Neurally mediated propagating discrete clustered contractions superimposed on myogenic ripples in ex vivo segments of human ileum

2015 ◽  
Vol 308 (1) ◽  
pp. G1-G11 ◽  
Author(s):  
Merel H. Kuizenga ◽  
Tiong C. Sia ◽  
Kelsi N. Dodds ◽  
Lukasz Wiklendt ◽  
John W. Arkwright ◽  
...  

Narrow muscle strips have been extensively used to study intestinal contractility. Larger specimens from laboratory animals have provided detailed understanding of mechanisms that underlie patterned intestinal motility. Despite progress in animal tissue, investigations of motor patterns in large, intact specimens of human gut ex vivo have been sparse. In this study, we tested whether neurally dependent motor patterns could be detected in isolated specimens of intact human ileum. Specimens ( n = 14; 7–30 cm long) of terminal ileum were obtained with prior informed consent from patients undergoing colonic surgery for removal of carcinomas. Preparations were set up in an organ bath with an array of force transducers, a fiberoptic manometry catheter, and a video camera. Spontaneous and distension-evoked motor activity was recorded, and the effects of lidocaine, which inhibits neural activity, were studied. Myogenic contractions (ripples) occurred in all preparations (6.17 ± 0.36/min). They were of low amplitude and formed complex patterns by colliding and propagating in both directions along the specimen at anterograde velocities of 4.1 ± 0.3 mm/s and retrogradely at 4.9 ± 0.6 mm/s. In five specimens, larger amplitude clusters of contractions were seen (discrete clustered contractions), which propagated aborally at 1.05 ± 0.13 mm/s and orally at 1.07 ± 0.09 mm/s. These consisted of two to eight phasic contractions that aligned with ripples. These motor patterns were abolished by addition of lidocaine (0.3 mM). The ripples continued unchanged in the presence of this neural blocking agent. These results demonstrate that both myogenic and neurogenic motor patterns can be studied in isolated specimens of human small intestine.

2021 ◽  
Vol 22 (21) ◽  
pp. 11615
Author(s):  
Geoffrey Van den Bergh ◽  
Sofie De Moudt ◽  
Astrid Van den Branden ◽  
Ellen Neven ◽  
Hanne Leysen ◽  
...  

Arterial media calcification (AMC) is predominantly regulated by vascular smooth muscle cells (VSMCs), which transdifferentiate into pro-calcifying cells. In contrast, there is little evidence for endothelial cells playing a role in the disease. The current study investigates cellular functioning and molecular pathways underlying AMC, respectively by, an ex vivo isometric organ bath set-up to explore the interaction between VSMCs and ECs and quantitative proteomics followed by functional pathway interpretation. AMC development, which was induced in mice by dietary warfarin administration, was proved by positive Von Kossa staining and a significantly increased calcium content in the aorta compared to that of control mice. The ex vivo organ bath set-up showed calcified aortic segments to be significantly more sensitive to phenylephrine induced contraction, compared to control segments. This, together with the fact that calcified segments as compared to control segments, showed a significantly smaller contraction in the absence of extracellular calcium, argues for a reduced basal NO production in the calcified segments. Moreover, proteomic data revealed a reduced eNOS activation to be part of the vascular calcification process. In summary, this study identifies a poor endothelial function, next to classic pro-calcifying stimuli, as a possible initiator of arterial calcification.


2020 ◽  
pp. bjophthalmol-2020-317214
Author(s):  
Hasan Naveed ◽  
Fong May Chew ◽  
Hanbin Lee ◽  
Edward Hughes ◽  
Mayank A Nanavaty

