential to make a breakthrough in the management of these diseases tomorrow.
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Affiliation(s)
- Hiroshi Fukui
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Kashihara, Japan
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Fukui H. Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation? Inflamm Intest Dis 2016; 1:135-145. [PMID: 29922669 DOI: 10.1159/000447252] [Citation(s) in RCA: 249] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Accepted: 05/30/2016] [Indexed: 12/13/2022] Open
Abstract
Background Increased intestinal permeability due to barrier dysfunction is supposed to cause microbial translocation which may induce low-grade inflammation in various diseases. However, this series of events has not been comprehensively evaluated yet. Summary Intestinal epithelial barrier dysfunction and increased permeability have been described in patients with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), alcoholic liver disease, nonalcoholic steatohepatitis (NASH), liver cirrhosis, acute pancreatitis, primary biliary cholangitis (PBC), type 1 and type 2 diabetes, chronic kidney disease, chronic heart failure (CHF), depression, and other diseases. Most clinical reports used either permeability assays of challenge tests or measurement of circulating bacterial markers like endotoxin for assessment of 'the leaky gut'. The intestinal permeability assessed by the challenge tests has often been related to the changes of tight junction proteins in the epithelium or circulating endotoxin levels. In patients with IBD, alcoholic liver disease, NASH, liver cirrhosis, PBC, obstructive jaundice, severe acute pancreatitis, and CHF, endotoxemia and proinflammatory cytokinemia have been found in addition to increased permeability. In the serum of patients with IBS and depression, antiflagellin antibodies and antilipid A antibodies were detected, respectively, together with increased permeability and proinflammatory cytokinemia. The site of infection, which is localized to the intestine in IBD and IBS, includes various extraintestinal organs in other diseases. The relation of gut dysbiosis to intestinal barrier dysfunction has gradually been clarified. Key Messages Although no direct cause-and-effect relationship has been confirmed, all clinical and experimental data suggest the importance of intestinal hyperpermeability in the inflammatory changes of various diseases. Increased intestinal permeability is a new target for disease prevention and therapy. Considering the close relationship of 'the leaky gut' and gut dysbiosis to the major diseases, we can conclude that meticulous dietetic and probiotic approaches to recover healthy microbiota have the potential to make a breakthrough in the management of these diseases tomorrow.
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Affiliation(s)
- Hiroshi Fukui
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Kashihara, Japan
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Xin X, Dai W, Wu J, Fang L, Zhao M, Zhang P, Chen M. Mechanism of intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease: An observational study. Exp Ther Med 2016; 12:1331-1336. [PMID: 27588054 PMCID: PMC4997986 DOI: 10.3892/etm.2016.3493] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Accepted: 06/02/2016] [Indexed: 02/07/2023] Open
Abstract
The aim of the present study was to investigate intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease (COPD). Male Sprague Dawley rats (n=40) were evenly randomized into control and COPD groups and the COPD model was established by regulated exposure to cigarette smoke for 6 months. Histopathological changes of the lung and intestinal tissues were detected by hematoxylin and eosin staining. Expression of the tight junction proteins occludin and zona occludens-1 (ZO-1) in the intestinal tissues were analyzed by western blotting, serum diamine oxidase (DAO) activity was detected by spectrophotometry, the urinary lactulose to mannitol ratio (L/M) was evaluated by high performance liquid chromatography, and intestinal tissue secretion of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-8 were detected by ELISA. Lung histopathology revealed thinned alveolar walls, ruptured alveolar septa, enlarged and deformed alveoli, and the formation of bullae and emphysema due to alveolar fusion in the COPD group, while intestinal histopathology indicated clearly swollen intestines with darkened and gray mucosa, neutrophil infiltration of the intestinal mucosal and regional epithelial shedding. The occludin and ZO-1 expression levels were significantly lower in the COPD group compared with those in the corresponding control group (P<0.05), while the urinary L/M ratio was significantly higher (P<0.05). Furthermore, the serum DAO activity and secretion of TNF-α, IFN-γ and IL-8 in the intestinal tissues were significantly higher in the COPD group than in the control group (each P<0.05). Dysfunctional and structural changes were observed in the intestinal mucosal barrier in COPD model rats, which may be associated with the increased intestinal inflammatory responses.
