Characteristics of reflux and gastric electrical activity in gastroesophageal reflux disease with ineffective esophageal motility.

OBJECTIVES: The impact of ineffective esophageal motility (IEM) on gastroesophageal reflux disease (GERD) remains unknown, and abnormal esophageal motility often coexists with abnormal gastric motility. We aimed to investigate the role of IEM in GERD and its relationship with gastric electrical activity. METHODS: Patients diagnosed as GERD based on GERD-questionnaire score ≥8 in our hospital from January 2020 to June 2022 were included. All patients underwent 24-h multichannel intraluminal impedance-pH monitoring, high-resolution manometry, and electrogastrogram and were categorized into the normal esophageal motility (NEM) and IEM groups, respectively. Reflux characteristics and gastric electric activity were compared between the two groups, and the correlation between gastric electric activity and reflux was analyzed. RESULTS: Acid exposure time, total reflux episodes, and DeMeester score in the IEM group were higher than those in the NEM group. Distal mean nocturnal baseline impedance was significantly lower in the IEM group. Compared with the NEM group, the power ratio (PR) of fundus, antrum and pylorus and premeal and postmeal normal wave ratio of antrum were significantly lower in IEM. The total reflux episodes were negatively correlated with the PR of fundus and pylorus, and the DeMeester score was negatively correlated with the PR of corpus and pylorus. CONCLUSIONS: IEM may lead to increased reflux, resulting in esophageal mucosal damage. There may be consistency between abnormal esophageal motility and gastric motility.

Comparison of the gastric acid inhibition function among lansoprazole, pantoprazole, and their respective stereoisomers in healthy Chinese subjects
.

OBJECTIVE: This study was conducted to evaluate the difference in acid inhibition function among lansoprazole (LPZ), pantoprazole (PPZ), and their respective stereoisomers following single and multiple intravenous doses in healthy Chinese subjects. MATERIALS AND METHODS: The dosage groups were set as follows: 30 mg single and multiple intravenous administrations of LPZ or R-LPZ, 40 mg single and multiple intravenous administrations of PPZ or S-PPZ. Subjects received an intravenous infusion of LPZ, R-LPZ, PPZ, or S-PPZ injection in sterile saline solution (100 mL/h, 60 minutes), respectively. The intragastric pH was sampled every second for 24 hours at baseline and for 24 hours after drug administration. The baseline-adjusted pharmacodynamic (PD) parameters include ΔMean (pH), ΔMedian (pH), ΔTpH≥3 (%), ΔTpH≥4 (%), ΔTpH≥6 (%), and ΔAUECph-tτ1-τ2. The PD parameters were evaluated in different time intervals (0 - 24 hours, 0 - 4 hours and 14 - 24 hours). RESULTS: After a single dose, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ and PPZ was 56.6 ± 19.6, 53.1 ± 23.3, 35.6 ± 24.9 and 26.8 ± 30.2, respectively. The ΔTpH≥6 (%) was 50.7 ± 26.1, 41.4 ± 26.2, 25.4 ± 24.9 and 22.1 ± 27.6, respectively. The ΔAUECph-τ1-τ was 45,564 ± 16,107, 41,798 ± 16,153, 31,914 ± 17,304 and 20,744 ± 21,500, respectively. Statistically significant differences were found with R-LPZ vs. S-PPZ, R-LPZ vs. PPZ, LPZ vs. S-PPZ and LPZ vs. PPZ. The average TpH≥4 of R-LPZ, LPZ, S-PPZ, and PPZ was (47.2 ± 26.1) minutes, (49.6 ± 19.3) minutes, (56.1 ± 23.7) minutes, and (72.1 ± 27.3) minutes, respectively. Statistically significant differences were found with R-LPZ vs. PPZ (p = 0.009) and LPZ vs. PPZ (p = 0.019). After multiple doses, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ, and PPZ was 71.7 ± 20.2, 63.5 ± 19.4, 59.5 ± 17.8 and 64.0 ± 22.4, respectively. The ΔTpH≥6 (%) was 64.0 ± 22.2, 52.0 ± 19.2, 49.6 ± 20.4 and 50.9 ± 23.8, respectively. The ΔAUECph-τ1-τ was 326,149 ± 94,839, 288,565 ± 93,279, 296,189 ± 83,412 and 300,960 ± 108,057, respectively. No statistically significant differences were found in baseline-adjusted PD parameters during all time periods after multiple doses. CONCLUSION: After a single dose, the mean gastric pH inhibition value of R-LPZ was the highest, followed by LPZ, then S-PPZ and PPZ. R-LPZ and LPZ provided significantly better pH control compared with PPZ and S-PPZ in healthy subjects. The onset time of R-LPZ was the fastest and R-LPZ can provide better acid inhibition during sleeping time. After multiple doses, the mean values in all PD parameters of R-LPZ were the highest, the values of LPZ, S-PPZ, and PPZ were similar. However, no significant difference was found in acid inhibition among these four drugs after multiple doses.

