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Hirotsu T, Taniguchi K, Nishimura R. Exploring factors predicting the effectiveness of oral semaglutide in Japanese individuals with type 2 diabetes switching from dipeptidyl peptidase 4 inhibitors: a pilot study. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2025; 6:1520389. [PMID: 40196376 PMCID: PMC11973326 DOI: 10.3389/fcdhc.2025.1520389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 03/06/2025] [Indexed: 04/09/2025]
Abstract
Introduction Oral semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved for the treatment of type 2 diabetes mellitus (T2DM). Findings from randomized controlled trials (RCTs) and real-world studies indicate that oral semaglutide leads to significant improvements in HbA1c and body weight, comparable to those observed with injectable GLP-1 RAs. Consequently, oral semaglutide is expected to significantly reduce barriers to initiating GLP-1 RA therapy in individuals with diabetes and may lead to an increased transition from dipeptidyl peptidase-4 inhibitors (DPP-4is) to GLP-1 RA therapy. This study was conducted to prospectively investigate the clinical characteristics predicting the achievement of HbA1c < 7% (52 mmol/mol) in Japanese individuals with T2DM who switched from DPP-4is to oral semaglutide. Methods The study enrolled a total of 74 patients who switched from DPP-4is to oral semaglutide between December 2021 and October 2022, with the dose being uptitrated to achieve HbA1c < 7% (52 mmol/mol) in these patients. Results The study included a total of 44 individuals who achieved the target with oral semaglutide 3 mg (n=7), 7 mg (n=24), or 14 mg (n=13), and 17 individuals who did not (un-achieved group; n=17), based on their clinical characteristics and hematological findings. In the comparison between the Un-achieved group and the Achieved (3 to 14 mg) group, the proportions of "Current alcohol drinking (p = 0.030)" and "Current alcohol drinking and smoking (p = 0.029)" were higher in the Un-achieved group, whereas the proportion of "Taking 31 minutes or longer to have breakfast after drug administration (p = 0.022)" was higher in the Achieved (3 to 14 mg) group. A logistic regression analysis using the stepwise method identified "No current history of both smoking and alcohol drinking (0.083[0.014-0.485]; p = 0.006)" and "Taking 31 minutes or longer to eat breakfast after drug administration (0.117[0.029-0.480]; p = 0.003)" as factors predicting the achievement of the HbA1c < 7% (52 mmol/mol). Conclusion Study findings suggest when considering switching T2D patients from DPP-4is to oral semaglutide, a detailed assessment of "current alcohol drinking and smoking status" and "the duration between the administration of oral semaglutide and breakfast" may be useful as a predictive indicator for achieving HbA1c < 7% (52 mmol/mol).
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Affiliation(s)
- Takao Hirotsu
- Department of Diabetes, Endocrinology and Hematology, Fuji Municipal Central Hospital, Fuji, Japan
| | - Kanta Taniguchi
- Department of Internal Medicine, Taniguchi Medical Clinic, Fujinomiya, Japan
| | - Rimei Nishimura
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Minato, Japan
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Cui J, Xie F, Yue H, Xie C, Ma J, Han H, Fang M, Yao F. Physical activity and constipation: A systematic review of cohort studies. J Glob Health 2024; 14:04197. [PMID: 39575759 PMCID: PMC11583288 DOI: 10.7189/jogh.14.04197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2024] Open
Abstract
Background Constipation significantly impacts quality of life and is a common public health issue. For affected individuals, especially those who are inactive and experience constipation symptoms, it is recommended to engage in physical activity (PA) to improve their condition. However, the relationship between PA and improvement in constipation remains unclear. We performed this systematic review of cohort studies to evaluate this potential association. Methods We systematically searched the Embase, Cochrane Library, PubMed, and CINAHL databases for all cohort studies examining the relationship between PA and constipation from the inception of the databases up to 5 November 2023. We calculated the reported risk ratios (RRs) and 95% confidence intervals (CIs), conducted a random effects model, and performed a subgroup analysis based on factors such as gender, geographic region, and PA intensity to comprehensively explore the link between PA and constipation. Furthermore, we used the Newcastle-Ottawa Scale to evaluate the quality of the studies included in our analysis. Results The analysis included 13 studies with 119 426 participants and 63 713 cases. The results indicated that higher levels of PA were associated with a decreased risk of constipation compared with lower levels of PA (RR = 0.69; 95% CI = 0.88-0.83) and moderate levels of PA (RR = 0.87; 95% CI = 0.79-0.95). Furthermore, adherence to international PA guidelines was correlated with a significantly reduced risk of constipation (RR = 0.87; 95% CI = 0.81-0.93). Notably, the risk of constipation was lowered among Asian populations (RR = 0.67; 95% CI = 0.56-0.79) and Oceanian populations (RR = 0.72; 95% CI = 0.63-0.83) who engaged in regular PA. Moreover, when comparing the risk of constipation between men and women collectively, PA was associated with a 34% lower risk (RR = 0.66; 95% CI = 0.55-0.80). Conclusions The study findings indicated that moderate to high levels of PA significantly reduced the risk of constipation, showing a negative correlation between PA and constipation. Registration PROSPERO: CRD42023479653.
