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Papers by Ross Butler

Research paper thumbnail of Rapid and simultaneous quantification of rhamnose, mannitol, and lactulose in urine by HPLC for estimating intestinal permeability in pediatric practice

Research paper thumbnail of Inhibitory effects of dietary calcium on iron absorption in proximal intestine - an animal model

Research paper thumbnail of Mechanism of interaction of dietary calcium on intestinal non- haeme iron absorption during weaning

Research paper thumbnail of Bioactive factors and bowel disease

Background -Increasingly, nature is being exploited as a rich resource for the targeted developme... more Background -Increasingly, nature is being exploited as a rich resource for the targeted development of new treatment modalities for diseases and disorders affecting the gastrointestinal system. These naturally-sourced agents, known as bioactives, can be derived from a surprisingly broad range of sources, varying from mammalian and marine species through to insects, plants, fungi and even bacteria. The spectrum of gastrointestinal conditions these bioactive factors could potentially treat, or prevent, is equally diverse, encompassing ulcerative and inflammatory conditions affecting all regions of the alimentary system, from the mouth, oesophagus and stomach, through to the small intestine and colon. The development and implementation of rigorously-controlled animal model systems of gastrointestinal disease is greatly facilitating the pre-clinical development of newly-identified bioactive agents. In addition to determining indications of clinical efficacy, these experimental model systems have the further capacity to provide important mechanistic information on the likely mode of action of the bioactives in vivo. Objective -Intestinal mucositis is a serious ulcerative condition that develops primarily in the upper small bowel of cancer patients undergoing chemotherapy or abdominal radiotherapy. The aetiology of the condition is a result of the inability of chemotherapy agents to discriminate between rapidly-dividing tumour cells and the normal, rapidlydividing cells which line the intestine. Often, the severity of intestinal mucositis may be the factor that limits chemotherapy dose, and hence the likelihood of tumour ablation. We utilized a rat model of chemotherapy-induced mucositis to assess the potential efficacy of several newly-developed agents. These included: (1) the herbal extract, Iberogast; (2) an extract derived from grape seeds (GSE); (3) Emu Oil and (4) the bacterium, Streptococcus thermophilus (TH-4). Design -Two rat models of intestinal mucositis were established to investigate the potential efficacy of the bioactive agents. Model 1 was induced in male Sprague Dawley rats by administration of the antimetabolite drug, methotrexate. Model 2 was induced in female Dark Agouti (DA) rats by administration of 5-Fluorouracil (5-FU). Use of the female DA rat enables further studies to be conducted in the breast cancer setting, since these rats will develop breast cancer following administration of a mammary adenocarcinoma cell suspension. In each model, the bioactive agents were gavaged daily (1 ml) for 5 days prior to chemotherapy, continuing until kill at days 2, 3 and 4 after chemotherapy. Analyses included essential metabolic parameters (body weight, food and water intake, urine and faecal output) and the non-invasive 13 C-sucrose breath test. Biochemical analyses included intestinal sucrase and myeloperoxidase activity. Qualitative and quantitative histological analyses were conducted on specimens of proximal, mid and distal jejunoileum. Outcomes -Iberogast partially protected the upper small intestine from chemotherapy damage, although the effect was lost in the more distal regions of the small intestine, presumably due to enzymatic degradation. Grape Seed Extract resulted in reduced inflammation in the upper small intestine as evidenced by a decrease in myeloperoxidase activity. Moreover, there were indications of residual GSE bioactivity in the distal ileum, as determined by improvements in villus and crypt integrity. Streptococcus thermophilus TH-4 almost normalized the 13 C-sucrose breath test after chemotherapy and improved histological parameters of intestinal integrity, identifying TH-4 as a new probiotic species. Importantly, Emu Oil resulted in a highly significant reduction in acute intestinal inflammation, combined with a significant stimulation of mucosal regeneration after chemotherapy. This could represent a new mechanism of action for Emu Oil, the accelerated intestinal re-growth potentially representing the result of an increase in enterocyte proliferation. Conclusion -Through disparate mechanisms, naturally-sourced bioactive agents and formulations are demonstrating therapeutic promise as dietary adjuncts to chemotherapy regimens. The capacity for these agents to target different regions of the intestine suggests indications for intestinal disorders beyond chemotherapy-induced mucositis. Although mechanistic studies are in their early stages, it is likely that mammalian-, bacterial-and plantsourced bioactive agents could be developed further to provide a new therapeutic strategy to accompany conventional medical approaches for diseases and disorders of the small and large bowel. References 1. KL Tooley, GS Howarth, GP Davidson and RN Butler. Oral ingestion of Streptococcus thermophilus diminishes severity of small intestinal mucositis in methotrexate treated rats.