Acid exposure in patients with gastroesophageal reflux disease is associated with esophageal dysmotility.

OBJECTIVE: To explore the correlation between reflux disease and abnormal esophageal motility in patients with gastroesophageal reflux disease (GERD). METHODS: Participants (patients with GERD and controls) who underwent 24-h impedance-pH monitoring (MII-pH monitoring) and high-resolution manometry between January 2012 and February 2017 were retrospectively studied. The patients were divided into two groups (acid reflux and nonacid reflux) based on their MII-pH monitoring data. Reflux episodes, endoscopic findings, and esophageal dynamic parameters were assessed and compared. RESULTS: A total of 142 patients were included (acid reflux [n = 58], nonacid reflux [n = 60], control group [n = 24]). There were more patients with esophagitis and more severe esophageal mucosal injury in the acid reflux group than in the nonacid reflux group. The acid reflux group had reduced lower esophageal sphincter (LES) basal pressure, shorter LES length, lower esophageal pressure and distal contractile integral index than the nonacid reflux group. Patients in the acid reflux group had more large breaks and a higher incidence of type II and III esophagogastric junction morphology than those in the nonacid reflux group. Acid exposure time, the incidence of long-term acid reflux, recumbent acid reflux, and the incidence of acid and nonacid reflux had a significant negative correlation with esophageal body motility or LES function. CONCLUSION: This study suggests that an increase in esophageal acid exposure is correlated with an increase in esophageal dysmotility in patients with GERD.

Safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole sodium injections after single and multiple intravenous doses in healthy Chinese subjects.

PURPOSE: The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole (PPZ) sodium injections following single and multiple intravenous doses in healthy Chinese subjects. METHODS: The dosage groups were set as followed: 20 mg of single and multiple intravenous administration of S-(-)-PPZ, 40 mg of single and multiple intravenous administration of S-(-)-PPZ or pantoprazole, and 80 mg of single dosage group of S-(-)-PPZ. Subjects were sampled for pharmacokinetic analysis and were monitored for 24-h intragastric pH prior to and 48-h intragastric pH after administration for the pharmacodynamic study. The pharmacokinetic and pharmacodynamic parameters were compared between S-(-)-PPZ and PPZ. Safety was evaluated on the basis of adverse events, vital signs, laboratory tests, and physical examination. RESULTS: All adverse events were mild and of limited duration. Maximum plasma concentration and area under the concentration-time curve for S-(-)-PPZ were dose proportional over the range of 20-80 mg following a single intravenous administration. Elimination rate constant and half-life observed statistical difference from a single dose to multiple doses in 40 mg of S-(-)-PPZ groups. After administration of a single dose, the mean 24-h intragastric pH value was observed higher in 80-mg group than in 40- and 20-mg groups. Slightly increase of intragastric pH was found after a single dose of 40 mg S-(-)-PPZ than 40 mg PPZ; however, the differences were not statistically significant. CONCLUSIONS: Twice daily of 40 mg S-(-)-PPZ sodium injections is effective in achieving satisfying acid inhibition. Compared with plasma R-(+)-PPZ levels, most subjects presented more potent and prolonged suppression of gastric acid of S-(-)-PPZ, while a few subjects showed faster metabolic rate of S-(-)-PPZ in vivo.

Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects.

Background: Not all patients with acid-related disorders receiving proton pump inhibitor (PP) treatment get adequate gastric pH control. The genetic variation of receptors, metabolic enzymes, and transporters are known to cause failures of therapies. We have conducted a study to evaluate the influence of gastric H+/K+-ATPase, CYP2C19, and ABCB1 polymorphisms on the pharmacokinetic and pharmacodynamic profiles of dexlansoprazole injection in healthy Chinese subjects. Methods: A total of 51 subjects were enrolled for pharmacokinetic and pharmacodynamic study after a single intravenous administration of 20 or 30 mg dexlansoprazole. Plasma concentrations were determined using a chiral liquid chromatography-mass spectrometry method. The intragastric pH and baseline-adjusted intragastric pH parameters were introduced to evaluate the pharmacodynamic characters. Genotyping was performed by polymerase chain reaction. Results: The pharmacokinetic parameters were significantly influenced by CYP2C19 phenotypes, and gastric acid secretion inhibition were affected by both gastric H+/K+-ATPase and CYP2C19 polymorphisms. Gastric H+/K+-ATPase genotypes had greater effects than CYP2C19 genotypes on the suppression of gastric acid secretion. Conclusion: Gastric H+/K+-ATPase polymorphism may be one of the main reasons that cause insufficient gastric acid inhibition.