PurposeTo assess whether pars plana vitrectomy (PPV) is an aerosol-generating procedure (AGP) in an ex vivo experimental model.MethodsIn this ex vivo study on 10 porcine eyes, optical particle counter was used to measure particles ≤10 μm using cumulative mode in the six in-built channels: 0.3 μm, 0.5 μm, 1 μm, 2.5 μm, 5 μm and 10 μm aerosols during PPV. Two parts of the study were as follows: (1) to assess the pre-experimental baseline aerosol count in the theatre environment where there are dynamic changes in temperature and humidity and (2) to measure aerosol generation with 23-gauge and 25-gauge set-up. For each porcine eye, five measurements were taken for each consecutive step in the experiment including pre-PPV, during PPV, fluid–air exchange (FAX) and venting using a flute with 23-gauge set-up and a chimney with 25-gauge set-up. Therefore, a total of 200 measurements were recorded.ResultsWith 23-gauge and 25-gauge PPV, there was no significant difference in aerosol generation in all six channels comparing pre-PPV versus PPV or pre-PPV versus FAX. Venting using flute with 23-gauge PPV showed significant reduction of aerosol ≤1 μm. Air venting using chimney with 25-gauge set-up showed no significant difference in aerosol of ≤1 μm. For cumulative aerosol counts of all particles measuring ≤5 μm, compared with pre-PPV, PPV or FAX, flute venting in 23-gauge set-up showed significant reduction unlike the same comparison for chimney venting in 25-gauge set-up.ConclusionPPV and its associate steps do not generate aerosols ≤10 μm with 23-gauge and 25-gauge set-ups.


Author(s):  
Beata Modzelewska ◽  
Marcin Jóźwik ◽  
Tomasz Kleszczewski ◽  
Stanisław Sulkowski ◽  
Maciej Jóźwik

Objective: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. Design: This was a controlled and prospective ex vivo study. Setting: The work was conducted as a collaboration between 4 academic departments. Materials and Methods: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. Results: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). Limitations: These results require now to be placed into a firm clinical context. Conclusions: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.


Author(s):  
Lina Y Alkaissi ◽  
Martin E Winberg ◽  
Stéphanie DS Heil ◽  
Staffan Haapaniemi ◽  
Pär Myrelid ◽  
...  

Abstract Background The first visible signs of Crohn’s disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human α-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P &lt; 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P &lt; 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P &lt; 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
D. Kuetting ◽  
J. Luetkens ◽  
A. Faron ◽  
A. Isaak ◽  
U. Attenberger ◽  
...  

AbstractOur aim was to investigate the diagnostic yield of rapid T1-mapping for the differentiation of malignant and non-malignant effusions in an ex-vivo set up. T1-mapping was performed with a fast modified Look-Locker inversion-recovery (MOLLI) acquisition and a combined turbo spin-echo and inversion-recovery sequence (TMIX) as reference. A total of 13 titrated albumin-solutions as well as 48 samples (29 ascites/pleural effusions from patients with malignancy; 19 from patients without malignancy) were examined. Samples were classified as malignant-positive histology, malignant-negative histology and non-malignant negative histology. In phantom analysis both mapping techniques correlated with albumin-content (MOLLI: r = − 0.97, TMIX: r = − 0.98). MOLLI T1 relaxation times were shorter in malignancy-positive histology fluids (2237 ± 137 ms) than in malignancy-negative histology fluids (2423 ± 357 ms) as well as than in non-malignant-negative histology fluids (2651 ± 139 ms); post hoc test for all intergroup comparisons: < 0.05. ROC analysis for differentiation between malignant and non-malignant effusions (malignant positive histology vs. all other) showed an (AUC) of 0.89 (95% CI 0.77–0.96). T1 mapping allows for non-invasive differentiation of malignant and non-malignant effusions in an ex-vivo set up.


Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 92 ◽  
Author(s):  
Alexis Matute ◽  
Jessica Tabart ◽  
Jean-Paul Cheramy-Bien ◽  
Bernard Pirotte ◽  
Claire Kevers ◽  
...  

The real impact of polyphenol-rich vegetable and fruit juice intake on cardiovascular health remains a matter of controversy. In the present study, rat aorta segments immersed in an organ bath (OB) were used to explore whether the total polyphenol content and/or individual phenolic compound contents of 22 commercial vegetable (n = 3) and fruit juices [(citrus (n = 5), berries (n = 10), apple (n = 2), pineapple (n = 2)] might be associated with vascular tone. Red juices (particularly blackcurrant) and lemon juice caused the most marked vasorelaxation, its amplitude being endothelium dependent or not according to the volume ratio of juice to initial OB solution Vjuice/VOBS). At volume ratios 5% and 10%, both the juice and OB total polyphenol for all juices and total anthocyanin contents for berry juices significantly correlated with aorta vasorelaxation intensity. This was not the case for total or individual flavonols (except kaempferol) or for total or individual flavanols (except epigallocatechin gallate). If one relates our measured concentrations of individual phenolic compounds in OB to what is known about their physiological concentrations, and given our evidenced correlations between compound concentrations and vasorelaxation intensity, kaempferol, epigallocatechin gallate and peonidin-3-O-glucoside seem to emerge as the interesting phenolic compounds likely to be responsible for the potent vasorelaxation observed with fruit juices, and more particularly blackcurrant ones. Clinical investigation is required, however, to confirm our observations.


