Changes In Intraluminal Pressure Research Articles

Predicting the activation states of the muscles governing upper esophageal sphincter relaxation and opening.

The swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation and deactivation of neural inputs to these muscles, including the intrinsic cricopharyngeus (CP) and extrinsic submental (SM) muscles, results in their mechanical activation or deactivation, which changes the diameter of the lumen, alters the intraluminal pressure, and ultimately reduces or promotes flow of content. By measuring the changes in diameter, using intraluminal impedance, and the concurrent changes in intraluminal pressure, it is possible to determine when the muscles are passively or actively relaxing or contracting. From these "mechanical states" of the muscle, the neural inputs driving the specific motor behaviors of the UES can be inferred. In this study we compared predictions of UES mechanical states directly with the activity measured by electromyography (EMG). In eight subjects, pharyngeal pressure and impedance were recorded in parallel with CP- and SM-EMG activity. UES pressure and impedance swallow profiles correlated with the CP-EMG and SM-EMG recordings, respectively. Eight UES muscle states were determined by using the gradient of pressure and impedance with respect to time. Guided by the level and gradient change of EMG activity, mechanical states successfully predicted the activity of the CP muscle and SM muscle independently. Mechanical state predictions revealed patterns consistent with the known neural inputs activating the different muscles during swallowing. Derivation of "activation state" maps may allow better physiological and pathophysiological interpretations of UES function.

Brief serotonin exposure initiates arteriolar inward remodeling processes in vivo that involve transglutaminase activation and actin cytoskeleton reorganization.

Inward remodeling of the resistance vasculature is strongly associated with life-threatening cardiovascular events. Previous studies have demonstrated that both actin polymerization and the activation of transglutaminases mediate early stages of the transition from a structurally normal vessel to an inwardly remodeled one. Ex vivo studies further suggest that a few hours of exposure to vasoconstrictor agonists induces inward remodeling in the absence of changes in intraluminal pressure. Here we report that a short, 10-min, topical exposure to serotonin (5-HT) + N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME) was sufficient to initiate inward remodeling processes in rat cremasteric feed arterioles (100-200 μm lumen diameter), in vivo. Addition of the transglutaminase inhibitor, cystamine, blocked the in vivo remodeling. We further demonstrate that, in isolated arterioles, 5-HT + l-NAME activates transglutaminases and modulates the phosphorylation state of cofilin, a regulator of actin depolymerization. The 5-HT + l-NAME-induced remodeling process in isolated arterioles was also inhibited by an inhibitor of Lim Kinase, the kinase that phosphorylates and inactivates cofilin. Therefore, our results indicate that a brief vasoconstriction induced by 5-HT + l-NAME is able to reduce the passive structural diameter of arterioles through processes that are dependent on the activation of transglutaminases and Lim kinase, and the subsequent phosphorylation of cofilin.

Implication of nanofibers in oral drug delivery.

Nanofibers has gained significant prominence in recent years due to its wide applications in medicinal pharmacy, textile, tissue engineering and in various drug delivery system. In oral drug delivery system (DDS), nanofibers can be delivered as Nanofiber scaffolds, electrosponge nanofibers as oral fast delivery system, multilayered nanofiber loaded mashes, surface modified cross-linked electrospun nanofibers. Nanofibers are of 50- 1000 nm size fibres having large surface area, high porosity, small pore size, low density. Various approaches for formulation of nanofibers are molecular assembly, thermally induced phase separation, electrospining. Most commonly used by using electrospining polymer nanofibres with different range can be produced collective usage of electro spinning with pharmaceutical polymers offers novel tactics for developing drug delivery system (DDS). Different polymers used in preparation of nanofibers include biodegradable hydrophilic polymers, hydrophobic polymers and amphiphilic polymers. Electrospun nanofibers are often used to load insoluble drugs for enhancing their dissolution properties due to their high surface area per unit mass. Besides the water insoluble drugs freely water soluble sodium can also spun into the fibers. The most commonly polymers used for nanofibers are gelatin, dextran, nylon, polystyrene, polyacrylonitrile, polycarbonate, polyimides, poly vinyl alchol, polybenzimidazole. Delivery systems reviewed rely on temporal control, changes in pH along the GIT, the action of local enzymes to trigger drug release, and changes in intraluminal pressure. Dissolution of enteric polymer coatings due to a change in local pH and reduction of azo-bonds to release an active agent are both used in commercially marketed products. In vitro and in vivo studies have demonstrated that the release rates of drugs from these nanofiber formulations are enhanced compared to those from original drug substance. This review is focused on the different type of polymers used, different used in the preparation of nanofibers, cytotoxicity studies and application of nanofiber by using oral drug delivery.

