An experimental method to identify neurogenic and myogenic active mechanical states of intestinal motility

Excitatory and inhibitory enteric neural input to intestinal muscle acting on ongoing myogenic activity determines the rich repertoire of motor patterns involved in digestive function. The enteric neural activity cannot yet be established during movement of intact intestine in vivo or in vitro. We propose the hypothesis that is possible to deduce indirectly, but reliably, the state of activation of the enteric neural input to the muscle from measurements of the mechanical state of the intestinal muscle. The fundamental biomechanical model on which our hypothesis is based is the “three-element model” proposed by Hill. Our strategy is based on simultaneous video recording of changes in diameters and intraluminal pressure with a fiber-optic manometry in isolated segments of rabbit colon. We created a composite spatiotemporal map (DPMap) from diameter (DMap) and pressure changes (PMaps). In this composite map rhythmic myogenic motor patterns can readily be distinguished from the distension induced neural peristaltic contractions. Plotting the diameter changes against corresponding pressure changes at each location of the segment, generates “orbits” that represent the state of the muscle according to its ability to contract or relax actively or undergoing passive changes. With a software developed in MatLab, we identified twelve possible discrete mechanical states and plotted them showing where the intestine actively contracted and relaxed isometrically, auxotonically or isotonically, as well as where passive changes occurred or was quiescent. Clustering all discrete active contractions and relaxations states generated for the first time a spatio-temporal map of where enteric excitatory and inhibitory neural input to the muscle occurs during physiological movements. Recording internal diameter by an impedance probe proved equivalent to measuring external diameter, making possible to further develop similar strategy in vivo and humans.Australian National Health and Medical Research Counci

Effect of wall compliance on peristaltic transport of a Newtonian fluid in an asymmetric channel

Peristaltic transport of an incompressible viscous fluid in an asymmetric compliant channel is studied. The channel asymmetry is produced by choosing the peristaltic wave train on the walls to have different amplitudes and phases. The fluid-solid interaction problem is investigated by considering equations of motion of both the fluid and the deformable boundaries. The driving mechanism of the muscle is represented by assuming the channel walls to be compliant. The phenomenon of the “mean flow reversal” is discussed. The effect of wave amplitude ratio, width of the channel, phase difference, wall elastance, wall tension, and wall damping on mean-velocity and reversal flow has been investigated. The results reveal that the reversal flow occurs near the boundaries which is not possible in the elastic symmetric channel case

Magnetic resonance imaging biomarkers of gastrointestinal motor function and fluid distribution

Magnetic resonance imaging (MRI) is a well established technique that has revolutionized diagnostic radiology. Until recently, the impact that MRI has had in the assessment of gastrointestinal motor function and bowel fluid distribution in health and in disease has been more limited, despite the novel insights that MRI can provide along the entire gastrointestinal tract. MRI biomarkers include intestinal motility indices, small bowel water content and whole gut transit time. The present review discusses new developments and applications of MRI in the upper gastrointestinal tract, the small bowel and the colon reported in the literature in the last 5 years

Abnormal Smooth Muscle Contraction Alters Gut Motility and Propagates Epithelial invasion in the Larval Zebrafish Intestine