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Affiliation(s)
- Jiahe Cui
- Shanghai municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fangfang Xie
- Shanghai municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hongyu Yue
- Shanghai municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chaoqun Xie
- School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jianwen Ma
- School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Haotian Han
- School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Min Fang
- School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fei Yao
- Shanghai municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Stavely R, Ott LC, Rashidi N, Sakkal S, Nurgali K. The Oxidative Stress and Nervous Distress Connection in Gastrointestinal Disorders. Biomolecules 2023; 13:1586. [PMID: 38002268 PMCID: PMC10669114 DOI: 10.3390/biom13111586] [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: 09/08/2023] [Revised: 10/19/2023] [Accepted: 10/23/2023] [Indexed: 11/26/2023] Open
Abstract
Oxidative stress is increasingly recognized as a central player in a range of gastrointestinal (GI) disorders, as well as complications stemming from therapeutic interventions. This article presents an overview of the mechanisms of oxidative stress in GI conditions and highlights a link between oxidative insult and disruption to the enteric nervous system (ENS), which controls GI functions. The dysfunction of the ENS is characteristic of a spectrum of disorders, including neurointestinal diseases and conditions such as inflammatory bowel disease (IBD), diabetic gastroparesis, and chemotherapy-induced GI side effects. Neurons in the ENS, while essential for normal gut function, appear particularly vulnerable to oxidative damage. Mechanistically, oxidative stress in enteric neurons can result from intrinsic nitrosative injury, mitochondrial dysfunction, or inflammation-related pathways. Although antioxidant-based therapies have shown limited efficacy, recognizing the multifaceted role of oxidative stress in GI diseases offers a promising avenue for future interventions. This comprehensive review summarizes the literature to date implicating oxidative stress as a critical player in the pathophysiology of GI disorders, with a focus on its role in ENS injury and dysfunction, and highlights opportunities for the development of targeted therapeutics for these diseases.
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Affiliation(s)
- Rhian Stavely
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Leah C. Ott
- Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Niloufar Rashidi
- Institute for Health and Sport, Victoria University, St Albans, VIC 3021, Australia
| | - Samy Sakkal
- Institute for Health and Sport, Victoria University, St Albans, VIC 3021, Australia
| | - Kulmira Nurgali
- Institute for Health and Sport, Victoria University, St Albans, VIC 3021, Australia
- Department of Medicine Western Health, The University of Melbourne, St Albans, VIC 3021, Australia
- Regenerative Medicine and Stem Cell Program, Australian Institute for Musculoskeletal Science (AIMSS), St Albans, VIC 3021, Australia
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Laitman JT, Albertine KH, Smith HF. Expanding understanding of the autonomic nervous system with a dash of Flemish charm, Belgian beer, and unrelenting camaraderie: The Anatomical Record raises a glass to J-P Timmermans. Anat Rec (Hoboken) 2023; 306:2217-2221. [PMID: 37475180 DOI: 10.1002/ar.25292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 07/06/2023] [Indexed: 07/22/2023]
Affiliation(s)
- Jeffrey T Laitman
- Center for Anatomy and Functional Morphology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Kurt H Albertine
- Center for Anatomy and Functional Morphology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Pediatrics, University of Utah School of Mediicne, Salt Lake City, Utah, USA
| | - Heather F Smith
- Center for Anatomy and Functional Morphology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Anatomy, Midwestern University, Gendale, Arizona, USA
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Lee DU, Fan GH, Hastie DJ, Addonizio EA, Prakasam VN, Ahern RR, Seog KJ, Karagozian R. The Impact of Malnutrition on the Hospital and Infectious Outcomes of Patients Admitted With Alcoholic Hepatitis: 2011 to 2017 Analysis of US Hospitals. J Clin Gastroenterol 2022; 56:349-359. [PMID: 33769393 DOI: 10.1097/mcg.0000000000001528] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 02/06/2021] [Indexed: 01/13/2023]
Abstract
GOALS We specifically evaluate the effect of malnutrition on the infection risks of patients admitted with alcoholic hepatitis using a national registry of hospitalized patients in the United States. BACKGROUND Malnutrition is a common manifestation of alcoholic hepatitis that affects patient outcomes. STUDY 2011 to 2017 National Inpatient Sample was used to isolated patients with alcoholic hepatitis, stratified using malnutrition (protein-calorie malnutrition, sarcopenia, and weight loss/cachexia) and matched using age, gender, and race with 1:1 nearest neighbor matching method. Endpoints included mortality and infectious endpoints. RESULTS After matching, there were 10,520 with malnutrition and 10,520 malnutrition-absent controls. Mortality was higher in the malnutrition cohort [5.02 vs. 2.29%, P<0.001, odds ratio (OR): 2.25, 95% confidence interval (CI): 1.93-2.63], as were sepsis (14.2 vs. 5.46, P<0.001, OR: 2.87, 95% CI: 2.60-3.18), pneumonia (10.9 vs. 4.63%, P<0.001, OR: 2.51, 95% CI: 2.25-2.81), urinary tract infection (14.8 vs. 9.01%, P<0.001, OR: 1.76, 95% CI: 1.61-1.91), cellulitis (3.17 vs. 2.18%, P<0.001, OR: 1.47, 95% CI: 1.24-1.74), cholangitis (0.52 vs. 0.20%, P<0.001, OR: 2.63, 95% CI: 1.59-4.35), and Clostridium difficile infection (1.67 vs. 0.91%, P<0.001, OR: 1.85, 95% CI: 1.44-2.37). In multivariate models, malnutrition was associated with mortality [P<0.001, adjusted odds ratio (aOR): 1.61, 95% CI: 1.37-1.90] and infectious endpoints: sepsis (P<0.001, aOR: 2.42, 95% CI: 2.18-2.69), pneumonia (P<0.001, aOR: 2.19, 95% CI: 1.96-2.46), urinary tract infection (P<0.001, aOR: 1.68, 95% CI: 1.53-1.84), cellulitis (P<0.001, aOR: 1.46, 95% CI: 1.22-1.74), cholangitis (P=0.002, aOR: 2.27, 95% CI: 1.36-3.80), and C. difficile infection (P<0.001, aOR: 1.89, 95% CI: 1.46-2.44). CONCLUSION This study shows the presence of malnutrition is an independent risk factor of mortality and local/systemic infections in patients admitted with alcoholic hepatitis.
