Serum citrulline levels correlate with enteral tolerance and bowel length in infants with short bowel syndrome

Rhoads, J. Marc; Plunkett, Emily; Galanko, Joseph A.; Lichtman, Steven N.; Taylor, Lesli; Maynor, Angela; Weiner, Timothy M.; Freeman, Katherine; Guarisco, J. Lindhe; Wu, Guo Yao

doi:10.1016/j.jpeds.2004.12.027

Cited by 138 publications

(92 citation statements)

References 17 publications

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“…The activation was most evident in immunohistochemical stains as a "light up" of phospho-p70 S6K staining in epithelial cells lining the lower 20 -25% of the villi. An increase in p70 S6K abundance and activity occurred in the face of a significantly decreased mucosal mass, as evidenced by histological examination (Table 2) as well as by a reduced circulating level of citrulline, an amino acid that is synthesized exclusively in the intestine and serves as a marker of intestinal mass (Table 4) (46). mTOR has been shown to regulate dietary effects on liver and muscle protein synthesis (1,24,24).…”

Section: Intestinal P70 S6k Is Activated During Rotavirus Enteritismentioning

confidence: 99%

Intestinal ribosomal p70^S6Ksignaling is increased in piglet rotavirus enteritis

Rhoads

Corl

Harrell

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Recent identification of the mammalian target of rapamycin (mTOR) pathway as an amino acid-sensing mechanism that regulates protein synthesis led us to investigate its role in rotavirus diarrhea. We hypothesized that malnutrition would reduce the jejunal protein synthetic rate and mTOR signaling via its target, ribosomal p70 S6 kinase (p70S6K). Newborn piglets were artificially fed from birth and infected with porcine rotavirus on day 5 of life. Study groups included infected (fully fed and 50% protein calorie malnourished) and noninfected fully fed controls. Initially, in “worst-case scenario studies,” malnourished infected piglets were killed on days 1, 3, 5, and 11 postinoculation, and jejunal samples were compared with controls to determine the time course of injury and p70S6Kactivation. Using a 2 × 2 factorial design, we subsequently determined if infection and/or malnutrition affected mTOR activation on day 3. Western blot analysis and immunohistochemistry were used to measure total and phosphorylated p70S6K; [3H]phenylalanine incorporation was used to measure protein synthesis; and lactase specific activity and villus-crypt dimensions were used to quantify injury. At the peak of diarrhea, the in vitro jejunal protein synthetic rate increased twofold (compared with the rate in the uninfected pig jejunum), concomitant with increased jejunal p70S6Kphosphorylation (4-fold) and an increased p70S6Klevel (3-fold, P < 0.05). Malnutrition did not alter the magnitude of p70S6Kactivation. Immunolocalization revealed that infection produced a major induction of cytoplasmic p70S6Kand nuclear phospho-p70S6K, mainly in the crypt. A downregulation of semitendinosus muscle p70S6Kphosphorylation was seen at days 1–3 postinoculation. In conclusion, intestinal activation of p70S6Kwas not inhibited by malnutrition but was strongly activated during an active state of mucosal regeneration.

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Section: Intestinal P70 S6k Is Activated During Rotavirus Enteritismentioning

confidence: 99%

Intestinal ribosomal p70^S6Ksignaling is increased in piglet rotavirus enteritis

Rhoads

Corl

Harrell

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The clinical study of Rhoads et al [24] , found that there was a correlation between serum citrulline levels and enteral tolerance, and levels of serum citrulline could be used as a predictive test. In our study, fifteenth day serum citrulline levels were significantly lower than those in other groups.…”

Section: Discussionmentioning

confidence: 99%

Effects of microalgae chlorella species crude extracts on intestinal adaptation in experimental short bowel syndrome

