scholarly journals Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans

2004 ◽  
Vol 286 (2) ◽  
pp. G278-G284 ◽  
Author(s):  
Kwang-Jae Lee ◽  
Rita Vos ◽  
Jozef Janssens ◽  
Jan Tack
Keyword(s):  
Healthy Subjects ◽  
Gastric Fundus ◽  
Acid Exposure ◽  
Gastric Distension ◽  
Gastric Accommodation ◽  
Double Blind ◽  
Gastric Tone ◽  
Acid Infusion ◽  
Duodenal Acidification ◽  
Double Blind Design

Decreased acid clearance and increased exposure to acid of the duodenum have been reported in a subset of functional dyspepsia patients. However, the mechanism by which increased duodenal acid exposure may affect symptoms is unclear. The aim of the present study was to investigate the effects of duodenal acidification on proximal gastric tone and mechanosensitivity in humans. An infusion tube with a pH electrode attached was positioned in the second part of the duodenum, and a barostat bag was located in the gastric fundus. In 12 healthy subjects, fundic tone and sensitivity to distensions were assessed before and during duodenal infusion of 0.1 N hydrochloric acid or saline in a randomized, double-blind design. In 10 healthy subjects, meal-induced accommodation was measured during duodenal infusion of acid or saline. Acid infusion in the duodenum significantly increased fundic compliance and decreased fasting fundic tone. This was accompanied by a significant decrease in the pressures and the corresponding wall tensions at the thresholds for discomfort. During infusion of acid, significantly higher perception and symptom scores were obtained for the same distending pressures. The meal-induced fundic relaxation was significantly smaller during acid infusion compared with saline infusion. In conclusion, duodenal acidification induces proximal gastric relaxation, increases sensitivity to gastric distension, and inhibits gastric accommodation to a meal. Through these mechanisms, increased duodenal acid exposure may be involved in the pathogenesis of dyspeptic symptoms.

Influence of sildenafil on gastric sensorimotor function in humans

2004 ◽  
Vol 287 (5) ◽  
pp. G988-G992 ◽  
Author(s):  
Giovanni Sarnelli ◽  
Daniel Sifrim ◽  
Jozef Janssens ◽  
Jan Tack
Keyword(s):  
Gastric Emptying ◽  
Healthy Subjects ◽  
Soluble Guanylate Cyclase ◽  
Therapeutic Potential ◽  
Muscle Relaxation ◽  
Gastric Wall ◽  
Gastric Volume ◽  
Gastric Fundus ◽  
Smooth Muscle Relaxation ◽  
Gastric Accommodation

After a meal, the proximal stomach relaxes probably through the activation of nitrergic neurons in the gastric wall. Nitric oxide-induced smooth muscle relaxation involves activation of soluble guanylate cyclase, with cGMP production, which is then degradated by phosphodiesterase-5 (PDE-5). The aim of this study was to investigate the effect of sildenafil, a selective PDE-5 inhibitor, on fasting and postprandial proximal gastric volume and on gastric emptying rates in humans. A gastric barostat was used to study gastric compliance and perception to isobaric distension in healthy subjects before and after placebo ( n = 13) or sildenafil, 50 mg ( n = 15). In 10 healthy subjects, two gastric barostat studies were performed in randomized order to study the effect of placebo or sildenafil on postprandial gastric relaxation. Similarly, solid and liquid gastric emptying rates were studied in 12 healthy subjects. Sildenafil significantly increased fasting intragastric volume (141 ± 15 vs. 163 ± 15 ml, P < 0.05) and volumes of first perception. Sildenafil induced a higher and prolonged gastric relaxation either at 30 min (357 ± 38 vs. 253 ± 42 ml, P < 0.05) or 60 min (348 ± 49 vs. 247 ± 38 ml, P < 0.05) after the meal. Sildenafil did not alter solid half-emptying time but significantly delayed liquid emptying (43 ± 4 vs. 56 ± 4 min, P < 0.01). In conclusion, sildenafil significantly increases postprandial gastric volume and slows liquid emptying rate, confirming that meal-induced accommodation in humans involves the activation of a nitrergic pathway. The effect of sildenafil on gastric fundus suggests a therapeutic potential for phosphodiesterase inhibitors in patients with impaired gastric accommodation.

scholarly journals Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway

2020 ◽  
Vol 318 (3) ◽  
pp. G574-G581
Author(s):  
Feng Ye ◽  
Yi Liu ◽  
Shiying Li ◽  
Sujuan Zhang ◽  
Robert D. Foreman ◽  
...  
Keyword(s):  
Nerve Stimulation ◽  
Sacral Nerve Stimulation ◽  
Gastric Fundus ◽  
Vagal Activity ◽  
Sprague Dawley ◽  
Gastric Accommodation ◽  
Gastric Tone ◽  
Efferent Activity ◽  
Sacral Nerve ◽  
Efferent Pathway

Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450–500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway. NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.