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Affiliation(s)
- David U Lee
- Liver Center, Division of Gastroenterology, Tufts Medical Center, Washington Street, Boston, MA
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Gonzalez Z, Herlihy D, Phan C, Diaz J, Dominguez K, McCallum R. Alcohol and gastric motility: pathophysiological and therapeutic implications. J Investig Med 2020; 68:965-971. [PMID: 32447287 DOI: 10.1136/jim-2020-001327] [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] [Accepted: 04/29/2020] [Indexed: 01/16/2023]
Abstract
Alcohol has been associated with alterations in gastric motility. The literature identifies that various factors play a role in alcohol's effect on gastric emptying including differences in alcohol concentration, osmolarity, caloric content, amino acids as well as different processing techniques (fermentation vs distillation). Additionally, chronic alcohol consumption has been shown to alter the myenteric nitrergic system resulting in impaired gastrointestinal motor function, and it also has an inhibitory effect on the release of several neurotransmitters that play a key role in gastrointestinal motility, including acetylcholine. Whether social or limited intake of alcohol could have a therapeutic role has not been apparent. Serendipitously, we have identified a therapeutic role for alcohol with a meal in the entity of dumping syndrome (DS) where there is postprandial rapid emptying of voluminous and hyperosmolar gastric contents into the small bowel. In the clinical setting of DS attributed to impaired vagal nerve function, there was normalization of gastric emptying and resolution of accompanying symptoms when drinking a glass of wine before and during meals. We propose that alcohol's anticholinergic effect was augmented in the setting of vagal nerve denervation resulting in slowing of gastric emptying and in alleviation of symptoms of early DS. This review article provides an in-depth analysis of the published literature on alcohol and gastric motility focusing on the accumulated knowledge that may have clinical application and relevance.
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Affiliation(s)
- Zorisadday Gonzalez
- Gastroenterology, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA
| | - Daniel Herlihy
- Gastroenterology, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA
| | - Cong Phan
- Paul L Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA
| | - Jesus Diaz
- Nuclear Medicine, University Medical Center of El Paso, El Paso, Texas, USA
| | - Kenneth Dominguez
- Nuclear Medicine, University Medical Center of El Paso, El Paso, Texas, USA
| | - Richard McCallum
- Gastroenterology, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA
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Bangamwabo JB, Chetwood JD, Dusabejambo V, Ntirenganya C, Nuki G, Nkurunziza A, Kieffer KA, Jones M, Walker TD. Prevalence and sociodemographic determinants of dyspepsia in the general population of Rwanda. BMJ Open Gastroenterol 2020; 7:e000387. [PMID: 32381743 PMCID: PMC7222881 DOI: 10.1136/bmjgast-2020-000387] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 03/09/2020] [Accepted: 03/27/2020] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Dyspepsia accounts for a significant burden of worldwide disease, but there is a relative paucity of data from the sub-Saharan African setting. We undertook to describe the burden, risk factors and severity of dyspepsia across Rwanda. METHODS We performed a population-based clustered cross-sectional survey between November 2015 and January 2016, nationwide in Rwanda, using the Short Form Leeds Dyspepsia Questionnaire to describe the presence and severity of dyspepsia, and the Short Form Nepean Dyspepsia Index to describe the concomitant quality of life effects. Univariate and multivariate logistic regression models were constructed to correlate measured sociodemographic factors with dyspepsia. RESULTS The prevalence of clinically significant dyspepsia in the general Rwandan population was 14.2% (283/2000). The univariate factors that significantly predicted severity were gender, profession, socioeconomic status, and non-steroidal anti-inflammatory drug, aspirin and alcohol use, with gender, current smoking, aspirin use both in the past and currently, and alcohol use in the past remaining significant on multivariate modelling. Dyspeptics had a significantly lower gastrointestinal-related quality of life, though the sociodemographic factors measured did not modify the observed quality of life. CONCLUSION Dyspepsia is prevalent in the Rwandan setting and is associated with a significant burden on quality of life. More work is required to determine the pathological entities involved, and the optimal approach to mitigating this burden.
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Affiliation(s)
| | | | - Vincent Dusabejambo
- Department of Internal Medicine, Kigali University Teaching Hospital, Kigali, Rwanda
- Department of Internal Medicine, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda
| | - Cyprien Ntirenganya
- Department of Internal Medicine, University Teaching Hospital of Butare, Butare, Rwanda
| | | | - Arcade Nkurunziza
- Kibungo Hospital, Kibungo, Eastern Province, Rwanda
- Department of Internal Medicine, Kibungo Referral Hospital, Ngoma District, Rwanda
| | - Kelly A Kieffer
- Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
| | - Michael Jones
- Psychology Faculty, Macquarie University, Sydney, New South Wales, Australia
| | - Timothy D Walker
- Calvary Mater Newcastle, Waratah, New South Wales, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
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Grau KR, Zhu S, Peterson ST, Helm EW, Philip D, Phillips M, Hernandez A, Turula H, Frasse P, Graziano VR, Wilen CB, Wobus CE, Baldridge MT, Karst SM. The intestinal regionalization of acute norovirus infection is regulated by the microbiota via bile acid-mediated priming of type III interferon. Nat Microbiol 2020; 5:84-92. [PMID: 31768030 PMCID: PMC6925324 DOI: 10.1038/s41564-019-0602-7] [Citation(s) in RCA: 86] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 10/03/2019] [Indexed: 01/07/2023]
Abstract
Evidence has accumulated to demonstrate that the intestinal microbiota enhances mammalian enteric virus infections1. For example, we and others previously reported that commensal bacteria stimulate acute and persistent murine norovirus infections2-4. However, in apparent contradiction of these results, the virulence of murine norovirus infection was unaffected by antibiotic treatment. This prompted us to perform a detailed investigation of murine norovirus infection in microbially deplete mice, revealing a more complex picture in which commensal bacteria inhibit viral infection of the proximal small intestine while simultaneously stimulating the infection of distal regions of the gut. Thus, commensal bacteria can regulate viral regionalization along the intestinal tract. We further show that the mechanism underlying bacteria-dependent inhibition of norovirus infection in the proximal gut involves bile acid priming of type III interferon. Finally, the regional effects of the microbiota on norovirus infection may result from distinct regional expression profiles of key bile acid receptors that regulate the type III interferon response. Overall, these findings reveal that the biotransformation of host metabolites by the intestinal microbiota directly and regionally impacts infection by a pathogenic enteric virus.
