Effects of standard meal and treadmill exercise test on cutaneous gastrointestinal electrogram in healthy subjects / 中华消化杂志

Objective:To explore the effects of standard meal and treadmill exercise test on body surface gastrointestinal electrogram in healthy subjects, and to provide more evidence for the clinical application of gastrointestinal electrogram.Methods:From January to June 2021, a total of 100 healthy asymptomatic volunteers underwent gastrointestinal electrogram after fasting, standard meal and treadmill exercise test. After the subjects fasted for more than 8 hours, the gastrointestinal electrogram was performed after the subjects were lying flat, quiet, and breathing steadily, electrodes were placed on the the body surface projection positions of the gastric body, the lesser curvature, the greater curvature, the antrum, the ascending colon, the transverse colon, the descending colon, and the rectum. The fasting gastrointestinal electrogram was recorded for 6 min. Then lay for 5 to 10 min after the standard meal (100 g bread, 250 mL milk), the postprandial gastrointestinal electrogram was recorded for 6 min. And lay for 5 to 10 min after treadmill exercise test, then the postexercise gastrointestinal electrogram was recorded for 6 min. The frequency and amplitude of gastrointestinal electrogram waveforms of the three time points were compared, and the percentage of gastrointestinal electrical rhythm disorder, and slow wave frequency instability coefficient were also compared. Stratified analysis of gastric motility was performed according to age, sex and body mass index. Paired t-test, Pearson Chi-squared test, continuity correction Chi-squared test, Fisher′s exact method and Speraman correlation were used for statistical analysis. Results:The standard meal did not obviously affect the mean frequency of the gastric electrocardiogram, however the mean amplitude of gastric electrocardiogram significantly increased after standard meal compared with that of fasting, especially in the electrodes placed at lesser curvature((148.5±8.7) μV vs.(113.2±5.0)μV ), greater curvature((176.3±11.3) μV vs.(126.1±7.3) μV), and antrum((161.8±10.6) μV vs.(117.6±4.91) μV), and the differences were statistically significant( t=4.63, 4.63 and 3.99, all P< 0.001). There were no significant changs in rhythm and stability of the gastric electrocardiogram. The mean frequency of intestinal electrograms at the ascending colon, the transverse colon, the descending colon, and the rectum decreased after the standard meal compared with that of fasting ((10.8±0.2) count per minute(cpm) vs.(11.5±0.2) cpm, (10.5±0.2) cpm vs.(11.2±1.6) cpm, (10.9±0.2) cpm vs.(11.7±0.2) cpm, (11.1±0.2) cpm vs.(11.8±0.2) cpm), and the differences were statistically significant ( t=3.82, 4.55, 4.39, and 3.98, all P<0.001); the mean amplitude of the ascending colon, the transverse colon, and the rectum increased compared with that of fasting ((129.8±6.1) μV vs. (110.9±6.4) μV, (119.6±4.1) μV vs. (101.3±4.7) μV, (124.1±4.6) μV vs. (106.2±5.7) μV), and the differences were statistically significant ( t=2.62, 3.76, and 3.16; P=0.010, <0.001, =0.002); and the number of leads with enteroelectric rhythm disorder increased (398 vs. 389, the total number of leads is 400), and the difference was statistically significant( χ2=7.31, P=0.026). The mean frequency of gastric electricity after treadmill exercise in electrode placed at antrum increased compared with that after standard meal ((3.4±0.4) cpm vs.(3.3±0.3) cpm), and the differences were statistically significant( t=2.45, P=0.016), and the mean amplitude of gastric electricity in electrodes placed at gastric body, lesser curvature and antrum increased compared with those after standard meal((160.2±8.6) μV vs. (133.9±6.4) μV, (178.1±10.0) μV vs. (148.5±8.7) μV, (202.5±10.2) μV vs. (161.8±10.6) μV), and the differences were statistically significant ( t=2.30, 2.35, and 2.48; P=0.024, 0.021, and 0.015). Treadmill exercise affected the rhythm and stability of gastric electricity, and the number of electrodes with instable and abnormal coefficient frequency slow-wave significantly increased (25 vs. 1, the total number of electrodes is 400), and the difference was statistically significant( χ2=22.90, P<0.001). There was no significant change in the mean frequency of the colonic electricity after treadmill exercise compared with that after standard meal, however the mean amplitude of intestinal electrical waveform at the ascending colon, the transverse colon, the descending colon, and the rectum increased compared with those after standard meal((171.2±8.4) μV vs. (129.8±6.1) μV, (166.1±7.7) μV vs. (119.6±4.1) μV, (147.2±7.2) μV vs. (121.1±4.9) μV, (149.6±7.3) μV vs. (124.1±4.6) μV), and the differences were statistically significant( t=3.51, 5.49, 3.09, and 2.83; P=0.001, <0.001, =0.003, and=0.006), which affected the rhythm and stability of the colonic electricity, and the number of electrodes with instable and abnormal coefficient frequency slow-wave significantly increased (10 vs. 3, the total number of electrodes is 400, χ2=4.04, P=0.040). Gender was correlated with mean frequency of gastric electricity after standrdmeal and treadmill exercise test and mean amplitude of fasting and standard postprandial gastric electricity( r=0.242, -0.272, 0.286, 0.242; P=0.015, 0.006, 0.004, 0.015), and with mean amplitude of fasting and standard postprandial electricity( r=0.225, 0.460; P=0.024, <0.001). Age was only associated with mean frequency of fasting gastric electricity( r=-0.214, P=0.033). Body mass index was correlated with mean gastric electrical amplitude after fasting, standard meal and treadmill exercise( r=-0.347, -0.260, -0.211; P<0.001, =0.009, =0.036), as well as with the mean gastric electricity frequency after treadmill exercise ( r=0.242, P=0.016). Body mass index was correlated with the mean amplitude and frequency of fasting and standard postprandial intestinal electricity ( r=-0.261, -0.296, -0.400, -0.286; P=0.009, =0.003, < 0.001, =0.003). In the healthy volunteers with female gender and body mass index < 24 kg/m 2, there were statistically significant differences in the changes of gastric motility after standard meal (Fisher′s exact method, P=0.022 and 0.024). Conclusion:Both standard meal and treadmill exercise test affect gastrointestinal electrical activity, and exercise caused more changes in gastrointestinal electrical activity than standard meal.