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Affiliation(s)
- Xiaofeng Xin
- Department of Respiratory Medicine, Nanjing Jingling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China
| | - Wei Dai
- Department of Respiratory Medicine, Nanjing Jingling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China
| | - Jie Wu
- Department of Respiratory Medicine, Nanjing Jingling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China
| | - Liping Fang
- Department of Respiratory Medicine, Nanjing Jingling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China
| | - Ming Zhao
- Department of Respiratory Medicine, Nanjing Jingling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China
| | - Pengpeng Zhang
- Department of Respiratory Medicine, Nanjing Jingling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China
| | - Min Chen
- Department of Respiratory Medicine, Nanjing Jingling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China
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Jaipuria J, Bhandari V, Chawla AS, Singh M. Intra-abdominal pressure: Time ripe to revise management guidelines of acute pancreatitis? World J Gastrointest Pathophysiol 2016; 7:186-98. [PMID: 26909242 PMCID: PMC4753186 DOI: 10.4291/wjgp.v7.i1.186] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 09/08/2015] [Accepted: 11/03/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To systematically review evidence on pathophysiology of intra-abdominal pressure (IAP) in acute pancreatitis (AP) with its clinical correlates. METHODS Systematic review of available evidence in English literature with relevant medical subject heading terms on PubMed, Medline and Scopus with further search from open access sources on internet as suggested by articles retrieved. RESULTS Intra-abdominal hypertension (IAH) is increasingly gaining recognition as a point of specific intervention with potential to alter disease outcome and improve mortality in AP. IAH can be expected in at least 17% of patients presenting with diagnosis of AP to a typical tertiary care hospital (prevalence increasing to 50% in those with severe disease). Abdominal compartment syndrome can be expected in at least 15% patients with severe disease. Recent guidelines on management of AP do not acknowledge utility of surveillance for IAP other than those by Japanese Society of Hepato-Biliary-Pancreatic Surgery. We further outline pathophysiologic mechanisms of IAH; understanding of which advances our knowledge and helps to coherently align common observed variations in management related conundrums (such as fluid therapy, nutrition and antibiotic prophylaxis) with potential to further individualize treatment in AP. CONCLUSION We suggest that IAP be given its due place in future practice guidelines and that recommendations be formed with help of a broader panel with inclusion of clinicians experienced in management of IAH.
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Landahl P, Ansari D, Andersson R. Severe Acute Pancreatitis: Gut Barrier Failure, Systemic Inflammatory Response, Acute Lung Injury, and the Role of the Mesenteric Lymph. Surg Infect (Larchmt) 2015; 16:651-656. [PMID: 26237406 DOI: 10.1089/sur.2015.034] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Severe acute pancreatitis (AP) often leads to distant organ dysfunction with a high morbidity and mortality rate. The most common and earliest organ to fail is the lungs, but the exact pathophysiological mechanisms underlying the disease are still unclear. No successful targeted therapy exists, and treatment is limited to organ supportive care. It is believed that the gut is involved in the development of distant organ failure, as severe AP is associated with changes in the microcirculation, gut permeability/motility, bacterial translocation, and activation of the gut-associated lymphoid tissue (GALT). Experimental evidence implicates the mesenteric lymph as a primary route for these toxic factors to gain access to the systemic circulation. This literature overview was made to survey these mechanisms and the potential of surgical interventions on the thoracic duct as a means of therapy. METHODS Review of the pertinent English-language literature. RESULTS In experimental studies, interruption of mesenteric lymphatic flow has preventive qualities for acute lung injury (ALI) in the setting of critical illness with various etiologies. Experimentally, diversion of mesenteric lymph is able to prevent ALI if done before its development, whereas a later intervention partially reduces the lung damage. Few studies have investigated surgical approaches to the thoracic duct in human beings under these circumstances, and the ones that have been performed are of low quality and have conflicting results. It seems likely that the intervention would need to be performed prior to the development of ALI to obtain maximum benefits, which complicates its application clinically, because prediction of ALI cannot today be done with high precision. CONCLUSION Studies are ongoing to identify the factors carried in mesenteric lymph that may cause end-organ failure (e.g., ALI) and, once recognized, might allow the development of novel targeted agents that would modify the disease course.