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Affiliation(s)
- Katrina R Grau
- Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA
| | - Shu Zhu
- Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA
| | - Stefan T Peterson
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA
| | - Emily W Helm
- Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA
| | - Drake Philip
- Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA
| | - Matthew Phillips
- Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA
| | - Abel Hernandez
- Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA
| | - Holly Turula
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA
| | - Philip Frasse
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA
| | - Vincent R Graziano
- Departments of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, CT, USA
| | - Craig B Wilen
- Departments of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, CT, USA
| | - Christiane E Wobus
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA
| | - Megan T Baldridge
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA.
| | - Stephanie M Karst
- Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
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The Dietary Management of Patients with Irritable Bowel Syndrome: A Narrative Review of the Existing and Emerging Evidence. Nutrients 2019; 11:nu11092162. [PMID: 31505870 PMCID: PMC6770052 DOI: 10.3390/nu11092162] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 08/29/2019] [Accepted: 09/04/2019] [Indexed: 12/21/2022] Open
Abstract
Even though irritable bowel syndrome (IBS) has been known for more than 150 years, it still remains one of the research challenges of the 21st century. According to the current diagnostic Rome IV criteria, IBS is characterized by abdominal pain associated with defecation and/or a change in bowel habit, in the absence of detectable organic causes. Symptoms interfere with the daily life of patients, reduce health-related quality of life and lower the work productivity. Despite the high prevalence of approximately 10%, its pathophysiology is only partly understood and seems multifactorial. However, many patients report symptoms to be meal-related and certain ingested foods may generate an exaggerated gastrointestinal response. Patients tend to avoid and even exclude certain food products to relieve their symptoms, which could affect nutritional quality. We performed a narrative paper review of the existing and emerging evidence regarding dietary management of IBS patients, with the aim to enhance our understanding of how to move towards an individualized dietary approach for IBS patients in the near future.
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Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones. Nutrients 2019; 11:nu11081824. [PMID: 31394793 PMCID: PMC6723613 DOI: 10.3390/nu11081824] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 08/05/2019] [Indexed: 12/15/2022] Open
Abstract
Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.
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Bódi N, Szalai Z, Bagyánszki M. Nitrergic Enteric Neurons in Health and Disease-Focus on Animal Models. Int J Mol Sci 2019; 20:ijms20082003. [PMID: 31022832 PMCID: PMC6515552 DOI: 10.3390/ijms20082003] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 04/17/2019] [Accepted: 04/18/2019] [Indexed: 12/14/2022] Open
Abstract
Nitrergic enteric neurons are key players of the descending inhibitory reflex of intestinal peristalsis, therefore loss or damage of these neurons can contribute to developing gastrointestinal motility disturbances suffered by patients worldwide. There is accumulating evidence that the vulnerability of nitrergic enteric neurons to neuropathy is strictly region-specific and that the two main enteric plexuses display different nitrergic neuronal damage. Alterations both in the proportion of the nitrergic subpopulation and in the total number of enteric neurons suggest that modification of the neurochemical character or neuronal death occurs in the investigated gut segments. This review aims to summarize the gastrointestinal region and/or plexus-dependent pathological changes in the number of nitric oxide synthase (NOS)-containing neurons, the NO release and the cellular and subcellular expression of different NOS isoforms. Additionally, some of the underlying mechanisms associated with the nitrergic pathway in the background of different diseases, e.g., type 1 diabetes, chronic alcoholism, intestinal inflammation or ischaemia, will be discussed.
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Affiliation(s)
- Nikolett Bódi
- Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary.
| | - Zita Szalai
- Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary.
| | - Mária Bagyánszki
- Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Hungary.
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Van de Putte P, Vernieuwe L, Jerjir A, Verschueren L, Tacken M, Perlas A. When fasted is not empty: a retrospective cohort study of gastric content in fasted surgical patients†. Br J Anaesth 2018; 118:363-371. [PMID: 28203725 DOI: 10.1093/bja/aew435] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/06/2016] [Indexed: 01/17/2023] Open
Abstract
Background Perioperative aspiration leads to significant morbidity and mortality. Point-of-care gastric ultrasound is an emerging tool to assess gastric content at the bedside. Methods We performed a retrospective cohort study of baseline gastric content on fasted elective surgical patients. The primary outcome was the incidence of full stomach (solid content or >1.5 ml kg−1 of clear fluid). Secondary outcomes included: gastric volume distribution (entire cohort, each antral grade); the association between gastric fullness, fasting intervals, and co-morbidities; anaesthetic management changes and incidence of aspiration. Results We identified 538 patients. Thirty-two patients (6.2%) presented with a full stomach. Nine of these (1.7%) had solid content and 23 (4.5%) had clear fluid >1.5 ml kg−1. An empty stomach was documented in 480 (89.8%) patients. The examination was inconclusive in the remaining 20 patients (5.0%). As expected, increasing antral grade was correlated with larger antral cross-sectional area and higher gastric volume (P<0.001). Of the 32 patients with a full stomach, only six had a documented risk factor for prolonged gastric emptying. The anaesthetic management was changed in all nine patients with solid content. No aspiration was reported. Conclusions This retrospective cohort study suggests that a small proportion of elective surgical patients may present with a full stomach despite the recommended duration of fasting. Further research is needed to establish the clinical implications of these findings in the elective setting. At present, the clinical role of gastric ultrasound continues to be for the evaluation of gastric contents to guide management when the risk of aspiration is uncertain or unknown.
