Progress of ulcerative colitis patients during the COVID-19 pandemic.

BACKGROUND: We have previously demonstrated that the first wave of the coronavirus disease 2019 (COVID-19) pandemic caused exacerbations in ulcerative colitis (UC) patients, probably through psychological and physical stress. However, successive waves of the COVID-19 pandemic continuously followed the first. The effects of this chronic stress on the disease condition in UC patients are of interest. AIM: To clarify the effect of chronic stress from COVID-19 on disease condition in patients aggravated after the first wave. METHODS: Our previous study investigated 289 consecutive UC outpatients treated in one center during March and April 2020, the period of the first wave of the COVID-19 pandemic. In this study, an identical group of 289 UC patients was evaluated using UC-disease activity index (UC-DAI), endoscopic mucosal appearance score, and Matts pathological grade scoring. RESULTS: Of the 289 UC patients included in the study in 2020, 10 patients dropped out as of 2021 and another 11 patients dropped out as of 2022, making three groups for 2020, 2021 and 2022. No significant differences in characteristics were found among the three groups. UC-DAI scores had aggravated during the period of the first wave of the COVID-19 pandemic, but significantly recovered in 2021 and remained stable in 2022. Matts grade scores significantly recovered in 2021 from those in 2020 and remained stable in 2022. CONCLUSION: Disease activity of UC patients recovered in 2021 and remained stable in 2022, aggravated by the stress of the first wave of COVID-19 in 2020 despite persistence of the pandemic.

COVID-19 pandemic and exacerbation of ulcerative colitis.

BACKGROUND: In 2020, the world faced the unprecedented crisis of coronavirus disease 2019 (COVID-19). Besides the infection and its consequences, COVID-19 also resulted in anxiety and stress resulting from severe restrictions on economic and social activities, including for patients with ulcerative colitis (UC). Fresh acute stress exerts stronger influences than continuous stress on UC patients. We therefore hypothesized that the first wave of the COVID-19 pandemic would have serious effects on UC patients and performed this retrospective control study. AIM: To determine whether the first wave of the COVID-19 pandemic would have serious effects on UC patients included in a retrospective controlled study. METHODS: A total of 289 consecutive UC outpatients seen in March and April 2020 were included in this study. Modified UC disease activity index (UC-DAI) scores on the day of entry and at the previous visit were compared. An increase of ≥ 2 was considered to indicate exacerbation. The exacerbation rate was also compared with that in 256 consecutive control patients independently included in the study from the same period of the previous year in the same manner. RESULTS: No significant differences in patient characteristics or pharmacotherapies before entry were seen between the groups. Mean UC-DAI score was significantly higher in subjects during the first wave of COVID-19 (0.67 + 0.07) compared to the previous visit (0.26 + 0.04; P = 0.0000). The exacerbation rate was significantly increased during the first wave of COVID-19, as compared with the previous year (15.9% [46/289] vs 8.9% [23/256]; P = 0.0151). CONCLUSION: This study demonstrated that the COVID-19 pandemic caused exacerbations in UC patients, probably through psychological and physical stress.

Reversal of the tolerance phenomenon by the intermittent administration of a histamine H2-receptor antagonist.

BACKGROUND AND AIM: The attenuated antisecretory activity of H2-receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. A previous study indicated that Helicobacter pylori (H. pylori) infection prevents the occurrence of tolerance to H2RA. In the present study, we investigated whether intermittent (every other day) administration prevents the tolerance phenomenon in H. pylori-negative patients. METHODS: Ten H. pylori-negative, healthy volunteers were included in the study. All of the patients underwent two courses of H2RA (lafutidine) administration: 21-day continuous administration (every day), followed by 21-day intermittent administration (every other day), with at least a 21-day lafutidine-free period between the first and second courses. All of the patients were examined by ambulatory intragastric pH monitoring five times: before medication, and on days 1 and 21 of the first (continuous) and second (intermittent) courses of lafutidine (10 mg b.d.) in a crossover fashion. RESULTS: The continuous administration of lafutidine had a significantly attenuated, acid-suppressing effect in H. pylori-negative patients, and showed evidence of the tolerance phenomenon. However, the tolerance phenomenon was not observed through intermittent administration. CONCLUSIONS: These results demonstrated that in H. pylori-negative patients, tolerance to H2RA, induced by continuous lafutidine administration, was reversed by subsequent intermittent administration.

Helicobacter pylori causes runx3 gene methylation and its loss of expression in gastric epithelial cells, which is mediated by nitric oxide produced by macrophages.

Previous reports have indicated that Helicobacter pylori (H. pylori) causes epigenetic changes of certain genes such as cancer suppression genes, which may be associated with carcinogenesis. However, the mechanism by which it causes epigenetic changes in certain genes and not in others is unclear. Presently, we focused on a cancer suppression gene, runx3, and demonstrated the following: (1) H. pylori induces nitric oxide (NO) production in macrophages. (2) NO causes methylation of runx3 in epithelial cells. (3) H. pylori induces the methylation of epithelial cells in the presence of macrophages, which is reversed by an NO-specific inhibitor. These results indicate that H. pylori-induced methylation is mediated by NO, and suggest that NO may be a key to the mechanism of how H. pylori causes epigenetic changes in certain genes. Additionally, we demonstrated that lipopolysaccharide, as well as H. pylori, induces NO-mediated methylation, indicating that other inflammation inducers beside H. pylori might induce aberrant methylation of runx3.

