Browsing by Subject "Motility"

Now showing 1 - 7 of 7
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    American Neurogastroenterology and Motility Society (ANMS) Task Force Recommendations for Resumption of Motility Laboratory Operations During the COVID-19 Pandemic
    (American Neurogastro­enterology and Motility Society (ANMS), 2020-05-17) Baker, Jason R.; Moshiree, Baha; Rao, Satish; Neshatian, Leila; Nguyen, Linda; Chey, William D.; Saad, Richard; Garza, Jose; Waseem, Shamaila; Khan, Abraham R.; Pandolfino, John E.; Gyawali, C. Prakash; Department of Pediatrics, IU School of Medicine
    The ANMS organized a Task Force for developing guidance strategies regarding re-opening of motility laboratories. This document describes how to stratify urgency of motility physiologic procedures, screen prior to the procedures, optimize personal protective equipment (PPE) utilization, clean and prepare the motility laboratory space during the COVID-19 pandemic.
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    CRMP2 Is Involved in Regulation of Mitochondrial Morphology and Motility in Neurons
    (MDPI, 2021-10-17) Brustovetsky, Tatiana; Khanna, Rajesh; Brustovetsky, Nickolay; Pharmacology and Toxicology, School of Medicine
    Regulation of mitochondrial morphology and motility is critical for neurons, but the exact mechanisms are unclear. Here, we demonstrate that these mechanisms may involve collapsin response mediator protein 2 (CRMP2). CRMP2 is attached to neuronal mitochondria and binds to dynamin-related protein 1 (Drp1), Miro 2, and Kinesin 1 light chain (KLC1). Treating neurons with okadaic acid (OA), an inhibitor of phosphatases PP1 and PP2A, resulted in increased CRMP2 phosphorylation at Thr509/514, Ser522, and Thr555, and augmented Drp1 phosphorylation at Ser616. The CRMP2-binding small molecule (S)-lacosamide ((S)-LCM) prevented an OA-induced increase in CRMP2 phosphorylation at Thr509/514 and Ser522 but not at Thr555, and also failed to alleviate Drp1 phosphorylation. The increased CRMP2 phosphorylation correlated with decreased CRMP2 binding to Drp1, Miro 2, and KLC1. (S)-LCM rescued CRMP2 binding to Drp1 and Miro 2 but not to KLC1. In parallel with CRMP2 hyperphosphorylation, OA increased mitochondrial fission and suppressed mitochondrial traffic. (S)-LCM prevented OA-induced alterations in mitochondrial morphology and motility. Deletion of CRMP2 with a small interfering RNA (siRNA) resulted in increased mitochondrial fission and diminished mitochondrial traffic. Overall, our data suggest that the CRMP2 expression level and phosphorylation state are involved in regulating mitochondrial morphology and motility in neurons.
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    Distension-Induced Gastric Contraction is Attenuated in an Experimental Model of Gastric Restraint
    (Springer Verlag, 2010-08-13) Lu, Xiao; Guo, Xiaomei; Mattar, Samer G.; Navia, Jose A.; Kassab, Ghassan S.; Biomedical Engineering, School of Engineering and Technology
    Background Gastric distension has important implications for motility and satiety. The hypothesis of this study was that distension affects the amplitude and duration of gastric contraction and that these parameters are largely mediated by efferent vagus stimulation. Methods A novel isovolumic myograph was introduced to test these hypotheses. The isovolumic myograph isolates the stomach and records the pressure generated by the gastric contraction under isovolumic conditions. Accordingly, the phasic changes of gastric contractility can be documented. A group of 12 rats were used under in vivo conditions and isolated ex vivo conditions and with two different gastric restraints (small and large) to determine the effect of degree of restraint. Results The comparison of the in vivo and ex vivo contractility provided information on the efferent vagus mediation of gastric contraction, i.e., the in vivo amplitude and duration reached maximum of 12.6±2.7 mmHg and 19.8±5.6 s in contrast to maximum of 5.7±0.9 mmHg and 7.3±1.3 s in ex vivo amplitude and duration, respectively. The comparison of gastric restraint and control groups highlights the role of distension on in vivo gastric contractility. The limitation of gastric distension by restraint drastically reduced the maximal amplitude to below 2.9±0.2 mmHg. Conclusions The results show that distension-induced gastric contractility is regulated by both central nervous system and local mechanisms with the former being more substantial. Furthermore, the gastric restraint significantly attenuates gastric contractility (decreased amplitude and shortened duration of contraction) which is mediated by the efferent vagus activation. These findings have important implications for gastric motility and physiology and may improve our understanding of satiety.