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Affiliation(s)
- P Van de Putte
- Department of Anesthesiology, AZ Monica, Campus Deurne, F. Pauwelslei 1, 2100, Deurne, Belgium
| | - L Vernieuwe
- Department of Anaesthesiology, University Hospital Antwerp, Edegem, Belgium
| | - A Jerjir
- Department of Anaesthesiology, University Hospital Leuven, Leuven, Belgium
| | - L Verschueren
- Department of Anaesthesiology, University Hospital Antwerp, Edegem, Belgium
| | - M Tacken
- Department of Anaesthesiology, UMC Radboud, Nijmegen, The Netherlands
| | - A Perlas
- Department of Anaesthesia and Pain Management, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, ON, Canada
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Wu G, Liu Y, Liu Y, Zhang L, Zhao H, Liu L, Zhao C, Feng W. FGF 21 deficiency slows gastric emptying and reduces initial blood alcohol concentration in mice exposed to acute alcohol in fasting state. Biochem Biophys Res Commun 2018; 497:46-50. [PMID: 29448103 DOI: 10.1016/j.bbrc.2018.01.189] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2018] [Accepted: 01/31/2018] [Indexed: 12/18/2022]
Abstract
Excess alcohol consumption can lead to alcoholic liver disease. Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple physiologic functions. Previous study demonstrated that FGF21 deficiency exacerbated alcohol-induced liver injury and exogenous FGF21 administration protected liver from chronic alcohol-induced injury. In this study, we aimed to explore the role of FGF21 in alcohol metabolism in mice. FGF21 knockout (KO) mice and the wild type(WT) control mice were divided into two groups and fasted for 24 h followed by a bonus of alcohol treatment at a dose of 5 g/kg body weight via gavage. Serum alcohol concentration was measured after gavage at 0.5, 2, 3, 4 and 6 h, respectively. At the end, gastric and liver tissues were collected. Serum alcohol concentration of KO mice was significantly lower than that of WT at 0.5 h after alcohol expose. There were no significant differences in alcohol dehydrogenase (ADH) activity and aldehyde dehydrogenase 2 (ALDH2) activity in gastric and liver tissues between WT and the KO mice. However, gastric emptying time of KO mice was much longer than that of WT mice. In addition, the intestinal permeability and serum GLP-1 level of KO mice were significantly higher than that of WT mice. These results suggest that FGF21 deficiency slow gastric emptying rate and indirectly influence initial alcohol metabolism in mice exposed to acute alcohol. Our findings provide additional information for understanding the gastrointestinal mechanism of alcoholic liver disease and other alcohol use disorders.
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Affiliation(s)
- Guicheng Wu
- Department of Hepatology, Chongqing Three Gorges Central Hospital, Chongqing, 404000, China; Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
| | - Yanlong Liu
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Yunhuan Liu
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Lihua Zhang
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Haiyang Zhao
- Institute of Virology, Wenzhou University, Wenzhou, Zhejiang, 325027, China
| | - Liming Liu
- Institute of Virology, Wenzhou University, Wenzhou, Zhejiang, 325027, China
| | - Cuiqing Zhao
- Institute of Virology, Wenzhou University, Wenzhou, Zhejiang, 325027, China
| | - Wenke Feng
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY, 40202, USA; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Institute of Virology, Wenzhou University, Wenzhou, Zhejiang, 325027, China.
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Abstract
Research and clinical experience with vagotomy have confirmed that damage to the central nervous system severely affects physiological movement in the gastrointestinal system. The aim of this study was to investigate the effects of synchronized dual-pulse gastric electrical stimulation (SGES) on the apoptosis of enteric neurons and the possible pathways involved in these effects in vagotomized rats. For this purpose, Male Sprague-Dawley (SD) rats were randomized into a control group, an early subdiaphragmatic vagotomized group (ESDV group), an early subdiaphragmatic vagotomized group with short-term SGES (ESDV + SSGES group), a terminal subdiaphragmatic vagotomized group (TSDV group) and a terminal subdiaphragmatic vagotomized group with long-term SGES (TSDV + LSGES group). The expression levels of connexin 43 (Cx43), glial cell line-derived neurotrophic factor (GDNF), p-Akt, pan-Akt and PGP9.5 were assessed by RT-qPCR, western blot analysis and immunofluorescence staining. Apoptosis was determined by terminal-deoxynucleoitidyl transferase-mediated nick-end labeling (TUNEL) assay. We found that Cx43 expression was decreased in the ESDV and TSDV groups, but was significantly upregulated in the SSGES and LSGES groups. In addition, the GDNF and PGP9.5 expression levels were significantly decreased in the ESDV group compared with the control and TSDV groups and were upregulated in both the SSGES and LSGES groups. The LSGES group exhibited a clear increase in p-Akt expression compared with the TSDV group. Fewer TUNEL-positive cells were observed in the SSGES and LSGES groups than in the ESDV and TSDV groups. More TUNEL-positive cells were found in the stomach of rats subjected to subdiaphragmatic vagotomy. On the whole, our data indicate that SGES improved enteric neuronal survival, possibly through GDNF and the phosphatidylinositol 3-kinase (PI3K)/Akt pathways.
