Jarrett M.,University of Washington |
Heitkemper M.,University of Washington |
Czyzewski D.,Baylor College of Medicine |
Czyzewski D.,Texas Childrens Hospital |
And 3 more authors.
Journal of Pain | Year: 2012
Adults with irritable bowel syndrome (IBS) have been reported to have alterations in autonomic nervous system function as measured by vagal activity via heart rate variability. Whether the same is true for children is unknown. We compared young children 7 to 10 years of age with functional abdominal pain (FAP) or IBS to healthy children (HC) and explored the relationship of vagal activity and sympathovagal balance to psychological distress and stool type. Children completed questionnaires, kept a 2-week pain/stool diary, and wore a 24-hour Holter monitor to assess vagal activity. Group comparisons on vagal activity were controlled for age and body mass index. Indicators of vagal activity and sympathovagal balance did not differ between FAP/IBS children (70 girls, 30 boys) and HC (44 girls, 18 boys). Psychological distress measures were generally higher in FAP/IBS than HC, primarily in girls. Exploratory analyses suggest a potential negative correlation between vagal activity and psychological distress in FAP/IBS girls but not boys. In contrast to reports in women, no differences were found in vagal activity between FAP/IBS and HC. Preliminary findings suggest that in girls with FAP/IBS there is an inverse relationship between vagal activity and psychological distress. Perspective: The results from this study suggest a possible relationship between emotional state and vagal activity in prepubertal girls (but not boys) with FAP/IBS. Age and/or duration of symptoms may explain our contrasting findings versus adults with IBS. © 2012 by the American Pain Society.
Wang Y.,China Agricultural University |
Wang Y.,Childrens Nutrition Research Center |
Guan X.,Childrens Nutrition Research Center |
Guan X.,Baylor College of Medicine
American Journal of Physiology - Endocrinology and Metabolism | Year: 2010
Glucagon-like peptide-2 (GLP-2) is a neuropeptide secreted from endocrine cells in the gut and neurons in the brain. GLP-2 stimulates intestinal crypt cell proliferation and mucosal blood flow while decreasing gastric emptying and gut motility. However, a GLP-2-mediated signaling network has not been fully established in primary cells. Since the GLP-2 receptor mRNA and protein were highly expressed in the mouse hippocampus, we further characterized that human 125I-labeled GLP-2 1-33 specifically bound to cultured hippocampal neurons with Kd = 0.48 nM, and GLP-2 acutely induced subcellular translocalization of the early gene c-Fos. Using the whole cell patch clamp, we recorded barium currents (I Ba) flowing through voltage-gated Ca 2+ channels (VGCC) in those neurons in the presence of GLP-2 with and without inhibitors. We showed that GLP-2 (20 nM) enhanced the whole cell I Ba mediated by L-type VGCC that was defined using an L-type Ca 2+ channel blocker (nifedipine, 10 μM). Moreover, GLP-2-potentiation of L-type VGCC was abolished in neurons pretreated with a PKA inhibitor (PKI 14- 22, 1 μM). Finally, using a fluorescent nonmetabolized glucose analog (6-NBDG) tracing imaging, we showed that glucose was taken up directly by cultured neurons. GLP-2 increased 2-deoxy-D-[ 3H]glucose uptake that was dependent upon dosage, activation of PKA, and potentiation of L-type VGCC. We conclude that GLP-2 potentiates L-type VGCC activity through activating PKA signaling, partially stimulating glucose uptake by primary cultured hippocampal neurons. The potentiation of L-type VGCC may be physiologically relevant to GLP-2-induced neuroendocrine modulation of neurotransmitter release and hormone secretion. Copyright © 2010 the American Physiological Society.
Mayer E.A.,University of California at Los Angeles |
Savidge T.,Baylor College of Medicine |
Savidge T.,Texas Childrens Microbiome Center |
Savidge T.,Texas Childrens Hospital |
And 3 more authors.
Gastroenterology | Year: 2014
Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined role for dysbiosis in the development of IBS symptoms has been established through characterization of altered intestinal microbiota in IBS patients and reported improvement of subjective symptoms after its manipulation with prebiotics, probiotics, or antibiotics. It remains to be determined whether IBS symptoms are caused by alterations in brain signaling from the intestine to the microbiota or primary disruption of the microbiota, and whether they are involved in altered interactions between the brain and intestine during development. We review the potential mechanisms involved in the pathogenesis of IBS in different groups of patients. Studies are needed to better characterize alterations to the intestinal microbiome in large cohorts of well-phenotyped patients, and to correlate intestinal metabolites with specific abnormalities in gut-brain interactions. © 2014 by the AGA Institute.