Involvement of TRPM4 in Stretch‐Induced Modulation of Lymphatic Pumping

Rhythmic and phasic contractions of collecting lymphatic vessels are critically involved in tissue fluid homeostasis and immune response. This contractile activity, or lymphatic pumping, is exquisitely regulated by luminal fluid pressure. However, the molecular contributors of stretch‐induced lymphatic pumping are not known. Some members of the TRP channel family, in particular TRPM4,have been shown to respond to stretch or pressure and to contribute to myogenic vasoconstriction and vascular response to stretch.Using pressure myography, electrophysiology, pharmacology and quantitative real‐time PCR, we tested the hypothesis that TRPM4 is also a major contributor of the lymphatic vessel response to stretch.We demonstrated the expression of TRPM4 mRNA in rat mesenteric lymphatic vessels and showed that the contraction frequency of the vessels pressurized at 3 mmHg was inhibited in a concentration‐dependent manner by the TRPM4 blocker 9‐phenanthrol (IC50=1.2 µM). The blocker (10 µM) also inhibited the pressure‐induce increase in contraction frequency in an endothelium‐independent manner and caused a hyperpolarization of the lymphatic muscle. These findings suggest an important role for TRPM4 in the ability of lymphatic vessels to adapt their contractile activity to changes in intraluminal lymph pressure.

Upper esophageal sphincter mechanical states analysis: a novel methodology to describe UES relaxation and opening.

The swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation of neural inputs to these muscles, the intrinsic cricopharyngeus muscle and extrinsic suprahyoid muscles, results in their contraction or relaxation, which changes the diameter of the lumen, alters the intraluminal pressure and ultimately inhibits or promotes flow of content. This relationship that exists between the changes in diameter and concurrent changes in intraluminal pressure has been used previously to calculate the “mechanical states” of the muscle; that is when the muscles are passively or actively, relaxing or contracting. Diseases that alter the neural pathways to these muscles can result in weakening the muscle contractility and/or decreasing the muscle compliance, all of which can cause dysphagia. Detecting these changes in the mechanical state of the muscle is difficult and as the current interpretation of UES motility is based largely upon pressure measurement (manometry), subtle changes in the muscle function during swallow can be missed. We hypothesized that quantification of mechanical states of the UES and the pressure-diameter properties that define them, would allow objective characterization of the mechanisms that govern the timing and extent of UES opening during swallowing. To achieve this we initially analyzed swallows captured by simultaneous videofluoroscopy and UES pressure with impedance recording. From these data we demonstrated that intraluminal impedance measurements could be used to determine changes in the internal diameter of the lumen when compared to videofluoroscopy. Then using a database of pressure-impedance studies, recorded from young and aged healthy controls and patients with motor neuron disease, we calculated the UES mechanical states in relation to a standardized swallowed bolus volume, normal aging and dysphagia pathology. Our results indicated that eight different mechanical states were almost always seen during healthy swallowing and some of these calculated changes in muscle function were consistent with the known neurally dependent phasic discharge patterns of cricopharyngeus muscle activity during swallowing. Clearly defined changes in the mechanical states were observed in motor neuron disease when compared to age matched healthy controls. Our data indicate that mechanical state predictions were simple to apply and revealed patterns consistent with the known neural inputs activating the different muscles during swallowing.

Involvement of cholinergic nicotinic receptors in the menthol-induced gastric relaxation