Research paper thumbnail of Rapid and simultaneous quantification of rhamnose, mannitol, and lactulose in urine by HPLC for estimating intestinal permeability in pediatric practice

Clinical chemistry, 1996

Determination of intestinal permeability by measuring nonmetabolized sugars has been used to asse... more Determination of intestinal permeability by measuring nonmetabolized sugars has been used to assess the integrity of intestinal mucosa. We have developed and validated a modified HPLC method for determining the concentration of L-rhamnose, mannitol, and lactulose in urine, using an amine-modified silica column and refractive index detection. Probe sugars are simultaneously resolved within 18 min. The calibration curve for each sugar is linear to 20 mmol/L. The minimum detectable concentration of lactulose is 0.05 mmol/L. Recovery of probe sugars is between 99.3% and 105.1%. Overall precision (CV) of estimation of probe sugars ranges from 4.2% to 6.5%. In 14 urine samples from healthy children who ingested the test solution containing 1 g of L-rhamnose, 1 g of mannitol, and 5 g of lactulose, the 5-h urinary excretion ratios of lactulose/rhamnose and lactulose/mannitol were 0.047 +/- 0.018 and 0.021 +/- 0.010 (mean +/- SD), respectively. This method presents a rapid, convenient, and p...

Research paper thumbnail of Effect of dehydroepiandrosterone on pentose phosphate pathway activity in the rat colon

International Journal of Biochemistry, 1993

1. The effects of fasting and fasting followed by refeeding on the activities of the oxidative pe... more 1. The effects of fasting and fasting followed by refeeding on the activities of the oxidative pentose pathway (OPP) and the non-oxidative pentose pathway (NOPP) were estimated by the rate of production of 14CO2 from [1-14C] glucose in isolated rat colonocytes, and the production of hexose 6-phosphates from ribose 5-phosphate in rat colonic cytosols, respectively. 2. The OPP activity in colonocytes from rats in the fasted state was 50% lower when compared to colonocytes from rats refed after a fast. This indicated induction of the rate-limiting enzyme of the OPP, glucose 6-P dehydrogenase (G6-PDH) in the latter instance. No effect on the maximal catalytic activity of the enzymes of the NOPP was seen in colonocytes from rats refed after a fast compared with colonocytes from rats in the fasted state. 3. Isolated colonocytes obtained from the distal colon of rats refed after a fast, showed a significant decrease (30%) in OPP activity when incubated with 50 microM dehydroepiandrosterone (DHEA). A similar degree of inhibition was seen with 10 mM butyrate (P < 0.05). In contrast, using colonic cytosols, both DHEA and butyrate had no effect on the maximal catalytic activity of the NOPP. 4. Intraperitoneal injection (i.p.) of DHEA in rats refed after a fast showed a significant increase in the maximal catalytic activity of the NOPP in the distal colon (46%; P < 0.05). A similar elevation in the maximal catalytic activity of the NOPP was seen in the distal colon of DHEA treated pair-fed rats (43%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Developmental changes and fructose absorption in children: effect on malabsorption testing and dietary management

Nutrition Reviews, 2013

Fructose malabsorption came to prominence in the pediatric arena as so-called &am... more Fructose malabsorption came to prominence in the pediatric arena as so-called "apple juice diarrhea," with excess consumption of fructose being linked to gastrointestinal symptoms such as diarrhea and abdominal pain. Over the past two decades the amount of fructose in children's diets has been increasing in the United States. A test for fructose malabsorption has yet to be fully validated, due mainly to the lack of an established etiology. In animal models, however, the fructose transporter GLUT5 is developmentally regulated, and this could be consistent with the greater susceptibility of children, especially toddlers, to fructose malabsorption. Additionally, the available evidence indicates the fructose breath hydrogen test has no apparent diagnostic utility in infants younger than 1 year; it may, therefore, be advisable to test for malabsorption by dietary exclusion in these patients. The present review aims to expound on the biological basis for fructose malabsorption in children and evaluate the current evidence for diagnostic procedures in order to identify clinical testing strategies that can be recommended and areas where further investigation is required.

Research paper thumbnail of Bovine Colostrum Supplementation During Running Training Increases Intestinal Permeability

Nutrients, 2009

Endurance exercise training can increase intestinal permeability which may contribute to the deve... more Endurance exercise training can increase intestinal permeability which may contribute to the development of gastrointestinal symptoms in some athletes. Bovine colostrum (BC) supplementation reduces intestinal permeability induced by non-steroidal anti-inflammatory drugs. This study aimed to determine whether BC could also reduce intestinal permeability induced by endurance exercise. Thirty healthy adult males (25.0 ± 4.7 yr; mean ± SD) completed eight weeks of running three times per week for 45 minutes at their lactate threshold while consuming 60 g/day of BC, whey protein (WP) or control (CON). Intestinal permeability was assessed at baseline and after eight weeks by measuring the ratio of urinary lactulose (L) and rhamnose (R) excretion. After eight weeks the L/R ratio increased significantly more in volunteers consuming BC (251 ± 140%) compared with WP (21 ± 35%, P < 0.05) and CON (−7 ± 13%, P < 0.02). The increase in intestinal permeability with BC may have been due to BC inducing greater leakiness of tight junctions between enterocytes or by increasing macromolecular transport as it does in