Coordinated smooth muscle contraction is critical for force production and proper functioning of numerous organ systems. Activation at the myosin motor domain via phosphorylated myosin light chain (phospho-MLC) remains the primary signal to initiate contraction, but it is now appreciated that there are additional force modulators also present in smooth muscle. One particularly well studied modulatory protein is Caldesmon (CaD), which has been implicated in controlling contractile force in vascular smooth muscle, however little is known of CaD\u27s physiological role in vivo. Studies in vitro have shown that CaD inhibits actomyosin interactions and that this effect is reversed after phosphorylation, allowing for greater force propagation. Since a number of gastrointestinal (GI) tract and vascular disorders are known to be a result of aberrant force production, closely monitoring CaD\u27s functional properties may provide insight into common contractile defects. We took advantage of the transparent nature of the intestine in larval zebrafish to study CaD\u27s effect on smooth muscle contraction in a vertebrate model. We initiated these studies by examining propulsive peristalsis in the larval intestine after knockdown of endogenous smooth muscle CaD protein. We next measured the role of CaD in the absence of phospho-MLC to better understand its function in disease states where myosin activation is perturbed. Using extensive live imaging analysis, we show that disrupting CaD function within intestinal smooth muscle can significantly increase GI motility, with and without phospho-MLC, highlighting CaD\u27s ability to independently modulate contractile force. In addition, previous work on a mutant, meltdown (mlt), in our lab has uncovered a smooth muscle myosin (myh11) mutation leading to increased contractile force and premature CaD phosphorylation. Interestingly, in the mlt mutant intestinal epithelial invasion was observed pointing to the unique role for force propagation in initiating cell invasion. We show that CaD is necessary for mlt epithelial invasion to occur, as knockdown of CaD causes the invasive phenotype in heterozygous mlt, which otherwise appear wild type. To gain a better understanding of the crosstalk between muscle contraction and epithelial invasion, we performed a genetic screen for modifier mutants of the mlt phenotype. From the screen, we discovered two enhancer mutants of mlt that contained missense mutations in unique protein domains of MYH11 that alter the contractile function of smooth muscle. These mutations (S237Y and L1287M) occur in both the motor domain and helical tail domain of the protein, suggesting that alterations in distinct regions of myosin can result in abnormal contraction and potentially lead to invasion in underlying cells. Since a number of myosin mutations have been implicated in vascular disease and colon cancer, these studies provide insight into the diversity and mechanistic consequences of mutated myosin in altering smooth muscle contraction and epithelial cell invasion

Advances and Current Challenges in Intestinal in vitro Model Engineering: A Digest

The physiological environment of the intestine is characterized by its variegated composition, numerous functions and unique dynamic conditions, making it challenging to recreate the organ in vitro. This review outlines the requirements for engineering physiologically relevant intestinal in vitro models, mainly focusing on the importance of the mechano-structural cues that are often neglected in classic cell culture systems. More precisely: the topography, motility and flow present in the intestinal epithelium. After defining quantitative descriptors for these features, we describe the current state of the art, citing relevant approaches used to address one (or more) of the elements in question, pursuing a progressive conceptual construction of an "ideal" biomimetic intestinal model. The review concludes with a critical assessment of the currently available methods to summarize the important features of the intestinal tissue in the light of their different applications

Ultrasound imaging for assessing functions of the GI tract

Objective: In the following review we outline how ultrasound can be used to measure physiological processes in the gastrointestinal tract. Approach: We have investigated the potential of ultrasound in assessing gastrointestinal physiology including original research regarding both basic methodology and clinical applications. Main results: Our main findings show the use of ultrasound to study esophageal motility, measure volume and contractility of the stomach, assess motility, wall thickness, and perfusion of the small bowel, and evaluate wall vascularization and diameters of the large bowel. Significance: Ultrasound is a widely accessible technology that can be used for both scientific and clinical purposes. Being radiation-free and user friendly, the examination can be frequently repeated enabling longitudinal studies. Furthermore, it does not influence normal GI physiology, thus being useful to estimate motility and subtle changes in physiology. Accordingly, ultrasound scanning and physiological measurements may make a big difference for the scientist and the doctor; and for the patients who receive an efficient work-up.publishedVersio

