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1. Optimization of the non-invasive 13C-sucrose breath test in a rat model of methotrexate-induced mucositis

Author

Katie L. Tooley, Gordon S. Howarth, Kerry A. Lymn, Ross N. Butler, Tooley, KL, Howarth, GS, Lymn, KA, and Butler, RN

Subjects
Sucrose, Cancer Research, medicine.medical_treatment, specificity, chemotherapy, Toxicology, Gastroenterology, Eating, chemistry.chemical_compound, Intestine, Small, Pharmacology (medical), Carbon Isotopes, medicine.diagnostic_test, Organ Size, Dose–response relationship, Breath Tests, Oncology, Female, Sucrase, medicine.drug, Mucositis, Antimetabolites, Antineoplastic, medicine.medical_specialty, Rat model, Sensitivity and Specificity, methotrexate, Internal medicine, medicine, Animals, SBT, time-course, reproducibility, Pharmacology, Breath test, Chemotherapy, Reproducibility, Dose-Response Relationship, Drug, sucrose breath test, business.industry, Body Weight, medicine.disease, Rats, Disease Models, Animal, Methotrexate, mucositis, chemistry, business
Abstract

Purpose In order to determine the sensitivity and specificity of the test and to optimize experimental conditions utilizing the SBT in a rat model of chemotherapy-induced small intestinal damage. Methods Initially, a 13C-sucrose dose-response study was performed in rats to determine an optimal sucrose concentration for the SBT; then applied to assess chemotherapy-induced intestinal damage. A further study was conducted to establish a SBT time-course of methotrexate-induced small intestinal damage and repair. Animals were killed at 96 or 144 h. Results A sucrose concentration of 0.25 g/ml was optimal (20% CV) for reproducibility and detection of intestinal damage. Maximal damage occurred at 72 h, small intestinal repair was initiated by 96 h and continued at 144 h post-MTX, as determined by the SBT and confirmed by biochemical analyses. Levels of sensitivity and specificity for the SBT were 98 and 94%, respectively. Conclusions The SBT is a reliable non-invasive marker of small intestinal health and damage with a high degree of sensitivity and specificity. Refereed/Peer-reviewed

Published
2009
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2. The effects of formula feeding on physiological and immunological parameters in the gut of neonatal rats

Author

Gordon S. Howarth, Ross N. Butler, Irmeli A. Penttila, Kerry A. Lymn, Katie L. Tooley, Tooley, KL, Howarth, GS, Butler, RN, Lymn, KA, and Penttila, IA

Subjects
medicine.medical_specialty, Physiology, Clinical Sciences, Breast milk, Lactase activity, Enteral Nutrition, Ileum, Internal medicine, Weight Loss, medicine, Animals, Rats, Wistar, intestine, Lactase, Nutrition and Dietetics, necrotizing enterocolitis, Gastric emptying, Milk, Human, business.industry, prematurity, Gastroenterology, immuno-regulation, Silastic, medicine.disease, Cannula, Rats, Intestines, Endocrinology, Breast Feeding, nutrition, Animals, Newborn, Breath Tests, Gastric Emptying, Necrotizing enterocolitis, Models, Animal, breast milk, Nutrition physiology, business, formula milk, CD8
Abstract

A unique model of formula feeding in the neonatal rat was utilized to investigate the effects of an enterally delivered artificial milk formula on clinically relevant immunological and biological characteristics in the gut, compared to naturally reared pups. Hooded Wistar rat pups were randomly allocated to two treatment groups: formula-fed (FF) or naturally suckled (NS). A flexible silastic intra-gastric cannula was surgically implanted into the FF pups, through which an artificial rat milk supplement was continuously delivered from day 4 to day 10 of life. Rat pups were sacrificed at 10 days of age. Body weight, small intestinal weight, mucosal CD8(+) cell numbers, and ileal lactase activity in FF animals were significantly decreased compared to their NS counterparts (P < 0.05). Numbers of eosinophils, mucosal mast cells, CD4(+) T-cells, ileal villus height and gastric emptying times were significantly increased in FF pups (P < 0.05). We have developed a new rat model of artificial feeding which possesses important immunological and biological similarities to the premature human infant. Refereed/Peer-reviewed

Published
2008

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