Yoshiko Fujikawa

Enteric glial cells are associated with stress-induced colonic hyper-contraction in maternally separated rats.

Enteric glial cells (EGCs) play important roles in enteric integrity and regulation of gastrointestinal function. However, whether EGCs undergo pathophysiological changes in stress‐associated gastrointestinal disorders is unknown. We investigated structural and functional alterations in colonic EGCs and their roles in colonic contraction in an irritable bowel syndrome (IBS) model.

Disorder of autonomic nervous system and its vulnerability to external stimulation in functional dyspepsia

To elucidate the role of autonomic nervous system in functional dyspepsia patients, we examined 24-h heart rate variability: the basal levels, responses after lunch, cold pressor and mental arithmetic tests, and the efficacy of an autonomic drug (tofisopam). The high-frequency component (HF: 0.15–0.40 Hz) and the ratio of HF to the low-frequency component (LF: 0.04–0.15 Hz; LF/HF ratio) were used as indicators of parasympathetic and sympathetic autonomic nervous system function. The HF component in the 24-h, daytime, and nighttime was low in 86.7%, 97.8%, and 66.7% of patients (n = 45) and the LF/HF ratio was high in 51.1%, 73.3%, and 26.6% of patients. Gastrointestinal symptom tended to be severe in patients with autonomic nervous system disorder (p = 0.085). The abnormal response in HF component after lunch occurred in 38.2% (13/34) of patients who revealed a greater tendency towards in indigestion score (p = 0.061). Delays in recovery to the basal autonomic nervous system level after stimulus of the cold pressor and the mental arithmetic tests occurred in parts of patients. Tofisopam partially improved autonomic nervous system dysfunction and abdominal pain/indigestion. Imbalanced autonomic nervous system function and vulnerability for recovery from external stimuli were observed in functional dyspepsia patients, which was associated with dyspeptic symptoms.

High prevalence of gastroesophageal reflux symptoms in patients with non-alcoholic fatty liver disease associated with serum levels of triglyceride and cholesterol but not simple visceral obesity.

Background/Aims: Visceral obesity is commonly involved in the pathogenesis of gastroesophageal reflux disease (GERD) and non-alcoholic fatty liver disease (NAFLD). However, other characteristic factors different from visceral obesity are associated with the pathogenesis of NAFLD. We investigated the prevalence of GERD symptoms in patients with NAFLD and its associated risk factors. Methods: NAFLD (n = 96) and controls (n = 139) were enrolled in this study. GERD symptoms were evaluated by using a frequency scale for the symptoms of GERD. Results: GERD symptom score and its prevalence rate were higher in the NAFLD group (7.4 ± 0.7, 37%) than those seen in the control groups (4.5 ± 0.4, 20%), which was independent of sex, age, and body mass index (BMI). GERD symptoms were correlated with insulin resistance (r = 0.167, p = 0.011), total cholesterol (T-CHO) (r = 0.138, p = 0.034), triglyceride (TG) (r = 0.178, p = 0.006), or immunoreactive insulin (r = 0.173, p = 0.008) but not BMI (r = 0.089, p = 0.175). GERD symptoms of the NAFLD group were significantly severer in the higher group of T-CHO and TG levels than those in the lower group. Multivariate analysis proved that risk factors related to GERD symptoms were TG (OR 3.96, 95% CI 1.31–11.9) and T-CHO (OR 3.39, 95% CI 1.11–10.3). Conclusion: The severity and prevalence of GERD symptoms in patients with NAFLD were high, which was associated with serum levels of TG and T-CHO but not BMI.

Structural changes in gastric glial cells and delayed gastric emptying as responses to early life stress and acute adulthood stress in rats

AIM Enteric glial cells (EGCs) modulate colonic motility in a maternal separation model. We aimed to investigate structural changes in gastric EGC and gastric emptying as responses to maternal separation and acute adulthood stress in rats to elucidate the pathophysiological roles of gastric EGC. MAIN METHODS As a chronic stress, we subjected male Wistar rats to 3h of maternal separation during postnatal days 2-14. As an acute adulthood stress (7weeks of age), we used the 8-h water-immersion method. We morphologically evaluated gastric EGCs using whole-mount longitudinal muscle-myenteric plexus preparations. We analyzed gastric emptying by the phenol red method. KEY FINDING The area of EGC processes that apparently overlapped with neurons increased according to stress intensity (acute stress, 10.4%; maternal separation, 10.2%; maternal separation plus acute stress, 26.6%; control, 5.0%). Ratios of morphologically changed leaf-like processes to the total processes were 8.1%, acute stress; 10.3%, maternal separation; 4.0%, control. Ratio dramatically increased in the combined stress group (20.5%, p=0.026 vs. control). The mean bulging head area of leaf-like processes in the combined stress group was greater by 6.4μm(2) (control, 2.4μm(2); p=0.042). Gastric emptying in the maternal separation group was gradually delayed (104.1% at 7weeks, 66.7% at 17weeks, and 48.5% at 48weeks; p<0.05, respectively). Gastric emptying in the combined stress group tended to be delayed at 17weeks (45.7% vs. 81% in controls, p=0.066). SIGNIFICANCE Gastric EGCs exhibited structural changes according to stress intensity, which may be associated with stress-induced dysfunction of the stomach.