The role of visceral manipulation in rehabilitation

Στόχος: η οσφυαλγία, ο αυχενικός πόνος, η δυσμηνόρροια, η χρόνια δυσκοιλιότητα, το σύνδρομο ευερέθιστου εντέρου είναι καταστάσεις που μπορεί να εκδηλωθούν χωρίς συγκεκριμένη παθολογική αιτιολογία με σοβαρά και χρόνια συμπτώματα και αφορούν πολλούς ανθρώπους επιφέροντας μεγάλο οικονομικό βάρος στα συστήματα υγειονομικής περίθαλψης. Η αντιμετώπιση αυτών των καταστάσεων από τη σύγχρονη ιατρική και τους κλάδους αποκατάστασης αποτελεί πρόκληση λόγω των διαφορετικών και σύνθετων αιτιών αυτών των συνθηκών. Η σπλαγχνική κινητοποίηση (ΣΚ) είναι μια ρουτίνα ειδικών και ευγενών κινήσεων που εφαρμόζονται στους ιστούς των κοιλιακών, θωρακικών και πυελικών περιοχών που βρίσκονται τα όργανα, με πολλά υποσχόμενα αποτελέσματα σε διάφορες ιατρικές καταστάσεις. Σκοπός της παρούσας μελέτης είναι η διερεύνηση του γενικού ρόλου της ΣΚ, με ποιά είδη παθολογικών καταστάσεων σχετίζεται και η αποτελεσματικότητά της σε αυτές. Αποτελέσματα: Υπάρχουν πολλές έρευνες σχετικά με το ρόλο και την αποτελεσματικότητα της ΣΚ σε διάφορες ιατρικές καταστάσεις. Σημαντικά θετικά αποτελέσματα αναφέρονται σε ασθενείς με οσφυαλγία μετά από σπλαχνική δια χειρός θεραπεία. Επιπλέον, υπάρχουν ισχυρές ενδείξεις ότι η εφαρμογή σπλαχνικής θεραπείας βελτιώνει τα συμπτώματα σε ασθενείς με γαστρεντερολογικά συμπτώματα, ιδιαίτερα ασθενείς με σύνδρομο ευερέθιστου εντέρου και δυσκοιλιότητα. Πολύ σημαντική πτυχή της ΣΚ που αποδεικνύεται πειραματικά είναι η αποτελεσματικότητα της στην λύση περιτοναϊκών συμφύσεων και η πρόληψη του μετεγχειρητικού ειλεού. Ωστόσο, τα σημερινά στοιχεία περιορίζονται από τον μικρό αριθμό ελεγχόμενων κλινικών δοκιμών που έχουν διεξαχθεί σε αυτόν τον τομέα και για συγκεκριμένες ασθένειες υπάρχουν μόνο αναφορές περιστατικών. Έτσι, προτείνεται περισσότερη επιστημονική έρευνα σχετικά με τους μηχανισμούς και την αποτελεσματικότητα του σπλαχνικού χειρισμού στην αποκατάσταση. Πηγές δεδομένων: η βιβλιογραφική ανασκόπηση έγινε μετά από αναζήτηση ιατρικών και οστεοπαθητικών βάσεων δεδομένων (PubMed, Osteopathic Research Digital Repository, Physiotherapy Evidence Database (PEDro)Objective: Low back pain, cervical pain, dysmenorrhea, chronic constipation, irritable bowel syndrome are conditions that can manifest with no specific pathological etiology with severe and chronic symptoms, concerning a lot of people with major financial burden to the healthcare systems. Treatment of these conditions by modern medicine and rehabilitation disciplines is challenging due to different and complex causes of this kind of conditions. Visceral manipulation (VM) is a routine of specific and gentle movements applied to the tissues of abdominal, thoracic and pelvic regions that organs are lying in, with promising results on several medical conditions. The aim of this study is to explore the general role of VM, with which kind of medical conditions or pathologies is associated with and the effectiveness on them. Results: There are a lot of researches about the role and the effectiveness of VM on several conditions. Significant positive effects are reported in patients with low back pain after visceral manual therapy. Additionally, there is strong evidence that application of visceral treatment ameliorates symptoms in patient with gastroenterological symptoms especially, patients with irritable bowel syndrome and constipation. Very important aspect of VM proven experimentally is it’s efficacy on lysing peritoneal adhesions and prevention of postoperative ileus. However, the current evidence is limited by the small number of controlled clinical trials that have been conducted in this field and for particular diseases there are only case reports. Thus, it is suggested more scientific investigation on the mechanisms and the efficacy of visceral manipulation on rehabilitation. Data sources: A literature review will be undertaken by searching medical and osteopathic databases (PubMed, Osteopathic Research Digital Repository, Physiotherapy Evidence Database (PEDro)

A retrospective analysis to identify characteristics associated with bone fractures observed in patients who undergo the Foker process

Thesis (M.A.)--Boston UniversityIntroduction: Esophageal atresia (EA), a rare anomaly characterized by a gap within the esophageal tract, causes serious complications in newborn infants. Surgery is the only treatment available to cure EA. This study focuses on Long Gap Esophageal Atresia (LGEA) reconstructive surgery using the Foker process for in vivo growth induction of the esophagus. This process incorporates multiple surgeries that take place over a period of weeks to months. Patients undergoing LGEA surgery may be at greater risk for bone fracture, due to poor nutritional status, administration of certain medications and prolonged periods of immobility. Other risk factors contributing to bone fragility include low birth weight and other congenital anomalies. This study uses a retrospective analysis to determine which variables may contribute to fractures in patients who have undergone the Foker procedure. Objectives: Clinical characteristics (age, gestational age, associated congenital anomalies, total Foker surgical procedures, Foker process duration and total days of administered paralytics) associated with fractures in patients who underwent the Foker procedure were determined. [TRUNCATED