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Ye Z, Tan Q, Woltemate S, Tan X, Römermann D, Grassl GA, Vital M, Seidler U, Kini A. Escherichia coli Nissle Improves Short-Chain Fatty Acid Absorption and Barrier Function in a Mouse Model for Chronic Inflammatory Diarrhea. Inflamm Bowel Dis 2025; 31:1109-1120. [PMID: 39708301 PMCID: PMC11985405 DOI: 10.1093/ibd/izae294] [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: 06/25/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND Defects in SLC26A3, the major colonic Cl-/HCO3- exchanger, result in chloride-rich diarrhea, a reduction in short-chain fatty acid (SCFA)-producing bacteria, and a high incidence of inflammatory bowel disease in humans and in mice. Slc26a3-/- mice are, therefore, an interesting animal model for spontaneous but mild colonic inflammation and for testing strategies to reverse or prevent the inflammation. This study investigates the effect of Escherichia coli Nissle (EcN) application on the microbiome, SCFA production, barrier integrity, and mucosal inflammation in slc26a3-/- mice. METHODS In vivo fluid absorption and bicarbonate secretion were assessed in the gut of slc26a3+/+ and slc26a3-/- mice before and during luminal perfusion with 100 mM sodium acetate. Age-matched slc26a3+/+ and slc26a3-/- mice were intragastrically gavaged twice daily with 2 × 108 CFU/100 µL of EcN for 21 days. Body weight and stool water content were assessed daily, and stool and tissues were collected for further analysis. RESULTS Addition of sodium acetate to the lumen of the proximal colon significantly increased fluid absorption and luminal alkalinization in the slc26a3-/- mice. Gavage with EcN resulted in a significant increase in SCFA levels and the expression of SCFA transporters in the slc26a3-/- cecum, the predominant habitat of EcN in mice. This was accompanied by an increase in mucus-producing goblet cells and a decrease in the expression of inflammatory markers as well as host defense antimicrobial peptides. EcN did not improve the overall diversity of the luminal microbiome but resulted in a significant increase in SCFA producers Lachnospiraceae and Ruminococcaceae in the slc26a3-/- feces. CONCLUSIONS These findings suggest that EcN is able to proliferate in the inflamed cecum, resulting in increased microbial SCFA production, decreased inflammation, and improved gut barrier properties. In sufficient dosage, probiotics may thus be an effective anti-inflammatory strategy in the diseased gut.
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Affiliation(s)
- Zhenghao Ye
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Qinghai Tan
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- Department of Gastroenterology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Sabrina Woltemate
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
| | - Xinjie Tan
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dorothee Römermann
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Guntram A Grassl
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
- German Centre for Infection Research DZIF, Partner Site Hannover-Braunschweig, Braunschweig, Germany
| | - Marius Vital
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
| | - Ursula Seidler
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Archana Kini
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
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Ye Z, Kini A, Tan Q, Woltemate S, Vital M, Nikolovska K, Seidler U. Oral tributyrin treatment affects short-chain fatty acid transport, mucosal health, and microbiome in a mouse model of inflammatory diarrhea. J Nutr Biochem 2025; 138:109847. [PMID: 39870330 DOI: 10.1016/j.jnutbio.2025.109847] [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: 08/08/2024] [Revised: 12/05/2024] [Accepted: 01/22/2025] [Indexed: 01/29/2025]
Abstract
Butyrate may decrease intestinal inflammation and diarrhea. This study investigates the impact of oral application of sodium butyrate (NaB) and tributyrin (TB) on colonic butyrate concentration, SCFA transporter expression, colonic absorptive function, barrier properties, inflammation, and microbial composition in the colon of slc26a3-/- mice, a mouse model for inflammatory diarrhea. In vivo fluid absorption and bicarbonate secretory rates were evaluated in the cecum and mid-colon of slc26a3+/+ and slc26a3-/- mice before and during luminal perfusion of NaB-containing saline and were significantly stimulated in both slc26a3+/+ and slc26a3-/- colon by NaB. Age-matched slc26a3+/+ and slc26a3-/- mice were either fed chow containing 5% NaB or gavaged twice daily with TB for 21 d. Food and water intake, weight, and stool water content were assessed daily. Stool and tissues were collected for further analysis of SCFA production, barrier integrity, mucosal inflammation, and microbiome analysis by 16S rRNA gene sequencing. 5% NaB diet did not exert a significant impact on SCFA levels, mucus barrier, or inflammatory markers, but significantly increased oral water intake. TB gavage treatment increased the expression of SCFA transporters Mct1 and Smct1, mucus content and microbial diversity, and decreased the neutrophil marker Lipocalin 2, Phospholipase A2, and the antimicrobial peptide Reg3b in the slc26a3-/- cecum. However, TB treatment also resulted in an increase in inflammatory markers such as TNFα, Il-1β and CD3e in the wildtype mucosa. While there are some benefits with TB ingestion for barrier properties and microbial composition in the diseased cecum, potentially detrimental effects were noted in the healthy colon.
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Affiliation(s)
- Zhenghao Ye
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Archana Kini
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Qinghai Tan
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; Department of Gastroenterology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Sabrina Woltemate
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
| | - Marius Vital
- Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
| | - Katerina Nikolovska
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Ursula Seidler
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
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Shrestha R, Mehta K, Dahanayake D, Yadav M, Nakarmi K, Bista P, Rai S, Pham T, Stewart BT. Feasibility of a randomized controlled trial of enteral vs intravenous resuscitation for adults with major burn injuries in Nepal. Burns 2025; 51:107347. [PMID: 39798346 DOI: 10.1016/j.burns.2024.107347] [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: 07/08/2024] [Revised: 11/11/2024] [Accepted: 12/07/2024] [Indexed: 01/15/2025]
Abstract
INTRODUCTION Enterally-based resuscitation (EResus) is safe, efficacious, and has operational advantages, particularly in low-resource settings. However, there is a lack of real-world effectiveness studies and evidence-based protocols, which hinders implementation. To address this gap, we conducted a feasibility study ahead of a randomized controlled trial (RCT) of enterally based versus usual resuscitation at a tertiary burn center in Nepal which had no prior clinical trial experience. We aimed to assess the feasibility of conducting collaborative and prospective clinical research in this setting, the acceptability of the intervention, and compliance with the resuscitation and study protocols. METHODS We enrolled and randomized 30 participants. We collected quantitative and qualitative data from participants via resuscitation flowsheets (n = 30), along with in-depth interviews conducted before and after resuscitations with participants (n = 12) and providers (n = 45). Evidence of the capabilities to perform the trial as designed, the acceptability of the intervention, and compliance with the study and resuscitation protocols was identified and described through systematic evaluations of recruitment efficiency, protocol adherence, data collection accuracy, high patient consent rates, and detailed feedback collected through in-depth interviews with participants and providers. RESULTS We demonstrated successful research collaboration through the maintenance of weekly study meetings, real-time WhatsApp communication, and funding that allowed for sustainable infrastructure development in Nepal. Screening of 562 burn patients resulted in 33 eligible participants, with a high acceptance rate, as 30 consented to enroll (91 % consent rate). The trial achieved high fidelity in resuscitation protocols, with 93 % adherence to the prescribed enteral resuscitation volumes. No participant dropped out during the study period, indicating strong retention and protocol adherence. CONCLUSION This study established the feasibility of performing a randomized trial in a low-resource context with no prior trial experience. Enterally-based resuscitation is an acceptable and favored intervention with a high rate of enrollment. Hospital staff were able to follow the study and resuscitation protocols with high fidelity, though some optimization was requested. With this evidence of feasibility, the trial will continue enrollment, and the future data may provide valuable insights for advancing burn resuscitation in low-resource settings.
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Affiliation(s)
- Raslina Shrestha
- Department of Burns, Plastics and Reconstructive Surgery, Kirtipur Hospital, Kathmandu, Nepal; Department of General Surgery, Mayo Clinic GSOM, MN, United States
| | - Kajal Mehta
- Department of Surgery, University of Washington School of Medicine, Seattle, WA, United States
| | | | - Manish Yadav
- Department of Burns, Plastics and Reconstructive Surgery, Kirtipur Hospital, Kathmandu, Nepal
| | - Kiran Nakarmi
- Department of Burns, Plastics and Reconstructive Surgery, Kirtipur Hospital, Kathmandu, Nepal
| | - Pariwesh Bista
- Department of Burns, Plastics and Reconstructive Surgery, Kirtipur Hospital, Kathmandu, Nepal
| | - Shankar Rai
- Department of Burns, Plastics and Reconstructive Surgery, Kirtipur Hospital, Kathmandu, Nepal
| | - Tam Pham
- Department of Surgery, University of Washington School of Medicine, Seattle, WA, United States; Harborview Injury Prevention and Research Center, United States
| | - Barclay T Stewart
- Department of Surgery, University of Washington School of Medicine, Seattle, WA, United States; Harborview Injury Prevention and Research Center, United States.
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Mateus Rodríguez JA, Rodríguez Sanz P, Kostandyan E, Palacios Sanchez R, Pino Roque ML, Chaves Vasquez P, Roy Millán P. Mitigating Diarrhoea-Related Inflammation in Frail Older Adults with Postbiotic-Enhanced Oral Rehydration Solution: Insights from a Randomised, Double-Blind, Placebo-Controlled Study. Geriatrics (Basel) 2025; 10:34. [PMID: 40126284 PMCID: PMC11932196 DOI: 10.3390/geriatrics10020034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 02/19/2025] [Accepted: 02/21/2025] [Indexed: 03/25/2025] Open
Abstract
Background/Objectives: Diarrhoea in older adults can lead to dehydration and malnutrition, impaired gut barrier function, and reduced quality of life. Unresolved inflammation during diarrhoea episodes contributes to relapse and complications. This randomised study evaluated the effects of a novel oral rehydration solution (ORS) with the postbiotic ABB C22®, known for its anti-inflammatory properties, on diarrhoea-associated inflammation in an elderly population. Methods: A randomised, double-blind, placebo-controlled, parallel-group trial was conducted at two hospital centres in Barcelona, Spain. Forty-seven participants aged ≥65 years with diarrhoea (n = 47) were randomised (1:1) to receive either ABB C22®-enriched ORS or placebo ORS for up to 14 days. Randomization was stratified by centre using a computer-generated sequence. Participants, caregivers, and outcome assessors were blinded. Primary endpoints were changes in faecal inflammatory biomarkers (calprotectin and lactoferrin) and blood immunoglobulin A. Secondary endpoints included changes in stool consistency (Bristol Stool Scale) and treatment tolerability. Results: Of the 47 participants, 42 completed the trial (21 per group). At day 14, the ORS + ABB C22® group showed greater reductions in faecal calprotectin and lactoferrin levels compared to the placebo group. Lactoferrin-positive cases were halved by day 3 in the intervention group. Stool consistency improved in both groups. No adverse events were reported in either group. Conclusions: ABB C22®-enriched ORS exhibited superior anti-inflammatory effects compared to standard ORS while achieving similar improvements in stool consistency. These findings suggest that postbiotic-enriched formulations represent a promising approach to better address the management of diarrhoea which is often accompanied by gut inflammation. The study protocol was registered in ClinicalTrials.gov (NCT06738420; date: 16 December 2024).
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Affiliation(s)
- Julian Andrés Mateus Rodríguez
- Hospital d’Atenció Intermedia Colisée Barcelona Isabel Roig, 08030 Barcelona, Spain; (P.R.S.); (R.P.S.); (M.L.P.R.)
- Hospital Mare de Déu de la Mercè, Hermanas Hospitalarias, 08042 Barcelona, Spain; (E.K.); (P.C.V.); (P.R.M.)
| | - Patricia Rodríguez Sanz
- Hospital d’Atenció Intermedia Colisée Barcelona Isabel Roig, 08030 Barcelona, Spain; (P.R.S.); (R.P.S.); (M.L.P.R.)
| | - Edgar Kostandyan
- Hospital Mare de Déu de la Mercè, Hermanas Hospitalarias, 08042 Barcelona, Spain; (E.K.); (P.C.V.); (P.R.M.)
| | - Rubén Palacios Sanchez
- Hospital d’Atenció Intermedia Colisée Barcelona Isabel Roig, 08030 Barcelona, Spain; (P.R.S.); (R.P.S.); (M.L.P.R.)
| | - María Luz Pino Roque
- Hospital d’Atenció Intermedia Colisée Barcelona Isabel Roig, 08030 Barcelona, Spain; (P.R.S.); (R.P.S.); (M.L.P.R.)
- Facultat d’Infermeria, Universitat de Barcelona, 08907 Barcelona, Spain
| | - Patricia Chaves Vasquez
- Hospital Mare de Déu de la Mercè, Hermanas Hospitalarias, 08042 Barcelona, Spain; (E.K.); (P.C.V.); (P.R.M.)
| | - Pedro Roy Millán
- Hospital Mare de Déu de la Mercè, Hermanas Hospitalarias, 08042 Barcelona, Spain; (E.K.); (P.C.V.); (P.R.M.)
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Chatterjee R, Chandra A, George A, Dasgupta S. Oral Rehydration Solution: A Landmark Discovery in Medicine and the Legacy of Dr. Dilip Mahalanabis. Am J Med 2025; 138:384-386. [PMID: 39571879 DOI: 10.1016/j.amjmed.2024.10.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 10/31/2024] [Indexed: 12/19/2024]
Affiliation(s)
- Rupak Chatterjee
- Department of Tropical Medicine, Calcutta School of Tropical Medicine, Kolkata, India
| | - Atanu Chandra
- Department of Internal Medicine, Bankura Sammilani Medical College, Bankura, India.
| | - Alex George
- Department of Tropical Medicine, Calcutta School of Tropical Medicine, Kolkata, India
| | - Sugata Dasgupta
- Department of Critical Care Medicine, IPGMER and SSKM Hospital, Kolkata, India
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Liu XY, Chi YF, Wu YS, Chai JK. Research progress and considerations on oral rehydration therapy for the prevention and treatment of severe burn shock: A narrative review. Burns 2024; 50:107160. [PMID: 39322503 DOI: 10.1016/j.burns.2024.04.012] [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: 10/20/2023] [Revised: 03/17/2024] [Accepted: 04/29/2024] [Indexed: 09/27/2024]
Abstract
Severe burns are a significant cause of life-threatening conditions in both peacetime and wartime. Shock is a critical complication during the early stages of burn injury, contributing substantially to mortality and long-term disability. Effective fluid resuscitation is crucial for preventing and treating shock, with prompt administration being vital. However, timely intravenous fluid resuscitation is often challenging, and errors in resuscitation significantly contribute to mortality. Therefore, exploring a more rapid and effective non-invasive method of fluid resuscitation is necessary. Oral rehydration therapy (ORT) has shown considerable potential in this regard. This paper reviews ORT's historical development and current research progress, discussing its application in early anti-shock treatment for burns. While ORT is generally safe, potential complications like diarrhoea, vomiting, and abdominal discomfort must be noted, particularly if the rehydration rate is too rapid or if gastrointestinal issues exist. Careful patient assessment and monitoring are essential during ORT administration. Based on a comprehensive review of relevant research, we present provisional guidelines for ORT in burn patients. These guidelines aim to inform clinical practice but should be applied cautiously due to limited clinical evidence. Implementation must be tailored to the patient's condition under healthcare supervision, with adjustments according to evolving circumstances: ① Initiation timing: Start as soon as possible, and the ideal start time is usually within 6 h after injury. ② Rate of application: Employing a fractional administration approach, wherein small quantities of approximately 150-250 millilitres are provided for each instance and the initial fluid rate of oral rehydration can be simplified to 100 mL/kg/24 h. ③ Composition combination: In addition to essential salts and glucose, the oral rehydration solution can incorporate various anti-inflammatory and cellular protection constituents.