Research paper thumbnail of Effect of baclofen on esophagogastric motility and gastroesophageal reflux in children with gastroesophageal reflux disease: A randomized controlled trial

The Journal of Pediatrics, 2006

To evaluate the effect of baclofen, a gamma-amino-butyric-acid B receptor agonist that inhibits t... more To evaluate the effect of baclofen, a gamma-amino-butyric-acid B receptor agonist that inhibits transient lower esophageal sphincter relaxation (TLESR), on the rates of TLESR, gastroesophageal reflux (GER), and gastric emptying (GE) in children with GER disease. The efficacy of 0.5 mg/kg baclofen was evaluated in a randomized, double-blinded, placebo-controlled trial in 30 children. Patients were intubated with a manometric/pH assembly and given 250 mL of cow&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s milk. Esophageal motility and pH were then measured for 2 hours (control period). Baclofen or placebo was then administered, and 1 hour later 250 mL of milk was given again and measurements performed for another 2 hours (test period). The GE rate was measured by the (13)C octanoate breath test. Baclofen significantly reduced the incidence of TLESR (mean, 7.3 +/- 1.5 vs 3.6 +/- 1.2 TLESR/2 hours; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) and acid GER (mean 4.2 +/- 0.7 vs 1.7 +/- 1.0 TLESR + GER/2 hours; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) during the test period compared with the control period. Baclofen significantly accelerated the GE rate (median [interquartile range], GE(t1/2), 61 minutes [39, 81 minutes] vs 114 minutes [67, 170 minutes]; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). Baclofen had no effect on the swallowing rate, pattern of esophageal peristalsis, or lower esophageal sphincter pressure. Baclofen reduces GER in children by inhibiting the triggering of TLESR. Baclofen also accelerates GE.

Research paper thumbnail of Is Small-bowel Bacterial Overgrowth an Underdiagnosed Disorder in Children With Gastrointestinal Symptoms?

Journal of Pediatric Gastroenterology and Nutrition, 2011

Small-bowel bacterial overgrowth (SBBO) has been implicated in chronic abdominal pain and irritab... more Small-bowel bacterial overgrowth (SBBO) has been implicated in chronic abdominal pain and irritable bowel syndrome in children. This was a retrospective study that aimed to assess the occurrence of SBBO by the lactulose breath hydrogen test in children referred primarily for investigation of carbohydrate malabsorption (n = 287). There were profiles indicative of SBBO in 16% (39/250) of hydrogen-producing children. This indicated that SBBO may be more common in children with gastrointestinal symptoms and apparent carbohydrate malabsorption than previously recognised.

Research paper thumbnail of Cellular Mucosal Defense During Helicobacter pylori Infection: A Review of the Role of Glutathione and the Oxidative Pentose Pathway

Helicobacter, 2005

Helicobacter pylori is the primary cause of gastritis and peptic ulcer disease and is known to in... more Helicobacter pylori is the primary cause of gastritis and peptic ulcer disease and is known to infect greater than 50% of the world&amp;amp;amp;amp;amp;amp;#39;s population. It is also known to lead to the onset of gastric cancer and unless treated, lasts throughout life in most individuals. Mouse models of H. pylori infection have improved our ability to study this organism and can be used to investigate the host mucosal response to the infection, particularly the early events postinoculation. Previous studies have shown that H. pylori infection leads to an increased production of reactive oxygen species within the gastric mucosa which are thought to play a major role in the mediation of associated disease. Recent studies have shown differences in the availability of an important antioxidant, glutathione, during chronic H. pylori infection. The availability of glutathione is primarily controlled by the activity of the oxidative pentose pathway. This review proposes that the severity of inflammation and damage associated with H. pylori infection is dependent on the ability of mucosal cells to counteract the increased load of reactive oxygen species. It is hypothesized that the oxidative pentose pathway and glutathione availability are important factors modulating this response. It is suggested that the therapeutic regulation of glutathione availability could provide a novel method for preventing or reducing the damage caused during H. pylori infection.

Research paper thumbnail of T1320 The Herbal Extract, Iberogast, Partially Improves Small Intestinal Integrity in Rats with Mucositis Induced By 5-Fluorouracil

Gastroenterology, 2008

... PDF. No abstract is available. To read the body of this article, please view the PDF online. ... more ... PDF. No abstract is available. To read the body of this article, please view the PDF online. PII: S0016-5085(08)62476-2. doi:10.1016/S0016-5085(08)62476-2. © 2008AGA Institute. Published by Elsevier Inc. All rights reserved. ...

Research paper thumbnail of W1834 Small Bowel Bacterial Overgrowth in Symptomatic Children – An Under-Diagnosed Disorder?