We have previously demonstrated that menthol reduces murine gastric tone in part through a neural mechanism, involving adrenergic pathways and reduction of ongoing release of acetylcholine from enteric nerves. In the present study we aimed to verify whether the gastric relaxation to menthol may be triggered by interaction with neural receptors or ionic channels proteins, such as transient receptor potential (TRP)-melastatin8 (TRPM8), TRP-ankyrin 1 (TRPA1), 5-hydroxytriptamine 3 (5-HT3) receptor or cholinergic nicotinic receptors. Spontaneous mechanical activity was detected in vitro as changes in intraluminal pressure from isolated mouse stomach. Menthol (0.3−30mM) induced gastric relaxation which was not affected by 5-benzyloxytryptamine, a TRPM8 receptor antagonist, HC030031, a TRPA1 channel blocker. In addition, allylisothiocyanate, a TRPA1 agonist, but not (2S,5R)-2-Isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexanecarboximide, a selective TRPM8 agonist, induced gastric relaxation. Genic expression of TRPA1, but not of TRPM8, was revealed in mouse stomach. Indeed, menthol-induced gastric relaxation was significantly reduced by hexamethonium, cholinergic nicotinic receptor antagonist. Menthol, at concentrations that failed to affect gastric tone, reduced the contraction induced by dimethylphenylpiperazinium, nicotinic receptor agonist. The joint application of hexamethonium and atropine, muscarinc receptor antagonist, or hexamethonium and phentholamine, α-adrenergic receptor antagonist, did not produce any additive reduction of the relaxant response to menthol. Lastly, ondansetron, a 5-HT3 receptor antagonist, was ineffective. In conclusion, our study suggests that nicotinic receptors, but not TRP and 5-HT3 receptors, are molecular targets for menthol inducing murine gastric relaxation, ultimately due to the reduction of acetylcholine release from enteric nerves.

Laryngeal collapse as a primary disease in English Bull Terriers

Laryngeal collapse is a progressive condition characterised by a loss of cartilage rigidity which allows medial deviation of the rostral laryngeal cartilages (Pink and others 2006, Torrez and Hunt 2006,...

Structural remodeling of coronary resistance arteries: effects of age and exercise training.

Age is known to induce remodeling and stiffening of large-conduit arteries; however, little is known of the effects of age on remodeling and mechanical properties of coronary resistance arteries. We employed a rat model of aging to investigate whether 1) age increases wall thickness and stiffness of coronary resistance arteries, and 2) exercise training reverses putative age-induced increases in wall thickness and stiffness of coronary resistance arteries. Young (4 mo) and old (21 mo) Fischer 344 rats remained sedentary or underwent 10 wk of treadmill exercise training. Coronary resistance arteries were isolated for determination of wall-to-lumen ratio, effective elastic modulus, and active and passive responses to changes in intraluminal pressure. Elastin and collagen content of the vascular wall were assessed histologically. Wall-to-lumen ratio increased with age, but this increase was reversed by exercise training. In contrast, age reduced stiffness, and exercise training increased stiffness in coronary resistance arteries from old rats. Myogenic responsiveness was reduced with age and restored by exercise training. Collagen-to-elastin ratio (C/E) of the wall did not change with age and was reduced with exercise training in arteries from old rats. Thus age induces hypertrophic remodeling of the vessel wall and reduces the stiffness and myogenic function of coronary resistance arteries. Exercise training reduces wall-to-lumen ratio, increases wall stiffness, and restores myogenic function in aged coronary resistance arteries. The restorative effect of exercise training on myogenic function of coronary resistance arteries may be due to both changes in vascular smooth muscle phenotype and expression of extracellular matrix proteins.

Sa2046 Effect of RM-131 on Circular Smooth Muscle Cells in Human and Mouse Colon and on Colonic Intraluminal Pressure in Conscious Mice