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Affiliation(s)
- Xiang-Yu Liu
- Graduate School, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing 100853, China; Senior Department of Burns & Plastic Surgery, Institute of Burn in the Fourth Medical Centre, Chinese PLA General Hospital, Fucheng Road 51, Haidian District, Beijing 100048, China
| | - Yun-Fei Chi
- Senior Department of Burns & Plastic Surgery, Institute of Burn in the Fourth Medical Centre, Chinese PLA General Hospital, Fucheng Road 51, Haidian District, Beijing 100048, China
| | - Yu-Shou Wu
- Graduate School, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing 100853, China; Senior Department of Burns & Plastic Surgery, Institute of Burn in the Fourth Medical Centre, Chinese PLA General Hospital, Fucheng Road 51, Haidian District, Beijing 100048, China
| | - Jia-Ke Chai
- Senior Department of Burns & Plastic Surgery, Institute of Burn in the Fourth Medical Centre, Chinese PLA General Hospital, Fucheng Road 51, Haidian District, Beijing 100048, China.
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Wang B, Wei X, Zhao X, Wang W, Deng J, Yang H. A Review on In Vivo Research Dehydration Models and Application of Rehydration Strategies. Nutrients 2024; 16:3566. [PMID: 39458559 PMCID: PMC11510460 DOI: 10.3390/nu16203566] [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: 08/19/2024] [Revised: 09/23/2024] [Accepted: 10/13/2024] [Indexed: 10/28/2024] Open
Abstract
Background: Dehydration, a common condition where the amount water lost from the body exceeds intake, disrupts metabolic processes and negatively impacts health and performance. Rehydration, the process of restoring body fluids and electrolytes to normal levels, is crucial for maintaining physiological health. In vivo dehydration models are experimental systems used to study the effects of dehydration on living organisms. However, a comprehensive summary of in vivo models and the application of human rehydration strategies is lacking. Methods: This review provides a comprehensive overview of various in vivo models and rehydration strategies. Results: In vivo models, stimulated by fluid restriction, exercise, thermal exposure, and chemicals, have been used to study dehydration. Importantly, the principles, characteristics, and limitations of the in vivo models are also discussed, along with rehydration administration methods, including oral, intestinal, intravenous, subcutaneous, and intraperitoneal routes. Additionally, rehydration strategies and the application for managing different dehydration conditions both in daily life and clinical settings have been summarized. Conclusions: Overall, this review aims to enhance the understanding of the conditions in which in vivo dehydration models and rehydration strategies are applicable, thereby advancing research into the physiological and pathological mechanisms of dehydration and supporting the development of effective rehydration therapies.
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Affiliation(s)
- Boyuan Wang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Xiaolu Wei
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Xiyan Zhao
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Weimin Wang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Jianjun Deng
- State Key Laboratory of Vegetable Biobreeding, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China;
| | - Haixia Yang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
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Francalancia S, Mehta K, Shrestha R, Phuyal D, Bikash D, Yadav M, Nakarmi K, Rai S, Sharar S, Stewart BT, Fudem G. Consumer focus group testing with stakeholders to generate an enteral resuscitation training flipbook for primary health center and first-level hospital providers in Nepal. Burns 2024; 50:1160-1173. [PMID: 38472005 PMCID: PMC11116054 DOI: 10.1016/j.burns.2024.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 01/30/2024] [Accepted: 02/08/2024] [Indexed: 03/14/2024]
Abstract
INTRODUCTION Enteral resuscitation (EResus) is operationally advantageous to intravenous resuscitation for burn-injured patients in some low-resource settings. However, there is minimal guidance and no training materials for EResus tailored to non-burn care providers. We aimed to develop and consumer-test a training flipbook with doctors and nurses in Nepal to aid broader dissemination of this life-saving technique. MATERIALS AND METHODS We used individual cognitive interviews with Nepali (n = 12) and international (n = 4) burn care experts to define key elements of EResus and specific concepts for its operationalization at primary health centers and first-level hospitals in Nepal. Content, prototype illustrations, and wireframe layouts were developed and revised with the burn care experts. Subsequently, eight consumer testing focus groups with Nepali stakeholders (5-10 people each) were facilitated. Prompts were generated using the Questionnaire Appraisal System (QAS) framework. The flipbook was iteratively revised and tested based on consumer feedback organized according to the domains of clarity, assumptions, knowledge/memory, and sensitivity/bias. RESULTS AND DISCUSSION The flipbook elements were iterated until consumers made no additional requests for changes. Examples of consumer inputs included: clarity-minimize medical jargon, add shrunken organs and wilted plants to represent burn shock; assumptions-use locally representative figures, depict oral rehydration salts sachet instead of a graduated bottle; knowledge/memory-clarify complex topics, use Rule-of-9 s and depict approximately 20% total body surface area to indicate the threshold for resuscitation; sensitivity/bias-reduce anatomic illustration details (e.g. urinary catheter placement, body contours). CONCLUSION Stakeholder engagement, consumer testing, and iterative revision can generate knowledge translation products that reflect contextually appropriate education materials for inexperienced burn providers. The EResus Training Flipbook can be used in Nepal and adapted to other contexts to facilitate the implementation of EResus globally.
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Affiliation(s)
| | - Kajal Mehta
- Department of Surgery, University of Washington, Seattle, WA, USA
| | - Raslina Shrestha
- Kirtipur Hospital Phect Nepal Cleft and Burn Center, Kathmandu, Nepal
| | - Diwakar Phuyal
- Kirtipur Hospital Phect Nepal Cleft and Burn Center, Kathmandu, Nepal
| | - Das Bikash
- Kirtipur Hospital Phect Nepal Cleft and Burn Center, Kathmandu, Nepal
| | - Manish Yadav
- Kirtipur Hospital Phect Nepal Cleft and Burn Center, Kathmandu, Nepal
| | - Kiran Nakarmi
- Kirtipur Hospital Phect Nepal Cleft and Burn Center, Kathmandu, Nepal
| | - Shankar Rai
- Kirtipur Hospital Phect Nepal Cleft and Burn Center, Kathmandu, Nepal
| | - Sam Sharar
- Department of Surgery, University of Washington, Seattle, WA, USA
| | - Barclay T Stewart
- Department of Surgery, University of Washington, Seattle, WA, USA; Division of Trauma, Burn, and Critical Care Surgery, Department of Surgery, University of Washington, Seattle, WA, USA
| | - Gary Fudem
- Department of Surgery, University of Washington, Seattle, WA, USA
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Abstract
The perception of taste and flavour (a combination of taste, smell, and chemesthesis), here also referred to as chemosensation, enables animals to find high-value foods and avoid toxins. Humans have learned to use unpalatable and toxic substances as medicines, yet the importance of chemosensation in this process is poorly understood. Here, we generate tasting-panel data for botanical drugs and apply phylogenetic generalised linear mixed models to test whether intensity and complexity of chemosensory qualities as well as particular tastes and flavours can predict ancient Graeco-Roman drug use. We found chemosensation to be strongly predictive of therapeutic use: botanical drugs with high therapeutic versatility have simple yet intense tastes and flavours, and 21 of 22 chemosensory qualities predicted at least one therapeutic use. In addition to the common notion of bitter tasting medicines, we also found starchy, musky, sweet, and soapy drugs associated with versatility. In ancient Greece and Rome, illness was thought to arise from imbalance in bodily fluids or humours, yet our study suggests that uses of drugs were based on observed physiological effects that are often consistent with modern understanding of chemesthesis and taste receptor pharmacology.
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Affiliation(s)
- Marco Leonti
- Department of Biomedical Sciences, University of Cagliari, Cittadella UniversitariaMonserratoItaly
| | - Joanna Baker
- School of Biological Sciences, University of ReadingReadingUnited Kingdom
| | - Peter Staub
- Department of Biomedical Sciences, University of Cagliari, Cittadella UniversitariaMonserratoItaly
| | - Laura Casu
- Department of Life and Environmental Sciences, University of Cagliari, Cittadella UniversitariaMonserratoItaly
| | - Julie Hawkins
- School of Biological Sciences, University of ReadingReadingUnited Kingdom
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Jones IF, Nakarmi K, Wild HB, Nsaful K, Mehta K, Shrestha R, Roubik D, Stewart BT. Enteral Resuscitation: A Field-Expedient Treatment Strategy for Burn Shock during Wartime and in Other Austere Settings. EUROPEAN BURN JOURNAL 2024; 5:23-37. [PMID: 39600011 PMCID: PMC11571826 DOI: 10.3390/ebj5010003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 01/10/2024] [Accepted: 01/12/2024] [Indexed: 11/29/2024]
Abstract
Burn injuries are a constant threat in war. Aspects of the modern battlefield increase the risk of burn injuries and pose challenges for early treatment. The initial resuscitation of a severely burn-injured patient often exceeds the resources available in front-line medical facilities. This stems mostly from the weight and volume of the intravenous fluids required. One promising solution to this problem is enteral resuscitation with an oral rehydration solution. In addition to being logistically easier to manage, enteral resuscitation may be able to mitigate secondary injuries to the gut related to burn shock and systemic immunoinflammatory activation. This has been previously studied in burn patients, primarily using electrolyte solutions, with promising results. Modern ORS containing sodium, potassium, and glucose in ratios that maximize gut absorption may provide additional benefits as a resuscitation strategy, both in terms of plasma volume expansion and protection of the barrier and immune functions of the gut mucosa. While enteral resuscitation is promising and should be used when other options are not available, further research is needed to refine an optimal implementation strategy.
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Affiliation(s)
- Ian F. Jones
- Madigan Army Medical Center, Tacoma, WA 98431, USA
| | - Kiran Nakarmi
- Nepal Cleft and Burn Center, Kirtipur 44600, Nepal (R.S.)
| | - Hannah B. Wild
- Department of Surgery, University of Washington, Seattle, WA 98195, USA (K.M.)
| | - Kwesi Nsaful
- Department of Plastic, Reconstructive Surgery and Burns Unit, 37 Military Hospital, Accra GA008, Ghana;
| | - Kajal Mehta
- Department of Surgery, University of Washington, Seattle, WA 98195, USA (K.M.)
| | | | - Daniel Roubik
- United States Army Medical Corps, San Antonio, TX 98234, USA
| | - Barclay T. Stewart
- Department of Surgery, University of Washington, Seattle, WA 98195, USA (K.M.)
- Harborview Injury Prevention and Research Center, Seattle, WA 98104, USA
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Chu T, Yottasan P, Goncalves LDS, Oak AA, Lin R, Tse M, Donowitz M, Cil O. Calcium-sensing receptor activator cinacalcet for treatment of cyclic nucleotide-mediated secretory diarrheas. Transl Res 2024; 263:45-52. [PMID: 37678755 PMCID: PMC11071643 DOI: 10.1016/j.trsl.2023.09.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 07/24/2023] [Accepted: 09/01/2023] [Indexed: 09/09/2023]
Abstract
Cyclic nucleotide elevation in intestinal epithelial cells is the key pathology causing intestinal fluid loss in secretory diarrheas such as cholera. Current secretory diarrhea treatment is primarily supportive, and oral rehydration solution is the mainstay of cholera treatment. There is an unmet need for safe, simple and effective diarrhea treatments. By promoting cAMP hydrolysis, extracellular calcium-sensing receptor (CaSR) is a regulator of intestinal fluid transport. We studied the antidiarrheal mechanisms of FDA-approved CaSR activator cinacalcet and tested its efficacy in clinically relevant human cell, mouse and intestinal organoid models of secretory diarrhea. By using selective inhibitors, we found that cAMP agonists-induced secretory short-circuit currents (Isc) in human intestinal T84 cells are mediated by collective actions of apical membrane cystic fibrosis transmembrane conductance regulator (CFTR) and Clc-2 Cl- channels, and basolateral membrane K+ channels. 30 μM cinacalcet pretreatment inhibited all 3 components of forskolin and cholera toxin-induced secretory Isc by ∼75%. In mouse jejunal mucosa, cinacalcet inhibited forskolin-induced secretory Isc by ∼60% in wild type mice, with no antisecretory effect in intestinal epithelia-specific Casr knockout mice (Casr-flox; Vil1-cre). In suckling mouse model of cholera induced by oral cholera toxin, single dose (30 mg/kg) oral cinacalcet treatment reduced intestinal fluid accumulation by ∼55% at 20 hours. Lastly, cinacalcet inhibited forskolin-induced secretory Isc by ∼75% in human colonic and ileal organoids. Our findings suggest that CaSR activator cinacalcet has antidiarrheal efficacy in distinct human cell, organoid and mouse models of secretory diarrhea. Considering its excellent clinical safety profile, cinacalcet can be repurposed as a treatment for cyclic nucleotide-mediated secretory diarrheas including cholera.
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Affiliation(s)
- Tifany Chu
- Department of Pediatrics, University of California, San Francisco, California
| | - Pattareeya Yottasan
- Department of Pediatrics, University of California, San Francisco, California
| | | | - Apurva A Oak
- Department of Pediatrics, University of California, San Francisco, California
| | - Ruxian Lin
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ming Tse
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mark Donowitz
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Onur Cil
- Department of Pediatrics, University of California, San Francisco, California.
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12
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Stewart BT, Nsaful K, Allorto N, Man Rai S. Burn Care in Low-Resource and Austere Settings. Surg Clin North Am 2023; 103:551-563. [PMID: 37149390 DOI: 10.1016/j.suc.2023.01.014] [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] [Indexed: 05/08/2023]
Abstract
More than 95% of the 11 million burns that occur annually happen in low-resource settings, and 70% of those occur among children. Although some low- and middle-income countries have well-organized emergency care systems, many have not prioritized care for the injured and experience unsatisfactory outcomes after burn injury. This chapter outlines key considerations for burn care in low-resource settings.
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Affiliation(s)
- Barclay T Stewart
- University of Washington, UW Medicine Regional Burn Center, Harborview Medical Center, Seattle, WA, USA.
| | - Kwesi Nsaful
- Department of Plastic, Reconstructive Surgery and Burns Unit, Ghana Navy, 37 Military Hospital, Accra, Ghana
| | - Nikki Allorto
- Head Pietermaritzburg Metropolitan Burn Service, Pietermaritzburg, KwaZulu Natal, South Africa
| | - Shankar Man Rai
- National Academy of Medical Sciences, Nepal Cleft and Burn Center at Kirtipur Hospital, Kathmandu, Nepal
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13
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Sun ZB, Zhang X, Yan Y, Xu JL, Lu X, Ren Q. The Effect of Buckwheat Resistant Starch on Intestinal Physiological Function. Foods 2023; 12:foods12102069. [PMID: 37238887 DOI: 10.3390/foods12102069] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/05/2023] [Accepted: 05/19/2023] [Indexed: 05/28/2023] Open
Abstract
Resistant starch appears to have promising effects on hypertension, cardiovascular and enteric illness. The influence of resistant starch on intestinal physiological function has drawn great attention. In this study, we first analyzed the physicochemical characteristics, including the crystalline properties, amylose content, and anti-digestibility among different types of buckwheat-resistant starch. The influence of resistant starch on the physiological functions of the mouse intestinal system, contained defecation, and intestinal microbes were also evaluated. The results showed that the crystalline mold of buckwheat-resistant starch changed from A to B + V after acid hydrolysis treatment (AHT) and autoclaving enzymatic debranching treatment (AEDT). The amylose content in AEDT was higher than in AHT and raw buckwheat. Moreover, the anti-digestibility of AEDT was also stronger than that in AHT and raw buckwheat. The buckwheat-resistant starch can promote bowel intestinal tract movement. The quantity of intestinal microbe was regulated by buckwheat-resistant starch. Our research demonstrates an effective preparation method for improving the quality of buckwheat-resistant starch and found that buckwheat-resistant starch has the role of adjusting the distribution of the intestinal flora and maintaining the health of the body.