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    IMPAIRED FUNCTION OF FANCONI ANEMIA TYPE C DEFICIENT MACROPHAGES
    (2012-03-16) Liu, Ying; Haneline, Laura S.; Dent, Alexander L.; He, Johnny J.; Srour, Edward F.; Yoder, Mervin C.
    Fanconi anemia (FA) is a genetic disorder characterized by bone marrow (BM) failure. Previous studies suggest that FA patients exhibit alterations in immunologic function. However, it is unclear whether the immune defects are immune cell autonomous or secondary to leucopenia from evolving BM failure. The aim of the current study was to determine whether FA type C deficient (Fancc-/-) macrophages exhibit impaired function and contribute to an altered inflammatory response. In this study, primary peritoneal macrophage function and the inflammatory response of Fancc-/- immune cells after in vivo intraperitoneal (IP) administration of lipopolysaccharide (LPS) were assessed. Fancc-/- peritoneum exhibit normal macrophage distribution at baseline. However, Fancc-/- macrophages exhibit reduced adhesion both on fibronectin and endothelial cells, impaired migration toward monocyte chemotactic protein-1 (MCP-1) and macrophages-colony stimulating factor (M-CSF), and altered phagocytosis of E.coli and ImmunoglobulinG (IgG)-labeled latex beads compared to WT. An altered F-actin reorganization and impaired activation of RhoA were observed in Fancc-/- macrophages. After single LPS injection IP, Fancc-/- mice exhibited decreased macrophage recruitment, reduced peripheral inflammatory monocytes and impaired myeloid colony formation in presence of M-CSF. Upon M-CSF stimulation, Fancc-/- BM derived macrophages (BMDM) showed a decreased phosphorylation of AKT and ERK compared to WT, leading to reduced proliferation. Collectively, these data suggest that Fancc-/- macrophages and subsequent defects in adhesion, migration, phagocytosis, and recruitment in vivo. These data also support a Fancc-/- macrophage cells autonomous defect predisposing to an altered inflammatory response.
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    Involvement of CRMP2 in Regulation of Mitochondrial Morphology and Motility in Huntington’s Disease
    (MDPI, 2021-11-15) Brustovetsky, Tatiana; Khanna, Rajesh; Brustovetsky, Nickolay; Pharmacology and Toxicology, School of Medicine
    Mitochondrial morphology and motility (mitochondrial dynamics) play a major role in the proper functioning of distant synapses. In Huntington's disease (HD), mitochondria become fragmented and less motile, but the mechanisms leading to these changes are not clear. Here, we found that collapsin response mediator protein 2 (CRMP2) interacted with Drp1 and Miro 2, proteins involved in regulating mitochondrial dynamics. CRMP2 interaction with these proteins inversely correlated with CRMP2 phosphorylation. CRMP2 was hyperphosphorylated in postmortem brain tissues of HD patients, in human neurons derived from induced pluripotent stem cells from HD patients, and in cultured striatal neurons from HD mouse model YAC128. At the same time, CRMP2 interaction with Drp1 and Miro 2 was diminished in HD neurons. The CRMP2 hyperphosphorylation and dissociation from Drp1 and Miro 2 correlated with increased fission and suppressed motility. (S)-lacosamide ((S)-LCM), a small molecule that binds to CRMP2, decreased its phosphorylation at Thr 509/514 and Ser 522 and rescued CRMP2's interaction with Drp1 and Miro 2. This was accompanied by reduced mitochondrial fission and enhanced mitochondrial motility. Additionally, (S)-LCM exerted a neuroprotective effect in YAC128 cultured neurons. Thus, our data suggest that CRMP2 may regulate mitochondrial dynamics in a phosphorylation-dependent manner and modulate neuronal survival in HD.