2012 ◽  
Vol 107 (10) ◽  
pp. 2742-2755 ◽  
Author(s):  
Max Eickenscheidt ◽  
Martin Jenkner ◽  
Roland Thewes ◽  
Peter Fromherz ◽  
Günther Zeck

Electrical stimulation of retinal neurons offers the possibility of partial restoration of visual function. Challenges in neuroprosthetic applications are the long-term stability of the metal-based devices and the physiological activation of retinal circuitry. In this study, we demonstrate electrical stimulation of different classes of retinal neurons with a multicapacitor array. The array—insulated by an inert oxide—allows for safe stimulation with monophasic anodal or cathodal current pulses of low amplitude. Ex vivo rabbit retinas were interfaced in either epiretinal or subretinal configuration to the multicapacitor array. The evoked activity was recorded from ganglion cells that respond to light increments by an extracellular tungsten electrode. First, a monophasic epiretinal cathodal or a subretinal anodal current pulse evokes a complex burst of action potentials in ganglion cells. The first action potential occurs within 1 ms and is attributed to direct stimulation. Within the next milliseconds additional spikes are evoked through bipolar cell or photoreceptor depolarization, as confirmed by pharmacological blockers. Second, monophasic epiretinal anodal or subretinal cathodal currents elicit spikes in ganglion cells by hyperpolarization of photoreceptor terminals. These stimuli mimic the photoreceptor response to light increments. Third, the stimulation symmetry between current polarities (anodal/cathodal) and retina-array configuration (epi/sub) is confirmed in an experiment in which stimuli presented at different positions reveal the center-surround organization of the ganglion cell. A simple biophysical model that relies on voltage changes of cell terminals in the transretinal electric field above the stimulation capacitor explains our results. This study provides a comprehensive guide for efficient stimulation of different retinal neuronal classes with low-amplitude capacitive currents.


2007 ◽  
Vol 329 ◽  
pp. 761-766 ◽  
Author(s):  
Y. Zhang ◽  
Masato Yoshioka ◽  
Shin-Ichiro Hira

At present, a commercially available magnetic barrel machine equipped with permanent magnets has some faults arising from constructional reason. That is, grinding or finishing ability is different from place to place in the machining region, resulting in the limitation on the region we can use in the container of workpieces. Therefore, in this research, authors made the new magnetic barrel machine equipped with three dimensional (3D) magnet arrangement to overcome these faults. The grinding ability of the new 3D magnetic barrel machine converted was experimentally examined, and compared with that of the traditional magnetic barrel machine. As a result, it was shown that we can use much broader region in the new 3D machine. It was also shown that the grinding ability became higher. The distribution of barrel media in action was recorded by means of a high speed video camera. It was clarified that the media rose up higher and were distributed more uniformly in the container by the effect of the magnet block newly set up. It was supposed that this must be the reason for the above-mentioned improvement of grinding ability.


1992 ◽  
Vol 160 (S15) ◽  
pp. 56-60 ◽  
Author(s):  
C. Labrid ◽  
E. Mocaër ◽  
A. Kamoun

Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and with biochemical and animal-behavioural properties which are strikingly different from those of classical tricyclics. Unlike the latter, which decrease serotonin (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.g. fluoxetine) have opposite effects. On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other tricyclics prolong it, and it enhances attention, learning, and memory in laboratory animals, while classical tricyclics have opposite effects. However, the relationships between these effects of tianeptine in animal experiments and their relevance to clinical findings remain to be determined.


2015 ◽  
Vol 118 (9) ◽  
pp. 1113-1121 ◽  
Author(s):  
Yet Hoi Hong ◽  
Tony Frugier ◽  
Xinmei Zhang ◽  
Robyn M. Murphy ◽  
Gordon S. Lynch ◽  
...  

Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSμ−/−and nNOSμ+/+mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor NG-monomethyl-l-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSμ−/−and nNOSμ+/+mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (∼4%) were detected in muscles from nNOSμ−/−mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSμ.


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