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Affiliation(s)
- Zhan-Bin Sun
- School of Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing 100048, China
| | - Xiao Zhang
- School of Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing 100048, China
| | - Yi Yan
- School of Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing 100048, China
| | - Jia-Liang Xu
- School of Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing 100048, China
| | - Xin Lu
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Qing Ren
- School of Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing 100048, China
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14
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Aghsaeifard Z, Heidari G, Alizadeh R. Understanding the use of oral rehydration therapy: A narrative review from clinical practice to main recommendations. Health Sci Rep 2022; 5:e827. [PMID: 36110343 PMCID: PMC9464461 DOI: 10.1002/hsr2.827] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 06/24/2022] [Accepted: 08/24/2022] [Indexed: 11/30/2022] Open
Abstract
Background and Aims Fluid loss due to diarrhea remains a significant cause of mortality among children under the age of 5. Methods Oral rehydration therapy (ORT) is a first-line therapeutic measure to compensate the volume loss due to diarrhea and vomiting among gastroenteritis patients. Despite adequate knowledge, the practice of ORT is limited, particularly in developing countries. Results Several recommendations are provided regarding the use of ORT to treat hypovolemia, however, the information regarding its adequate usage is restricted within the healthcare centers and professionals. Conclusion This review highlights the importance of providing recommendations regarding the use of ORT. We also discuss the barriers and alternatives that might limit its use.
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Affiliation(s)
- Ziba Aghsaeifard
- Department of Internal Medicine, Sina HospitalTehran University of Medical SciencesTehranIran
| | - Ghobad Heidari
- Department of PediatricsLorestan University of Medical SciencesKhorramabadIran
| | - Reza Alizadeh
- Department of Anesthesiology and Intensive Care, Faculty of MedicineAJA University of Medical SciencesTehranIran
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15
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Das R, Sobi RA, Sultana AA, Nahar B, Bardhan PK, Luke L, Fontaine O, Ahmed T. A double-blind clinical trial to compare the efficacy and safety of a multiple amino acid-based ORS with the standard WHO-ORS in the management of non-cholera acute watery diarrhea in infants and young children: "VS002A" trial protocol. Trials 2022; 23:706. [PMID: 36008819 PMCID: PMC9403960 DOI: 10.1186/s13063-022-06601-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 07/25/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Diarrhea is the second deadliest disease for under-five children globally and the situation is more serious in developing countries. Oral rehydration solution (ORS) is being used as a standard treatment for acute watery diarrhea for a long time. Our objective is to compare the efficacy of amino acid-based ORS "VS002A" compared to standard glucose-based WHO-ORS in infants and young children suffering from acute non-cholera watery diarrhea. METHODS It is a randomized, double-blind, two-cell clinical trial at Dhaka Hospital of icddr,b. A total of 312 male children aged 6-36 months old with acute non-bloody watery diarrhea are included in this study. Intervention arm participants get amino acid-based ORS (VS002A) and the control arm gets standard glucose-based WHO-ORS. The primary efficacy endpoint is the duration of diarrhea in the hospital. DISCUSSION Oral rehydration therapy (ORT) with the present ORS formulation has certain limitations - it does not reduce the volume, frequency, or duration of diarrhea. Additionally, the failure of present standard ORS to significantly reduce stool output likely contributes to the relatively limited use of ORS by mothers as they do not feel that ORS is helping their child recover from the episode of diarrhea. Certain neutral amino acids (e.g., glycine, L-alanine, L-glutamine) can enhance the absorption of sodium ions and water from the gut. By using this concept, a shelf-stable, sugar-free amino acid-based hydration medicinal food named 'VS002A' that effectively rehydrates, and improves the barrier function of the bowel following infections targeting the gastrointestinal tract has been developed. If the trial shows significant benefits of VS002A use, this may provide evidence to support consideration of the use of VS002A in the present WHO diarrhea management guidelines. Conversely, if there is no evidence of benefit, these results will reaffirm the current guidelines. TRIAL REGISTRATION ClinicalTrials.gov NCT04677296 . Registered on December 21, 2020.
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Affiliation(s)
- Rina Das
- International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
- Department of Environmental Health Sciences, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
| | - Rukaeya Amin Sobi
- International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Al-Afroza Sultana
- International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Baitun Nahar
- International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Pradip Kumar Bardhan
- International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Laura Luke
- Science & Technology, Entrinsic Bioscience Inc., Boston, MA, USA
| | - Olivier Fontaine
- Science & Technology, Entrinsic Bioscience Inc., Boston, MA, USA
| | - Tahmeed Ahmed
- International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
- James P. Grant School of Public Health, BRAC University, Dhaka, 1212, Bangladesh
- Department of Global Health, University of Washington, Seattle, WA, 98104, USA
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16
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Gyedu A, Mehta K, Baidoo H, Addo D, Abdullah M, Mesic A, Samosorn A, Cancio LC, Nakarmi K, Stewart BT. Preferences for Oral Rehydration Drinks among Healthy Individuals in Ghana: A Single-Blind, Cross-Sectional Survey to Inform Implementation of an Enterally Based Resuscitation Protocol for Burn Injury. Burns 2022; 49:820-829. [PMID: 35715342 DOI: 10.1016/j.burns.2022.05.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 05/12/2022] [Accepted: 05/13/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Enterally based resuscitation for major burn injuries has been suggested as a simple, operationally superior, and effective resuscitation strategy for use in austere contexts. However, key information to support its implementation is lacking, including palatability and acceptability of widely available rehydration drinks. METHODS We performed a single-blinded, cross-sectional survey of 60 healthy children (5-14 years), adults (15-54 years) and older adults (≥55 years) to determine palatability and overall acceptability of five oral rehydration solutions (ORS) and a positive control drink (Sprite Zero®) in Ghana. Quantitative data were described and differences between our control drink and the others across age groups were visually examined with Likert plots. Qualitative responses were analyzed using a content analysis framework. RESULTS Twenty participants in each age group completed the study. Participants were as young as 5 years and as old as 84 years. Nearly two thirds of the sample identified as male (n = 38, 63% of all participants). The positive control was reported to taste 'good or 'very good' by the majority of participants (89%) followed by lemon-flavored ORS (78%) and orange-flavored ORS (78%). Conversely, homemade and low-osmolarity ORS were reported to taste 'good' or 'very good' by only 20% and 15% of participants, respectively. There were no major taste differences across the age groups. However, children more frequently reported positively (i.e., tastes 'good' or 'very good') about flavored and sweet drinks than did adults and older adults. When faced with the hypothetical situation of being critically injured and needing resuscitation, participants tended to be more agreeable to consuming all the drinks, even low-osmolarity and homemade ORS. CONCLUSIONS These findings can be used to support the development of protocols that may be more acceptable among patients undergoing enterally based resuscitation, thus improving the effectiveness of the treatment. Specifically, enterally based resuscitation should likely include citrus-flavored ORS when available, given superior palatability and the fact that different flavor additives for patients of different ages do not seem necessary.
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Affiliation(s)
- Adam Gyedu
- Department of Surgery, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
| | - Kajal Mehta
- Department of Surgery, University of Washington, Seattle, WA, USA.
| | - Hilary Baidoo
- University Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
| | - Dorcas Addo
- University Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
| | - Mohammed Abdullah
- University Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
| | - Aldina Mesic
- Department of Global Health, University of Washington, Seattle, WA, USA.
| | - Angela Samosorn
- US Army Institute of Surgical Research, Fort Sam Houston, TX, USA; US Army Nurse Corps, San Antonio, TX, USA.
| | | | | | - Barclay T Stewart
- Department of Surgery, University of Washington, Seattle, WA, USA; Harborview Injury Prevention & Research Center, Seattle, WA, USA; UW Medicine Regional Burn Center, Seattle, WA, USA.
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17
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Snapper H, Cheshire WP. Oral and intravenous hydration in the treatment of orthostatic hypotension and postural tachycardia syndrome. Auton Neurosci 2022; 238:102951. [PMID: 35123367 DOI: 10.1016/j.autneu.2022.102951] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 12/07/2021] [Accepted: 01/25/2022] [Indexed: 01/21/2023]
Abstract
Hydration with water and salt is the mainstay of treatment for autonomic nervous system disorders that impair orthostatic tolerance. The goal is to expand intravascular volume to compensate for the downward displacement of blood volume that occurs when standing and thereby sustain cerebral perfusion and restore quality of life. Despite strong consensus recommendations for salt supplementation as standard treatment of these disorders, published evidence of benefit is relatively weak, and no randomized clinical trials have occurred. This review summarizes the physiological rationale for hydration and evaluates the literature on oral and intravenous hydration in the treatment of neurogenic orthostatic hypotension, postural tachycardia syndrome, and recurrent vasovagal syncope. We conclude that oral salt replacement is indicated for treatment of neurogenic orthostatic hypotension because these patients have excessive renal sodium excretion, and for treatment of chronic orthostatic intolerance because these patients are often hypovolemic. As not all patients are able to tolerate sufficient oral hydration, there is also a role for intravenous volume-loading in severe cases of postural tachycardia syndrome. We offer guidance, based on review of the literature and the clinical judgment of a cardiologist and neurologist with experience treating autonomic disorders, regarding the option of ongoing intravenous hydration for treatment of severe, refractory cases of postural tachycardia syndrome.
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Affiliation(s)
- Howard Snapper
- Department of Cardiology, Wellstar Healthcare System, Marietta, GA 30060, USA.
| | - William P Cheshire
- Division of Autonomic Disorders, Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA
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18
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Li Z, Zhu G, Li C, Lai H, Liu X, Zhang L. Which Probiotic Is the Most Effective for Treating Acute Diarrhea in Children? A Bayesian Network Meta-Analysis of Randomized Controlled Trials. Nutrients 2021; 13:4319. [PMID: 34959871 PMCID: PMC8706888 DOI: 10.3390/nu13124319] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/22/2021] [Accepted: 11/25/2021] [Indexed: 12/13/2022] Open
Abstract
Acute diarrhea is a major cause of morbidity and mortality in children under five. Probiotics are beneficial for treating acute diarrhea in children, but unclear which specific probiotic is the most effective. We performed a Bayesian network meta-analysis to examine the comparative effectiveness of probiotics. By searching EMBASE, PubMed, and the Cochrane Library up to 31 March 2021, randomized clinical trials (RCTs) on probiotics for treating acute diarrhea in children were included. Primary outcomes included the duration of diarrhea and diarrhea lasting ≥2 days, and secondary outcomes included the mean stool frequency on day 2 and duration of hospitalization, fever, and vomiting. We assessed the certainty of the evidence of outcomes according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline. Eighty-four studies with twenty-one different interventions in 13,443 children were included. For the primary outcomes, moderate evidence indicated that, Lactobacillus reuteri [mean difference (MD) = -0.84 day; 95% confidence interval (CI), -1.39, -0.29], Bifidobacterium lactis (MD = -0.98 day; 95%CI, -1.82, -0.14), Saccharomyces boulardii (MD = -1.25 day; 95%CI, -1.59, -0.91), Lactobacillus species (spp.) plus Bifidobacterium spp. plus Saccharomyces spp. (MD = -1.19 day; 95%CI, -1.81, -0.58), and Bacillus spp. plus Enterococcus spp. plus Clostridium spp. (MD = -1.1 day; 95%CI, -1.84, -0.35) significantly reduced the duration of diarrhea when compared with placebo. Saccharomyces boulardii [Odds ratio (OR) = 0.22; 95%CI, 0.11, 0.41] and Lactobacillus reuteri (OR = 0.23; 95%CI, 0.090, 0.60) significantly reduced the risk of diarrhea lasting ≥2 days when compared with placebo or no treatment, with moderate evidence. Among all probiotics, Saccharomyces boulardii may be the most effective in reducing both duration of diarrhea (compared with placebo) and risk of diarrhea lasting ≥2 days (compared with placebo or no treatment), with moderate evidence. To be conclusive, Saccharomyces boulardii may be the most effective probiotic for treating acute diarrhea in children, followed by several other single-strain and multi-strain probiotics.
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Affiliation(s)
- Zengbin Li
- China-Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China; (Z.L.); (G.Z.); (H.L.)
| | - Guixian Zhu
- China-Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China; (Z.L.); (G.Z.); (H.L.)
| | - Chao Li
- Department of Epidemiology and Biostatistics, School of Public Health, Global Health Institute, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China; (C.L.); (X.L.)
| | - Hao Lai
- China-Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China; (Z.L.); (G.Z.); (H.L.)
| | - Xin Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Global Health Institute, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China; (C.L.); (X.L.)
| | - Lei Zhang
- China-Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China; (Z.L.); (G.Z.); (H.L.)
- Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC 3053, Australia
- Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC 3800, Australia
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
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Tharabenjasin P, Ferraris RP, Choowongkomon K, Pongkorpsakol P, Worakajit N, Sawasvirojwong S, Pabalan N, Na-Bangchang K, Muanprasat C. β-eudesmol but not atractylodin exerts an inhibitory effect on CFTR-mediated chloride transport in human intestinal epithelial cells. Biomed Pharmacother 2021; 142:112030. [PMID: 34426253 DOI: 10.1016/j.biopha.2021.112030] [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: 02/15/2021] [Revised: 07/13/2021] [Accepted: 08/07/2021] [Indexed: 11/19/2022] Open
Abstract
Oriental herbal medicine with the two bioactive constituents, β-eudesmol (BE) and atractylodin (AT), has been used as a remedy for gastrointestinal disorders. There was no scientific evidence reporting their antidiarrheal effect and underpinning mechanisms. Therefore, we aimed to investigate the anti-secretory activity of these two compounds in vitro. The inhibitory effect of BE and AT on cAMP-induced Cl- secretion was evaluated by Ussing chamber in human intestinal epithelial (T84) cells. Short-circuit current (ISC) and apical Cl- current (ICl-) were measured after adding indirect and direct cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activator. MTT assay was used to determine cellular cytotoxicity. Protein-ligand interaction was investigated by in silico molecular docking analysis. BE, but not AT concentration-dependently (IC50 of ~1.05 µM) reduced cAMP-mediated, CFTRinh-172 inhibitable Cl- secretion as determined by transepithelial ISC across a monolayer of T84 cells. Potency of CFTR-mediated ICl- inhibition by BE did not change with the use of different CFTR activators suggesting a direct blockage of the channel active site(s). Pretreatment with BE completely prevented cAMP-induced ICl-. Furthermore, BE at concentrations up to 200 µM (24 h) had no effect on T84 cell viability. In silico studies indicated that BE could best dock onto dephosphorylated structure of CFTR at ATP-binding pockets in nucleotide-binding domain (NBD) 2 region. These findings provide the first evidence for the anti-secretory effect of BE involving inhibition of CFTR function. BE represents a promising candidate for the therapeutic or prophylactic intervention of diarrhea resulted from intestinal hypersecretion of Cl.