Gastroenterology, 2010

Small bowel bacterial overgrowth (SSBO) is characterised by a wide range of clinical manifestatio... more Small bowel bacterial overgrowth (SSBO) is characterised by a wide range of clinical manifestations, including abdominal discomfort and chronic diarrhoea. It is commonly believed that SBBO is more prevalent in older adults and relatively uncommon in children without co-existing morbidities in developed countries. We reviewed breath hydrogen testing (BHT) with a lactulose substrate, a non-absorbable synthetic disaccharide, which can be used to detect SBBO. A retrospective analysis was carried out on patients aged ≤15 years referred to the breath testing clinic at the Women's and Children's Hospital for testing for carbohydrate malabsorption between 2003 and 2007. A lactulose BHT was routinely administered to these patients tested to determine if they produced hydrogen. The lactulose breath test was performed using 6.68g (10mL) of lactulose (Duphalac) dissolved in 90mL of water and breath samples were collected at 30min intervals for 150min. A positive breath test for SBBO was defined as a rise in hydrogen production of ≥10ppm sustained over two consecutive timepoints in the initial 90min of the test. Data was analysed from 228 children, 15.8% (n=36) of whom had hydrogen values of <10ppm at all timepoints and were classified as non-hydrogen producers. Of the hydrogen-producing children aged from 1 month to 15 years (n=192), 15.1% (n=29) displayed hydrogen profiles indicative of SBBO. Of these, 4/ 29 were referred for query SBBO and the remainder were referred for suspected carbohydrate malabsorption. The average hydrogen production (ppm) in those classified as having SBBO was significantly higher (p<0.05) at all timepoints than in those who were classified as negative for SBBO. This study suggests that SBBO is present in 15% of hydrogen-producing children primarily investigated for carbohydrate malabsorption, and is more likely to be a contributing factor in gastrointestinal symptoms than previously thought. These results highlight the need for physicians assessing paediatric patients exhibiting gastrointestinal symptoms to consider breath testing for SBBO as a line of investigation.

Research paper thumbnail of Non-invasive measurement of a fermentation pattern shift in infants during the first three months of life

Research paper thumbnail of Partial attenuation of 5-fluorouracil (5-FU)-induced intestinal mucositis by pretreatment with insulin-like growth factor-I (IGF-I) in rats

Gastroenterology, 2003

Gastroenterology, Volume 124, Issue 4, Pages A597, April 2003, Authors:Jodie L. Dyer; Ross N. But... more Gastroenterology, Volume 124, Issue 4, Pages A597, April 2003, Authors:Jodie L. Dyer; Ross N. Butler; Cory J. Xian; Gordon S. Howarth.

Research paper thumbnail of Maximal catalytic activity of the non-oxidative pentose pathway: A new marker of colonic transformation

Research paper thumbnail of The non-oxidative pentose phosphate pathway (NOPP) in helicobacter pylori — A potential therapeutic target?

Research paper thumbnail of Yoghurts Containing Probiotics Reduce Disruption of the Small Intestinal Barrier in Methotrexate-Treated Rats

Digestive Diseases and Sciences, 2008

Small intestinal permeability was employed to assess the efficacy of commercially available yoghu... more Small intestinal permeability was employed to assess the efficacy of commercially available yoghurts containing probiotics in a rat model of methotrexate (MTX)-induced mucositis. Male Sprague-Dawley rats were allocated to four groups (n = 8): MTX + water, MTX + cow’s milk yoghurt (CY; fermented with Lactobacillus johnsonii), MTX + sheep’s milk yoghurt (SY; containing Lactobacillus bulgaricus and Streptococcus thermophilus), and saline. Treatment gavage occurred twice daily for 7 days

Research paper thumbnail of The Effects of Formula Feeding on Physiological and Immunological Parameters in the Gut of Neonatal Rats

Digestive Diseases and Sciences, 2009

A unique model of formula feeding in the neonatal rat was utilized to investigate the effects of ... more 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 &lt; 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 &lt; 0.05). We have developed a new rat model of artificial feeding which possesses important immunological and biological similarities to the premature human infant.

Research paper thumbnail of Probiotics in pediatric gastrointestinal disorders

Current Opinion in Pediatrics, 2000

Probiotics have been defined most recently as living microorganisms which, upon ingestion in cert... more Probiotics have been defined most recently as living microorganisms which, upon ingestion in certain numbers, exact health benefits beyond inherent general nutrition. They have been a part of human nutrition for centuries, but in recent years they have been more closely studied for their potential to improve health and treat disease. This review of probiotics is not extensive, highlighting the most recent reviews and well controlled clinical studies in both animals and humans. The safety issues are also discussed as well as potential mechanisms of action. The importance of studying each probiotic bacterium individually in each condition where a health benefit is claimed is highlighted by Lactobacillus GG, the most widely studied probiotic which has proven benefit in reducing the severity and duration of viral diarrhea but no benefit against bacterial diarrhea.