Safety, tolerability, pharmacokinetics and pharmacodynamics of dexlansoprazole injection in healthy Chinese subjects.

PURPOSE: This study was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of dexlansoprazole injection in healthy subjects. METHODS: Dexlansoprazole (20-90 mg) or lansoprazole (30 mg) was administrated intravenously to healthy male and female volunteers. All the subjects were sampled for pharmacokinetic (PK) analysis and 64 of them were monitored for 24-h intragastric pH prior to and after administration in the pharmacodynamic (PD) study. RESULTS: Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-τ) for dexlansoprazole injection was dose-proportional over the range of 20-90 mg following a single intravenous administration. Total clearance and half-life (t1/2) was independent of dose, and ranged from 4.69 L/h to 5.85 L/h and from 1.24 h to 2.17 h, respectively. A single dose of dexlansoprazole (30 mg) resulted in higher gastric pH compared to that of lansoprazole, evidenced by a mean 24-h gastric pH of 6.1 ± 1.2 (lansoprazole: 5.4 ± 1.1) and 24-h gastric pH > 6 post drug dose holding time of 64.2 ± 21.0% (lansoprazole: 49.5 ± 21.5%). CONCLUSION: Dexlansoprazole injection was safe and well tolerated for up to 5-day repeated intravenous administration dose of 30 mg. The recommended dosage for dexlansoprazole injection is 30 mg for an adequate gastric acid control.

Antifibrotic effect of total flavonoids of Astmgali Radix on dimethylnitrosamine-induced liver cirrhosis in rats.

OBJECTIVE: To study the effect of total flavonoids of Astmgali Radix (TFA) on liver cirrhosis induced with dimethylnitrosamine (DMN) in rats, and the effect on peroxisome proliferator-activated receptor γ (PPARγ), uncoupling protein 2 (UCP2) and farnesoid X receptor (FXR). METHODS: Fifty-three Sprague-Dawley rats were randomly divided into a control group (10 rats) and a DMN group (43 rats). Rats in the DMN group were given DMN for 4 weeks and divided randomly into a model group (14 rats), a low-dosage TFA group (14 rats) and a high-dosage TFA group (15 rats) in the 3rd week. Rats were given TFA for 4 weeks at the dosage of 15 and 30 mg/kg in the low- and high-TFA groups, respectively. At the end of the experiment blood and liver samples were collected. Serum liver function and liver tissue hydroxyproline content were determined. hematoxylin-eosin (HE), Sirus red and immunohistochemical stainings of collagen I, smooth muscle actin (α-SMA) was conducted in paraffinembedded liver tissue slices. Real time polymerase chain reaction (PCR) was adopted to determine PPARγ, UCP2 and FXR mRNA levels. Western blot was adopted to determine protein levels of collagen I, α-SMA, PPARγ, UCP2 and FXR. RESULTS: Compared with the model group, TFA increased the ratio of liver/body weight (low-TFA group P<0.05, high-TFA group P<0.01), improved liver biochemical indices (P<0.01 for ALT, AST, GGT in both groups, P<0.05 for albumin and TBil in the high-TFA group) and reduced liver tissue hydroxproline content (P<0.01 in both groups) in treatment groups significantly. HE staining showed that TFA alleviated liver pathological changes markedly and Sirus red staining showed that TFA reduced collagen deposition, alleviated formation and extent of liver pseudolobule. Collagen I and α-SMA immunohistochemical staining showed that staining area and extent markedly decreased in TFA groups compared with the model group. TFA could increase PPARγ, it regulated target UCP2, and FXR levels significantly compared with the model group (in the low-TFA group all P<0.05, in the high group all P<0.01). CONCLUSION: TFA could improve liver function, alleviate liver pathological changes, and reduce collagen deposition and formation of liver pseudolobule in rats with liver cirrhosis. The antifibrotic effect of TFA was through regulating PPARγ signal pathway and the interaction with FXR.