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Affiliation(s)
- Phuntila Tharabenjasin
- Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klongnung, Klongluang, Pathum Thani 10120, Thailand
| | - Ronaldo P Ferraris
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ 07946, USA
| | - Kiattawee Choowongkomon
- Department of Biochemistry, Faculty of Science, Kasetsart University, Ngam Wong Wan Rd, Ladyaow, Chatuchak, Bangkok 10900, Thailand
| | - Pawin Pongkorpsakol
- Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok 10210, Thailand
| | - Nichakorn Worakajit
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Pla, Bang Phli, Samut Prakan 10540, Thailand
| | - Sutthipong Sawasvirojwong
- Department of Pathology, Faculty of Medicine, Chulalongkorn University, Phayathai Rd, Pathumwan, Bangkok 10330, Thailand
| | - Noel Pabalan
- Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klongnung, Klongluang, Pathum Thani 10120, Thailand
| | - Kesara Na-Bangchang
- Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Klongnung, Klongluang, Pathum Thani 10120, Thailand; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Rangsit Center, Thammasat University (Rangsit Campus), Klongnung, Klongluang, Pathum Thani 10120, Thailand
| | - Chatchai Muanprasat
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Pla, Bang Phli, Samut Prakan 10540, Thailand.
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20
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Disher AE, Stewart KL, Bach AJE, Stewart IB. Contribution of Dietary Composition on Water Turnover Rates in Active and Sedentary Men. Nutrients 2021; 13:nu13062124. [PMID: 34205676 PMCID: PMC8234797 DOI: 10.3390/nu13062124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 06/05/2021] [Accepted: 06/16/2021] [Indexed: 11/16/2022] Open
Abstract
Body water turnover is a marker of hydration status for measuring total fluid gains and losses over a 24-h period. It can be particularly useful in predicting (and hence, managing) fluid loss in individuals to prevent potential physical, physiological and cognitive declines associated with hypohydration. There is currently limited research investigating the interrelationship of fluid balance, dietary intake and activity level when considering body water turnover. Therefore, this study investigates whether dietary composition and energy expenditure influences body water turnover. In our methodology, thirty-eight males (19 sedentary and 19 physically active) had their total body water and water turnover measured via the isotopic tracer deuterium oxide. Simultaneous tracking of dietary intake (food and fluid) is carried out via dietary recall, and energy expenditure is estimated via accelerometery. Our results show that active participants display a higher energy expenditure, water intake, carbohydrate intake and fibre intake; however, there is no difference in sodium or alcohol intake between the two groups. Relative water turnover in the active group is significantly greater than the sedentary group (Mean Difference (MD) [95% CI] = 17.55 g·kg-1·day-1 [10.90, 24.19]; p = < 0.001; g[95% CI] = 1.70 [0.98, 2.48]). A penalised linear regression provides evidence that the fibre intake (p = 0.033), water intake (p = 0.008), and activity level (p = 0.063) predict participants' relative body water turnover (R2= 0.585). In conclusion, water turnover is faster in individuals undertaking regular exercise than in their sedentary counterparts, and is, in part, explained by the intake of water from fluid and high-moisture content foods. The nutrient analysis of the participant diets indicates that increased dietary fibre intake is also positively associated with water turnover rates. The water loss between groups also contributes to the differences observed in water turnover; this is partly related to differences in sweat output during increased energy expenditure from physical activity.
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Affiliation(s)
- Alice E. Disher
- School of Exercise and Nutrition Sciences, Queensland University of Technology, Brisbane 4059, Australia; (A.E.D.); (K.L.S.); (A.J.E.B.)
| | - Kelly L. Stewart
- School of Exercise and Nutrition Sciences, Queensland University of Technology, Brisbane 4059, Australia; (A.E.D.); (K.L.S.); (A.J.E.B.)
| | - Aaron J. E. Bach
- School of Exercise and Nutrition Sciences, Queensland University of Technology, Brisbane 4059, Australia; (A.E.D.); (K.L.S.); (A.J.E.B.)
- National Climate Change Adaptation Research Facility (NCCARF), Griffith University, Gold Coast 4222, Australia
| | - Ian B. Stewart
- School of Exercise and Nutrition Sciences, Queensland University of Technology, Brisbane 4059, Australia; (A.E.D.); (K.L.S.); (A.J.E.B.)
- Correspondence:
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21
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Wubetu AD, Engda AS, Yigzaw HB, Mulu GB. Oral Rehydration Therapy Utilization and Associated Factors Among Children with Diarrhea in Debre Berhan, Ethiopia, 2020. Pediatric Health Med Ther 2021; 12:251-258. [PMID: 34104039 PMCID: PMC8180307 DOI: 10.2147/phmt.s312460] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 05/17/2021] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND Oral rehydration therapy is a critical intervention to save the lives of children during episodes of diarrhea and vomiting. However, millions of children die every year due to failure to replace fluid effectively. Nearly all dehydration-related deaths can be preventable by prompt administration of rehydration therapy. The current study aimed to assess oral rehydration therapy utilization and associated factors among children with diarrhea in Debre Berhan town. METHODS Community-based cross-sectional study was conducted from February to March 2020. The study participants were selected by systematic random sampling. The first household was selected randomly by the lottery method. The collected data were checked for completeness and relevance, and then entered into EPI data and transferred to SPSS for analysis. Multivariate logistic regression was used to determine the ORT utilization and predictor variables. A p-value less than 0.05 was considered a cutoff point for statistical significance for all statistical tests. RESULTS The study included 233 participants with a 99% response rate. Among them, 73% [95% Cl: 66.8 78.6] of caregivers had given oral rehydration therapy to their children. Previous use of oral rehydration therapy [AOR: 5.3, Cl: 2.1-13.32], health-seeking behavior [AOR: 5.7, Cl: 2.07-15.6], knowledge about oral rehydration therapy [AOR: 4.2, Cl: 1.7-10.46], caregivers' perception of tooth eruption [AOR: 3.13, Cl: 1.08-9], weaning as causes of diarrhea [AOR: 6.7, Cl: 2.49-17.9], and recognize the severity sign of dehydration [AOR: 5.6, Cl: 2.16-14.7] became significant factors of oral rehydration therapy. CONCLUSION Nearly two-thirds of the mothers give oral rehydration therapy while their child develops diarrhea. Mothers had previous oral rehydration therapy, good health-seeking behavior, knowledge about oral rehydration therapy, caregivers' perception of tooth eruption, and weaning as causes of diarrhea. Signs to recognize the severity of dehydration were important factors with oral rehydration therapy utilization. It will be better to give mothers special attention to hindering factors from giving oral rehydration therapy for their beloved child during diarrheal disease.
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Affiliation(s)
- Abate Dargie Wubetu
- Debre Berhan University, College of Health Science, Department of Psychiatry, Debre Berhan, Amhara, Ethiopia
| | - Abayneh Shewangzaw Engda
- Debre Berhan University, College of Health Science, Department of Psychiatry, Debre Berhan, Amhara, Ethiopia
| | - Hailu Belay Yigzaw
- Adigrat University, College of Health Science, Department of Psychiatry, Adigrat, Tigray, Ethiopa
| | - Getaneh Baye Mulu
- Debre Berhan University, College of Health Science, Department of Nursing, Debre Berhan, Amhara, Ethiopia
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22
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Unique Regulation of Intestinal Villus Epithelial Cl -/HCO 3- Exchange by Cyclooxygenase Pathway Metabolites of Arachidonic Acid in a Mouse Model of Spontaneous Ileitis. Int J Mol Sci 2021; 22:ijms22084171. [PMID: 33920650 PMCID: PMC8074161 DOI: 10.3390/ijms22084171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/09/2021] [Accepted: 04/13/2021] [Indexed: 11/16/2022] Open
Abstract
Electrolytes (NaCl) and fluid malabsorption cause diarrhea in inflammatory bowel disease (IBD). Coupled NaCl absorption, mediated by Na+/H+ and Cl-/HCO3- exchanges on the intestinal villus cells brush border membrane (BBM), is inhibited in IBD. Arachidonic acid metabolites (AAMs) formed via cyclooxygenase (COX) or lipoxygenase (LOX) pathways are elevated in IBD. However, their effects on NaCl absorption are not known. We treated SAMP1/YitFc (SAMP1) mice, a model of spontaneous ileitis resembling human IBD, with Arachidonyl Trifluoro Methylketone (ATMK, AAM inhibitor), or with piroxicam or MK-886, to inhibit COX or LOX pathways, respectively. Cl-/HCO3- exchange, measured as DIDS-sensitive 36Cl uptake, was significantly inhibited in villus cells and BBM vesicles of SAMP1 mice compared to AKR/J controls, an effect reversed by ATMK. Piroxicam, but not MK-886, also reversed the inhibition. Kinetic studies showed that inhibition was secondary to altered Km with no effects on Vmax. Whole cell or BBM protein levels of Down-Regulated in Adenoma (SLC26A3) and putative anion transporter-1 (SLC26A6), the two key BBM Cl-/HCO3- exchangers, were unaltered. Thus, inhibition of villus cell Cl-/HCO3- exchange by COX pathway AAMs, such as prostaglandins, via reducing the affinity of the exchanger for Cl-, and thereby causing NaCl malabsorption, could significantly contribute to IBD-associated diarrhea.
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23
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Magwalivha M, Ngandu JPK, Traore AN, Potgieter N. Prevalence and Genetic Characterisation of Human Sapovirus from Children with Diarrhoea in the Rural Areas of Vhembe District, South Africa, 2017-2020. Viruses 2021; 13:393. [PMID: 33804579 PMCID: PMC8000493 DOI: 10.3390/v13030393] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/24/2021] [Accepted: 02/24/2021] [Indexed: 12/29/2022] Open
Abstract
Diarrhoeal disease is considered an important cause of morbidity and mortality in developing areas, and a large contributor to the burden of disease in children younger than five years of age. This study investigated the prevalence and genogroups of human sapovirus (SV) in children ≤5 years of age in rural communities of Vhembe district, South Africa. Between 2017 and 2020, a total of 284 stool samples were collected from children suffering with diarrhoea (n = 228) and from children without diarrhoea (n = 56). RNA extraction using Boom extraction method, and screening for SV using real-time PCR were done in the lab. Positive samples were subjected to conventional RT-PCR targeting the capsid fragment. Positive sample isolates were genotyped using Sanger sequencing. Overall SV were detected in 14.1% (40/284) of the stool samples (16.7% (38/228) of diarrhoeal and 3.6% (2/56) of non-diarrhoeal samples). Significant correlation between SV positive cases and water sources was noted. Genogroup-I was identified as the most prevalent strain comprising 81.3% (13/16), followed by SV-GII 12.5% (2/16) and SV-GIV 6.2% (1/16). This study provides valuable data on prevalence of SV amongst outpatients in rural and underdeveloped communities, and highlights the necessity for further monitoring of SV circulating strains as potential emerging strains.
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Affiliation(s)
- Mpho Magwalivha
- Department of Microbiology, School of Mathematical and Natural Sciences, University of Venda, Thohoyandou 0950, South Africa; (J.-P.K.N.); (A.N.T.); (N.P.)
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24
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Yap YA, Mariño E. Dietary SCFAs Immunotherapy: Reshaping the Gut Microbiota in Diabetes. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1307:499-519. [PMID: 32193865 DOI: 10.1007/5584_2020_515] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Diet-microbiota related inflammatory conditions such as obesity, autoimmune type 1 diabetes (T1D), type 2 diabetes (T2D), cardiovascular disease (CVD) and gut infections have become a stigma in Western societies and developing nations. This book chapter examines the most relevant pre-clinical and clinical studies about diet-gut microbiota approaches as an alternative therapy for diabetes. We also discuss what we and others have extensively investigated- the power of dietary short-chain fatty acids (SCFAs) technology that naturally targets the gut microbiota as an alternative method to prevent and treat diabetes and its related complications.
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Affiliation(s)
- Yu Anne Yap
- Infection and Immunity Program, Biomedicine Discovery Institute, Department of Biochemistry, Monash University, Melbourne, VIC, Australia
| | - Eliana Mariño
- Infection and Immunity Program, Biomedicine Discovery Institute, Department of Biochemistry, Monash University, Melbourne, VIC, Australia.
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25
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Yap YA, McLeod KH, McKenzie CI, Gavin PG, Davalos-Salas M, Richards JL, Moore RJ, Lockett TJ, Clarke JM, Eng VV, Pearson JS, Hamilton-Williams EE, Mackay CR, Mariño E. An acetate-yielding diet imprints an immune and anti-microbial programme against enteric infection. Clin Transl Immunology 2021; 10:e1233. [PMID: 33489123 PMCID: PMC7809703 DOI: 10.1002/cti2.1233] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 11/16/2020] [Accepted: 12/09/2020] [Indexed: 12/19/2022] Open
Abstract
Objectives During gastrointestinal infection, dysbiosis can result in decreased production of microbially derived short‐chain fatty acids (SCFAs). In response to the presence of intestinal pathogens, we examined whether an engineered acetate‐ or butyrate‐releasing diet can rectify the deficiency of SCFAs and lead to the resolution of enteric infection. Methods We tested whether a high acetate‐ or butyrate‐producing diet (HAMSA or HAMSB, respectively) condition Citrobacterrodentium infection in mice and assess its impact on host‐microbiota interactions. We analysed the adaptive and innate immune responses, changes in gut microbiome function, epithelial barrier function and the molecular mechanism via metabolite sensing G protein‐coupled receptor 43 (GPR43) and IL‐22 expression. Results HAMSA diet rectified the deficiency in acetate production and protected against enteric infection. Increased SCFAs affect the expression of pathogen virulence genes. HAMSA diet promoted compositional and functional changes in the gut microbiota during infection similar to healthy microbiota from non‐infected mice. Bacterial changes were evidenced by the production of proteins involved in acetate utilisation, starch and sugar degradation, amino acid biosynthesis, carbohydrate transport and metabolism. HAMSA diet also induced changes in host proteins critical in glycolysis, wound healing such as GPX1 and epithelial architecture such as EZR1 and PFN1. Dietary acetate assisted in rapid epithelial repair, as shown by increased colonic Muc‐2, Il‐22, and anti‐microbial peptides. We found that acetate increased numbers of colonic IL‐22 producing TCRαβ+CD8αβ+ and TCRγδ+CD8αα+ intraepithelial lymphocytes expressing GPR43. Conclusion HAMSA diet may be an effective therapeutic approach for fighting inflammation and enteric infections and offer a safe alternative that may impact on human health.