Research paper thumbnail of Rapid and simultaneous quantification of rhamnose, mannitol, and lactulose in urine by HPLC for estimating intestinal permeability in pediatric practice

Research paper thumbnail of Inhibitory effects of dietary calcium on iron absorption in proximal intestine - an animal model

Research paper thumbnail of Mechanism of interaction of dietary calcium on intestinal non- haeme iron absorption during weaning

Research paper thumbnail of Bioactive factors and bowel disease

Background -Increasingly, nature is being exploited as a rich resource for the targeted developme... more Background -Increasingly, nature is being exploited as a rich resource for the targeted development of new treatment modalities for diseases and disorders affecting the gastrointestinal system. These naturally-sourced agents, known as bioactives, can be derived from a surprisingly broad range of sources, varying from mammalian and marine species through to insects, plants, fungi and even bacteria. The spectrum of gastrointestinal conditions these bioactive factors could potentially treat, or prevent, is equally diverse, encompassing ulcerative and inflammatory conditions affecting all regions of the alimentary system, from the mouth, oesophagus and stomach, through to the small intestine and colon. The development and implementation of rigorously-controlled animal model systems of gastrointestinal disease is greatly facilitating the pre-clinical development of newly-identified bioactive agents. In addition to determining indications of clinical efficacy, these experimental model systems have the further capacity to provide important mechanistic information on the likely mode of action of the bioactives in vivo. Objective -Intestinal mucositis is a serious ulcerative condition that develops primarily in the upper small bowel of cancer patients undergoing chemotherapy or abdominal radiotherapy. The aetiology of the condition is a result of the inability of chemotherapy agents to discriminate between rapidly-dividing tumour cells and the normal, rapidlydividing cells which line the intestine. Often, the severity of intestinal mucositis may be the factor that limits chemotherapy dose, and hence the likelihood of tumour ablation. We utilized a rat model of chemotherapy-induced mucositis to assess the potential efficacy of several newly-developed agents. These included: (1) the herbal extract, Iberogast; (2) an extract derived from grape seeds (GSE); (3) Emu Oil and (4) the bacterium, Streptococcus thermophilus (TH-4). Design -Two rat models of intestinal mucositis were established to investigate the potential efficacy of the bioactive agents. Model 1 was induced in male Sprague Dawley rats by administration of the antimetabolite drug, methotrexate. Model 2 was induced in female Dark Agouti (DA) rats by administration of 5-Fluorouracil (5-FU). Use of the female DA rat enables further studies to be conducted in the breast cancer setting, since these rats will develop breast cancer following administration of a mammary adenocarcinoma cell suspension. In each model, the bioactive agents were gavaged daily (1 ml) for 5 days prior to chemotherapy, continuing until kill at days 2, 3 and 4 after chemotherapy. Analyses included essential metabolic parameters (body weight, food and water intake, urine and faecal output) and the non-invasive 13 C-sucrose breath test. Biochemical analyses included intestinal sucrase and myeloperoxidase activity. Qualitative and quantitative histological analyses were conducted on specimens of proximal, mid and distal jejunoileum. Outcomes -Iberogast partially protected the upper small intestine from chemotherapy damage, although the effect was lost in the more distal regions of the small intestine, presumably due to enzymatic degradation. Grape Seed Extract resulted in reduced inflammation in the upper small intestine as evidenced by a decrease in myeloperoxidase activity. Moreover, there were indications of residual GSE bioactivity in the distal ileum, as determined by improvements in villus and crypt integrity. Streptococcus thermophilus TH-4 almost normalized the 13 C-sucrose breath test after chemotherapy and improved histological parameters of intestinal integrity, identifying TH-4 as a new probiotic species. Importantly, Emu Oil resulted in a highly significant reduction in acute intestinal inflammation, combined with a significant stimulation of mucosal regeneration after chemotherapy. This could represent a new mechanism of action for Emu Oil, the accelerated intestinal re-growth potentially representing the result of an increase in enterocyte proliferation. Conclusion -Through disparate mechanisms, naturally-sourced bioactive agents and formulations are demonstrating therapeutic promise as dietary adjuncts to chemotherapy regimens. The capacity for these agents to target different regions of the intestine suggests indications for intestinal disorders beyond chemotherapy-induced mucositis. Although mechanistic studies are in their early stages, it is likely that mammalian-, bacterial-and plantsourced bioactive agents could be developed further to provide a new therapeutic strategy to accompany conventional medical approaches for diseases and disorders of the small and large bowel. References 1. KL Tooley, GS Howarth, GP Davidson and RN Butler. Oral ingestion of Streptococcus thermophilus diminishes severity of small intestinal mucositis in methotrexate treated rats.