Background and Aims: RM-131 is a synthetic ghrelin agonist that has been found to significantly accelerate gastric emptying, intestinal transit and colonic filling. The mechanism(s) through which smooth muscle cells of gastrointestinal tract respond to RM-131 is not known. We studied the effect of RM-131 on circular smooth muscle cells of human and mouse colon in vitro and on colonic intraluminal pressure in conscious mice. Methods: SJL/J mice and human colonic tissue were used in this study. Normal human colon was obtained from surgical excess tissue. The use of mice was approved by Mayo Institutional Animal Care and Use Committee and the use of human biopsy specimens was approved by Institutional Review Board. Muscle strips without the mucosa from mouse colon and human colon strips were placed in a recording chamber for intracellular recording. The recording chamber was superfused with oxygenized normal Krebs solution at 37°C. A bipolar stimulating electrode was placed on both sides of the muscle strip for electric field stimulation to elicit inhibitory junction potentials (IJPs). To test the effect of RM-131 on colonic intraluminal pressure in conscious mice, a miniaturized pressure transducer catheter was introduced into the colon such that the middle of the pressure sensor was 2.5 cm proximal to the anus. Results: RM-131 (0.25 μM) significantly hyperpolarized the resting membrane potential for human colonic circular smooth muscle cells by 2.8±0.7 mV (P<0.01, n=9) and in mouse preparations by 3.4±0.4 mV (P<0.01, n=6). RM-131 had no significant effect on either the fast IJP or the slow IJP. Ghrelin (1 μM) also hyperpolarized the resting membrane potential of circular smooth muscle cells in all cells recorded from human preparations by 3.5±1.4 mV (P=0.06, n=3) and in mouse preparations by 3.8±0.8 mV (P<0.01, n=7). Ghrelin also had no significant effect on either the fast IJP or slow IJP. For intraluminal pressure recordings, RM-131 or control saline was applied via intraperitoneal injection. Intraluminal pressure changes with RM-131 or saline were normalized with their pre-control. In the RM-131 treated group, intraluminal pressure was 0.57±0.05 (n=8) which was significantly less compared to the control group (0.82±0.08, n=8), suggesting that RM131 significantly reduced colonic tone. Conclusions: Our results suggest that RM-131 decreases colonic tone by hyperpolarizing the resting membrane potential of circular smooth muscle cells and decreases the excitability of colonic circular smooth muscle cells. These effects of RM-131 are likely the basis for the decrease in colonic intraluminal pressure. The previously reported increase in upper GI contractility together with a decrease in colonic intraluminal pressure position RM-131 for the treatment of functional gastrointestinal disorders.

Sa2047 Estrogen Causes Relaxation of Human Gallbladder via G Protein-Coupled Estrogen Receptors

Background and Aims: RM-131 is a synthetic ghrelin agonist that has been found to significantly accelerate gastric emptying, intestinal transit and colonic filling. The mechanism(s) through which smooth muscle cells of gastrointestinal tract respond to RM-131 is not known. We studied the effect of RM-131 on circular smooth muscle cells of human and mouse colon in vitro and on colonic intraluminal pressure in conscious mice. Methods: SJL/J mice and human colonic tissue were used in this study. Normal human colon was obtained from surgical excess tissue. The use of mice was approved by Mayo Institutional Animal Care and Use Committee and the use of human biopsy specimens was approved by Institutional Review Board. Muscle strips without the mucosa from mouse colon and human colon strips were placed in a recording chamber for intracellular recording. The recording chamber was superfused with oxygenized normal Krebs solution at 37°C. A bipolar stimulating electrode was placed on both sides of the muscle strip for electric field stimulation to elicit inhibitory junction potentials (IJPs). To test the effect of RM-131 on colonic intraluminal pressure in conscious mice, a miniaturized pressure transducer catheter was introduced into the colon such that the middle of the pressure sensor was 2.5 cm proximal to the anus. Results: RM-131 (0.25 μM) significantly hyperpolarized the resting membrane potential for human colonic circular smooth muscle cells by 2.8±0.7 mV (P<0.01, n=9) and in mouse preparations by 3.4±0.4 mV (P<0.01, n=6). RM-131 had no significant effect on either the fast IJP or the slow IJP. Ghrelin (1 μM) also hyperpolarized the resting membrane potential of circular smooth muscle cells in all cells recorded from human preparations by 3.5±1.4 mV (P=0.06, n=3) and in mouse preparations by 3.8±0.8 mV (P<0.01, n=7). Ghrelin also had no significant effect on either the fast IJP or slow IJP. For intraluminal pressure recordings, RM-131 or control saline was applied via intraperitoneal injection. Intraluminal pressure changes with RM-131 or saline were normalized with their pre-control. In the RM-131 treated group, intraluminal pressure was 0.57±0.05 (n=8) which was significantly less compared to the control group (0.82±0.08, n=8), suggesting that RM131 significantly reduced colonic tone. Conclusions: Our results suggest that RM-131 decreases colonic tone by hyperpolarizing the resting membrane potential of circular smooth muscle cells and decreases the excitability of colonic circular smooth muscle cells. These effects of RM-131 are likely the basis for the decrease in colonic intraluminal pressure. The previously reported increase in upper GI contractility together with a decrease in colonic intraluminal pressure position RM-131 for the treatment of functional gastrointestinal disorders.