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Affiliation(s)
- Yu Anne Yap
- Department of Biochemistry and Molecular Biology Infection and Immunity Program Biomedicine Discovery Institute Monash University Clayton, Melbourne VIC Australia
| | - Keiran H McLeod
- Department of Biochemistry and Molecular Biology Infection and Immunity Program Biomedicine Discovery Institute Monash University Clayton, Melbourne VIC Australia
| | - Craig I McKenzie
- Department of Biochemistry and Molecular Biology Infection and Immunity Program Biomedicine Discovery Institute Monash University Clayton, Melbourne VIC Australia
| | - Patrick G Gavin
- The University of Queensland Diamantina Institute The University of Queensland Brisbane QLD Australia
| | - Mercedes Davalos-Salas
- Department of Biochemistry and Molecular Biology Infection and Immunity Program Biomedicine Discovery Institute Monash University Clayton, Melbourne VIC Australia
| | - James L Richards
- Department of Biochemistry and Molecular Biology Infection and Immunity Program Biomedicine Discovery Institute Monash University Clayton, Melbourne VIC Australia
| | - Robert J Moore
- Department of Microbiology Infection and Immunity Program Biomedicine Discovery Institute Monash University Clayton, Melbourne VIC Australia.,School of Science RMIT University Bundoora VIC Australia
| | | | | | - Vik Ven Eng
- Department of Microbiology Infection and Immunity Program Biomedicine Discovery Institute Monash University Clayton, Melbourne VIC Australia.,Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton, Melbourne VIC Australia
| | - Jaclyn S Pearson
- Department of Microbiology Infection and Immunity Program Biomedicine Discovery Institute Monash University Clayton, Melbourne VIC Australia.,Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton, Melbourne VIC Australia.,Department of Molecular and Translational Research Monash University Clayton, Melbourne VIC Australia
| | - Emma E Hamilton-Williams
- The University of Queensland Diamantina Institute The University of Queensland Brisbane QLD Australia
| | - Charles R Mackay
- Department of Microbiology Infection and Immunity Program Biomedicine Discovery Institute Monash University Clayton, Melbourne VIC Australia
| | - Eliana Mariño
- Department of Biochemistry and Molecular Biology Infection and Immunity Program Biomedicine Discovery Institute Monash University Clayton, Melbourne VIC Australia
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26
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Gona PN, Gona CM, Chikwasha V, Haruzivishe C, Rao SR, Mapoma CC. Oral rehydration solution coverage in under 5 children with diarrhea: a tri-country, subnational, cross-sectional comparative analysis of two demographic health surveys cycles. BMC Public Health 2020; 20:1716. [PMID: 33198701 PMCID: PMC7670726 DOI: 10.1186/s12889-020-09811-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 10/30/2020] [Indexed: 11/16/2022] Open
Abstract
Background More than 3 million children under 5 years in developing countries die from dehydration due to diarrhea, a preventable and treatable disease. We conducted a comparative analysis of two Demographic Health Survey (DHS) cycles to examine changes in ORS coverage in Zimbabwe, Zambia and Malawi. These surveys are cross-sectional conducted on a representative sample of the non-institutionalized individuals. Methods The sample is drawn using a stratified two-stage cluster sampling design with census enumeration areas, typically, selected first as primary sampling units (PSUs) and then a fixed number of households from each PSU. We examined national and sub-regional prevalence of ORS use during a recent episode of diarrhea (within 2 weeks of survey) using DHSs for 2007–2010 (1st Period), and 2013–2016 (2nd Period). Weighted proportions of ORS were obtained and multivariable- design-adjusted logistic regression analysis was used to obtain Odds Ratios (aORs) and 95% confidence intervals (CIs) and weighted proportions of ORS coverage. Results Crude ORS coverage increased from 21.0% (95% CI: 17.4–24.9) in 1st Period to 40.5% (36.5–44.6) in 2nd Period in Zimbabwe; increased from 60.8% (56.1–65.3) to 64.7% (61.8–67.5) in Zambia; and decreased from 72.3% (68.4–75.9) to 64.6% (60.9–68.1) in Malawi. The rates of change in coverage among provinces in Zimbabwe ranged from 10.3% over the three cycles (approximately 10 years) in Midlands to 44.2% in Matabeleland South; in Zambia from − 9.5% in Eastern Province to 24.4% in Luapula; and in Malawi from − 16.5% in the Northern Province to − 3.2% in Southern Province. The aORs for ORS use was 3.95(2.66–5.86) for Zimbabwe, 2.83 (2.35–3.40) for Zambia, and, 0.71(0.59–0.87) for Malawi. Conclusion ORS coverage increased in Zimbabwe, stagnated in Zambia, but declined in Malawi. Monitoring national and province-level trends of ORS use illuminates geographic inequalities and helps identify priority areas for targeting resource allocation.. Provision of safe drinking-water, adequate sanitation and hygiene will help reduce the causes and the incidence of diarrhea. Health policies to strengthen access to appropriate treatments such as vaccines for rotavirus and cholera and promoting use of ORS to reduce the burden of diarrhea should be developed and implemented. Supplementary Information The online version contains supplementary material available at 10.1186/s12889-020-09811-1.
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27
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de Jonge HR, Ardelean MC, Bijvelds MJC, Vergani P. Strategies for cystic fibrosis transmembrane conductance regulator inhibition: from molecular mechanisms to treatment for secretory diarrhoeas. FEBS Lett 2020; 594:4085-4108. [PMID: 33113586 PMCID: PMC7756540 DOI: 10.1002/1873-3468.13971] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 09/22/2020] [Accepted: 10/15/2020] [Indexed: 02/06/2023]
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) is an unusual ABC transporter. It acts as an anion‐selective channel that drives osmotic fluid transport across many epithelia. In the gut, CFTR is crucial for maintaining fluid and acid‐base homeostasis, and its activity is tightly controlled by multiple neuro‐endocrine factors. However, microbial toxins can disrupt this intricate control mechanism and trigger protracted activation of CFTR. This results in the massive faecal water loss, metabolic acidosis and dehydration that characterize secretory diarrhoeas, a major cause of malnutrition and death of children under 5 years of age. Compounds that inhibit CFTR could improve emergency treatment of diarrhoeal disease. Drawing on recent structural and functional insight, we discuss how existing CFTR inhibitors function at the molecular and cellular level. We compare their mechanisms of action to those of inhibitors of related ABC transporters, revealing some unexpected features of drug action on CFTR. Although challenges remain, especially relating to the practical effectiveness of currently available CFTR inhibitors, we discuss how recent technological advances might help develop therapies to better address this important global health need.
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Affiliation(s)
- Hugo R. de Jonge
- Department of Gastroenterology & HepatologyErasmus University Medical CenterRotterdamThe Netherlands
| | - Maria C. Ardelean
- Department of Neuroscience, Physiology and PharmacologyUniversity College LondonUK
- Department of Natural SciencesUniversity College LondonUK
| | - Marcel J. C. Bijvelds
- Department of Gastroenterology & HepatologyErasmus University Medical CenterRotterdamThe Netherlands
| | - Paola Vergani
- Department of Neuroscience, Physiology and PharmacologyUniversity College LondonUK
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Inhibition of CFTR-mediated intestinal chloride secretion by a fungus-derived arthropsolide A: Mechanism of action and anti-diarrheal efficacy. Eur J Pharmacol 2020; 885:173393. [DOI: 10.1016/j.ejphar.2020.173393] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 07/10/2020] [Accepted: 07/20/2020] [Indexed: 11/19/2022]
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Posovszky C, Buderus S, Classen M, Lawrenz B, Keller KM, Koletzko S. Acute Infectious Gastroenteritis in Infancy and Childhood. DEUTSCHES ARZTEBLATT INTERNATIONAL 2020; 117:615-624. [PMID: 33263539 PMCID: PMC7805585 DOI: 10.3238/arztebl.2020.0615] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 01/26/2020] [Accepted: 06/29/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Despite the introduction of vaccination against rotavirus, and even though it can often be treated on an outpatient basis, acute infectious gastroenteritis is nevertheless the second most common non-traumatic cause of emergency hospitaliza - tion in children aged 1 to 5 years, accounting for approximately 9% of cases (39 410 cases in 2017). The most common path - ogens are viruses (47% rotavirus, 29% norovirus, and 14% adenovirus). METHODS This review is based on publications retrieved by a selective search in PubMed employing the terms "acute gastro - enteritis children" AND "dehydration" OR "rehydration" OR "prevention," and by manual searching (based, for example, on reference lists and expert knowledge), with subsequent evaluation including consideration of the relevant guidelines. RESULTS The degree of dehydration can be judged from weight loss and other clinical findings. In 17 randomized controlled trials conducted on a total of 1811 children with mild or moderate dehydration, oral rehydration with oral rehydration solution was just as effective as intravenous rehydration with respect to weight gain, duration of diarrhea, and fluid administration, and was associated with shorter hospital stays (weighted mean difference, -1.2 days; 95% confidence interval [-2.38; -0.02]). Oral rehydration therapy failed in 4% of patients [1; 7]. In children who are vomiting or who refuse oral rehydration solution, continuous nasogastric application is just as effective as intravenous rehydration and is the treatment of first choice. CONCLUSION In Germany, children with mild or moderate dehydration are often hospitalized for intravenous rehydration therapy, despite the good evidence supporting ambulatory oral rehydration. Obstacles to intersectoral care, the nursing shortage, and inadequate reimbursement must all be overcome in order to reduce unnecessary hospitalizations and thereby lessen the risk of nosocomial infection.
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Affiliation(s)
- Carsten Posovszky
- Department of Pediatric and Adolescent Medicine, University Medical Center Ulm
| | - Stephan Buderus
- Department of Pediatrics, GFO-Kliniken Bonn, St. Marienhospital Bonn
| | - Martin Classen
- Department of Pediatric and Adolescent Medicine, Klinikum Links der Weser and Klinikum Bremen-Mitte, Bremen
| | | | | | - Sibylle Koletzko
- Department of Pediatric and Adolescent Medicine, Dr. von Hauner Children’s Hospital, LMU Klinikum der Universität München
- Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland
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30
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Koepsell H. Glucose transporters in the small intestine in health and disease. Pflugers Arch 2020; 472:1207-1248. [PMID: 32829466 PMCID: PMC7462918 DOI: 10.1007/s00424-020-02439-5] [Citation(s) in RCA: 148] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 07/11/2020] [Accepted: 07/17/2020] [Indexed: 12/23/2022]
Abstract
Absorption of monosaccharides is mainly mediated by Na+-D-glucose cotransporter SGLT1 and the facititative transporters GLUT2 and GLUT5. SGLT1 and GLUT2 are relevant for absorption of D-glucose and D-galactose while GLUT5 is relevant for D-fructose absorption. SGLT1 and GLUT5 are constantly localized in the brush border membrane (BBM) of enterocytes, whereas GLUT2 is localized in the basolateral membrane (BLM) or the BBM plus BLM at low and high luminal D-glucose concentrations, respectively. At high luminal D-glucose, the abundance SGLT1 in the BBM is increased. Hence, D-glucose absorption at low luminal glucose is mediated via SGLT1 in the BBM and GLUT2 in the BLM whereas high-capacity D-glucose absorption at high luminal glucose is mediated by SGLT1 plus GLUT2 in the BBM and GLUT2 in the BLM. The review describes functions and regulations of SGLT1, GLUT2, and GLUT5 in the small intestine including diurnal variations and carbohydrate-dependent regulations. Also, the roles of SGLT1 and GLUT2 for secretion of enterohormones are discussed. Furthermore, diseases are described that are caused by malfunctions of small intestinal monosaccharide transporters, such as glucose-galactose malabsorption, Fanconi syndrome, and fructose intolerance. Moreover, it is reported how diabetes, small intestinal inflammation, parental nutrition, bariatric surgery, and metformin treatment affect expression of monosaccharide transporters in the small intestine. Finally, food components that decrease D-glucose absorption and drugs in development that inhibit or downregulate SGLT1 in the small intestine are compiled. Models for regulations and combined functions of glucose transporters, and for interplay between D-fructose transport and metabolism, are discussed.
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Affiliation(s)
- Hermann Koepsell
- Institute for Anatomy and Cell Biology, University of Würzburg, Koellikerstr 6, 97070, Würzburg, Germany.
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31