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Affiliation(s)
- Nian Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Kun Li
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Shuangning Song
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Jie Chen
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
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Binge Drinking of Ethanol during Adolescence Induces Oxidative Damage and Morphological Changes in Salivary Glands of Female Rats. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:7323627. [PMID: 27579155 PMCID: PMC4992539 DOI: 10.1155/2016/7323627] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 07/01/2016] [Accepted: 07/05/2016] [Indexed: 01/06/2023]
Abstract
This study investigates morphological and biochemistry effects of binge ethanol consumption in parotid (PG) and submandibular (SG) salivary glands of rats from adolescence to adulthood. Female Wistar rats (n = 26) received ethanol at 3 g/kg/day (20% w/v) for 3 consecutive days/week from the 35th until the 62nd day of life. Animals were treated in two periods: 1 week (G1) and 4 weeks (G2), with a control (treated with distilled water) and an ethanol group to each period. In morphological analysis, morphometric and immunohistochemistry evaluation for smooth muscle actin (αSMA), cytokeratin-18 (CK-18), and vimentin (VIM) were made. Biochemical changes were analyzed by concentration of nitrites and levels of malondialdehyde (MDA). The difference between groups in each analysis was evaluated by Mann-Whitney U test or Student's t-test (p ≤ 0.05). PG showed, at one week of ethanol exposure, lower CK-18 and α-SMA expression, as well as MDA levels. After four weeks, lower CK-18 and higher MDA levels were observed in PG exposed to ethanol, in comparison to control group. SG showed lower α-SMA expression after 1 and 4 weeks of ethanol exposure as well as higher MDA levels after 1 week. Ethanol binge consumption during adolescence promotes tissue and biochemical changes with only one-week binge in acinar and myoepithelial PG cells.
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16
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McKenzie YA, Bowyer RK, Leach H, Gulia P, Horobin J, O'Sullivan NA, Pettitt C, Reeves LB, Seamark L, Williams M, Thompson J, Lomer MCE. British Dietetic Association systematic review and evidence-based practice guidelines for the dietary management of irritable bowel syndrome in adults (2016 update). J Hum Nutr Diet 2016; 29:549-75. [PMID: 27272325 DOI: 10.1111/jhn.12385] [Citation(s) in RCA: 231] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The first British Dietetic Association (BDA) guidelines for the dietary management of irritable bowel syndrome (IBS) in adults were published in 2012. Subsequently, there has been a wealth of new research. The aim of this work was to systematically review the evidence for the role of diet in the management of IBS and to update the guidelines. METHODS Twelve questions relating to diet and IBS were defined based on review of the previous guideline questions, current evidence and clinical practice. Chosen topics were on healthy eating and lifestyle (alcohol, caffeine, spicy food, elimination diets, fat and fluid intakes and dietary habits), milk and dairy, dietary fibre, fermentable carbohydrates, gluten, probiotics and elimination diets/food hypersensitivity. Data sources were CINAHL, Cochrane Register of Controlled Trials, Embase, Medline, Scopus and Web of Science up to October 2015. Studies were assessed independently in duplicate using risk of bias tools specific to each included study based on inclusion and exclusion criteria for each question. National Health and Medical Research Council grading evidence levels were used to develop evidence statements and recommendations, in accordance with Practice-based Evidence in Nutrition Global protocol used by the BDA. RESULTS Eighty-six studies were critically appraised to generate 46 evidence statements, 15 clinical recommendations and four research recommendations. The IBS dietary algorithm was simplified to first-line (healthy eating, provided by any healthcare professional) and second-line [low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) to be provided by dietitian] dietary advice. CONCLUSIONS These guidelines provide updated comprehensive evidence-based details to achieve the successful dietary management of IBS in adults.
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Affiliation(s)
| | - R K Bowyer
- Department of Nutrition and Dietetics, Great Western Hospitals NHS Foundation Trust, Swindon, UK
| | - H Leach
- Department of Nutrition and Dietetics, Southampton NHS Foundation Trust, Southampton, UK
| | - P Gulia
- Dr Ashok Ayurveda Clinic, Birmingham, UK
| | - J Horobin
- Department of Nutrition and Dietetics, North Middlesex University Hospital NHS Trust, London, UK
| | - N A O'Sullivan
- Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences Division, King's College London, London, UK
| | - C Pettitt
- Faculty of Medicine, Imperial College London, London, UK
| | - L B Reeves
- Allergy Services, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - L Seamark
- Specialist Gastroenterology Community Dietetic Service, Somerset Partnership NHS Foundation Trust, Bridgwater, UK
| | - M Williams
- Specialist Gastroenterology Community Dietetic Service, Somerset Partnership NHS Foundation Trust, Bridgwater, UK
| | | | - M C E Lomer
- Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences Division, King's College London, London, UK.,Department of Nutrition and Dietetics, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK
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Bagyánszki M, Bódi N. Gut region-dependent alterations of nitrergic myenteric neurons after chronic alcohol consumption. World J Gastrointest Pathophysiol 2015; 6:51-57. [PMID: 26301118 PMCID: PMC4540706 DOI: 10.4291/wjgp.v6.i3.51] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/27/2015] [Accepted: 06/02/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic alcohol abuse damages nearly every organ in the body. The harmful effects of ethanol on the brain, the liver and the pancreas are well documented. Although chronic alcohol consumption causes serious impairments also in the gastrointestinal tract like altered motility, mucosal damage, impaired absorption of nutrients and inflammation, the effects of chronically consumed ethanol on the enteric nervous system are less detailed. While the nitrergic myenteric neurons play an essential role in the regulation of gastrointestinal peristalsis, it was hypothesised, that these neurons are the first targets of consumed ethanol or its metabolites generated in the different gastrointestinal segments. To reinforce this hypothesis the effects of ethanol on the gastrointestinal tract was investigated in different rodent models with quantitative immunohistochemistry, in vivo and in vitro motility measurements, western blot analysis, evaluation of nitric oxide synthase enzyme activity and bio-imaging of nitric oxide synthesis. These results suggest that chronic alcohol consumption did not result significant neural loss, but primarily impaired the nitrergic pathways in gut region-dependent way leading to disturbed gastrointestinal motility. The gut segment-specific differences in the effects of chronic alcohol consumption highlight the significance the ethanol-induced neuronal microenvironment involving oxidative stress and intestinal microbiota.