Age-related symptom and life quality changes in women with irritable bowel syndrome.

AIM: To explore age-related changes in symptoms and quality of life (QoL) of women with irritable bowel syndrome (IBS). METHODS: Two-hundred and fifty-four female adult outpatients with IBS attending the Department of Gastroenterology at the First Affiliated Hospital of Nanjing Medical University between January, 2008 and October, 2008 were approached. Patients with a history of abdominal surgery, mental illness or those who had recently taken psychotropic drugs were excluded. A physician obtained demographic and abdominal symptom data. All patients were asked to complete the Zung Self-Rated Anxiety and Depression Scale (SDS/SAS) and the IBS-specific QoL questionnaire. The patients were divided into six groups according to age, in 10-year increments: 18-27 years, 28-37 years, 38-47 years, 48-57 years, 58-67 years and 68-75 years (maximum 75 years). Age-related differences of abdominal pain or discomfort were analyzed using rank-sum tests. Differences in SDS/SAS and IBS-QoL scores between age groups were analyzed using one-way analysis of variance. Pearson's correlations evaluated potential associations between IBS symptoms, psychological factors and QoL in each age group. RESULTS: There were no differences in the distribution of IBS subtypes between age groups (χ(2) = 20.516, P = 0.153). Differences in the severity of abdominal pain/discomfort with age were statistically significant (χ(2) = 25.638, P < 0.001); patients aged 48-57 years, 58-67 years or 68-75 years had milder abdominal pain/discomfort than those in the younger age groups. The severity of anxiety or depressive symptoms did not differ between age groups (SDS, χ(2) = 390.845, P = 0.110; SAS, χ(2) = 360.071, P = 0.220). Differences of IBS-QoL scores were statistically significant between age groups (χ(2) = 1098.458, P = 0.011). The scores of patients in the 48-57-year group were lower than those in the 18-27-year and 28-37-year groups (48-57-year group vs 18-27-year group, 74.88 ± 8.76 vs 79.76 ± 8.63, P = 0.021; 48-57-year group vs 28-37-year group, 74.88 ± 8.76 vs 79.04 ± 8.32, P = 0.014). The scores in the 68-75-year group were lower than those in the 18-27-year, 28-37-year and 38-47-year groups (68-75-year group vs 18-27-year group, 71.98 ± 9.83 vs 79.76 ± 8.63, P = 0.003; 68-75-year group vs 28-37-year group, 71.98 ± 9.83 vs 79.04 ± 8.32, P = 0.002; 68-75-year group vs 38-47-year group,71.98 ± 9.83 vs 76.44 ± 8.15, P = 0.039). Anxiety and depression were negatively correlated with QoL in all age groups (SDS and QoL: 18-27-year group, r = -0.562, P = 0.005; 28-37-year group, r = -0.540, P < 0.001; 38-47-year group, r = -0.775, P < 0.001; 48-57-year group, r = -0.445, P = 0.001; 58-67-year group, r = -0.692, P < 0.001; 68-75-year group, r = -0.732, P < 0.001. SAS and QoL: 18-27-year group, r = -0.600, P = 0.002; 28-37-year group, r = -0.511, P < 0.001; 38-47-year group, r = -0.675, P < 0.001; 48-57-year group, r = -0.558, 58-67-year group, P = 0.001; r = -0.588, P < 0.001; 68-75-year group, r = -0.811, P < 0.001). A negative correlation between abdominal pain severity and QoL was found in patients aged more than 58 years (58-67-year group, r = -0.366, P = 0.017; 68-75-year group, r = -0.448, P = 0.048 ), but not in younger patients (18-27-year group, r = 0.080, P = 0.716; 28-37-year group, r = -0.063, P = 0.679; 38-47-year group, r = -0.029, P = 0.812; 48-57-year group, r = -0.022, P = 0.876). CONCLUSION: Factors affecting QoL should always be treated in IBS, especially emotional problems in young adults. Even mild abdominal pain should be controlled in elderly patients.

Changes in quality of life during biofeedback for people with puborectalis dyssynergia: generic and disease-specific measures.