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    Prevalence of small intestinal bacterial overgrowth in patients with gastroparesis: a systematic review and meta-analysis
    (Research Institute for Gastroenterology and Liver Diseases, 2023) Beas, Renato; Riva-Moscoso, Adrian; Montalvan-Sanchez, Eleazar; Príncipe-Meneses, Fortunato S.; Aljaras, Rawan; Ramirez, Mirian; Izquierdo-Veraza, Diego; Calderon, Gerardo; Medicine, School of Medicine
    Aim: We performed a systematic review and meta-analysis to identify the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with gastroparesis. Background: Several studies have suggested an association between SIBO and gastroparesis, which is characterized by delayed gastric emptying in the absence of mechanical obstruction. Methods: A comprehensive search was performed using MEDLINE, EMBASE, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) through January, 2022 for randomized controlled trials and observational studies reporting the prevalence of SIBO in gastroparesis. Pooled prevalence was estimated using a random effects model. Heterogeneity was assessed by using the inconsistency index (I2). Results: Among the 976 articles identified, 43 studies were selected for full text review. Six studies, with 385 patients, were deemed eligible for inclusion, with a perfect agreement between investigators (kappa=1.0). Overall, 379 patients were diagnosed with gastroparesis by gastric emptying scintigraphy and six were diagnosed with a wireless motility capsule. The pooled prevalence of SIBO was 41% (95% confidence interval 0.23-0.58). SIBO was diagnosed using jejunal aspirate cultures (N=15, 8.4%), lactulose breath test (N=80, 44.7%), glucose breath test (N=30, 16.8%), D-xylose breath test (N=52, 29.1%), and hydrogen breath test (N=2, 1.1%). Heterogeneity was significant and noted to be high at 91%. Only one study reported SIBO diagnosis in controls, therefore no pooled odds ratio was calculated. Conclusion: SIBO was present in almost half of the patients with gastroparesis. Future studies should examine and identify the association between SIBO and gastroparesis.
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    Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with idiopathic gastroparesis
    (Biomed Central, 2019-06-20) Herring, B. Paul; Chen, Meng; Mihaylov, Plamen; Hoggatt, April M.; Gupta, Anita; Nakeeb, Attila; Choi, Jennifer N.; Wo, John M.; Cellular and Integrative Physiology, School of Medicine
    BACKGROUND: Gastric emptying is impaired in patients with gastroparesis whereas it is either unchanged or accelerated in obese individuals. The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in idiopathic gastroparesis and obesity. METHODS: Quantitative real time RT-PCR and whole transcriptome sequencing were used to compare the transcriptomes of lean individuals, obese individuals and either lean or obese individuals with idiopathic gastroparesis. RESULTS: Obesity leads to an increase in mRNAs associated with muscle contractility whereas idiopathic gastroparesis leads to a decrease in mRNAs associated with PDGF BB signaling. Both obesity and idiopathic gastroparesis were also associated with similar alterations in pathways associated with inflammation. CONCLUSIONS: Our findings show that obesity and idiopathic gastroparesis result in overlapping but distinct changes in the gastric muscularis transcriptome. Increased expression of mRNAs encoding smooth muscle contractile proteins may be contributing to the increased gastric motility observed in obese subjects, whereas decreased PDGF BB signaling may be contributing to the impaired motility seen in subjects with idiopathic gastroparesis.