Research paper thumbnail of Rapid and simultaneous quantification of rhamnose, mannitol, and lactulose in urine by HPLC for estimating intestinal permeability in pediatric practice

Clinical chemistry, 1996

Determination of intestinal permeability by measuring nonmetabolized sugars has been used to asse... more Determination of intestinal permeability by measuring nonmetabolized sugars has been used to assess the integrity of intestinal mucosa. We have developed and validated a modified HPLC method for determining the concentration of L-rhamnose, mannitol, and lactulose in urine, using an amine-modified silica column and refractive index detection. Probe sugars are simultaneously resolved within 18 min. The calibration curve for each sugar is linear to 20 mmol/L. The minimum detectable concentration of lactulose is 0.05 mmol/L. Recovery of probe sugars is between 99.3% and 105.1%. Overall precision (CV) of estimation of probe sugars ranges from 4.2% to 6.5%. In 14 urine samples from healthy children who ingested the test solution containing 1 g of L-rhamnose, 1 g of mannitol, and 5 g of lactulose, the 5-h urinary excretion ratios of lactulose/rhamnose and lactulose/mannitol were 0.047 +/- 0.018 and 0.021 +/- 0.010 (mean +/- SD), respectively. This method presents a rapid, convenient, and p...

Research paper thumbnail of Effect of dehydroepiandrosterone on pentose phosphate pathway activity in the rat colon

International Journal of Biochemistry, 1993

1. The effects of fasting and fasting followed by refeeding on the activities of the oxidative pe... more 1. The effects of fasting and fasting followed by refeeding on the activities of the oxidative pentose pathway (OPP) and the non-oxidative pentose pathway (NOPP) were estimated by the rate of production of 14CO2 from [1-14C] glucose in isolated rat colonocytes, and the production of hexose 6-phosphates from ribose 5-phosphate in rat colonic cytosols, respectively. 2. The OPP activity in colonocytes from rats in the fasted state was 50% lower when compared to colonocytes from rats refed after a fast. This indicated induction of the rate-limiting enzyme of the OPP, glucose 6-P dehydrogenase (G6-PDH) in the latter instance. No effect on the maximal catalytic activity of the enzymes of the NOPP was seen in colonocytes from rats refed after a fast compared with colonocytes from rats in the fasted state. 3. Isolated colonocytes obtained from the distal colon of rats refed after a fast, showed a significant decrease (30%) in OPP activity when incubated with 50 microM dehydroepiandrosterone (DHEA). A similar degree of inhibition was seen with 10 mM butyrate (P &lt; 0.05). In contrast, using colonic cytosols, both DHEA and butyrate had no effect on the maximal catalytic activity of the NOPP. 4. Intraperitoneal injection (i.p.) of DHEA in rats refed after a fast showed a significant increase in the maximal catalytic activity of the NOPP in the distal colon (46%; P &lt; 0.05). A similar elevation in the maximal catalytic activity of the NOPP was seen in the distal colon of DHEA treated pair-fed rats (43%; P &lt; 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Developmental changes and fructose absorption in children: effect on malabsorption testing and dietary management

Nutrition Reviews, 2013

Fructose malabsorption came to prominence in the pediatric arena as so-called &amp;amp;amp;am... more Fructose malabsorption came to prominence in the pediatric arena as so-called &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;apple juice diarrhea,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; with excess consumption of fructose being linked to gastrointestinal symptoms such as diarrhea and abdominal pain. Over the past two decades the amount of fructose in children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s diets has been increasing in the United States. A test for fructose malabsorption has yet to be fully validated, due mainly to the lack of an established etiology. In animal models, however, the fructose transporter GLUT5 is developmentally regulated, and this could be consistent with the greater susceptibility of children, especially toddlers, to fructose malabsorption. Additionally, the available evidence indicates the fructose breath hydrogen test has no apparent diagnostic utility in infants younger than 1 year; it may, therefore, be advisable to test for malabsorption by dietary exclusion in these patients. The present review aims to expound on the biological basis for fructose malabsorption in children and evaluate the current evidence for diagnostic procedures in order to identify clinical testing strategies that can be recommended and areas where further investigation is required.

Research paper thumbnail of Bovine Colostrum Supplementation During Running Training Increases Intestinal Permeability

Nutrients, 2009

Endurance exercise training can increase intestinal permeability which may contribute to the deve... more Endurance exercise training can increase intestinal permeability which may contribute to the development of gastrointestinal symptoms in some athletes. Bovine colostrum (BC) supplementation reduces intestinal permeability induced by non-steroidal anti-inflammatory drugs. This study aimed to determine whether BC could also reduce intestinal permeability induced by endurance exercise. Thirty healthy adult males (25.0 ± 4.7 yr; mean ± SD) completed eight weeks of running three times per week for 45 minutes at their lactate threshold while consuming 60 g/day of BC, whey protein (WP) or control (CON). Intestinal permeability was assessed at baseline and after eight weeks by measuring the ratio of urinary lactulose (L) and rhamnose (R) excretion. After eight weeks the L/R ratio increased significantly more in volunteers consuming BC (251 ± 140%) compared with WP (21 ± 35%, P < 0.05) and CON (−7 ± 13%, P < 0.02). The increase in intestinal permeability with BC may have been due to BC inducing greater leakiness of tight junctions between enterocytes or by increasing macromolecular transport as it does in