Kerem¹,

Salman²,

Paşaoğlu³

et al. 2008

WJG

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AIM:To evaluate the effects of chlorella crude extract (CCE) on intestinal adaptation in rats subjected to short bowel syndrome (SBS). METHODS: Wistar rats weighing 230-260 g were used in the study. After anesthesia a 75% small bowel resection was performed. Rats were randomized and divided into groups. Control group (n = 10): where 5% dextrose was given through a gastrostomy tube, Enteral nutrition (EN) group (n = 10): Isocaloric and isonitrogen EN (Alitraq, Abbott, USA), study group (n = 10): CCE was administrated through a gastrostomy tube. Rats were sacrificed on the fifteenth postoperative day and blood and tissue samples were taken. Histopathologic evaluation, intestinal mucosal protein and DNA levels, intestinal proliferation and apoptosis were determined in intestinal tissues, and total protein, albumin and citrulline levels in blood were studied. RESULTS: In rats receiving CCE, villus lengthening, crypt depth, mucosal DNA and protein levels, intestinal proliferation, and serum citrulline, protein and albumin levels were found to be significantly higher than those in control group. Apoptosis in CCE treated rats was significantly reduced when compared to EN group rats. CONCLUSION: CCE has beneficial effects on intestinal adaptation in experimental SBS.

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“…This test operates on the principle that a decrease in cell mass in the small intestine would results decreased serum concentrations of citrulline. This method has been applied in conditions including surgery, 55 celiac disease, 56 gastroenteritis (viral) 57 and small intestinal transplant rejection. 58 Recently, the serum citrulline test has been utilized to assess epithelial cell loss associated with chemotherapy in the small intestine with relative success.…”

Section: Methods For Assessing Small Intestinal Functionmentioning

confidence: 99%

Mucositis and non-invasive markers of small intestinal function

Tooley

Howarth²,

Butler³

2009

Cancer Biology & Therapy

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Mucositis is a common and debilitating side effect of chemotherapy that manifests due to the inability of chemotherapy agents to discriminate between normal and neoplastic cells. This results in ulcerating lesions lining the gastrointestinal tract. Moreover, the development of efficacious treatments for small intestinal mucositis has been hindered as the pathobiology of mucositis is still not fully understood. The small intestine is an extensive organ which is largely inaccessible by conventional means. Non-invasive biomarkers such as small intestinal permeability, H 2 breath tests, serum citrulline tests and the 13 C-sucrose breath test (SBT) have emerged as potential markers of small intestinal function. The SBT is emerging as the more appropriate biomarker to assess chemotherapy-induced mucositis in cancer patients and animal models, where it measures the decrease in sucrase activity associated with villus blunting and crypt disruption. The SBT has been successfully applied to detect mucositis induced by different classes of chemotherapy agents and has been used successfully to monitor small intestinal function with a range of candidate anti-mucositis treatments. We propose the SBT a superior biomarker of small intestinal function that could be successfully applied in clinical practice for monitoring the development of mucositis in cancer patients undergoing chemotherapy.

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Serum citrulline levels correlate with enteral tolerance and bowel length in infants with short bowel syndrome

Cited by 138 publications

References 17 publications

Intestinal ribosomal p70^S6Ksignaling is increased in piglet rotavirus enteritis

Intestinal ribosomal p70^S6Ksignaling is increased in piglet rotavirus enteritis

Effects of microalgae chlorella species crude extracts on intestinal adaptation in experimental short bowel syndrome

Mucositis and non-invasive markers of small intestinal function

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Serum citrulline levels correlate with enteral tolerance and bowel length in infants with short bowel syndrome

Cited by 138 publications

References 17 publications

Intestinal ribosomal p70S6Ksignaling is increased in piglet rotavirus enteritis

Intestinal ribosomal p70S6Ksignaling is increased in piglet rotavirus enteritis

Effects of microalgae chlorella species crude extracts on intestinal adaptation in experimental short bowel syndrome

Mucositis and non-invasive markers of small intestinal function

Contact Info

Product

Resources

About

Intestinal ribosomal p70^S6Ksignaling is increased in piglet rotavirus enteritis

Intestinal ribosomal p70^S6Ksignaling is increased in piglet rotavirus enteritis