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Relationship between patterns of alcohol consumption and gastrointestinal symptoms among patients with irritable bowel syndrome. Am J Gastroenterol 2013; 108:270-6. [PMID: 23295280 PMCID: PMC3697482 DOI: 10.1038/ajg.2012.414] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Heavy alcohol intake may exacerbate gastrointestinal (GI) symptoms in adults with irritable bowel syndrome (IBS); however, the role of alcohol in IBS is unclear. We investigated prospective associations between daily patterns of alcohol intake and next day's GI symptoms using daily diaries. METHODS In an observational study of women aged 18-48 years with IBS and healthy controls, participants recorded daily GI symptoms, alcohol intake, caffeine intake, and cigarette smoking for ≈ 1 month. GI symptoms included abdominal pain, abdominal bloating, intestinal gas, diarrhea, constipation, nausea, stomach pain, heartburn, and indigestion. Binge drinking was defined as 4+ alcohol-containing drinks/day. RESULTS Patterns of alcohol intake did not differ between IBS patients and controls. Although patterns of drinking were associated with GI symptoms among women with IBS, this was not the case with the healthy controls. The strongest associations for IBS patients were between binge drinking and the next day's GI symptoms (e.g., diarrhea, P=0.006; nausea, P=0.01; stomach pain, P=0.009; and indigestion, P=0.004), whereas moderate and light drinking either were not associated or weakly associated with GI symptoms. Associations between alcohol intake and GI symptoms were stronger for women with IBS-diarrhea than for IBS-constipation or IBS-mixed. Effects of binge drinking on GI symptoms were strongest when comparing between individuals (rather than within individuals). CONCLUSIONS Our findings indicate that IBS symptoms differ according to the pattern of alcohol intake among IBS patients, suggesting that the pattern of drinking may in part explain the inconsistent findings between alcohol and IBS symptoms.
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Wojtkiewicz J, Gonkowski S, Bladowski M, Majewski M. Characterisation of cocaine- and amphetamine- regulated transcript-like immunoreactive (CART-LI) enteric neurons in the porcine small intestine. Acta Vet Hung 2012; 60:371-81. [PMID: 22903082 DOI: 10.1556/avet.2012.032] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The aim of this study was to investigate the distribution and the number of cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) neurons and the co-localisation of CART with substance P (SP), somatostatin (SOM), nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) within the enteric nervous system (ENS) in the porcine small intestine. Accordingly, the myenteric plexus (MP), outer submucous plexus (OSP) and inner submucous plexus (ISP) of the small intestine (duodenum, jejunum and ileum) were studied by double-labelling immunofluorescence technique. CART-LI neurons were observed in all gut fragments and all types of intramural plexuses studied and amounted from 0.2 ± 0.1% in the ISP of ileum to 22.4 ± 2.4% in the MP of this segment. The co-localisation of CART and NOS or/and VIP was observed depending on the segment of the gut and the complexity of the intramural plexus. On the other hand, during this study the co-localisation of CART and SOM or/and SP was not observed. The present study, for the first time, presents a detailed description of the CART distribution pattern and co-localisation with other neuromodulators within the ENS of the porcine small intestine.
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Affiliation(s)
- Joanna Wojtkiewicz
- 1 University of Warmia and Mazury Division of Neurosurgery, Department of Neurology and Neurosurgery ul. Warszawska 30 10-082 Olsztyn Poland
| | - Sławomir Gonkowski
- 3 University of Warmia and Mazury Department of Clinical Physiology, Faculty of Veterinary Medicine Olsztyn Poland
| | - Marek Bladowski
- 2 University of Warmia and Mazury Department of Human Physiology, Faculty of Medical Sciences Olsztyn Poland
| | - Mariusz Majewski
- 2 University of Warmia and Mazury Department of Human Physiology, Faculty of Medical Sciences Olsztyn Poland
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Bagyánszki M, Bódi N. Diabetes-related alterations in the enteric nervous system and its microenvironment. World J Diabetes 2012; 3:80-93. [PMID: 22645637 PMCID: PMC3360223 DOI: 10.4239/wjd.v3.i5.80] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2011] [Revised: 04/06/2012] [Accepted: 05/11/2012] [Indexed: 02/05/2023] Open
Abstract
Gastric intestinal symptoms common among diabetic patients are often caused by intestinal motility abnormalities related to enteric neuropathy. It has recently been demonstrated that the nitrergic subpopulation of myenteric neurons are especially susceptible to the development of diabetic neuropathy. Additionally, different susceptibility of nitrergic neurons located in different intestinal segments to diabetic damage and their different levels of responsiveness to insulin treatment have been revealed. These findings indicate the importance of the neuronal microenvironment in the pathogenesis of diabetic nitrergic neuropathy. The main focus of this review therefore was to summarize recent advances related to the diabetes-related selective nitrergic neuropathy and associated motility disturbances. Special attention was given to the findings on capillary endothelium and enteric glial cells. Growing evidence indicates that capillary endothelium adjacent to the myenteric ganglia and enteric glial cells surrounding them are determinative in establishing the ganglionic microenvironment. Additionally, recent advances in the development of new strategies to improve glycemic control in type 1 and type 2 diabetes mellitus are also considered in this review. Finally, looking to the future, the recent and promising results of metagenomics for the characterization of the gut microbiome in health and disease such as diabetes are highlighted.