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Wiens KE, Lindstedt PA, Blacker BF, Johnson KB, Baumann MM, Schaeffer LE, Abbastabar H, Abd-Allah F, Abdelalim A, Abdollahpour I, Abegaz KH, Abejie AN, Abreu LG, Abrigo MRM, Abualhasan A, Accrombessi MMK, Acharya D, Adabi M, Adamu AA, Adebayo OM, Adedoyin RA, Adekanmbi V, Adetokunboh OO, Adhena BM, Afarideh M, Ahmad S, Ahmadi K, Ahmed AE, Ahmed MB, Ahmed R, Akalu TY, Alahdab F, Al-Aly Z, Alam N, Alam S, Alamene GM, Alanzi TM, Alcalde-Rabanal JE, Ali BA, Alijanzadeh M, Alipour V, Aljunid SM, Almasi A, Almasi-Hashiani A, Al-Mekhlafi HM, Altirkawi KA, Alvis-Guzman N, Alvis-Zakzuk NJ, Amini S, Amit AML, Andrei CL, Anjomshoa M, Anoushiravani A, Ansari F, Antonio CAT, Antony B, Antriyandarti E, Arabloo J, Aref HMA, Aremu O, Armoon B, Arora A, Aryal KK, Arzani A, Asadi-Aliabadi M, Atalay HT, Athari SS, Athari SM, Atre SR, Ausloos M, Awoke N, Ayala Quintanilla BP, Ayano G, Ayanore MA, Aynalem IV YA, Azari S, Azzopardi PS, Babaee E, Babalola TK, Badawi A, Bairwa M, Bakkannavar SM, Balakrishnan S, Bali AG, Banach M, Banoub JAM, Barac A, Bärnighausen TW, Basaleem H, Basu S, Bay VD, Bayati M, Baye E, Bedi N, Beheshti MMB, Behzadifar M, Behzadifar M, Bekele BB, Belayneh YM, Bell ML, et alWiens KE, Lindstedt PA, Blacker BF, Johnson KB, Baumann MM, Schaeffer LE, Abbastabar H, Abd-Allah F, Abdelalim A, Abdollahpour I, Abegaz KH, Abejie AN, Abreu LG, Abrigo MRM, Abualhasan A, Accrombessi MMK, Acharya D, Adabi M, Adamu AA, Adebayo OM, Adedoyin RA, Adekanmbi V, Adetokunboh OO, Adhena BM, Afarideh M, Ahmad S, Ahmadi K, Ahmed AE, Ahmed MB, Ahmed R, Akalu TY, Alahdab F, Al-Aly Z, Alam N, Alam S, Alamene GM, Alanzi TM, Alcalde-Rabanal JE, Ali BA, Alijanzadeh M, Alipour V, Aljunid SM, Almasi A, Almasi-Hashiani A, Al-Mekhlafi HM, Altirkawi KA, Alvis-Guzman N, Alvis-Zakzuk NJ, Amini S, Amit AML, Andrei CL, Anjomshoa M, Anoushiravani A, Ansari F, Antonio CAT, Antony B, Antriyandarti E, Arabloo J, Aref HMA, Aremu O, Armoon B, Arora A, Aryal KK, Arzani A, Asadi-Aliabadi M, Atalay HT, Athari SS, Athari SM, Atre SR, Ausloos M, Awoke N, Ayala Quintanilla BP, Ayano G, Ayanore MA, Aynalem IV YA, Azari S, Azzopardi PS, Babaee E, Babalola TK, Badawi A, Bairwa M, Bakkannavar SM, Balakrishnan S, Bali AG, Banach M, Banoub JAM, Barac A, Bärnighausen TW, Basaleem H, Basu S, Bay VD, Bayati M, Baye E, Bedi N, Beheshti MMB, Behzadifar M, Behzadifar M, Bekele BB, Belayneh YM, Bell ML, Bennett DA, Berbada DA, Bernstein RS, Bhat AG, Bhattacharyya K, Bhattarai S, Bhaumik S, Bhutta ZA, Bijani A, Bikbov B, Birihane IV BM, Biswas RK, Bohlouli S, Bojia I HAA, Boufous S, Brady OJ, Bragazzi NL, Briko AN, Briko NI, Britton GB, Burugina Nagaraja S, Busse R, Butt ZA, Cámera LLAA, Campos-Nonato IR, Cano J, Car J, Cárdenas R, Carvalho F, Castañeda-Orjuela CA, Castro F, Chanie WF, Chatterjee P, Chattu VK, Chichiabellu TYY, Chin KL, Christopher DJ, Chu DT, Cormier NM, Costa VM, Culquichicon C, Daba MS, Damiani G, Dandona L, Dandona R, Dang AK, Darwesh AM, Darwish AH, Daryani A, Das JK, Das Gupta R, Dash AP, Davey G, Dávila-Cervantes CA, Davis AC, Davitoiu DV, De la Hoz FP, Demis AB, Demissie DB, Demissie GD, Demoz GT, Denova-Gutiérrez E, Deribe K, Desalew A, Deshpande A, Dharmaratne SD, Dhillon P, Dhimal M, Dhungana GP, Diaz D, Dipeolu IO, Djalalinia S, Doyle KE, Dubljanin E, Duko B, Duraes AR, Ebrahimi Kalan M, Edinur HA, Effiong A, Eftekhari A, El Nahas N, El Sayed I, El Sayed Zaki M, El Tantawi M, Elema I TB, Elhabashy HR, El-Jaafary SI, Elkout H, Elsharkawy A, Elyazar IRF, Endalamaw A, Endalew DA, Eskandarieh S, Esteghamati A, Esteghamati S, Etemadi A, Ezekannagha O, Fareed M, Faridnia R, Farzadfar F, Fazlzadeh M, Feigin VL, Fereshtehnejad SM, Fernandes E, Filip I, Fischer F, Foigt NA, Folayan MO, Foroutan M, Franklin RC, Fukumoto T, Gad MM, Gayesa RT, Gebre T, Gebremedhin KB, Gebremeskel GG, Gesesew HA, Gezae KE, Ghadiri K, Ghashghaee A, Ghimire PR, Gill PS, Gill TK, Ginindza TGG, Gomes NGM, Gopalani SV, Goulart AC, Goulart BNG, Grada A, Gubari MIM, Gugnani HC, Guido D, Guimarães RA, Guo Y, Gupta R, Hafezi-Nejad N, Haile DH, Hailu GB, Haj-Mirzaian A, Haj-Mirzaian A, Hamadeh RR, Hamidi S, Handiso DW, Haririan H, Hariyani N, Hasaballah AI, Hasan MM, Hasanpoor E, Hasanzadeh A, Hassankhani H, Hassen HY, Hegazy MI, Heibati B, Heidari B, Hendrie D, Henry NJ, Herteliu C, Heydarpour F, Hidru I HDD, Hird TR, Hoang CL, Homaie Rad E, Hoogar P, Hoseini M, Hossain N, Hosseini M, Hosseinzadeh M, Househ M, Hsairi M, Hu G, Hussen MM, Ibitoye SE, Igumbor EU, Ilesanmi OS, Ilic MD, Imani-Nasab MH, Iqbal U, Irvani SSN, Islam SMS, Iwu CJ, Izadi N, Jaca A, Jahanmehr N, Jakovljevic M, Jalali A, Jayatilleke AU, Jha RP, Jha V, Ji JS, Jonas JB, Jozwiak JJ, Kabir A, Kabir Z, Kahsay A, Kalani H, Kanchan T, Karami Matin B, Karch A, Karim MA, Karimi-Sari H, Karki S, Kasaeian A, Kasahun GG, Kasahun YC, Kasaye HK, Kassa GG, Kassa GM, Kayode GA, Kazemi Karyani A, Kebede MM, Keiyoro PN, Kelbore AG, Kengne AP, Ketema DB, Khader YS, Khafaie MA, Khalid N, Khalilov R, Khan EA, Khan J, Khan I MN, Khan MS, Khatab K, Khater AM, Khater MM, Khayamzadeh M, Khazaei M, Khazaei S, Khosravi MH, Khubchandani J, Kiadaliri A, Kim YJ, Kimokoti RW, Kisa A, Kisa S, Kissoon N, KMShivakumar SKMMM, Kochhar S, Kolola T, Komaki H, Kosen S, Koul PA, Koyanagi A, Kraemer MUG, Krishan K, Kugbey N, Kumar GA, Kumar M, Kumar P, Kumar V, Kusuma D, La Vecchia C, Lacey B, Lad SD, Lal DK, Lam F, Lami FH, Lamichhane P, Lansingh VC, Lasrado S, Laxmaiah A, Lee PH, LeGrand KE, Leili M, Lenjebo TL, Leshargie CT, Levine AJ, Li S, Linn S, Liu S, Liu S, Lodha R, Longbottom J, Lopez JCF, Magdy Abd El Razek H, Magdy Abd El Razek M, Mahadeshwara Prasad DR, Mahasha PW, Mahotra NB, Majeed A, Malekzadeh R, Malta DC, Mamun AA, Manafi N, Manda AL, Manohar NDD, Mansournia MA, Mapoma CC, Maravilla JC, Martinez G, Martini S, Martins-Melo FR, Masaka A, Massenburg BB, Mathur MR, Mayala BK, Mazidi M, McAlinden C, Meharie BG, Mehndiratta MM, Mehta KM, Mekonnen TCC, Meles GG, Memiah PTN, Memish ZA, Mendoza W, Menezes RG, Mereta ST, Meretoja TJ, Mestrovic T, Miazgowski B, Mihretie KM, Miller TR, Mini GK, Mirrakhimov EM, Moazen B, Mohajer B, Mohamadi-Bolbanabad A, Mohammad DK, Mohammad KA, Mohammad Y, Mohammad Gholi Mezerji N, Mohammadibakhsh R, Mohammadifard N, Mohammed JA, Mohammed S, Mohebi F, Mokdad AH, Molokhia M, Monasta L, Moodley Y, Moore CE, Moradi G, Moradi M, Moradi-Joo M, Moradi-Lakeh M, Moraga P, Morales L, Moreno Velásquez I, Mosapour A, Mouodi S, Mousavi SM, Mozaffor I M, Muchie KF, Mulaw GF, Munro SB, Muriithi MK, Murray CJL, Murthy GVS, Musa KI, Mustafa G, Muthupandian S, Nabhan AF, Naderi M, Nagarajan AJ, Naidoo KS, Naik G, Najafi F, Nangia V, Nansseu JR, Nascimento BR, Nazari J, Ndwandwe DE, Negoi I, Netsere HBN, Ngunjiri JW, Nguyen CT, Nguyen HLT, Nguyen TH, Nigatu D, Nigatu SG, Ningrum DNA, Nnaji CA, Nojomi M, Nong VM, Norheim OF, Noubiap JJ, Nouraei Motlagh S, Oancea B, Ogah OS, Ogbo FA, Oh IH, Olagunju AT, Olagunju TO, Olusanya BO, Olusanya JO, Onwujekwe OE, Oren E, Ortega-Altamirano DVV, Osarenotor O, Osei FB, Owolabi MO, P A M, Padubidri JR, Pakhale S, Patel SK, Paternina-Caicedo AJ, Pathak A, Patton GC, Paudel D, Paulos K, Pepito VCF, Pereira A, Perico N, Pervaiz A, Pescarini JM, Piroozi B, Pirsaheb M, Postma MJ, Pourjafar H, Pourmalek F, Pourshams A, Poustchi H, Prada SI, Prasad N, Preotescu L, Quintana H, Rabiee N, Radfar A, Rafiei A, Rahim F, Rahimi-Movaghar A, Rahimi-Movaghar V, Rahman MHU, Rahman MA, Rahman SHAFIUR, Rajati F, Rana SM, Ranabhat CL, Rasella D, Rawaf DL, Rawaf S, Rawal L, Rawasia WF, Renjith V, Renzaho AMN, Resnikoff S, Reta MA, Rezaei N, Rezai MS, Riahi SM, Ribeiro AI, Rickard J, Rios-Blancas M, Roever L, Ronfani L, Roro EM, Ross JM, Rubagotti E, Rubino S, Saad AM, Sabde YD, Sabour S, Sadeghi E, Safari Y, Safari-Faramani R, Sagar R, Sahebkar A, Sahraian MA, Sajadi SM, Salahshoor MR, Salam N, Salamati P, Salem H, Salem I MRR, Salimi Y, Salimzadeh H, Samy AM, Sanabria J, Santric-Milicevic MM, Sao Jose BP, Saraswathy SYI, Sarkar K, Sarker AR, Sarrafzadegan I N, Sartorius B, Sathian B, Sathish T, Sawhney M, Saxena S, Schwebel DC, Senbeta IV AM, Senthilkumaran S, Sepanlou SG, Serván-Mori E, Shabaninejad H, Shafieesabet A, Shaikh MA, Shalash AS, Shallo SA, Shams-Beyranvand M, Shamsi M, Shamsizadeh M, Shannawaz M, Sharafi K, Sharifi H, Shehata HS, Sheikh A, Shetty BSK, Shibuya K, Shiferaw WS, Shifti DM, Shigematsu M, Shin JI, Shiri R, Shirkoohi R, Siabani S, Siddiqi TJ, Silva DAS, Singh A, Singh JA, Singh NP, Singh V, Sisay MM, Skiadaresi E, Sobhiyeh MR, Sokhan A, Soltani S, Somayaji R, Soofi M, Sorrie MB, Soyiri IN, Sreeramareddy CT, Sudaryanto A, Sufiyan MB, Suleria HAR, Sultana M, Sunguya BF, Sykes BL, Tabarés-Seisdedos R, Tabuchi T, Tadesse DB, Tarigan IU, Tasew AA, Tefera YM, Tekle MG, Temsah MH, Tesfay I BE, Tesfay FHH, Tessema B, Tessema ZT, Thankappan KR, Thomas N, Toma AT, Topor-Madry R, Tovani-Palone MRR, Traini E, Tran BX, Tran KB, Ullah I, Unnikrishnan B, Usman MS, Uzochukwu BSC, Valdez PR, Varughese S, Violante FS, Vollmer S, W/hawariat FG, Waheed Y, Wallin MT, Wang Y, Wang YP, Weaver M, Weji BG, Weldesamuel GT, Welgan CA, Werdecker A, Westerman R, Wiangkham T, Wiysonge CS, Wolde HF, Wondafrash DZ, Wonde TE, Worku GT, Wu AM, Xu G, Yadollahpour A, Yahyazadeh Jabbari SH, Yamada T, Yatsuya H, Yeshaneh A, Yilgwan CS, Yilma MT, Yip P, Yisma E, Yonemoto N, Yoon SJ, Younis MZ, Yousefifard M, Yousof HASA, Yu C, Yusefzadeh H, Zadey S, Zaidi Z, Zaman SB, Zamani M, Zandian H, Zepro NB, Zerfu TA, Zhang Y, Zhao XJG, Ziapour A, Zodpey S, Zuniga YMH, Hay SI, Reiner RC. Mapping geographical inequalities in oral rehydration therapy coverage in low-income and middle-income countries, 2000-17. Lancet Glob Health 2020; 8:e1038-e1060. [PMID: 32710861 PMCID: PMC7388204 DOI: 10.1016/s2214-109x(20)30230-8] [Show More Authors] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 03/19/2020] [Accepted: 04/28/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. METHODS We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000-17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2·5th and 97·5th percentiles of those 250 draws. FINDINGS While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62·6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000-7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910-68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. INTERPRETATION To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. FUNDING Bill & Melinda Gates Foundation.
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Fenton RA, Murali SK, Kaji I, Akiba Y, Kaunitz JD, Kristensen TB, Poulsen SB, Dominguez Rieg JA, Rieg T. Adenylyl Cyclase 6 Expression Is Essential for Cholera Toxin-Induced Diarrhea. J Infect Dis 2020; 220:1719-1728. [PMID: 30624615 DOI: 10.1093/infdis/jiz013] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 01/07/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Cholera toxin (CT)-induced diarrhea is mediated by cyclic adenosine monophosphate (cAMP)-mediated active Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR). Although the constitutive activation of adenylyl cyclase (AC) in response to CT is due to adenosine diphosphate ribosylation of the small G protein α-subunit activating CFTR with consequent secretory diarrhea, the AC isoform(s) involved remain unknown. METHODS We generated intestinal epithelial cell-specific adenylyl cyclase 6 (AC6) knockout mice to study its role in CT-induced diarrhea. RESULTS AC6 messenger RNA levels were the highest of all 9 membrane-bound AC isoforms in mouse intestinal epithelial cells. Intestinal epithelial-specific AC6 knockout mice (AC6loxloxVillinCre) had undetectable AC6 levels in small intestinal and colonic epithelial cells. No significant differences in fluid and food intake, plasma electrolytes, intestinal/colon anatomy and morphology, or fecal water content were observed between genotypes. Nevertheless, CT-induced fluid accumulation in vivo was completely absent in AC6loxloxVillinCre mice, associated with a lack of forskolin- and CT-induced changes in the short-circuit current (ISC) of the intestinal mucosa, impaired cAMP generation in acutely isolated small intestinal epithelial cells, and significantly impaired apical CFTR levels in response to forskolin. CONCLUSIONS AC6 is a novel target for the treatment of CT-induced diarrhea.
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Affiliation(s)
| | - Sathish K Murali
- Department of Biomedicine, Aarhus University, Denmark.,University of South Florida, Tampa
| | - Izumi Kaji
- Greater Los Angeles VA Healthcare System, California.,Department of Medicine, University of California, Los Angeles
| | - Yasutada Akiba
- Greater Los Angeles VA Healthcare System, California.,Department of Medicine, University of California, Los Angeles
| | - Jonathan D Kaunitz
- Greater Los Angeles VA Healthcare System, California.,Department of Medicine, University of California, Los Angeles
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Buccigrossi V, Lo Vecchio A, Bruzzese E, Russo C, Marano A, Terranova S, Cioffi V, Guarino A. Potency of Oral Rehydration Solution in Inducing Fluid Absorption is Related to Glucose Concentration. Sci Rep 2020; 10:7803. [PMID: 32385331 PMCID: PMC7210290 DOI: 10.1038/s41598-020-64818-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 04/14/2020] [Indexed: 11/24/2022] Open
Abstract
Oral rehydration solutions (ORSs) is the key treatment of acute diarrhea in children, as it restores the electrolyte balance by stimulating the intestinal sodium/glucose transporter SGLT1 to induce fluid absorption. The World Health Organization (WHO) and The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) proposed ORSs with different chemical compositions. The main agent of childhood acute gastroenteritis is rotavirus (RV). We evaluate the effects of ORS with different concentration of glucose and sodium on RV induced secretion. Ussing chambers technique was used for electophysiology experiments to evaluate ion fluid flux. ESPGHAN ORS (sodium 60 mmol/L and glucose 111 mmol/L) induced a more potent proabsorptive effect in Caco-2 cells than WHO ORS, and this effect depended on the sodium/glucose ratio. Titration experiments showed that RV-induced fluid secretion can be reverted to a proabsorptive direction when sodium and glucose concentration fall in specific ranges, specifically 45–60 mEq/L and 80–110 mM respectively. The results were confirmed by testing commercial ORSs. These findings indicated that ORS proabsorptive potency depends on sodium and glucose concentrations. Optimal ORS composition should be tailored to reduce RV-induced ion secretion by also considering palatability. These in vitro data should be confirmed by clinical trials.
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Affiliation(s)
- Vittoria Buccigrossi
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Andrea Lo Vecchio
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Eugenia Bruzzese
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Carla Russo
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Antonella Marano
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Sara Terranova
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Valentina Cioffi
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy
| | - Alfredo Guarino
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
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Abstract
Brett-Major and others remind us that pathogen lists for emerging infectious diseases aid in the development of tools that target specific pathogens (e.g., vaccines) and help attract financial support. These lists tell us what we need to have, not what we need to do. The authors call for more research on ways to prevent these diseases (e.g., platform technologies for vaccines) and mitigate disease impact. Vaccines and new treatments that target individual pathogens have many limitations. However, we might save lives by treating patients with inexpensive generic drugs that target common features of the host response to infection. Undertaking research on this approach to treatment is what we need to do.