Characterization of vascular endothelial and smooth muscle cell pathways and their contributions to myogenic and agonist‐mediated control (677.16)

Vascular smooth muscle cell contraction and relaxation is central to the local regulation of blood flow to tissue. At the arteriolar level, interactions between vascular endothelial cells and smooth muscel cells play critical role in determining the level of vascular tone. During mechanical and/or agonist stimulations, vascular Ca2+ dynamics are finely adjusted via a number of signaling pathways and the Ca2+ levels in the smooth muscle cells determine the level of contraction. To quantify how cellular Ca2+ dynamics are transformed into changes in vascular tone, we have constructed a cellular‐based model of isolated resistance vessel by integrating models of vessel wall mechanics, smooth muscle force generation, smooth muscle Ca2+ handling and electrophysiology with an endothelial electrophysiology and Ca2+ handling model. The dose‐response vasodilation and vasoconstriction data of different sizes of vessels in response to pharmacological vasoconstrictors and vasodilators, measured using a novel isovolumic myograph developed by Lu and Kassab are analyzed. The model simulates how changes in intraluminal pressure are used to maintain a constant vessel diameter during application of phenylephrine and acetylcholine. In order to simulate these sets of experimental data the model captures integrated vessel behavior including ionic (Ca2+, K+, Na+, etc.), IP3 and nitric oxide myoendothelial transport. Model analysis shows that α‐adrenergic pathways in smooth muscle and NO pathways in endothelium are sufficient to capture the experimentally observed phenylephrine and acetylcholine mediated responses.Grant Funding Source: NIH U01 HL118738, NSF CBET 1133260 and NIH P50‐GM094503

Effects of iodinated contrast media on a novel model of vasospasm due to subarachnoid hemorrhage (LB504)

Objective: Application of iodinated contrast media (CM) in patients with vasospasm after subarachnoid haemorrhage (SAH) may influence the vascular function of spastic brain vessels, with possible consequences for SAH morbidity and mortality. We developed an in vitro model of vasospasm post SAH to investigate the effects of CM on spontaneous myogenic tone and myogenic response of brain vessels.Methods: We used a model of isolated, pressurized rat superior cerebellar arteries. Coagulated blood was deployed in the chamber of a perfusion myograph to simulate SAH. Either vehicle or iodixanol was applied intraluminally. Vessel diameter was monitored in stable conditions and during controlled changes of intraluminal pressure. The myogenic response was quantified as the change in the diameter after each change in intraluminal pressure.Results: Vessels treated with coagulated blood developed a stronger spontaneous myogenic tone compared to the control groups (65.7% and 62.1% in comparison to 77.8% and 78.6% of initial diameter), as well as a significant decrease of the myogenic response. CM did not worsen the myogenic tone and the myogenic response. However, the myogenic response was significantly less impaired for higher pressure changes in vessels exposed to coagulated blood and CM in comparison to coagulated blood alone. The variability of the myogenic response was decreased in the groups receiving CM.Conclusion: Our in vitro model of cerebral vasospasm reflects the clinical evidence that the autoregulation of cerebral blood flow may be impaired after SAH. CM had no negative influence on vessel spontaneous myogenic tone and myogenic response in this model.

Functional roles of capsaicin-sensitive intrinsic neural circuit in the regulation of esophageal peristalsis in rats: in vivo studies using a novel method

A well-developed myenteric plexus exists in the esophagus composed of striated muscle layers, but its functional role in controlling peristaltic movements remains to be clarified. The purpose of this study was to clarify the role of a local neural reflex consisting of capsaicin-sensitive primary afferent neurons and intrinsic neurons in esophageal peristalsis. We firstly devised a method to measure peristaltic movement of esophagus in vivo in rats. Rats were anesthetized with urethane, and esophageal intraluminal pressure and propelled intraluminal liquid volume were recorded. In the experimental system, an intraluminal pressure stimulus evoked periodic changes in intraluminal pressure of the esophagus, which were consistently accompanied by intraluminal liquid propulsion. Bilateral vagotomy abolished changes in intraluminal pressure as well as liquid propulsion. These results indicate that the novel method is appropriate for inducing peristalsis in the esophagus composed of striated muscles. Then, by using the method, we examined functional roles of the local reflex in esophageal peristalsis. For that purpose, we used rats in which capsaicin-sensitive neurons had been destroyed. The esophagus of capsaicin-treated rats showed a multiphasic rise in intraluminal pressure, which may due to noncoordinated contractions of esophageal muscles, whereas a monophasic response was observed in the intact rat esophagus. In addition, destruction of capsaicin-sensitive neurons increased the propelled liquid volume and lowered the pressure threshold for initiating peristalsis. These results suggest that the local neural reflex consisting of capsaicin-sensitive neurons and intrinsic neurons contributes to coordination of peristalsis and suppresses mechanosensory function of vagal afferents in the esophagus.