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Affiliation(s)
- Mária Bagyánszki
- Mária Bagyánszki, Nikolett Bódi, Department of Physiology, Anatomy and Neuroscience, Faculty of Science, University of Szeged, H-6726 Szeged, Hungary
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Naumann CR, Zelig C, Napolitano PG, Ko CW. Nausea, vomiting, and heartburn in pregnancy: a prospective look at risk, treatment, and outcome. J Matern Fetal Neonatal Med 2012; 25:1488-93. [DOI: 10.3109/14767058.2011.644363] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Bagyánszki M, Torfs P, Krecsmarik M, Fekete E, Adriaensen D, Van Nassauw L, Timmermans JP, Kroese ABA. Chronic alcohol consumption induces an overproduction of NO by nNOS- and iNOS-expressing myenteric neurons in the murine small intestine. Neurogastroenterol Motil 2011; 23:e237-48. [PMID: 21470341 DOI: 10.1111/j.1365-2982.2011.01707.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND There are indications that alterations in the nitric oxide (NO) system of relaxation mediate gastrointestinal motor disturbances induced by chronic alcohol consumption (CAC). As CAC is known to inhibit the motility of the mouse small intestine, we investigated in this model if CAC affects basal NO synthesis by myenteric neurons and which NOS isoforms are involved. METHODS The instantaneous NO synthesis of individual neurons was optically measured in whole-mount preparations loaded with the NO synthesis indicator DAF-FM, and the expression of nNOS, iNOS and eNOS was determined by immunohistochemistry. KEY RESULTS The DAF-FM recordings showed that CAC induced an increase in neuronal NO synthesis (absolute fluorescence: control 34±12; CAC 140±56; mean±SD; P<0.0004). Neurons of control mice expressed the nNOS (29±3% of total) and iNOS (28±1%) isoforms. eNOS expression was observed in <0.5% of the neurons. Chronic alcohol consumption caused an increase in the proportion of iNOS-expressing neurons (to 33±5%; P<0.01) and a decrease in nNOS-expressing neurons (to 22±3%; P<0.0001), without altering the proportion of NO-producing neurons (control 55±13%; CAC 56± 11%; P=0.82). CONCLUSIONS & INFERENCES Chronic alcohol consumption induces a marked increase in NO synthesis by jejunal myenteric neurons, accompanied by an up-regulation of iNOS-expressing neurons and a downregulation of nNOS neurons. We conclude that the overproduction of NO may be a direct cause of gastrointestinal motility disturbances.
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Affiliation(s)
- M Bagyánszki
- Laboratory of Cell Biology & Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium
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Jing H, Qin J, Feng M, Wang T, Zhu J, Wang C, Wang F, Liu K, Li J, Liu C. Nitric oxide in enteric nervous system mediated the inhibitory effect of vasopressin on the contraction of circular muscle strips from colon in male rats. Neurogastroenterol Motil 2011; 23:e125-35. [PMID: 21166960 DOI: 10.1111/j.1365-2982.2010.01646.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Arginine vasopressin (AVP) is widely used in the treatment of critical diseases with hypotension, but the reports about its effect on gastrointestinal motility are controversial. The purpose of this study was to characterize the role of AVP in the regulation of colonic motility and the underlying mechanism. METHODS The contraction of the circular muscle strips (CM) of colon in male rats was monitored by a polygraph. The expressions of cytoplasmic inducible nitric oxide synthase (iNOS), I-κB, and the nuclear P65 in proximal colon were measured by Western blot. The V(1) receptors (V(1) Rs) and iNOS were localized by immunohistochemistry. The content of nitric oxide (NO) in the colon was measured by Griess reagent at the absorbance of 560 nm. KEY RESULTS Arginine vasopressin (10(-10) -10(-6) mol L(-1)) caused a concentration-dependent inhibition on CM contraction. Pretreatment with one of the following chemicals, including V-1880 (10(-7) mol L(-1)), TTX (10(-5) mol L(-1)), L-NAME (10(-4) mol L(-1)), NPLA (10(-7) mol L(-1)), SMT (10(-3) mol L(-1)), and PDTC (10(-3) mol L(-1)), attenuated the inhibitory effect of AVP on CM contraction. Arginine vasopressin increased the expression of iNOS and the content of NO in proximal colon. These effects were attenuated by pretreatment with PDTC (10(-3) mol L(-1)). Following AVP administration, the amount of cytoplasmic I-κB decreased, but that of nuclear P65 increased. Double immunofluorescence labeling revealed that V(1) Rs and iNOS were co-localized on the cells of myenteric plexus in proximal colon. CONCLUSIONS & INFERENCES Arginine vasopressin inhibited the contraction of CM in proximal colon. This effect was mediated by NO produced from NF-κB-iNOS pathway and neuronal NOS activation in myenteric plexus.
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Affiliation(s)
- H Jing
- Department of Physiology, Shandong University School of Medicine, Jinan, China
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