Intraluminal modulation of gastric sensitivity to distension: effects of hydrochloric acid and meal

2001 ◽  
Vol 280 (5) ◽  
pp. G904-G909 ◽  
Author(s):  
Benoit Coffin ◽  
Robert Chollet ◽  
Bernard Flourié ◽  
Marc Lémann ◽  
Claire Franchisseur ◽  
...  
Keyword(s):  
Hydrochloric Acid ◽  
Gastric Acid ◽  
Healthy Subjects ◽  
Gastric Distension ◽  
Wall Tension ◽  
Maximal Volume ◽  
Acid Infusion ◽  
Fixed Volume ◽  
Gastric Sensitivity ◽  
Meal Ingestion

Conscious sensations in response to gut distensions may be modulated by temporospatial interactions among different stimuli. This study investigated whether symptoms induced by gastric distension may be modified by hydrochloric acid (HCl) gastric infusion and meal ingestion. In nine healthy subjects, fixed pressure (isobaric) and fixed volume (isovolumetric) distensions were performed during continuous (4 ml/min) intragastric saline or HCl infusion, during fasting and after meal ingestion, until the maximal distension step defined as discomfort or a predefined maximal volume. During fasting isobaric distensions, the maximal distension step was significantly decreased during HCl compared with saline. The intragastric volumes were not significantly different, but the wall tension was significantly lower during HCl than saline. HCl increased gastric compliance. Meal ingestion relaxed the stomach and decreased the pressure at the maximal distension step during saline, but HCl did not further decrease it compared with fasting. During isovolumetric distensions, HCl also increased gastric compliance, but in both fasted and fed states it did not modify the maximal distension steps. In conclusion, sensations in response to gastric isobaric distensions, but not to isovolumetric distensions, are influenced by gastric acid infusion and meal ingestion. The effects of HCl might be related to a sensitization of mucosal mechanoreceptors.

Effects of the concentration and frequency of acid infusion on the development and maintenance of esophageal hyperalgesia in a human volunteer model

2008 ◽  
Vol 294 (4) ◽  
pp. G914-G917 ◽  
Author(s):  
Philip J. Matthews ◽  
Charles H. Knowles ◽  
Yang C. Chua ◽  
Claire Delaney ◽  
Anthony R. Hobson ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Electrical Stimulus ◽  
Human Model ◽  
Multiple Time ◽  
Model Design ◽  
Double Blind ◽  
Acid Infusion ◽  
Pain Thresholds ◽  
Multiple Time Points ◽  
Esophageal Hypersensitivity

Previous studies have demonstrated that a single 30-min distal esophageal infusion of concentrated (0.15 M, pH 0.8) hydrochloric acid (HCl) induces hyperalgesia to an electrical stimulus in a human model. The aim of this study was to refine this model using physiological acid concentrations (pH 1.8–4) in repeated short exposures. Two different cohorts of 10 volunteers underwent two studies. Study 1: randomization to four 5-min distal esophageal infusions of acid (0.15 M) or saline, 1 h apart. Double-blind measurements of baseline and postexposure proximal esophageal and chest wall pain thresholds (PTs) were performed to electrical stimulation at 30-min intervals throughout the study. Study 2: randomization to four 15-min infusions of 0.15, 0.075, and 0.01 M HCl and saline. In study 1, with multiple acid infusions, a significant progressive drop in PTs was observed in both areas tested ( P ≤ 0.0001). In study 2, increasing acid concentrations had a significant effect over multiple time points, P ≤ 0.0001. Similar initial reductions in PTs were observed for all acid concentrations compared with saline; however, hypersensitivity was shorter lasting with 0.01 M acid. In healthy subjects, esophageal hypersensitivity can be induced and maintained up to 4 h by repeated short-duration acid infusion and at physiological pH levels. This has implications for future model design and pathophysiological understanding of acid-related esophageal hypersensitivity.

scholarly journals Cerebellar rTMS in PSP: a Double-Blind Sham-Controlled Study Using Mobile Health Technology

2021 ◽  
Author(s):  
Andrea Pilotto ◽  
Maria Cristina Rizzetti ◽  
Alberto Lombardi ◽  
Clint Hansen ◽  
Michele Biggi ◽  
...  
Keyword(s):  
Digital Technology ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Health Technology ◽  
Controlled Study ◽  
Double Blind ◽  
Non Invasive ◽  
Lower Back ◽  
Before And After ◽  
Double Blind Design ◽  
Theta Burst