Pharmacokinetics, Pharmacodynamics and Safety of JES9501 after Single and Multiple Oral Administration in Healthy Subjects

BACKGROUND: JES9501 is dehydroevodiamine, the extract of Evodia rutaecarpa, expected to be a new therapeutic for Alzheimer disease. This study aims to investigate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of JES9501 after single or multiple dosing. METHODS: A double-blind, randomized, placebo-controlled, dose ascending, parallel study was conducted in healthy subjects. A single dose of JES9501 50.100.200.400 or 800 mg and multiple doses of JES9501 100.200 or 400 mg once-daily for 7days was administered. Serial blood and urine samples for PK evaluation were collected. Acetylcholinesterase (AChE) activity was measured for PD evaluation in multiple dose group. RESULTS: In the single dose study, means of dose-normalized peak concentration (Cmax) of 100.200.400 and 800 mg dose group are comparable except 50 mg dose group. Means of dose-normalized area under the plasma concentration-time curve (AUC) from dosing to the last quantifiable concentration of corresponding dose group were similar. At steady state in the multiple dose study, means of dose-normalized Cmax and AUC for dosing interval of 100.200 and 400 mg dose group decreased as the dose increased, however those were not relevant. There was no significant difference of AChE activity between three dosage groups and placebo group. Adverse events related to study drug were all mild and there were no remarkable findings. CONCLUSION: JES9501 was safe and well-tolerated after single or multiple doses in healthy male subjects. Further studies are warranted to evaluate the PK of optimized dosage form and to prove the drug effect in clinical trials for Alzheimer disease patients.

Level of anxiety and depression on volunteers in clinic trial / 中国病理生理杂志

0.05),and significantly higher than that of volunteers after trials(P