Kayoko Ozeki

Background: Orexin (OX) levels are elevated in the cerebrospinal fluid of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Objective: To investigate the efficacy of dual OX receptor antagonists (suvorexant and lemborexant) in an early-stage AD mouse model (App-KI). Methods: OX receptor gene expression was measured. Additionally, drug distribution and effects on motor activity following single oral administration of suvorexant and lemborexant were assessed. Furthermore, cognitive function, amyloid-β (Aβ) levels and uptake by microglia in the hippocampal CA1 region were evaluated following daily administration of suvorexant and lemborexant for 60 days. Results: OXR gene expression was highest in the lateral hypothalamus of wild-type mice and was also observed in other brain regions. OX1R gene expression was significantly increased in these brain regions in App-KI mice. In wild-type mice, brain concentrations of suvorexant peaked 20 to 40 min after administration, and those of lemborexant peaked 15 min after administration. Concentrations subsequently declined but remained detectable 24 h after administration. Additionally, motor activity decreased following the administration of either suvorexant or lemborexant; however, no difference in motor activity was observed compared to the control group 24 h later. Notably, the Y-maze test revealed that suvorexant and lemborexant mitigated cognitive impairment in App-KI mice. Furthermore, both drugs suppressed the accumulation of Aβ in the CA1 region of the hippocampus in App-KI mice. This was associated with increased Aβ uptake by activated microglia. Conclusions: The results suggest that suvorexant and lemborexant effectively suppresses the early stages of AD.

Background: A simple suspension method is used in medical practice to administer several orexin receptor antagonists for patients with dysphagia; however, detailed suspension and passage through catheter evaluations have not been performed. Therefore, to safely administer orexin receptor antagonists using the simple suspension method in patients with dysphagia, this study evaluated the disintegration, suspension, passage through the catheter, and drug recovery after passage of Belsomra ^® 20 mg (suvorexant), Dayvigo ^® 10 mg (lemborexant), and Quviviq ^® 50 mg (daridorexant) tablets through a catheter. Methods: Disintegration and suspension of Belsomra ^® 20 mg, Dayvigo ^® 10 mg, and Quviviq ^® 50 mg tablets, and passage through the catheter were visually confirmed. Drug recovery after passage through the catheter was quantified using liquid chromatography-mass spectrometry. Results: In this study, there was no disintegration and suspension of Belsomra ^® 20 mg tablets. However, Dayvigo ^® 10 mg and Quviviq ^® 50 mg tablets demonstrated disintegration and suspension, including passage through the catheter after rapid and complete disintegration. Drug recovery after catheter passage was >80% for Dayvigo ^® 10 mg without flushing and for Quviviq ^® 50 mg after two flushes. Conclusion: As the disintegration and suspension properties of Belsomra ^® 20 mg tablet could not be confirmed, the conventional simple suspension method is not suitable for this product. However, Dayvigo ^® 10 mg and Quviviq ^® 50 mg tablets showed potential suitability for the simple suspension method.

Eradication of Helicobacter pylori (H. pylori) is extremely important to reduce the risk of developing gastric ulcer and gastric cancer. However, in recent years, a decrease in the success rate of eradication has been reported due to an increase in antibiotic-resistant bacteria. In particular, there is concern in Japan about the impact of resistance to clarithromycin (CAM), metronidazole (MNZ), and amoxicillin (AMPC), which are used for primary and secondary eradication, on the difficulty of eradication. In this study, we investigated the susceptibility to AMPC, CAM, and MNZ in patients presenting to a university hospital for H. pylori eradication and evaluated the impact of each resistance pattern on the eradication success rate using logistic regression analysis. The results showed that the eradication success rate was significantly lower in patients with MNZ resistance, AMPC+MNZ resistance, CAM+MNZ resistance, and in patients resistant to all three types. This suggests that MNZ resistance has a significant impact on the success rate of H. pylori eradication and should be considered in future eradication strategies.

Background: Mild cognitive impairment (MCI) is a condition between healthy cognition and dementia with a high probability of progression to Alzheimer’s disease (AD). Elevated levels of orexin (OX) have been reported in the cerebrospinal fluid of patients with MCI and AD. Objective: To investigate the efficacy of dual OX receptor antagonists (suvorexant and lemborexant) in an early-stage AD mouse model (App-KI). Methods: The expression of the OX receptor gene, the levels of suvorexant and lemborexant in the brain after a single oral dose, and their effects on locomotor activity were investigated in wild-type mice. In addition, the cognitive function of wild-type and App-KI mice was assessed using the Y-maze test after oral administration of suvorexant or lemborexant once a day for 60 d. After the behavioral test, amyloid-beta levels were quantified in the hippocampal CA1 region of App-KI mice. Results: The expression of the OX receptor gene was highest in the lateral hypothalamus and was also observed in other brain regions. Drug levels peaked at 20–40 min for suvorexant and 15 min for lemborexant and declined, still detectable 24 h later. Locomotor activity was reduced after suvorexant or lemborexant administration; however, 24 h after administration, locomotor activity did not differ from the control group. In particular, the Y-maze test showed that suvorexant and lemborexant prevented cognitive impairment in App-KI mice. Furthermore, suvorexant and lemborexant suppressed amyloid-beta accumulation in the hippocampal CA1 region of App-KI mice. Conclusion: The results suggest that suvorexant and lemborexant effectively suppress the early stages of AD.

Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can lead to gastric atrophy. This study aimed to identify the factors associated with gastric atrophy in H. pylori eradication patients with drinking habits. Of the 250 patients who visited Hamamatsu University Hospital for H. pylori eradication and underwent eradication treatment between April 2017 and December 2020, 127 patients with drinking habits were included in this study. The degree of gastric atrophy of the patients was classified based on endoscopy. The relationship between patient attributes (sex, age, alcohol consumption, frequency of drinking, smoking status, and medication use) and a highly atrophic stomach was statistically analyzed. The results showed that gastric atrophy was significantly higher in males and in those aged 60 years or older and that gastric atrophy tended to be higher in those who drank 20 g or more per day and 5 days or more a week. There was also a trend toward higher atrophy in sake drinkers and lower atrophy in wine drinkers. This study provides useful knowledge for patient management and guidance after H. pylori eradication treatment and indicates the importance of comprehensive measures, including alcohol consumption control and lifestyle modification, especially for men and older people.

Objective: Pharmacies have a particularly important responsibility to supply medicine to disaster victims in order to save lives. This study investigated the characteristics of pharmacies that are well prepared for disasters as well as the efforts of the prefectural pharmaceutical association (PPA) to which the pharmacies belong. Methods: Questionnaires on matters related to disaster preparedness were mailed to 50 randomly selected pharmacies in each of Japan’s 47 prefectures as well as all 47 PPAs in Japan. Logistic regression analysis was performed to examine the association of pharmacy background and the activities of the PPA to which they belong with pharmacy disaster preparedness as well as the association with pharmacies’ awareness of disaster preparedness. Results: Pharmacies in prefectures that conducted disaster preparedness training at least three times a year were better prepared for disasters. In addition, pharmacies with high online utilization and high disaster-preparedness awareness were significantly more prepared for disasters. Conclusions: Pharmacies that can promptly provide medicine to disaster victims are considered to be well-prepared for disasters. The results suggest that pharmacy preparedness is also influenced by the disaster preparedness activities of their prefectures.

Eradication of Helicobacter pylori (H. pylori) is crucial to reduce the risk of developing gastric ulcers and gastric cancer. Although immunoglobulin E (IgE) levels and alcohol consumption have been shown to influence the failure of H. pylori eradication, the relationship between these factors and the mechanism of failure has not been clarified. Because high IgE levels are associated with eradication failure, the purpose of this study was to clarify the factors leading to high IgE levels. Completed questionnaires and blood test data were collected from patients who visited a university hospital for H. pylori eradication. Logistic regression analysis was per-formed to examine the relationship between high IgE levels and allergic diseases. We also examined the relationship between alcohol intake and high IgE levels. Linear regression analysis was performed on the relationship between the amount of alcohol consumed and IgE measurements. The results showed that patients with allergic diseases and those with high alcohol intake had significantly higher IgE levels. High IgE levels are a risk factor for failure of H. pylori eradication that is associated with drinking habits and alcohol consumption, and our results suggest that daily alcohol consumption should be avoided even in non-allergic patients.

Background: Helicobacter pylori is a cause of gastric cancer, and thus the eradication of this bacterium is very important. The success rate of primary eradication has been dramatically increased by the introduction of potassium-competitive acid blockers. However, H. pylori cannot be eradicated in all patients, and the contributing factors need to be clarified. Aim: Because allergy status may be a factor and considering research linking hay fever with eradication failure, the purpose of this study was to examine blood immunoglobulin E levels as a contributing factor in patients who were unable to eradicate H. pylori in a single eradication treatment and who underwent multiple eradication attempts. Methods: Questionnaire data were collected from 250 patients who visited the Department of Gastroenterology, Hamamatsu University School of Medicine, for H. pylori eradication. In addition, non-specific IgE levels in the blood were measured and analyzed with one-way analysis of variance. Multinomial logistic regression analysis was performed to examine the association between the number of eradication attempts and the IgE level (< 500 vs ≥ 500 IU/mL). Results: The mean IgE values were 188.4, 211.9, and 744.0 IU/mL in patients with one, two, and three or more eradication attempts, respectively (P < 0.05). The results of multinomial logistic regression analysis showed that attempting eradication three or more times was significantly associated with high levels of IgE, even after consideration of antibiotic sensitivity. Conclusion: H. pylori eradication was less likely in patients with high IgE. It is thus necessary to study the appropriate regimen for patients with high IgE levels.

Helicobacter pyloriis a cause of stomach cancer and peptic ulcer. For prevention, improving the eradication rate ofH. pyloriis crucial. However, the association between eradication and lifestyle of infected patients, including alcohol consumption, remains unclear. We explored associations between failed primary eradication therapy and drinking status by sex. This study involved 356 patients who visited a pharmacy with prescriptions for primaryH. pylorieradication therapy. We assessed drinking habits using a questionnaire. Data on patients with failed primary eradication were provided by the nearby local clinic. We performed logistic regression analysis to examine the effect of drinking habit and frequency of drinking on failed primary eradication by sex. The odds ratio of primary eradication failure in female patients with a drinking habit was 3.75 (P= 0.001), but that in male patients was not significant. The odds ratio tended to increase in relation to drinking frequency in women. Frequent consumption of alcohol is not only likely to affect eradication, but also has a large impact on the bodies of women, who are more susceptible than men to the effects of alcohol. Thus, women should take greater care in alcohol consumption.