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An amino acid-based oral rehydration solution (AA-ORS) enhanced intestinal epithelial proliferation in mice exposed to radiation.

ABSTRACT: Destruction of clonogenic cells in the crypt following irradiation are thought to cause altered gastrointestinal function. Previously, we found that an amino acid-based oral rehydration solution (AA-ORS) improved gastrointestinal function in irradiated mice. However, the exact mechanisms were unknown. Electrophysiology, immunohistochemistry, qPCR, and Western blot analysis were used to determine that AA-ORS increased proliferation, maturation, and differentiation and improved electrolyte and nutrient absorption in irradiated mice. A single-hit, multi-target crypt survival curve showed a significant increase in crypt progenitors in irradiated mice treated with AA-ORS for six days (8.8?±?0.4) compared to the saline-treated group (6.1?±?0.3; P?0 (4.8?±?0.1?Gy). The D_q values increased from 8.8?±?0.4?Gy to 10.5?±?0.5?Gy with AA-ORS treatment (P?+, without altering Bmi1 positive cells; (2) increased levels of proliferation markers (Ki-67, p-Erk, p-Akt and PCNA); (3) decreased apoptosis markers, such as cleaved caspase-3 and Bcl-2; and (4) increased expression and protein levels of NHE3 and SGLT1 in the brush border membrane. This study shows that AA-ORS increased villus height and improved electrolyte and nutrient absorption.

SUBMITTER: Yin L

PROVIDER: S-EPMC5120277 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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An amino acid-based oral rehydration solution (AA-ORS) enhanced intestinal epithelial proliferation in mice exposed to radiation.

Yin Liangjie L Gupta Reshu R Vaught Lauren L Grosche Astrid A Okunieff Paul P Vidyasagar Sadasivan S

Scientific reports 20161123

Destruction of clonogenic cells in the crypt following irradiation are thought to cause altered gastrointestinal function. Previously, we found that an amino acid-based oral rehydration solution (AA-ORS) improved gastrointestinal function in irradiated mice. However, the exact mechanisms were unknown. Electrophysiology, immunohistochemistry, qPCR, and Western blot analysis were used to determine that AA-ORS increased proliferation, maturation, and differentiation and improved electrolyte and nut ...[more]

PMID: 27876791

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Project description:BackgroundIn Bangladesh, pharmacy-purchased oral rehydration solution (ORS) is often used to treat diarrhea, including cholera. Over-the-counter sales have been used for epidemiologic surveillance in the past, but rarely, if ever, in low-income countries. With few early indicators for cholera outbreaks in endemic areas, diarrhea-related product sales may serve as a useful surveillance tool.Methodology/principal findingsWe tracked daily ORS sales at 50 pharmacies and drug-sellers in an urban Bangladesh community of 129,000 for 6-months while simultaneously conducting surveillance for diarrhea hospitalizations among residents. We developed a mobile phone based system to track the sales of ORS and deployed it in parallel with a paper-based system. Our objectives were to determine if the mobile phone system was practical and acceptable to pharmacists and drug sellers, whether data were reported accurately compared to a paper-based system, and whether ORS sales were associated with future incidence of cholera hospitalizations within the community. We recorded 47,215 customers purchasing ORS, and 315 hospitalized diarrhea cases, 22% of which had culture-confirmed cholera. ORS sales and diarrhea incidence were independently associated with the mean daily temperature; therefore both unadjusted and adjusted models were explored. Through unadjusted cross-correlation statistics and generalized linear models, we found increases in ORS sales were significantly associated with increases in hospitalized diarrhea cases up to 9-days later and hospitalized cholera cases up to one day later. After adjusting for mean daily temperature, ORS was significantly associated with hospitalized diarrhea two days later and hospitalized cholera one day later.Conclusions/significancePharmacy sales data may serve as a feasible and useful surveillance tool. Given the relatively short lagged correlation between ORS sales and diarrhea, rapid and accurate sales data are key. More work is needed in creating actionable algorithms that make use of this data and in understanding the generalizability of our findings to other settings.

Project description:BACKGROUND:Oral rehydration solution (ORS) is used to treat the dehydration caused by diarrhoeal diseases, including cholera. ORS formulations with an osmolarity (a measure of solute concentration) of ? 270 mOsm/L (ORS ? 270) are safe and more effective than ORS formulations with an osmolarity of ? 310 mOsm/L (ORS ? 310) for treating non-cholera diarrhoea. As cholera causes rapid electrolyte loss, it is important to know if these benefits are similar for people suffering from cholera. OBJECTIVES:To compare the safety and efficacy of ORS ?270 with ORS ? 310 for treating dehydration due to cholera. SEARCH METHODS:We searched the Cochrane Infectious Disease Group Specialized Register (April 2011), CENTRAL (The Cochrane Library Issue 4, 2011), MEDLINE (1966 to April 2011), EMBASE (1974 to April 2011), and LILACS (1982 to April 2011). We also contacted organizations and searched reference lists. SELECTION CRITERIA:Randomized controlled trials comparing ORS ? 270 with ORS ? 310 for treating adults and children with acute diarrhoea due to cholera. DATA COLLECTION AND ANALYSIS:Two reviewers independently applied eligibility criteria, assessed trial quality, and extracted data. We pooled dichotomous data using risk ratio (RR), pooled continuous data using mean difference (MD) or the standardized mean difference (SMD), and presented the results with 95% confidence intervals (CI). MAIN RESULTS:For glucose-based ORS, seven trials (718 participants) met the inclusion criteria. Biochemical hyponatraemia (blood sodium levels < 130 mmol/L) was more common with ORS ? 270 (RR 1.67, CI 1.09 to 2.57; 465 participants, four trials), while a higher level of severe biochemical hyponatraemia (blood sodium levels < 125 mmol/L) in the same group was not significant (RR 1.58, CI 0.62 to 4.04; 465 participants, four trials). No instances of symptomatic hyponatraemia or death were noted in the trials that intended to record them. We found no statistically significant difference in the need for unscheduled intravenous infusion. Analyses separating children and adults showed no obvious trends.Two trials also examined rice-based ORS. In the ORS ? 270 group, duration of diarrhoea was shorter (MD -11.42 hours, CI -13.80 to -9.04; 102 participants, two trials). AUTHORS' CONCLUSIONS:In people with cholera, ORS ? 270 is associated with biochemical hyponatraemia when compared with ORS ? 310, but there are no differences in terms of other outcomes. Although this risk does not appear to be associated with any serious consequences, the total patient experience in existing trials is small. Under wider practice conditions, especially where patient monitoring is difficult, caution is warranted.

Dataset Information

An amino acid-based oral rehydration solution (AA-ORS) enhanced intestinal epithelial proliferation in mice exposed to radiation.

Publications

An amino acid-based oral rehydration solution (AA-ORS) enhanced intestinal epithelial proliferation in mice exposed to radiation.

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