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Affiliation(s)
- Per Landahl
- Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital , Lund, Sweden
| | - Daniel Ansari
- Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital , Lund, Sweden
| | - Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital , Lund, Sweden
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Effects of rhubarb on intestinal flora and toll-like receptors of intestinal mucosa in rats with severe acute pancreatitis. Pancreas 2015; 44:799-804. [PMID: 25931256 DOI: 10.1097/mpa.0000000000000339] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE The aim of this study was to examine the effects of rhubarb on intestinal flora and toll-like receptors (TLRs) of intestinal mucosa in rats with severe acute pancreatitis (SAP). METHODS Healthy male Sprague-Dawley rats were randomly allocated into sham-operated surgical model of SAP without or with postoperative rhubarb treatment groups (7 in each group). Rats in with rhubarb group received 10% rhubarb decoction (1 mL/200 g) through tube feeding at every 8 hours during postoperative 24 hours. Serum amylase, amount of intestinal flora, and TLR2/TLR4 messenger RNA expression in intestinal mucosa were tested among 3 groups at postoperative 24 hours. RESULTS TLR2 and TLR4 messenger RNA expression levels in intestinal mucosa in SAP without rhubarb group were significantly higher than those in sham-operated or SAP with rhubarb groups (P < 0.05). The amount of intestinal lactobacilli and bifidobacteria in SAP without rhubarb group were significantly fewer than in those sham-operated group (P < 0.05) but not significantly different from those in SAP with rhubarb group (P > 0.05). The amount of intestinal Escherichia coli was relatively higher in SAP group than in sham-operated group (P > 0.05) but lesser in rhubarb treatment group (P > 0.05). CONCLUSIONS Rhubarb might maintain the intestinal mucosal barrier through regulating intestinal flora and inhibiting intestinal inflammatory response in rats with SAP.
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Serum interleukin 17 as an early prognostic biomarker of severe acute pancreatitis receiving continuous blood purification. Int J Artif Organs 2015; 38:192-8. [PMID: 25907530 DOI: 10.5301/ijao.5000406] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2015] [Indexed: 01/11/2023]
Abstract
BACKGROUND Severe acute pancreatitis (SAP) is associated with systemic inflammation, immunoparalysis, and sepsis, and may lead to vital organ failure and death. We evaluated the efficacy of serum interleukin 17 (IL-17) concentration for predicting eventual SAP severity and the clinical benefits of removing IL-17 by continuous veno-venous hemofiltration (CVVH). METHODS Patients were divided into 2 groups according to severity: Grade 1 (n = 18, SAP without organ dysfunction) and Grade 2 (n = 18, SAP with organ dysfunction). 20 healthy volunteers served as controls. All patients underwent 24-h CVVH and blood samples were taken at 0, 6, 12, and 24 h for measurement of bacterial load and serum IL-17, IL-6, and endotoxin. Clinical condition was graded by the sequential organ failure assessment (SOFA) score. RESULTS Baseline IL-17, IL-6, endotoxin, and bacterial load were higher in Grade 2 patients. SOFA scores improved significantly, and serum IL-17, IL-6, endotoxin, and bacterial load decreased significantly in all patients after CVVH. Serum IL-17 was significantly and positively correlated with IL-6, bacterial load, and endotoxin during CVVH treatment. In addition, post-CVVH serum IL-17 was directly correlated with SOFA scores on days 1 and 7, and with duration of hospital stay. Non-survivors showed both higher SOFA scores on day 1 and higher baseline IL-17 than survivors. CONCLUSIONS Earlier and higher serum IL-17 elevation predicted prolonged hospitalization, organ failure, and death, possibly by disrupting gut barrier function. CVVH can remove inflammatory cytokines from serum, including IL-17 and IL-6, thereby attenuating the inflammatory response and diminishing associated systemic complications.
