AIM: To investigate the vasoactive intestinal peptides(VIP) expression in irritable bowel syndrome(IBS) and trinitrobenzene sulfonic acid(TNBS) induced colitis.METHODS: The VIP gene expression and protein plasma level...AIM: To investigate the vasoactive intestinal peptides(VIP) expression in irritable bowel syndrome(IBS) and trinitrobenzene sulfonic acid(TNBS) induced colitis.METHODS: The VIP gene expression and protein plasma levels were measured in adult participants(45.8% male) who met Rome Ⅲ criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS.Plasma and colons were collected from naive and inflamed rats.Markers assessing inflammation(i.e.,weight changes and myeloperoxidase levels) were assessed on days 2,7,14 and 28 and compared to controls.Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws.IBS patients(n = 12) were age,gender,race,and BMI-matched with healthy controls(n = 12).Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay.Human gene expression of VIP was analyzed using a custom PCR array.RESULTS: TNBS induced colitis in the rats was confirmed with weight loss(13.7 ± 3.2 g) and increased myeloperoxidase activity.Visceral hypersensitivity tocolo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28.Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis.The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naive rats.This confirmed the induction of inflammation in rats following TNBS treatment.VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naive animals(P < 0.05).Likewise,the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls(P < 0.00001; 95%CI).VIP plasma protein was not significantly different when compared with controls(P = 0.193).CONCLUSION: Alterations in VIP expression may play a role in IBS.Therefore,a better understanding of the physiology of VIP could lead to new therapeutics.展开更多
AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus...AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus and Embase in February 2015.Date filters were applied from the year2009 and onward,and studies were limited to those written in the English language and those performed upon human subjects.The initial search yielded 797articles,out of which 38 were pulled for full text review and 27 were included for study analysis.Investigations were reviewed to determine study design,methodology and results,and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.RESULTS:Analysis of study data resulted in the abstraction of four key themes:Neurohormonal differences,anatomic measurements of brain structure and connectivity,differences in functional responsiveness of the brain during rectal distention,and confounding/correlating patient factors.Studies in this review noted alterations of glutamate in the left hippocampus(HIPP),commonalities across IBS subjects in terms of brain oscillation patterns,cortical thickness/gray matter volume differences,and neuroanatomical regions withincreased activation in patients with IBS:Anterio cingulate cortex,mid cingulate cortex,amygdala anterior insula,posterior insula and prefrontal cortex.A striking finding among interventions was the substantia influence that patient variables(e.g.,sex,psychologica and disease related factors)had upon the identification of neuroanatomical differences in structure and con nectivity.CONCLUSION:The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population.展开更多
基金Supported by National Institutes of Health grant,No.NS045614the Ruth L.Kirschstein National Research Service Award,No.1F31 DK083165-01A1 from the National Institute of Diabetes and Digestive and Kidney DiseasesDivision of Intramural Research,National Institute of Nursing Research,No.1ZIANR000018-01-05 to Henderson WA and Intramural Training Award to Del Valle-Pinero AY and Sherwin LB
文摘AIM: To investigate the vasoactive intestinal peptides(VIP) expression in irritable bowel syndrome(IBS) and trinitrobenzene sulfonic acid(TNBS) induced colitis.METHODS: The VIP gene expression and protein plasma levels were measured in adult participants(45.8% male) who met Rome Ⅲ criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS.Plasma and colons were collected from naive and inflamed rats.Markers assessing inflammation(i.e.,weight changes and myeloperoxidase levels) were assessed on days 2,7,14 and 28 and compared to controls.Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws.IBS patients(n = 12) were age,gender,race,and BMI-matched with healthy controls(n = 12).Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay.Human gene expression of VIP was analyzed using a custom PCR array.RESULTS: TNBS induced colitis in the rats was confirmed with weight loss(13.7 ± 3.2 g) and increased myeloperoxidase activity.Visceral hypersensitivity tocolo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28.Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis.The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naive rats.This confirmed the induction of inflammation in rats following TNBS treatment.VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naive animals(P < 0.05).Likewise,the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls(P < 0.00001; 95%CI).VIP plasma protein was not significantly different when compared with controls(P = 0.193).CONCLUSION: Alterations in VIP expression may play a role in IBS.Therefore,a better understanding of the physiology of VIP could lead to new therapeutics.
基金Supported by Division of Intramural ResearchNational Institute of Nursing Research to W.A.H.No.1ZIANR000018-01-05
文摘AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus and Embase in February 2015.Date filters were applied from the year2009 and onward,and studies were limited to those written in the English language and those performed upon human subjects.The initial search yielded 797articles,out of which 38 were pulled for full text review and 27 were included for study analysis.Investigations were reviewed to determine study design,methodology and results,and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.RESULTS:Analysis of study data resulted in the abstraction of four key themes:Neurohormonal differences,anatomic measurements of brain structure and connectivity,differences in functional responsiveness of the brain during rectal distention,and confounding/correlating patient factors.Studies in this review noted alterations of glutamate in the left hippocampus(HIPP),commonalities across IBS subjects in terms of brain oscillation patterns,cortical thickness/gray matter volume differences,and neuroanatomical regions withincreased activation in patients with IBS:Anterio cingulate cortex,mid cingulate cortex,amygdala anterior insula,posterior insula and prefrontal cortex.A striking finding among interventions was the substantia influence that patient variables(e.g.,sex,psychologica and disease related factors)had upon the identification of neuroanatomical differences in structure and con nectivity.CONCLUSION:The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population.