Salama S.A.,Baylor College of Medicine |
Mohammad M.A.,Childrens Nutrition Research Center |
Diaz-Arrastia C.R.,Baylor College of Medicine |
Kamel M.W.,Cairo University |
And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014
Objectives: Our objectives were to study whether E2 induces reprogramming of glucose metabolism in hESCs and to investigate the potential roles of PKM2 in E2-induced metabolic reprogramming and proliferation of these cells.Context: Proliferating cells reprogram their cellular glucose metabolism to meet the bioenergetic and biosynthetic demands and to maintain cellular redox homeostasis. Pyruvate kinase M (PKM) is a critical regulator of this metabolic reprogramming. However, whether estradiol-17β (E2) reprograms cellular metabolism to support proliferation of human primary endometrial stromal cells (hESCs) and the molecular basis of this reprogramming are not well understood.Methods: The oxygen consumption rate and extracellular acidification rate were assessed by a Seahorse XF24 analyzer. PKM2 expression was assessed by real-time RT-PCR and immunoblotting.Results: E2 induces a Warburg-like glucose metabolism in hESCs by inducing the expression of PKM. E2 also enhanced PKM splicing into the PKM2 isoform by upregulating the c-Myc-hnRNP axis. Furthermore, E2 induces PKM2 oxidation, phosphorylation, and nucleartranslocation. In addition to its glycolytic function, PKM2 physically interacted with estrogen receptor-α (ERα) and functioned as an ERα coactivator. Small-molecule PKM2 activators ameliorated ERa transcriptional activity and abrogated the E2-induced hESC proliferation.Conclusions: We show for the first time that E2-induced hESC proliferation is associated with a shift in glucose metabolism toward aerobic glycolysis, and the molecular basis for this metabolic shift is linked to the effects of E2 on PKM2. In addition, PKM2 acts as a transcriptional coactivator for ERa and small-molecule PKM2 activators inhibit ERα transcriptional activity and reduce E2-induced cell proliferation. Copyright © 2014 by the Endocrine Society.
Williams A.E.,Loyola University |
Heitkemper M.,University of Washington |
Self M.M.,Baylor College of Medicine |
Self M.M.,Texas Childrens Hospital |
And 5 more authors.
Journal of Pain | Year: 2013
Endogenous pain inhibition is often deficient in adults with chronic pain conditions including irritable bowel syndrome (IBS). It is unclear whether deficiencies in pain inhibition are present in young children with IBS. The present study compared endogenous pain inhibition, somatic pain threshold, and psychosocial distress in young girls with IBS versus controls. Girls with IBS did not show significant endogenous pain inhibition of heat pain threshold during a cold-pressor task in contrast to controls, who had significant pain inhibition. Girls with IBS did not differ from peers on measures of somatic pain but had more symptoms of depression, somatization, and anxiety than controls. When psychological variables were included as covariates, the difference in pain inhibition was no longer significant, although poor achieved power limits interpretation of these results. Higher-order cognitive processes including psychological variables may be contributing to observed pain inhibition. In girls with IBS, pain inhibition was positively related to the number of days without a bowel movement. To our knowledge, this is the first study to demonstrate deficiencies of endogenous pain inhibition in young children with IBS. Findings have implications for better understanding of onset and maintenance of IBS and other chronic pain conditions. Perspective: This study found that young girls with IBS have deficient endogenous pain inhibition compared to healthy girls, which is consistent with the literature on adults. This information can facilitate clinicians in identification of risk factors for onset/maintenance of IBS and other chronic pain conditions. © 2013 by the American Pain Society.
Kim S.,Baylor College of Medicine |
Kim S.,Childrens Nutrition Research Center |
Fonagy P.,Baylor College of Medicine |
Fonagy P.,University College London |
And 6 more authors.
Brain Research | Year: 2014
The neuropeptide oxytocin is importantly implicated in the emergence and maintenance of maternal behavior that forms the basis of the mother-infant bond. However, no research has yet examined the specific association between maternal oxytocin and maternal gaze, a key modality through which the mother makes social contact and engages with her infant. Furthermore, prior oxytocin studies have assessed maternal engagement primarily during episodes free of infant distress, while maternal engagement during infant distress is considered to be uniquely relevant to the formation of secure mother-infant attachment. Two patterns of maternal gaze, maternal gaze toward and gaze shifts away from the infant, were micro-coded while 50 mothers interacted with their 7-month-old infants during a modified still-face procedure. Maternal oxytocin response was defined as a change from baseline in the mother's plasma oxytocin level following interaction with her infant. The mother's oxytocin response was positively associated with the duration of time her gaze was directed toward her infant, while negatively associated with the frequency with which her gaze shifted away from her infant. Importantly, mothers who showed low/average oxytocin response demonstrated a significant decrease in their infant gaze during periods of infant distress, while such change was not observed in mothers with high oxytocin response. The findings underscore the involvement of oxytocin in regulating the mother's responsive engagement with her infant, particularly in times when the infant's need for access to the mother is greatest. This article is part of a Special Issue entitled Oxytocin and Social Behav. © 2014 Elsevier B.V. All rights reserved.