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Thandassery RB, Yadav TD, Dutta U, Appasani S, Singh K, Kochhar R. Hypotension in the first week of acute pancreatitis and APACHE II score predict development of infected pancreatic necrosis. Dig Dis Sci 2015; 60:537-542. [PMID: 24623313 DOI: 10.1007/s10620-014-3081-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2013] [Accepted: 02/17/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hypotension and intestinal mucosal ischemia lead to bacterial translocation from the gut lumen into systemic circulation. AIM The purpose of this study was to determine the strength of association between different types of organ failure (OF): hypotension (cardiovascular system failure), renal failure, respiratory failure, CNS failure and coagulopathy in the first week of acute pancreatitis (AP) and the subsequent development of infected pancreatic necrosis (IN). METHODS Consecutive patients with AP were evaluated for OF and its severity in the first week of hospital admission. Modified multiple organ failure score (MOFS) was used to identify and grade severity of OF. MOFS of ≥2, lasting for more than 48 h was defined as OF. Occurrence of IN (isolation of bacteria in necrosectomy specimen or image guided fine needle aspiration of pancreatic necrosis) was compared between groups with and without OF. RESULTS Of the 81 patients, mean age was 40.1 ± 14.4 years and 55 were males; 60 (74 %) patients had OF and 13 (16 %) patients had IN. Occurrence of IN was not significantly different between patients with OF (18.3 %) and without OF (14.3 %), p = 0.48. However IN occurred in 10 % of patients without and 33.7 % patients with hypotension, p = 0.01. The rest of the organ systems analyzed did not show any significant difference in occurrence of infected necrosis. On multivariate analysis independent predictors of occurrence of IN were hypotension (odds ratio, OR 2.5, p < 0.001) and APACHE II score at 24 h of hospital admission (OR 4.77, p < 0.001). CONCLUSION Hypotension in the first week of AP and APACHE II score predict development of IN.
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Affiliation(s)
- Ragesh Babu Thandassery
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
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Leal-Lopes C, Velloso FJ, Campopiano JC, Sogayar MC, Correa RG. Roles of Commensal Microbiota in Pancreas Homeostasis and Pancreatic Pathologies. J Diabetes Res 2015; 2015:284680. [PMID: 26347203 PMCID: PMC4544440 DOI: 10.1155/2015/284680] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Accepted: 07/09/2015] [Indexed: 12/12/2022] Open
Abstract
The pancreas plays a central role in metabolism, allowing ingested food to be converted and used as fuel by the cells throughout the body. On the other hand, the pancreas may be affected by devastating diseases, such as pancreatitis, pancreatic adenocarcinoma (PAC), and diabetes mellitus (DM), which generally results in a wide metabolic imbalance. The causes for the development and progression of these diseases are still controversial; therefore it is essential to better understand the underlying mechanisms which compromise the pancreatic homeostasis. The interest in the study of the commensal microbiome increased extensively in recent years, when many discoveries have illustrated its central role in both human physiology and maintenance of homeostasis. Further understanding of the involvement of the microbiome during the development of pathological conditions is critical for the improvement of new diagnostic and therapeutic approaches. In the present review, we discuss recent findings on the behavior and functions played by the microbiota in major pancreatic diseases and provide further insights into its potential roles in the maintenance of pancreatic steady-state activities.