Postprandial Symptoms Felt at the Lower Part of the Epigastrium and a Possible Association of Pancreatic Exocrine Dysfunction with the Pathogenesis of Functional Dyspepsia

Objective In symptom-dependent diseases such as functional dyspepsia (FD), matching the pattern of epigastric symptoms, including severity, kind, and perception site, between patients and physicians is critical. Additionally, a comprehensive examination of the stomach, duodenum, and pancreas is important for evaluating the origin of such symptoms. Methods FD-specific symptoms (epigastric pain, epigastric burning, early satiety, and postprandial fullness) and other symptoms (regurgitation, nausea, belching, and abdominal bloating) as well as the perception site of the above symptoms were investigated in healthy subjects using a new questionnaire with an illustration of the human body. A total of 114 patients with treatment-resistant dyspeptic symptoms were evaluated for their pancreatic exocrine function using N-benzoyl-L-tyrosyl-p-aminobenzoic acid. Results A total of 323 subjects (men:women, 216:107; mean age, 52.1 years old) were initially enrolled. Most of the subjects felt the FD-specific symptoms at the epigastrium, while about 20% felt them at other abdominal sites. About 30% of expressed as epigastric symptoms were FD-nonspecific symptoms. At the epigastrium, epigastric pain and epigastric burning were mainly felt at the upper part, and postprandial fullness and early satiety were felt at the lower part. The prevalence of patients with pancreatic exocrine dysfunction was 71% in the postprandial fullness group, 68% in the epigastric pain group, and 82% in the diarrhea group. Conclusion We observed mismatch in the perception site and expression between the epigastric symptoms of healthy subjects and FD-specific symptoms. Postprandial symptoms were often felt at the lower part of the epigastrium, and pancreatic exocrine dysfunction may be involved in the FD symptoms, especially for treatment-resistant dyspepsia patients.

Su1857 Intracellular Activity and Characteristic Features of Enteric Glial Cells Were Caused by Stimulation With Corticosterone

BACKGROUND: Slow waves generated by the interstitial cells of Cajal (ICC) coordinate gastric peristaltic contractions. Spatiotemporal profiling of normal human gastric slow wave activity, using high-resolution (HR) electrical mapping, has previously identified a region of increased velocity and amplitude in the distal stomach of dogs and humans. However, the specific anatomical and physiological details of this regional change in activation have not been characterized. This study applied HR mapping with anatomical registration to accurately quantify distal gastric slow wave activation in humans. METHODS: Patients with normal stomachs undergoing elective hepatobiliary or pancreatic surgery gave informed consent for in-vivo gastric mapping. HR serosal slow wave recordings were collected using flexible printed circuit board arrays (128-256 electrodes, 4-5 mm spacing) placed from the pylorus to mid corpus. Photographs were taken for anatomical registration. Activation times, velocities, amplitudes and frequencies were calculated, and regional variation evaluated. RESULTS: High resolution mapping was performed on n=6 patients (5 male, mean age: 52 years, range: 27-71 years). Activation maps were consistent and demonstrated normal organised aboral slow-wave propagation. A region of increased amplitude and velocity was identified in the distal antrum. The region commenced approximately 30 mm from the pylorus and ceased approximately 8 mm from the pylorus. Over this transition region of 22 mm, velocity increased from 3.6±0.0 mm/s to a peak of 7.5±0.1 mm/s distally (p<0.001). This velocity transition was accompanied by an increase in extracellular slow wave amplitude from 1.4±0.1 mV to 2.7±0.1mV (p<0.001). CONCLUSIONS: HR mapping was applied to accurately define the variation of slow wave activity in the terminal antrum of humans. This localized slow wave pattern is likely to contribute to the rapid propulsion of gastric contents against the pylorus, enhancing retropulsion, trituration and gastric emptying. These results will now be correlatedwith imaging findings. The cellular/ICC networkmechanisms responsible for this activity appear to be unknown