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Affiliation(s)
- David S. Fedson
- Address correspondence to David S. Fedson, 57, chemin du Lavoir, 01630 Sergy Haut, France. E-mail:
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Na +-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na + Recycling in Mouse Small Intestine. Int J Mol Sci 2020; 21:ijms21020376. [PMID: 31936130 PMCID: PMC7013606 DOI: 10.3390/ijms21020376] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 12/27/2019] [Accepted: 12/30/2019] [Indexed: 12/26/2022] Open
Abstract
Many nutrients are absorbed via Na+ cotransport systems, and therefore it is predicted that nutrient absorption mechanisms require a large amount of luminal Na+. It is thought that Na+ diffuses back into the lumen via paracellular pathways to support Na+ cotransport absorption. However, direct experimental evidence in support of this mechanism has not been shown. To elucidate this, we took advantage of claudin-15 deficient (cldn15-/-) mice, which have been shown to have decreased paracellular Na+ permeability. We measured glucose-induced currents (ΔIsc) under open- and short-circuit conditions and simultaneously measured changes in unidirectional 22Na+ fluxes (ΔJNa) in Ussing chambers. Under short-circuit conditions, application of glucose resulted in an increase in ΔIsc and unidirectional mucosal to serosal 22Na+ (∆JNaMS) flux in both wild-type and cldn15-/- mice. However, under open-circuit conditions, ΔIsc was observed but ∆JNaMS was strongly inhibited in wild-type but not in cldn15-/- mice. In addition, in the duodenum of mice treated with cholera toxin, paracellular Na+ conductance was decreased and glucose-induced ∆JNaMS increment was observed under open-circuit conditions. We concluded that the Na+ which is absorbed by Na+-dependent glucose cotransport is recycled back into the lumen via paracellular Na+ conductance through claudin-15, which is driven by Na+ cotransport induced luminal negativity.
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Balamurugan R, Pugazhendhi S, Balachander GM, Dharmalingam T, Mortimer EK, Gopalsamy GL, Woodman RJ, Meng R, Alpers DH, Manary M, Binder HJ, Brown IL, Young GP, Ramakrishna BS. Effect of Native and Acetylated Dietary Resistant Starches on Intestinal Fermentative Capacity of Normal and Stunted Children in Southern India. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:E3922. [PMID: 31618992 PMCID: PMC6843365 DOI: 10.3390/ijerph16203922] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 10/10/2019] [Accepted: 10/12/2019] [Indexed: 12/29/2022]
Abstract
The health benefits of dietary amylase resistant starch (RS) arise from intestinal microbial fermentation and generation of short chain fatty acids (SCFA). We compared the intestinal fermentative capability of stunted and nonstunted ('healthy') children in southern India using two types of RS: high amylose maize starch (HAMS) and acetylated HAMS (HAMSA). Twenty children (10 stunted and 10 healthy) aged 2 to 5 years were fed biscuits containing HAMS (10 g/day) for two weeks followed by a 2-week washout and then HAMSA biscuits (10 g/day) for 2 weeks. Fecal samples were collected at 3-4 day intervals and pH and SCFA analyzed. At entry, stunted children had lower SCFA concentrations compared to healthy children. Both types of RS led to a significant decrease in fecal pH and increase in fecal acetate and propionate in both healthy and stunted children. However, while HAMS increased fecal butyrate in both groups of children, HAMSA increased butyrate in healthy but not stunted children. Furthermore, healthy children showed a significantly greater increase than stunted children in both acetate and butyrate when fed either RS. No adverse effects were reported with either RS. Stunted children have impaired capacity to ferment certain types of RS which has implications for choice of RS in formulations aimed at improving microbial function in stunted children.
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Affiliation(s)
- Ramadass Balamurugan
- Wellcome Research Unit (Biochemistry), Christian Medical College, Vellore, Tamil Nadu 632004, India.
| | - Srinivasan Pugazhendhi
- Wellcome Research Unit (Biochemistry), Christian Medical College, Vellore, Tamil Nadu 632004, India.
| | - Gowri M Balachander
- Wellcome Research Unit (Biochemistry), Christian Medical College, Vellore, Tamil Nadu 632004, India.
| | - Tamilselvan Dharmalingam
- Wellcome Research Unit (Biochemistry), Christian Medical College, Vellore, Tamil Nadu 632004, India.
| | - Elissa K Mortimer
- College of Medicine and Public Health, Flinders University of South Australia, Bedford Park 5045, South Australia, Australia.
| | - Geetha L Gopalsamy
- College of Medicine and Public Health, Flinders University of South Australia, Bedford Park 5045, South Australia, Australia.
| | - Richard J Woodman
- College of Medicine and Public Health, Flinders University of South Australia, Bedford Park 5045, South Australia, Australia.
| | - Rosie Meng
- College of Medicine and Public Health, Flinders University of South Australia, Bedford Park 5045, South Australia, Australia.
| | - David H Alpers
- Washington University School of Medicine, Saint Louis, MO 63110, USA.
| | - Mark Manary
- Washington University School of Medicine, Saint Louis, MO 63110, USA.
| | - Henry J Binder
- Yale University School of Medicine, New Haven, CT 06510, USA.
| | - Ian L Brown
- Australian Cancer Research Foundation, Sydney 2000, Australia.
| | - Graeme P Young
- College of Medicine and Public Health, Flinders University of South Australia, Bedford Park 5045, South Australia, Australia.
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Doré V, Foster DM, Ru H, Smith GW. Comparison of oral, intravenous, and subcutaneous fluid therapy for resuscitation of calves with diarrhea. J Dairy Sci 2019; 102:11337-11348. [PMID: 31606222 PMCID: PMC7094336 DOI: 10.3168/jds.2019-16970] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 08/24/2019] [Indexed: 11/23/2022]
Abstract
Neonatal diarrhea remains the primary cause of mortality in dairy calves around the world, and optimal treatment protocols are needed. The main goals of therapy are to restore hydration and electrolyte concentrations, correct strong ion (metabolic) acidemia, and provide nutritional support. Administration of oral electrolyte solutions (OES) has long been the primary method used to treat neonatal diarrhea in humans and calves because OES are capable of addressing each of the primary goals of therapy. In calves with moderate dehydration, we hypothesized that oral electrolytes would be as good as or better than small volumes of intravenous (IV) or subcutaneous (SC) fluids. Therefore, the main goal of this study was to compare the ability of a commercially available oral electrolyte solution (OES) administered alone or in combination with hypertonic saline with small volumes of IV or SC fluid therapy to resuscitate calves with diarrhea. Thirty-three Holstein calves from 5 to 14 d of age were utilized in this clinical trial. Diarrhea and dehydration were induced by adding sucrose to the milk replacer. In addition, hydrochlorothiazide and spironolactone were given orally and furosemide intramuscularly. Depression status, clinical hydration scores, fecal consistency, and body weight were recorded at regular intervals. Treatment began when calves had severe diarrhea and had a decrease in plasma volume of at least 10%. Calves were randomly assigned to 1 of 4 treatment groups of 8 to 9 calves per group: (1) OES; (2) OES with hypertonic saline (4 mL/kg, IV); (3) IV fluids (lactated Ringer's, 2 L); or (4) SC fluids (lactated Ringer's, 2 L). Treatments were given at 0 and 12 h. Changes in plasma volume, blood pH, electrolyte levels, and physical examination scores were determined before therapy and again at 1, 2, 4, 8, and 12 h after each treatment. All 4 treatments were ultimately successful in improving hydration as well as increasing blood pH; however, animals in both groups that received OES had much faster resuscitation than those in either the IV or SC fluid group. In conclusion, oral electrolyte products remain the gold standard for resuscitating diarrheic calves with moderate dehydration and acidemia and will likely perform better than small volumes of IV lactated Ringer's solution. Subcutaneous fluids by themselves are a poor treatment option and should be only be used as supportive therapy following the initial correction of hypovolemia and metabolic acidosis.
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Affiliation(s)
- V Doré
- Department of Population, Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27607
| | - D M Foster
- Department of Population, Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27607
| | - H Ru
- Department of Population, Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27607
| | - G W Smith
- Department of Population, Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27607.
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Li YT, Xu H, Ye JZ, Wu WR, Shi D, Fang DQ, Liu Y, Li LJ. Efficacy of Lactobacillus rhamnosus GG in treatment of acute pediatric diarrhea: A systematic review with meta-analysis. World J Gastroenterol 2019; 25:4999-5016. [PMID: 31543689 PMCID: PMC6737314 DOI: 10.3748/wjg.v25.i33.4999] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Revised: 07/04/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Diarrhea is a major infectious cause of childhood morbidity and mortality worldwide. In clinical trials, Lactobacillus rhamnosus GG ATCC 53013 (LGG) has been used to treat diarrhea. However, recent randomized controlled trials (RCTs) found no evidence of a beneficial effect of LGG treatment.
AIM To evaluate the efficacy of LGG in treating acute diarrhea in children.
METHODS The EMBASE, MEDLINE, PubMed, Web of Science databases, and the Cochrane Central Register of Controlled Trials were searched up to April 2019 for meta-analyses and RCTs. The Cochrane Review Manager was used to analyze the relevant data.
RESULTS Nineteen RCTs met the inclusion criteria and showed that compared with the control group, LGG administration notably reduced the diarrhea duration [mean difference (MD) -24.02 h, 95% confidence interval (CI) (-36.58, -11.45)]. More effective results were detected at a high dose ≥ 1010 CFU per day [MD -22.56 h, 95%CI (-36.41, -8.72)] vs a lower dose. A similar reduction was found in Asian and European patients [MD -24.42 h, 95%CI (-47.01, -1.82); MD -32.02 h, 95%CI (-49.26, -14.79), respectively]. A reduced duration of diarrhea was confirmed in LGG participants with diarrhea for less than 3 d at enrollment [MD -15.83 h, 95%CI (-20.68, -10.98)]. High-dose LGG effectively reduced the duration of rotavirus-induced diarrhea [MD -31.05 h, 95%CI (-50.31, -11.80)] and the stool number per day [MD -1.08, 95%CI (-1.87, -0.28)].
CONCLUSION High-dose LGG therapy reduces the duration of diarrhea and the stool number per day. Intervention at the early stage is recommended. Future trials are expected to verify the effectiveness of LGG treatment.
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Affiliation(s)
- Ya-Ting Li
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Hong Xu
- Department of Orthopedics, Xiaoshan Traditional Chinese Medical Hospital, Hangzhou 310003, Zhejiang Province, China
| | - Jian-Zhong Ye
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Wen-Rui Wu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Ding Shi
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Dai-Qiong Fang
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Yang Liu
- Department of Orthopedics, Clinical Sciences, Lund, Lund University, Lund 22185, Sweden
| | - Lan-Juan Li
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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Wang Y, Mortimer EK, Katundu KGH, Kalanga N, Leong LEX, Gopalsamy GL, Christophersen CT, Richard AC, Shivasami A, Abell GCJ, Young GP, Rogers GB. The Capacity of the Fecal Microbiota From Malawian Infants to Ferment Resistant Starch. Front Microbiol 2019; 10:1459. [PMID: 31316490 PMCID: PMC6611432 DOI: 10.3389/fmicb.2019.01459] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Accepted: 06/11/2019] [Indexed: 01/10/2023] Open
Abstract
In Low and Middle-Income Countries (LMIC), weaning is associated with environmentally acquired and inflammation-associated enteric disorders. Dietary intake of high amylose maize starch (HAMS) can promote commensal fermentative bacteria and drive the production of short chain fatty acids (SCFAs). By stabilizing commensal gut microbiology, and stimulating the production of anti-inflammatory metabolites, HAMS supplementation might therefore influence enteric health. However, the extent to which the gut microbiota of LMIC infants are capable of fermenting HAMS is unclear. We assessed the capacity of the fecal microbiota from pre-weaning and weaning Malawian infants to ferment HAMS and produce SCFAs using an in vitro fermentation model. Fecal microbiota from both pre-weaning and weaning infants were able to ferment HAMS, as indicated by an increase in bacterial load and total SCFA concentration, and a reduction in pH. All of these changes were more substantial in the weaning group. Acetate production was observed with both pre-weaning and weaning groups, while propionate production was only observed in the weaning group. HAMS fermentation resulted in significant alterations to the fecal microbial community in the weaning group, with significant increases in levels of Prevotella, Veillonella, and Collinsella associated with propionate production. In conclusion, fecal microbiota from Malawian infants before and during weaning has the capacity to produce acetate through HAMS fermentation, with propionate biosynthetic capability appearing only at weaning. Our results suggest that HAMS supplementation might provide benefit to infants during weaning.
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Affiliation(s)
- Yanan Wang
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University, Adelaide, SA, Australia
| | - Elissa K. Mortimer
- Flinders University Global GI Health Unit, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
| | - Kondwani G. H. Katundu
- Division of Physiology, Biomedical Sciences Department, College of Medicine, University of Malawi, Blantyre, Malawi
| | - Noel Kalanga
- Department of Health Systems and Policy, School of Public Health, College of Medicine, University of Malawi, Blantyre, Malawi
| | - Lex E. X. Leong
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University, Adelaide, SA, Australia
| | - Geetha L. Gopalsamy
- Flinders University Global GI Health Unit, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
| | - Claus T. Christophersen
- School of Medical & Health Sciences, Edith Cowan University, Joondalup, WA, Australia
- School of Molecular & Life Sciences, Curtin University, Perth, WA, Australia
| | - Alyson C. Richard
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University, Adelaide, SA, Australia
| | - Aravind Shivasami
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University, Adelaide, SA, Australia
| | - Guy C. J. Abell
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
| | - Graeme P. Young
- Flinders University Global GI Health Unit, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia
| | - Geraint B. Rogers
- Infection and Immunity Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University, Adelaide, SA, Australia
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Rao MC. Physiology of Electrolyte Transport in the Gut: Implications for Disease. Compr Physiol 2019; 9:947-1023. [PMID: 31187895 DOI: 10.1002/cphy.c180011] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
We now have an increased understanding of the genetics, cell biology, and physiology of electrolyte transport processes in the mammalian intestine, due to the availability of sophisticated methodologies ranging from genome wide association studies to CRISPR-CAS technology, stem cell-derived organoids, 3D microscopy, electron cryomicroscopy, single cell RNA sequencing, transgenic methodologies, and tools to manipulate cellular processes at a molecular level. This knowledge has simultaneously underscored the complexity of biological systems and the interdependence of multiple regulatory systems. In addition to the plethora of mammalian neurohumoral factors and their cross talk, advances in pyrosequencing and metagenomic analyses have highlighted the relevance of the microbiome to intestinal regulation. This article provides an overview of our current understanding of electrolyte transport processes in the small and large intestine, their regulation in health and how dysregulation at multiple levels can result in disease. Intestinal electrolyte transport is a balance of ion secretory and ion absorptive processes, all exquisitely dependent on the basolateral Na+ /K+ ATPase; when this balance goes awry, it can result in diarrhea or in constipation. The key transporters involved in secretion are the apical membrane Cl- channels and the basolateral Na+ -K+ -2Cl- cotransporter, NKCC1 and K+ channels. Absorption chiefly involves apical membrane Na+ /H+ exchangers and Cl- /HCO3 - exchangers in the small intestine and proximal colon and Na+ channels in the distal colon. Key examples of our current understanding of infectious, inflammatory, and genetic diarrheal diseases and of constipation are provided. © 2019 American Physiological Society. Compr Physiol 9:947-1023, 2019.
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Affiliation(s)
- Mrinalini C Rao
- Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois, USA
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Civra A, Altomare A, Francese R, Donalisio M, Aldini G, Lembo D. Colostrum from cows immunized with a veterinary vaccine against bovine rotavirus displays enhanced in vitro anti-human rotavirus activity. J Dairy Sci 2019; 102:4857-4869. [PMID: 30981494 PMCID: PMC7127701 DOI: 10.3168/jds.2018-16016] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 02/24/2019] [Indexed: 12/31/2022]
Abstract
Human rotaviruses represent a major cause of severe diarrheal disease in infants and young children. The limited impact of oral vaccines on global estimates of rotavirus mortality and the suboptimal use of oral rehydration justify the need for alternative prophylactic and therapeutic strategies, especially for immunocompromised hosts. The protective effects of colostrum-the first milk produced during the initial 24 to 48 h after parturition-are well documented in the literature. In particular, the ingestion of hyperimmune bovine colostrum has been proposed as an alternative preventive approach against human rotavirus gastroenteritis. Although the immunization of pregnant cows with human rotavirus boosts the release of specific immunoglobulin G in bovine colostrum, it raises regulatory and safety issues. In this study, we demonstrated that the conventional bovine rotavirus vaccine is sufficient to enhance the anti-human rotavirus protective efficacy of bovine colostrum, thus providing a conservative approach to produce hyperimmune bovine colostrum, making it exploitable as a functional food.