Research paper thumbnail of Effect of baclofen on esophagogastric motility and gastroesophageal reflux in children with gastroesophageal reflux disease: A randomized controlled trial

The Journal of Pediatrics, 2006

To evaluate the effect of baclofen, a gamma-amino-butyric-acid B receptor agonist that inhibits t... more To evaluate the effect of baclofen, a gamma-amino-butyric-acid B receptor agonist that inhibits transient lower esophageal sphincter relaxation (TLESR), on the rates of TLESR, gastroesophageal reflux (GER), and gastric emptying (GE) in children with GER disease. The efficacy of 0.5 mg/kg baclofen was evaluated in a randomized, double-blinded, placebo-controlled trial in 30 children. Patients were intubated with a manometric/pH assembly and given 250 mL of cow&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s milk. Esophageal motility and pH were then measured for 2 hours (control period). Baclofen or placebo was then administered, and 1 hour later 250 mL of milk was given again and measurements performed for another 2 hours (test period). The GE rate was measured by the (13)C octanoate breath test. Baclofen significantly reduced the incidence of TLESR (mean, 7.3 +/- 1.5 vs 3.6 +/- 1.2 TLESR/2 hours; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) and acid GER (mean 4.2 +/- 0.7 vs 1.7 +/- 1.0 TLESR + GER/2 hours; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05) during the test period compared with the control period. Baclofen significantly accelerated the GE rate (median [interquartile range], GE(t1/2), 61 minutes [39, 81 minutes] vs 114 minutes [67, 170 minutes]; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). Baclofen had no effect on the swallowing rate, pattern of esophageal peristalsis, or lower esophageal sphincter pressure. Baclofen reduces GER in children by inhibiting the triggering of TLESR. Baclofen also accelerates GE.

Research paper thumbnail of Is Small-bowel Bacterial Overgrowth an Underdiagnosed Disorder in Children With Gastrointestinal Symptoms?

Journal of Pediatric Gastroenterology and Nutrition, 2011

Small-bowel bacterial overgrowth (SBBO) has been implicated in chronic abdominal pain and irritab... more Small-bowel bacterial overgrowth (SBBO) has been implicated in chronic abdominal pain and irritable bowel syndrome in children. This was a retrospective study that aimed to assess the occurrence of SBBO by the lactulose breath hydrogen test in children referred primarily for investigation of carbohydrate malabsorption (n = 287). There were profiles indicative of SBBO in 16% (39/250) of hydrogen-producing children. This indicated that SBBO may be more common in children with gastrointestinal symptoms and apparent carbohydrate malabsorption than previously recognised.

Research paper thumbnail of Cellular Mucosal Defense During Helicobacter pylori Infection: A Review of the Role of Glutathione and the Oxidative Pentose Pathway

Helicobacter, 2005

Helicobacter pylori is the primary cause of gastritis and peptic ulcer disease and is known to in... more Helicobacter pylori is the primary cause of gastritis and peptic ulcer disease and is known to infect greater than 50% of the world&amp;amp;amp;amp;amp;amp;#39;s population. It is also known to lead to the onset of gastric cancer and unless treated, lasts throughout life in most individuals. Mouse models of H. pylori infection have improved our ability to study this organism and can be used to investigate the host mucosal response to the infection, particularly the early events postinoculation. Previous studies have shown that H. pylori infection leads to an increased production of reactive oxygen species within the gastric mucosa which are thought to play a major role in the mediation of associated disease. Recent studies have shown differences in the availability of an important antioxidant, glutathione, during chronic H. pylori infection. The availability of glutathione is primarily controlled by the activity of the oxidative pentose pathway. This review proposes that the severity of inflammation and damage associated with H. pylori infection is dependent on the ability of mucosal cells to counteract the increased load of reactive oxygen species. It is hypothesized that the oxidative pentose pathway and glutathione availability are important factors modulating this response. It is suggested that the therapeutic regulation of glutathione availability could provide a novel method for preventing or reducing the damage caused during H. pylori infection.

Research paper thumbnail of T1320 The Herbal Extract, Iberogast, Partially Improves Small Intestinal Integrity in Rats with Mucositis Induced By 5-Fluorouracil

Gastroenterology, 2008

... PDF. No abstract is available. To read the body of this article, please view the PDF online. ... more ... PDF. No abstract is available. To read the body of this article, please view the PDF online. PII: S0016-5085(08)62476-2. doi:10.1016/S0016-5085(08)62476-2. © 2008AGA Institute. Published by Elsevier Inc. All rights reserved. ...

Research paper thumbnail of W1834 Small Bowel Bacterial Overgrowth in Symptomatic Children – An Under-Diagnosed Disorder?