Automated Detection and Measurement of Isolated Retinal Arterioles by a Combination of Edge Enhancement and Cost Analysis

Pressure myography studies have played a crucial role in our understanding of vascular physiology and pathophysiology. Such studies depend upon the reliable measurement of changes in the diameter of isolated vessel segments over time. Although several software packages are available to carry out such measurements on small arteries and veins, no such software exists to study smaller vessels (<50 µm in diameter). We provide here a new, freely available open-source algorithm, MyoTracker, to measure and track changes in the diameter of small isolated retinal arterioles. The program has been developed as an ImageJ plug-in and uses a combination of cost analysis and edge enhancement to detect the vessel walls. In tests performed on a dataset of 102 images, automatic measurements were found to be comparable to those of manual ones. The program was also able to track both fast and slow constrictions and dilations during intraluminal pressure changes and following application of several drugs. Variability in automated measurements during analysis of videos and processing times were also investigated and are reported. MyoTracker is a new software to assist during pressure myography experiments on small isolated retinal arterioles. It provides fast and accurate measurements with low levels of noise and works with both individual images and videos. Although the program was developed to work with small arterioles, it is also capable of tracking the walls of other types of microvessels, including venules and capillaries. It also works well with larger arteries, and therefore may provide an alternative to other packages developed for larger vessels when its features are considered advantageous.

Intracochlear pressure changes due to round window opening: a model experiment.

To preserve residual hearing in cochlea implantation, the electrode design has been refined and an atraumatic insertion of the cochlea electrode has become one aspect of cochlea implant research. The opening of the round window can be assumed to be a contributing factor in an atraumatic concept. The aim of our study was to observe intracochlear pressure changes due to different opening conditions of an artificial round window membrane. The experiments were performed in an artificial cochlea model. A round window was simulated with a polythene foil and a pressure sensor was placed in the helicotrema area to monitor intraluminal pressure changes. Openings of the artificial round window membrane were performed using different ways. Opening the artificial round window mechanically showed a biphasic behaviour of pressure change. Laser openings showed a unidirectional pressure change. The lowest pressure changes were observed when opening the artificial round window membrane using a diode laser. The highest pressure changes were seen when using a needle. The openings with the CO2 laser showed a negative intracochlear pressure and a loss of fluid. In our model experiments, we could prove that the opening of the artificial round window membrane causes various intracochlear pressure changes.

English

The role of bile acids on the gastrointestinal motility are contradictory, especially the role of mast cells mediators in this effect. Thus, cholic acid (CA) was examined for its&nbsp;in vitro&nbsp;action on the motility of the mice colon using different doses of CA (0.3, 30, 50, 100, 200, 300 and 500 &micro;M). The contractile activity of the colon segment was recorded as changes in intraluminal pressure under isovolumetric conditions. The mean amplitude of the peristaltic motor complexes and the frequency (interval) of phasic contractions were determined. In other experiments, to study the CA mode of action, tissues were preincubated with 5-HT3 antagonist (Granisetron hydrochloride), 5-HT4 antagonist (GR113808), H1 antagonist (Pyrilamine maleate salt) and protease activated receptor (PAR1) antagonist (BMS-200261) prior to challenge with CA (300 &micro;M). CA inhibitory effect on contractile activity might be&nbsp;via&nbsp;its antagonistic action on the 5-HT3, 5-HT4, H1 receptors and PAR1 with variable levels. In conclusion, CA perfusion, at certain concentration levels, induced significant physiological changes in colon motility that might propose its antagonistic action on the receptors of the mast cells neuromediators. &nbsp; Key words:&nbsp;Cholic acid, colonic motility, receptor antagonists, peristaltic motor complexes.