Camell C.,Baylor College of Medicine |
Smith C.W.,Baylor College of Medicine |
Smith C.W.,Childrens Nutrition Research Center
PLoS ONE | Year: 2013
Several studies have implicated fatty-acids as inflammatory regulators, suggesting that there may be a direct role for common dietary fatty-acids in regulating innate immune cells. In humans, a single high-fat meal increases systemic cytokines and leukocytes. In mice, short term high-fat feeding increases adipose tissue (AT) leukocytes and alters the inflammatory profile of AT macrophages. We have seen that short term high fat feeding to C57BL/6J male mice increases palmitic and oleic acid within AT depots, but oleic acid increase is highest in the mesenteric AT (MAT). In vitro, oleic acid increases M2 macrophage markers (CD206, MGL1, and ARG1) in a murine macrophage cell line, while addition of palmitic acid is able to inhibit that increase. Three day supplementation of a chow diet, with oleic acid, induced an increase in M2 macrophage markers in the MAT, but not in the epididymal AT. We tested whether increases in M2 macrophages occur during short term ad lib feeding of a high fat diet, containing oleic acid. Experiments revealed two distinct populations of macrophages were altered by a three day high milk-fat diet. One population, phenotypically intermediate for F4/80, showed diet-induced increases in CD206, an anti-inflammatory marker characteristic of M2 macrophages intrinsic to the AT. Evidence for a second population, phenotypically F4/80HICD11bHI macrophages, showed increased association with the MAT following short term feeding that is dependent on the adhesion molecule, ICAM-1. Collectively, we have shown that short term feeding of a high-fat diet changes two population of macrophages, and that dietary oleic acid is responsible for increases in M2 macrophage polarization. © 2013 Camell, Smith.
Iacobas I.,Baylor College of Medicine |
Iacobas I.,Center for Cell and Gene Therapy |
Vats A.,Baylor College of Medicine |
Vats A.,Center for Cell and Gene Therapy |
And 4 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2010
Cardiovascular disease is the number one cause of death and disability in the US. Understanding the biological activity of stem and progenitor cells, and their ability to contribute to the repair, regeneration and remodeling of the heart and blood vessels affected by pathological processes is an essential part of the paradigm in enabling us to achieve a reduction in related deaths. Both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are promising sources of cells for clinical cardiovascular therapies. Additional in vitro studies are needed, however, to understand their relative phenotypes and molecular regulation toward cardiovascular cell fates. Further studies in translational animal models are also needed to gain insights into the potential and function of both human ES-and iPS-derived cardiovascular cells, and enable translation from experimental and preclinical studies to human trials. © 2010 American Heart Association, Inc.
Albarran-Zeckler R.G.,Scripps Research Institute |
Albarran-Zeckler R.G.,Baylor College of Medicine |
Sun Y.,Baylor College of Medicine |
Sun Y.,Childrens Nutrition Research Center |
And 2 more authors.
Peptides | Year: 2011
Ghrelin is a hormone made in the stomach and known primarily for its growth hormone releasing and orexigenic properties. Nevertheless, ghrelin through its receptor, the GHS-R1a, has been shown to exert many roles including regulation of glucose homeostasis, memory & learning, food addiction and neuroprotection. Furthermore, ghrelin could promote overall health and longevity by acting directly in the immune system and promoting an extended antigen repertoire. The development of mice lacking either ghrelin (ghrelin-/-) or its receptor (ghsr-/-) have provided a valuable tool for determining the relevance of ghrelin and its receptor in these multiple and diverse roles. In this review, we summarize the most important findings and lessons learned from the ghrelin-/- and ghsr-/- mice. © 2011 Elsevier Inc. All rights reserved.
Shulman R.J.,Childrens Nutrition Research Center |
Ou C.-N.,Baylor College of Medicine |
Smith E.O.,Childrens Nutrition Research Center
Neonatology | Year: 2011
Background: The clinical measures of gastric residuals and abdominal distention are often used to guide feeding in preterm infants, but there are few data demonstrating their usefulness. Similarly, techniques are now available to investigate gastrointestinal (GI) function noninvasively and safely, but their ability to predict attainment of full gavage feedings and/or feeding volume in preterm infants is unclear. Objective: We sought to determine prospectively the potential relationships of attainment of full gavage feedings and feeding volume with clinical measures and noninvasive GI tests. Methods: Fifty preterm infants were followed prospectively. Daily tally was taken of gavage feeding intake, gastric residual volumes (GRVs; milliliters per day, number of GRVs >50% of the previous feeding volume, and number of GRVs >2 ml/kg), and abdominal distention. Infants underwent repeated measurement of lactase activity, GI permeability, fecal calprotectin concentration, and gastric emptying. Results: The number of GRVs >2 ml/kg tended to decrease with postnatal age (p = 0.06). Lactase activity and feeding volume in milliliters per kilogram per day prior to achieving full feedings were correlated (p = 0.007, β = 0.164). There was no correlation between feeding outcomes and GRV (ml/day), GRV >50%, GRV >2 ml/kg, small bowel, colonic, or whole bowel permeability, fecal calprotectin concentration, gastric emptying, or abdominal distention. Conclusions: GRV is unreliable in predicting attainment of full gavage feeding. Lactase activity is related to feeding volume. However, other noninvasive GI tests utilized were not predictive. These data cast doubt upon the utility of GRV in guiding feeding therapy. Randomized trials of different GRV management protocols are needed. Copyright © 2010 S. Karger AG, Basel.