Proton pump inhibitors and recurrent bleeding in peptic ulcer disease.

Peptic ulcer disease (PUD) is one of the main lesions responsible for upper gastrointestinal (GI) bleeding, as well as esophageal varices and Mallory-Weiss tear. Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs)/aspirin are the major responsible causes. In cases of upper GI bleeding, urgent endoscopy is performed after stabilization of vital signs. There are several modalities for controlling bleeding in PUD, such as ethanol injection or hypertonic saline with epinephrine. Recurrent bleeding occurs in 20% of patients after endoscopic therapy. The combination of endoscopic intervention and a proton pump inhibitor (PPI) is necessary to achieve hemostasis of active bleeding. It has been reported that high-dose omeprazole (80 mg bolus injection, then 8 mg/h continuous infusion for 72 h, then 40 mg/day orally for 1 week) can reduce recurrent bleeding, the need for surgery and mortality from hemorrhagic shock in patients with high-risk peptic ulcer bleeding, as compared with standard-dose omeprazole. The metabolism of PPIs is dependent upon P450 2C19 genotypes and the clinical usefulness of genotypic analysis remains to be determined.

Protective effect of n-3 polyunsaturated fatty acid on primary culture of rat hepatocytes.

BACKGROUND AND AIM: Recently, we reported on the beneficial clinical effects of eicosapentaenoic acid (EPA) in patients with primary biliary cirrhosis (PBC) who were unresponsive to ursodeoxycholic acid (UDCA). In this study we examined the effect of EPA on rat hepatocytes in primary culture. METHODS: Hepatocytes were isolated from rat liver by perfusion of collagenase and cultured with or without EPA. Cell damage induced by chenodeoxycholic acid (CDCA) was assessed by WST-8 assay and lactate dehydrogenase (LDH) release. PGE(2) and LTB(4) concentrations in the culture medium were measured by enzyme-linked immunosorbent assay (ELISA). cDNA was made from total RNA that was extracted from hepatocytes, and TaqMan polymerase chain reaction (PCR) was performed to assess the expression of CuZn and Mn superoxide dismutase (SOD) mRNA. RESULTS: When rat hepatocytes were cultured in the presence of EPA, the damage caused by CDCA was significantly decreased compared with cells cultured without EPA. Cytotoxicity significantly decreased in the presence of EPA. Furthermore, SOD mRNA expression was increased by adding EPA. These findings indicated that EPA protects cells by scavenging superoxide radicals ((*)O(2-)) mediated by SOD production. CONCLUSION: EPA has a direct protective effect on rat hepatocytes, which is in agreement with the clinical efficacy of EPA in PBC patients.

[PPI-test].

GERD (gastro esophageal reflux disease) is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Endoscopic-positive GERD can be easily diagnosed with endoscopy, while endoscopic-negative GERD cannot be. PPI test, which reveals the disorders by judging symptom-relief after PPI administration, is an effective tool for diagnosis of NERD, and extraesophageal GERD such as LPRD and bronchial asthma. Diagnostic power of PPI test is limited owing to the low PPI's cure rate against NERD, about 40%. PPI test-negative NERD is considered as non-acid associated NERD. Most of the NERD patients have the symptoms of functional dyspepsia(FD) for which the most effective medication is PPI administration, leading to the notion that subgroup of GERD and FD is considered as an acid associated disorder. This diagnostic entity is practical in a sense that anti-acid treatment is very effective for this disease. Besides, PPI test is a very useful tool to differentiate acid associated disorder from GERD and/or FD.

Effects of rabeprazole or famotidine during cardiac surgery on perioperative gastric and esophageal pH readings.

OBJECTIVES: Upper gastrointestinal bleeding, particularly from a stress-induced duodenal ulcer, is an extremely important perioperative complication in cardiovascular surgery. METHODS: In the present study, 33 patients undergoing elective open heart surgery between July 2000 and February 2001 were allocated to either a famotidine (FAM) or rabeprazole (RPZ) group to examine the perioperative gastric and esophageal pH readings, in conjunction with an investigation into the effect of infection with Helicobacter pylori (HP). RESULTS: Postoperative upper gastrointestinal bleeding did not occur in either group, and the intraoperative and postoperative mean gastric pH readings, as well as the holding time pH>6, suggested sufficient acid suppression by either drug. Gastric acid secretion was less strongly suppressed in HP-negative patients in the FAM group, but was unaffected by HP infection status in the RPZ group. CONCLUSION: The FAM group and RPZ group revealed a sufficient effect of gastric acid suppression. It was indicated that FAM had an insufficient effect of gastric acid suppression for HP-negative patients.

[Significance of PPI-test in the diagnosis of GERD].

Gastroesophageal reflux disease (GERD) is defined as 'Chronic symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus'. Reflux esophagitis refers to a subgroup of GERD patients with histopathologically demonstrated characteristic changes in the esophageal mucosa. Besides, GERD includes symptoms without endoscopic findings (endoscopic negative GERD) and extra-esophageal symptoms. Therefore, GERD cannot be diagnosed only by endoscopy. Three methods are indispensable in the diagnosis of GERD; endoscopy, evaluation of patient symptoms and acid reflux. Since 'Symptom relief is well correlated with the degree or suppression of gastric acid secretion in GERD', symptom in relation to acid reflux can be evaluated by PPI-test. Characteristics of PPI-test including extra-esophageal GERD diagnosis are discussed in this review.