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Affiliation(s)
- Camila Leal-Lopes
- Department of Biochemistry, Chemistry Institute, University of São Paulo, 05508-000 São Paulo, SP, Brazil
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Fernando J. Velloso
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Julia C. Campopiano
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Mari C. Sogayar
- Department of Biochemistry, Chemistry Institute, University of São Paulo, 05508-000 São Paulo, SP, Brazil
- Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, University of São Paulo, 05360-130 São Paulo, SP, Brazil
| | - Ricardo G. Correa
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
- *Ricardo G. Correa:
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Xu GF, Guo M, Tian ZQ, Wu GZ, Zou XP, Zhang WJ. Increased of serum high-mobility group box chromosomal protein 1 correlated with intestinal mucosal barrier injury in patients with severe acute pancreatitis. World J Emerg Surg 2014; 9:61. [PMID: 25926862 PMCID: PMC4414458 DOI: 10.1186/1749-7922-9-61] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 12/12/2014] [Indexed: 01/21/2023] Open
Abstract
Background Secondary infections are the leading cause of death in patients with severe acute pancreatitis (SAP). The gut represents the main source of pancreatic contamination and related septic complications. High-mobility group box chromosomal protein 1 (HMGB1) was recently identified to play an important role in the SAP intestinal mucosal barrier dysfunction. Objective To investigate the correlation of high-mobility group box 1 (HMGB1) with intestinal barrier injury and infections in patients with severe acute pancreatitis (SAP). Methods The serum levels of HMGB1, amylase, lipase, and biochemical indicators were measured in 80 patients with SAP at the time of admission. Furthermore, relationship between their serum HMGB1 levels and intestinal barrier injury, infection and other clinical factors were analyzed. Results The mean value of serum HMGB1 levels was significantly higher in patients with SAP (6.02 ± 2.42 ng/mL) than that in healthy volunteers (1.87 ± 0.63 ng/mL). Serum HMGB1 levels were significantly positively correlated with the Ranson score. The HMGB1 levels were higher in patients with infection during the clinical course, the HMGB1 levels in non-survivors were higher than those in survivors, and positively correlated with DAO activity, L/M ratio, the concentration of endotoxin (R = 0.484, P <0.01). Conclusions HMGBl level of patients with severe acute pancreatitis was significantly increased, and can be used as an important indicator to determine the intestinal barrier dysfunction and infection.
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Affiliation(s)
- Gui-Fang Xu
- Department of Gastroenterology, Nanjing Drum tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Ming Guo
- Department of Gastroenterology, Drum Tower Clinical College of Nanjing Traditional Chinese Medical University, Nanjing, China
| | - Zhi-Qiang Tian
- Department of General Surgery, 101st Hospital of People's Liberation Army, Wuxi, China
| | - Guo-Zhong Wu
- Department of General Surgery, 101st Hospital of People's Liberation Army, Wuxi, China
| | - Xiao-Ping Zou
- Department of Gastroenterology, Nanjing Drum tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Wei-Jie Zhang
- Department of Emergency, Nanjing Drum tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
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Wu LM, Sankaran SJ, Plank LD, Windsor JA, Petrov MS. Meta-analysis of gut barrier dysfunction in patients with acute pancreatitis. Br J Surg 2014; 101:1644-56. [PMID: 25334028 DOI: 10.1002/bjs.9665] [Citation(s) in RCA: 104] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2014] [Revised: 07/05/2014] [Accepted: 09/05/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND The gut is implicated in the pathogenesis of acute pancreatitis but there is discrepancy between individual studies regarding the prevalence of gut barrier dysfunction in patients with acute pancreatitis. The aim of this study was to determine the prevalence of gut barrier dysfunction in acute pancreatitis, the effect of different co-variables, and changes in gut barrier function associated with the use of various therapeutic modalities. METHODS A literature search was performed using PRISMA and MOOSE guidelines. Summary estimates were presented as pooled prevalence of gut barrier dysfunction and the associated 95 per cent c.i. RESULTS A total of 44 prospective clinical studies were included in the systematic review, of which 18 studies were subjected to meta-analysis. The pooled prevalence of gut barrier dysfunction was 59 (95 per cent c.i. 48 to 70) per cent; the prevalence was not significantly affected by disease severity, timing of assessment after hospital admission or type of test used, but showed a statistically significant association with age. Overall, nine of 13 randomized clinical trials reported a significant improvement in gut barrier function following intervention compared with the control group, but only three of six studies that used standard enteral nutrition reported a statistically significant improvement in gut barrier function after intervention. CONCLUSION Gut barrier dysfunction is present in three of five patients with acute pancreatitis, and the prevalence is affected by patient age but not by disease severity. Clinical studies are needed to evaluate the effect of enteral nutrition on gut function in acute pancreatitis.
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Affiliation(s)
- L M Wu
- Department of Surgery, University of Auckland, Auckland, New Zealand
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