Die Kolondivertikulose und ihre Komplikationen: Pathogenese, Klassifikation und Klinische Implikationen

Current understanding of the pathogenesis of colonic diverticulosis and its complications has certain implications for current therapy concepts, which are summarised here. Colonic diverticula in the Western world are pseudodiverticula predominating in the sigmoid colon. Pathogenesis is multifactorial and includes low-fibre diet, dysmotility, increased intraluminal pressure and morphological changes. Uncomplicated diverticulitis results from microperforations, contradicting the hypothesis of the "abscessed diverticulum". Administration of antibiotics for treatment is controversial. Complicated sigmoid diverticulitis is characterised by an intensive inflammatory infiltrate with macrophages. Immunosuppression and especially steroid intake are identified as risk factors. Nowadays, elective or emergency resection is generally recommended as therapy of first choice. However, contrary concepts with merely conservative treatment or drainage--even for perforated diverticulitis--are emerging. The pathogenesis of chronically recurrent diverticulitis is poorly understood and concepts are changing. Resection after the second episode is replaced by a risk-adapted strategy. Diverticular bleeding occurs due to rupture of a vas rectum at the fundus of the diverticulum. Conservative and endoscopic management is the first line and surgical resection plays a role as salvage-strategy in case of recurrent and life-threatening bleeding. Localising the bleeding, i.e., with angiography, is crucial prior to surgery. The pathophysiology of colonic diverticulosis is complex and incompletely understood and linked with several controversial issues, regarding treatment strategies.

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.

Gastric motility in ghrelin receptor knockout mice

The aim of this study was to investigate the effects and possible mechanisms of ghrelin receptor (GHS-R) deficiency on gastric motility in GHS-R deficient (Ghsr-/-) mice. Ghsr-/- and control (Ghsr+/+) mice were genotyped by PCR. The percentage of gastric emptying (GE%) was calculated following the intraperitoneal adminis-tration of ghrelin. Invitro, the contractile response of smooth muscle strips to ghrelin and electrical field stimulation (EFS) and the intraluminal pressure change of isolated stomach to carbachol were observed in an organ bath. The staining of nerve cells in the gastric muscle layer was performed by immunofluorescence. Delayed gastric emptying was observed in the Ghsr-/- mice; ghrelin enhanced the GE% in the Ghsr+/+ mice but had no effect on the GE% in the Ghsr-/- mice. Invitro, the response of the strips to ghrelin and EFS and the intraluminal pressure change to cabarchol was reduced in the Ghsr-/- mice. GHS-Rs were predominantly expressed on nerve cells in gastric muscle layers. The number of nerve cells was observed to be decreased in the Ghsr-/- mice. The delayed gastric emptying may relate to the loss of GHS-Rs and the reduction in the number of nerve cells in the gastric muscle layers of the GHS-R-deficient mice.

Spaceflight reduces vasoconstrictor responsiveness of skeletal muscle resistance arteries in mice

Cardiovascular adaptations to microgravity undermine the physiological capacity to respond to orthostatic challenges upon return to terrestrial gravity. The purpose of the present study was to investigate the influence of spaceflight on vasoconstrictor and myogenic contractile properties of mouse gastrocnemius muscle resistance arteries. We hypothesized that vasoconstrictor responses acting through adrenergic receptors [norepinephrine (NE)], voltage-gated Ca(2+) channels (KCl), and stretch-activated (myogenic) mechanisms would be diminished following spaceflight. Feed arteries were isolated from gastrocnemius muscles, cannulated on glass micropipettes, and physiologically pressurized for in vitro experimentation. Vasoconstrictor responses to intraluminal pressure changes (0-140 cmH(2)O), KCl (10-100 mM), and NE (10(-9)-10(-4) M) were measured in spaceflown (SF; n = 11) and ground control (GC; n = 11) female C57BL/6 mice. Spaceflight reduced vasoconstrictor responses to KCl and NE; myogenic vasoconstriction was unaffected. The diminished vasoconstrictor responses were associated with lower ryanodine receptor-2 (RyR-2) and ryanodine receptor-3 (RyR-3) mRNA expression, with no difference in sarcoplasmic/endoplasmic Ca(2+) ATPase 2 mRNA expression. Vessel wall thickness and maximal intraluminal diameter were unaffected by spaceflight. The data indicate a deficit in intracellular calcium release via RyR-2 and RyR-3 in smooth muscle cells as the mechanism of reduced contractile activity in skeletal muscle after spaceflight. Furthermore, the results suggest that impaired end-organ vasoconstrictor responsiveness of skeletal muscle resistance arteries contributes to lower peripheral vascular resistance and less tolerance of orthostatic stress in humans after spaceflight.