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Affiliation(s)
- Andrea Civra
- Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
| | - Alessandra Altomare
- Department of Pharmaceutical Sciences, Università degli Studi di Milano, 20133 Milan, Italy
| | - Rachele Francese
- Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
| | - Manuela Donalisio
- Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
| | - Giancarlo Aldini
- Department of Pharmaceutical Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
| | - David Lembo
- Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy.
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Abstract
Cholera infections caused by the gamma-proteobacterium Vibrio cholerae have ravaged human populations for centuries, and cholera pandemics have afflicted every corner of the globe. Fortunately, interventions such as oral rehydration therapy, antibiotics/antimicrobials, and vaccines have saved countless people afflicted with cholera, and new interventions such as probiotics and phage therapy are being developed as promising approaches to treat even more cholera infections. Although current therapies are mostly effective and can reduce disease transmission, cholera outbreaks remain deadly, as was seen during recent outbreaks in Haiti, Ethiopia, and Yemen. This is due to significant underlying political and socioeconomic complications, including shortages of vaccines and clean food and water and a lack of health surveillance. In this review, we highlight the strengths and weaknesses of current cholera therapies, discuss emerging technologies, and argue that a multi-pronged, flexible approach is needed to continue to reduce the worldwide burden of cholera.
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Affiliation(s)
- Brian Y Hsueh
- Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA
| | - Christopher M Waters
- Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA
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Abstract
AIM Exertional heastroke (EHS) can lead to acute kidney injury. Oral rehydration solution III (ORS III), recommended by WHO in 2004, is used to rehydrate children with gastroenteritis. This study aimed to characterize the renoprotective effect of ORS III in EHS rats. METHODS Rats were randomly divided into Group Control, Group EHS, Group EHS + Water, and Group EHS + ORS. Thirty minutes before the experiment, ORS III was orally administrated to Group EHS + ORS, Water was given to Group EHS + Water. Rats from Group EHS, Group EHS + Water and Group EHS + ORS were then forced to run until they fatigued. Core temperature (Tc) was monitored and 40.5 °C was considered as the onset of heatstroke. Serum creatinine (SCr), blood urea nitrogen (BUN) were measured using an automated biochemical analyzer. Serum neutrophil gelatinase-associated lipocalin (NGAL) was measured using an NGAL ELISA Kit. Light microscopy was used for kidney structural analysis. RESULTS SCr level in Group EHS was no different from Group Control (p > .05), while BUN and NGAL levels in Group EHS were higher than Group Control (p <.001, p < .001). SCr, BUN and NGAL concentrations in group EHS + Water were no different from Group EHS (p > .05). SCr, BUN levels in Group EHS + ORS were no different from Group EHS (p > .05). But NGAL levels were significant in these two groups (p = .012). Renal histopathologies of rats in Group EHS and Group EHS + Water showed flattened lumens filled with eosinophilic materials. The damage was milder in Group EHS + ORS, in which injured tubules showed degeneration of the tubular epithelium and sloughing of the brush border membrane. CONCLUSION ORS III could alleviate the kidney injury in EHS rats.
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Affiliation(s)
- Yufang Lin
- a Department of Nephrology , General Hospital of Northern Theater Command , Liaoning , China
| | - Yanning Zhang
- a Department of Nephrology , General Hospital of Northern Theater Command , Liaoning , China
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Utilisation of dietary fibre (non-starch polysaccharide and resistant starch) molecules for diarrhoea therapy: A mini-review. Int J Biol Macromol 2019; 122:572-577. [DOI: 10.1016/j.ijbiomac.2018.10.195] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 09/26/2018] [Accepted: 10/27/2018] [Indexed: 02/06/2023]
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Qi X, Tester RF. Starch containing formulations for diarrhoea therapy. Clin Nutr ESPEN 2018; 28:36-40. [PMID: 30390891 DOI: 10.1016/j.clnesp.2018.08.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 08/09/2018] [Indexed: 12/18/2022]
Abstract
Diarrhoea therapies in general include a number of approaches (depending on local practise and the cause of the diarrhoea) aimed at: (i) removing the cause (e.g. lactose in the diet); (ii) treating the cause of infection if present (e.g. antibiotics); (iii) reducing the effect of the cause (e.g. adsorbent); (iv) depressing gastric motility and secretions (e.g. various drugs); (v) probiotic bacteria with perhaps prebiotic energy sources and most importantly of all (vi) rehydration using rehydration salt solutions (oral rehydration therapy, ORT, using oral rehydration solutions, ORS). Glucose has been included in ORS formats for rapidly available energy since ORS formats were developed initially- but has the disadvantage of a high osmotic pressure. It is used in modern ORS formats to promote sodium absorption, however. The use of α-glucans (glucose containing oligo- or polysaccharides) in ORS formats is gaining ground in terms of utilisation for diarrhoea - a fairly recent approach to therapy in the western world. The use of different α-glucans in ORS formulations is discussed and strategies for the development further of therapies is investigated. This review is aimed at the scientific and medical communities.
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Affiliation(s)
- Xin Qi
- Glycologic Limited, 70 Cowcaddens Road, Glasgow, G4 0BA, UK.
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Chappell AJ, Simper TN. Nutritional Peak Week and Competition Day Strategies of Competitive Natural Bodybuilders. Sports (Basel) 2018; 6:sports6040126. [PMID: 30352979 PMCID: PMC6315482 DOI: 10.3390/sports6040126] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 10/11/2018] [Accepted: 10/22/2018] [Indexed: 01/09/2023] Open
Abstract
Bodybuilders utilize peaking strategies in a bid to fine-tune their aesthetics for competition day. The most prevalent peaking strategies utilized by natural bodybuilders are unreported in the current literature. Eighty-one (M-59, F-22) natural bodybuilders were recruited from competitions during the 2016 and 2017 British Natural Bodybuilder Federation seasons. Competitors completed a 34-item questionnaire designed to investigate peaking and contest day strategies. The questionnaire listed commonly utilized peaking strategies and provided additional space for qualitative information. Analysis of the data indicated that carbohydrate (CHO), water, and sodium manipulation were the most commonly utilized peaking strategies. The consumption of high glycemic index CHO was the most common competition day strategy. Only 6.2% of competitors reported following their regular diet the week prior to competition. The CHO manipulation strategies followed were similar to classical CHO loading, whereby bodybuilders attempt to maximize muscle glycogen concentrations. Furthermore, bodybuilders attempted to remove superfluous water by exploiting the diuretic/polyuria effect associated with water loading/restriction. The potentially deleterious effects of peaking on bodybuilders' health is considered and the efficacy of these strategies to enhance appearance is discussed. The findings of the present investigation are likely to be of interest to bodybuilders and their coaches.
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Affiliation(s)
- Andrew J Chappell
- Food and Nutrition Group, Sheffield School of Business, Sheffield Hallam University, Howard St. Sheffield S1 1WB, UK.
| | - Trevor N Simper
- Food and Nutrition Group, Sheffield School of Business, Sheffield Hallam University, Howard St. Sheffield S1 1WB, UK.
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O’Connell SM, Woodman RJ, Brown IL, Vincent DJ, Binder HJ, Ramakrishna BS, Young GP. Comparison of a sports-hydration drink containing high amylose starch with usual hydration practice in Australian rules footballers during intense summer training. J Int Soc Sports Nutr 2018; 15:46. [PMID: 30241477 PMCID: PMC6150988 DOI: 10.1186/s12970-018-0253-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 09/14/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Fluid deficits exceeding 1.6% can lead to physical and cognitive impairment in athletes. Sport drinks used by athletes are often hyper-osmolar but this is known to be suboptimal for rehydration in medical settings and does not utilize colonic absorptive capacity. Colonic absorption can be enhanced by fermentative production of short chain fatty acids (SCFA) from substrates such as high amylose maize starch (HAMS). This study therefore compared, in elite Australian Football League (AFL) players at the height of outdoor summer training, a novel dual-action sports oral rehydration strategy that contained HAMS as well as glucose, to their usual rehydration practices (Control). The primary outcome markers of hydration were hematocrit and body weight. METHODS A randomized single-blind crossover study was undertaken in thirty-one AFL players; twenty-seven completed the study which was conducted on four days (two days in the Intervention arm and two in Control arm). The Intervention arm was comprised a 50-100 g evening preload of an acetylated HAMS (Ingredion Pty Ltd) followed by consumption of a specially formulated sports oral rehydration solution (SpORS) drink during intense training and recovery. Players followed their usual hydration routine in the Control arm. Quantitative assessments of body weight, hematocrit and urine specific gravity were made at three time-points on each day of training: pre-training, post-training (90 min), and at end of recovery (30-60 min later). GPS tracking monitored player exertion. RESULTS Across the three time-points, hematocrit was significantly lower and body weight significantly higher in Intervention compared to Control arms (p < 0.02 and p = 0.001 respectively, mixed effects model). Weights were significantly heavier at all three assessment points for Intervention compared to Control arms (Δ = 0.30 ± 0.13, p = 0.02 pre-training; Δ = 0.43 ± 0.14, p = 0.002 post training; and Δ = 0.68 ± 0.14, p < 0.001 for recovery). Between the pre-training and end-of-recovery assessments, the Control arm lost 0.80 kg overall compared with 0.12 kg in the Intervention arm, an 85% lower reduction of bodyweight across the assessment period. CONCLUSION The combination of the significantly lower hematocrit and increased body weight in the Intervention arm represents better hydration not only at the end of training as well as following a recovery period but also at its commencement. The magnitude of the benefit seems sufficient to have an impact on performance and further studies to test this possibility are now indicated. TRIAL REGISTRATION Trial is listed on the Australian New Zealand Clinical Trials Registry ( ACTRN 12613001373763 ).
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Affiliation(s)
| | - Richard John Woodman
- Flinders Centre for Epidemiology and Biostatistics, Flinders University, GPO Box 2100, 5001 Adelaide, Australia
| | - Ian Lewis Brown
- Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, SA Australia
| | | | - Henry Joseph Binder
- Department of Internal Medicine, Yale School of Medicine, P.O. Box 208019, New Haven, CT 06520 USA
| | | | - Graeme Paul Young
- Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, SA Australia
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Prevalence of Human Sapovirus in Low and Middle Income Countries. Adv Virol 2018; 2018:5986549. [PMID: 30245718 PMCID: PMC6139206 DOI: 10.1155/2018/5986549] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 07/25/2018] [Indexed: 11/23/2022] Open
Abstract
Background Sapovirus (SV) infection is a public health concern which plays an important role in the burden of diarrhoeal diseases, causing acute gastroenteritis in people of all ages in both outbreaks and sporadic cases worldwide. Objective/Study Design The purpose of this report is to summarise the available data on the detection of human SV in low and middle income countries. A systematic search on PubMed and ScienceDirect database for SV studies published between 2004 and 2017 in low and middle income countries was done. Studies of SV in stool and water samples were part of the inclusion criteria. Results From 19 low and middle income countries, 45 published studies were identified. The prevalence rate for SV was 6.5%. A significant difference (P=0) in SV prevalent rate was observed between low income and middle income countries. Thirty-three (78.6%) of the studies reported on children and 8 (19%) studies reported on all age groups with diarrhoea. The majority (66.7%) of studies reported on hospitalised patients with acute gastroenteritis. Sapovirus GI was shown as the dominant genogroup, followed by SV-GII. Conclusion The detection of human SV in low and middle income countries is evident; however the reports on its prevalence are limited. There is therefore a need for systematic surveillance of the circulation of SV, and their role in diarrhoeal disease and outbreaks, especially in low and middle income countries.
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Gómez BI, McIntyre MK, Gurney JM, Chung KK, Cancio LC, Dubick MA, Burmeister DM. Enteral resuscitation with oral rehydration solution to reduce acute kidney injury in burn victims: Evidence from a porcine model. PLoS One 2018; 13:e0195615. [PMID: 29718928 PMCID: PMC5931460 DOI: 10.1371/journal.pone.0195615] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 03/26/2018] [Indexed: 01/07/2023] Open
Abstract
Intravenous (IV) resuscitation of burn patients has greatly improved outcomes and become a cornerstone of modern burn care. However, the heavy fluids and vascular access required may not be feasible in austere environments, mass casualty, or delayed transport scenarios. Enteral resuscitation has been proposed for these situations; we sought to examine the effectiveness of this strategy on improving burn-induced kidney injury. Anesthetized Yorkshire swine sustaining 40% TBSA full-thickness contact burns were randomized to three groups (n = 6/group): fluid deprivation, ad libitum water access, or 70 mL/kg/d Oral Rehydration Salt solution (ORS). Urine and blood were collected at baseline (BL), 6, 12, 24, 32, and 48h post-burn, at which point tissue was harvested and CT angiography performed. Although fluid consumption by ad libitum and ORS groups were matched (132±54mL/kg versus 120±24mL/kg, respectively), ORS intake increased urine output compared with water and no water (47.3±9.0 mL/kg versus 16.1±2.5 mL/kg, and 24.5±1.7 mL/kg respectively). Plasma creatinine peaked 6h following burn (1.67±0.07mg/dL) in all animals, but at 48h was comparable to BL in animals receiving water (1.23±0.06mg/dL) and ORS (1.30±0.09mg/dL), but not fluid deprived animals (1.56±0.05mg/dL) (P<0.05). Circulating levels of blood urea nitrogen steadily increased, but also decreased by 48h in animals receiving enteral fluids (P<0.05). Water deprivation reduced renal artery diameter (-1.4±0.17mm), whereas resuscitation with water (-0.44±0.14 mm) or ORS maintained it (-0.63±0.20 mm;P< 0.02). Circulating cytokines IL-1β, IL-6, IFNγ, and GM-CSF were moderately elevated in the fluid-deprived group. Taken together, the data suggest that enteral resuscitation with ORS rescues kidney function following burn injury. Incorporating enteral fluids may improve outcomes in resource-poor environments and possibly reduce IV fluid requirements to prevent co-morbidities associated with over-resuscitation. Studies into different volumes/types of enteral fluids are warranted. While ORS has saved many lives in cholera-associated dehydration, it should be investigated further for use in burn patients.
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Affiliation(s)
- Belinda I. Gómez
- United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States of America
| | - Matthew K. McIntyre
- United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States of America
| | - Jennifer M. Gurney
- United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States of America
- Brooke Army Medical Center, Fort Sam Houston, TX, United States of America
| | - Kevin K. Chung
- Brooke Army Medical Center, Fort Sam Houston, TX, United States of America
- Uniformed Services University of the Health Sciences, Bethesda, MD, United States of America
| | - Leopoldo C. Cancio
- United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States of America
- Brooke Army Medical Center, Fort Sam Houston, TX, United States of America
| | - Michael A. Dubick
- United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States of America
| | - David M. Burmeister
- United States Army Institute of Surgical Research, Fort Sam Houston, TX, United States of America
- * E-mail:
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Antirotaviral activity of bovine milk components: Extending the list of inhibitory proteins and seeking a better understanding of their neutralization mechanism. J Funct Foods 2018. [DOI: 10.1016/j.jff.2018.03.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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