Gastroenterology, 2010

Small bowel bacterial overgrowth (SSBO) is characterised by a wide range of clinical manifestatio... more Small bowel bacterial overgrowth (SSBO) is characterised by a wide range of clinical manifestations, including abdominal discomfort and chronic diarrhoea. It is commonly believed that SBBO is more prevalent in older adults and relatively uncommon in children without co-existing morbidities in developed countries. We reviewed breath hydrogen testing (BHT) with a lactulose substrate, a non-absorbable synthetic disaccharide, which can be used to detect SBBO. A retrospective analysis was carried out on patients aged ≤15 years referred to the breath testing clinic at the Women's and Children's Hospital for testing for carbohydrate malabsorption between 2003 and 2007. A lactulose BHT was routinely administered to these patients tested to determine if they produced hydrogen. The lactulose breath test was performed using 6.68g (10mL) of lactulose (Duphalac) dissolved in 90mL of water and breath samples were collected at 30min intervals for 150min. A positive breath test for SBBO was defined as a rise in hydrogen production of ≥10ppm sustained over two consecutive timepoints in the initial 90min of the test. Data was analysed from 228 children, 15.8% (n=36) of whom had hydrogen values of <10ppm at all timepoints and were classified as non-hydrogen producers. Of the hydrogen-producing children aged from 1 month to 15 years (n=192), 15.1% (n=29) displayed hydrogen profiles indicative of SBBO. Of these, 4/ 29 were referred for query SBBO and the remainder were referred for suspected carbohydrate malabsorption. The average hydrogen production (ppm) in those classified as having SBBO was significantly higher (p<0.05) at all timepoints than in those who were classified as negative for SBBO. This study suggests that SBBO is present in 15% of hydrogen-producing children primarily investigated for carbohydrate malabsorption, and is more likely to be a contributing factor in gastrointestinal symptoms than previously thought. These results highlight the need for physicians assessing paediatric patients exhibiting gastrointestinal symptoms to consider breath testing for SBBO as a line of investigation.

Research paper thumbnail of Non-invasive measurement of a fermentation pattern shift in infants during the first three months of life

Research paper thumbnail of Partial attenuation of 5-fluorouracil (5-FU)-induced intestinal mucositis by pretreatment with insulin-like growth factor-I (IGF-I) in rats

Gastroenterology, 2003

Gastroenterology, Volume 124, Issue 4, Pages A597, April 2003, Authors:Jodie L. Dyer; Ross N. But... more Gastroenterology, Volume 124, Issue 4, Pages A597, April 2003, Authors:Jodie L. Dyer; Ross N. Butler; Cory J. Xian; Gordon S. Howarth.

Research paper thumbnail of Maximal catalytic activity of the non-oxidative pentose pathway: A new marker of colonic transformation

Research paper thumbnail of The non-oxidative pentose phosphate pathway (NOPP) in helicobacter pylori — A potential therapeutic target?

Research paper thumbnail of Yoghurts Containing Probiotics Reduce Disruption of the Small Intestinal Barrier in Methotrexate-Treated Rats

Digestive Diseases and Sciences, 2008

Small intestinal permeability was employed to assess the efficacy of commercially available yoghu... more Small intestinal permeability was employed to assess the efficacy of commercially available yoghurts containing probiotics in a rat model of methotrexate (MTX)-induced mucositis. Male Sprague-Dawley rats were allocated to four groups (n = 8): MTX + water, MTX + cow’s milk yoghurt (CY; fermented with Lactobacillus johnsonii), MTX + sheep’s milk yoghurt (SY; containing Lactobacillus bulgaricus and Streptococcus thermophilus), and saline. Treatment gavage occurred twice daily for 7 days

Research paper thumbnail of The Effects of Formula Feeding on Physiological and Immunological Parameters in the Gut of Neonatal Rats

Digestive Diseases and Sciences, 2009

A unique model of formula feeding in the neonatal rat was utilized to investigate the effects of ... more 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 &lt; 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 &lt; 0.05). We have developed a new rat model of artificial feeding which possesses important immunological and biological similarities to the premature human infant.

Research paper thumbnail of Probiotics in pediatric gastrointestinal disorders

Current Opinion in Pediatrics, 2000

Probiotics have been defined most recently as living microorganisms which, upon ingestion in cert... more Probiotics have been defined most recently as living microorganisms which, upon ingestion in certain numbers, exact health benefits beyond inherent general nutrition. They have been a part of human nutrition for centuries, but in recent years they have been more closely studied for their potential to improve health and treat disease. This review of probiotics is not extensive, highlighting the most recent reviews and well controlled clinical studies in both animals and humans. The safety issues are also discussed as well as potential mechanisms of action. The importance of studying each probiotic bacterium individually in each condition where a health benefit is claimed is highlighted by Lactobacillus GG, the most widely studied probiotic which has proven benefit in reducing the severity and duration of viral diarrhea but no benefit against bacterial diarrhea.