AbstractThere are no effective treatments in progressive supranuclear palsy (PSP). The aim of this study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty PSP patients underwent a session of sham or real cerebellar rTMS in a crossover design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-s trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with increase in time without falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005), acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, in a double-blind design. These results should motivate larger and longer trials using non-invasive brain stimulation for PSP patients.

scholarly journals The Effects of Dietary Supplementation of Lactococcus lactis Strain Plasma on Skin Microbiome and Skin Conditions in Healthy Subjects—A Randomized, Double-Blind, Placebo-Controlled Trial

2021 ◽  
Vol 9 (3) ◽  
pp. 563
Author(s):  
Ryohei Tsuji ◽  
Kamiyu Yazawa ◽  
Takeshi Kokubo ◽  
Yuumi Nakamura ◽  
Osamu Kanauchi
Keyword(s):  
Gene Expression ◽  
Lactococcus Lactis ◽  
Healthy Subjects ◽  
Controlled Trial ◽  
Dietary Supplementation ◽  
Skin Microbiome ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Lactis Strain ◽  
Skin Conditions

(1) Background: Lactococcus lactis strain Plasma (LC-Plasma) is a unique strain which directly activates plasmacytoid dendritic cells, resulting in the prevention against broad spectrum of viral infection. Additionally, we found that LC-Plasma intake stimulated skin immunity and prevents Staphylococcus aureus epicutaneous infection. The aim of this study was to investigate the effect of LC-Plasma dietary supplementation on skin microbiome, gene expression in the skin, and skin conditions in healthy subjects. (2) Method: A randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Seventy healthy volunteers were enrolled and assigned into two groups receiving either placebo or LC-Plasma capsules (approximately 1 × 1011 cells/day) for 8 weeks. The skin microbiome was analyzed by NGS and qPCR. Gene expression was analyzed by qPCR and skin conditions were diagnosed by dermatologists before and after intervention. (3) Result: LC-Plasma supplementation prevented the decrease of Staphylococcus epidermidis and Staphylococcus pasteuri and overgrowth of Propionibacterium acnes. In addition, LC-Plasma supplementation suggested to increase the expression of antimicrobial peptide genes but not tight junction genes. Furthermore, the clinical scores of skin conditions were ameliorated by LC-Plasma supplementation. (4) Conclusions: Our findings provided the insights that the dietary supplementation of LC-Plasma might have stabilizing effects on seasonal change of skin microbiome and skin conditions in healthy subjects.

Methylphenidate reduces orienting bias in healthy individuals

2021 ◽  
pp. 026988112199688
Author(s):  
Leehe Peled-Avron ◽  
Hagar Gelbard Goren ◽  
Noa Brande-Eilat ◽  
Shirel Dorman-Ilan ◽  
Aviv Segev ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Asymmetric Effect ◽  
Healthy Individuals ◽  
Double Blind ◽  
Spatial Orienting ◽  
Individual Trait ◽  
Neurological Patients ◽  
Dopamine Signaling ◽  
First Time ◽  
Neural Effect

Background: Healthy individuals show subtle orienting bias, a phenomenon known as pseudoneglect, reflected in a tendency to direct greater attention toward one hemispace. Accumulating evidence indicates that this bias is an individual trait, and attention is preferentially directed contralaterally to the hemisphere with higher dopamine signaling. Administration of methylphenidate (MPH), a dopamine transporter inhibitor, was shown to normalize aberrant spatial attention bias in psychiatric and neurological patients, suggesting that the reduced orienting bias following administration of MPH reflects an asymmetric effect of the drug, increasing extracellular dopamine in the hemisphere with lower dopamine signaling. Aim: We predicted that, similarly to its effect on patients with brain pathology, MPH will reduce the orienting bias in healthy subjects. Methods: To test this hypothesis, we examined the behavioral effects of a single dose (20 mg) of MPH on orienting bias in 36 healthy subjects (18 females) in a randomized, double-blind placebo-controlled, within-subject design, using the greyscales task, which has been shown to detect subtle attentional biases in both patients and healthy individuals. Results/outcomes: Results demonstrate that healthy individuals vary in both direction and magnitude of spatial orienting bias and show reduced magnitude of orienting bias following MPH administration, regardless of the initial direction of asymmetry. Conclusions/interpretations: Our findings reveal, for the first time in healthy subjects, that MPH decreases spatial orienting bias in an asymmetric manner. Given the well-documented association between orienting bias and asymmetric dopamine signaling, these findings also suggest that MPH might exert a possible asymmetric neural effect in the healthy brain.

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