AIM: The aim of the study was to evaluate the changes in symptoms and quality of life in people with puborectalis dyssynergia after biofeedback by using Short Form-36 and Patient Assessment of Constipation Quality of Life Questionnaire. BACKGROUND: Biofeedback is an effective treatment in clinical symptoms for puborectalis dyssynergia. However, little is known about the degree of the variation in the quality of life for these people after biofeedback. METHOD: Thirty-six people with puborectalis dyssynergia were studied between June 2006 and March 2008. A bowel symptom record, a generic quality of life measure - the Short Form-36 and a disease-specific measure - the Patient Assessment of Constipation Quality of Life Questionnaire were recorded before and after biofeedback. FINDINGS: Thirty-one people rated their satisfaction with behavioural treatment as 'major' or 'fair' and substantial symptom improvements occurred. Before treatment, seven of Short Form-36 subscales (except bodily pain) were significantly lower in people with puborectalis dyssynergia than those in healthy individuals. Following treatment, all subcategories except general health showed improvement surpassing pretreatment baseline values and equalling those for normal. The total Patient Assessment of Constipation Quality of Life Questionnaire score also dramatically improved as did all subscales. The nurses continually encouraged the participants, increased participants' motivation and got good outcomes. CONCLUSION: Patient-centred functional status outcomes measured by general and disease-specific instruments give critical data, from which to inform patient management. The nurses should give psycho-social support and increase the participants' motivation during training.

[Insulin-like growth factor 1 regulates expression of stem cell factor through ERKMAPK signaling pathway in gastric smooth muscle cell].

OBJECTIVE: To explore the effect and the intracellular signal transduction pathway of insulin-like growth factor 1 (IGF-1) on the expression of stem cell factor (SCF) in gastric smooth muscle cells (SMC). METHODS: Gastric SMC from SD rats were cultured by enzymolysis and identified by α-actin immunofluorescence methods. Western blot and quantitative reverse transcription-polymerase chain reaction were used to examine the expression of SCF in gastric SMC:(1) The level of SCF after gastric SMC were cultured with IGF-1. (2) The level of SCF after IGF-1 receptor (IGF-1Rα) monoclonal antibody were added. (3) Another SMC were pretreated with specific mitogen-activated protein kinase (MEK) inhibitor PD-98059 and phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor LY-294002, and investigate expression of SCF in gastric SMC. RESULTS: A very low level of SCF was expressed in gastric SMC cultured in bovine serum free medium. A low concentration of IGF-1 (5 and 10 µg/L) had no effect on the expression of SCF (both P>0.05), but the expressions of SCF mRNA and protein increased in IGF-1 at a higher concentration (50, 100 and 150 µg/L) (2.79, 5.51 and 5.35-fold in protein respectively, 1.81, 2.54 and 2.38-fold in mRNA respectively, all P<0.05), and IGF-1 in 100 µg/L may be the effective final concentration (all P<0.05). The peak of SCF increment was at the 16th hour with IGF-1 (2.36-fold in protein, 5.51-fold in mRNA, all P<0.05). The expression of SCF could be inhibited by IGF-1 receptor monoclonal antibody in a dose-dependent manner (all P<0.05). The IGF-1-induced SCF expression was reduced significantly by a pretreatment of PD-98059 (23% in protein and 48% in mRNA, P<0.05). And LY-294002 had no effect on the expression of SCF (P>0.05). CONCLUSION: The SCF expression in gastric SMC is stimulated by IGF-1 in both dose- and time-dependent manners through IGF-1R in which ERKMAPK signal transduction may play an important role.

[The effects of biofeedback training on clinical symptoms, psychological status and quality of life in patients with functional constipation].

OBJECTIVE: To explore the effects of biofeedback training on clinical symptom, psychological state and quality of life in patients with functional constipation (FC). METHODS: Forty-nine patients with FC diagnosed by Rome III were enrolled and received biofeedback training. Bowel symptom measure, Zung's self-rating anxiety scale (SAS), self-rating depression scale (SDS) and Chinese version of the MOS 36-item short form healthy survey (SF-36) were recorded to assess the effects before and after treatment. RESULTS: After biofeedback training, clinical symptom of patients with FC was greatly improved: there was a very significant decrease in total and subscales scores of bowel symptom including spontaneous frequency of bowel movements, straining effort, sensation of anorectal obstruction/blockage, stool consistency and bloating. Patients with FC also improved their quality of life as well as psychological status after biofeedback. All subcategories of SF-36 including general health, physical function, bodily pain, role physical, vitality, social function, role emotion and mental health showed marked increase. Compared to the scores before biofeedback training, SAS (41.0±8.1 vs 46.5±11.9) and SDS (44.0±8.2 vs 51.2±11.5) scores decreased significantly after biofeedback training. CONCLUSION: Biofeedback training can improve clinical symptom, psychological status and quality of life in patients with FC.