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Article: Natriuretic Peptide-Based Novel Therapeutics: Long Journeys of Drug Developments Optimized for Disease States.

Ichiki, Tomoko / Jinno, Atsushi / Tsuji, Yoshihisa

2022 Volume 11, Issue 6

Abstract: The field of natriuretic peptides (NPs) as an endocrine hormone has been developing since 1979. There are three peptides in humans: atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which bind to the guanylyl cyclase-A (GC-A) ... ...

Abstract	The field of natriuretic peptides (NPs) as an endocrine hormone has been developing since 1979. There are three peptides in humans: atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which bind to the guanylyl cyclase-A (GC-A) receptor (also called natriuretic peptide receptor-A (NPR-A)), and C-type natriuretic peptide (CNP), which binds to the GC-B receptor (also called the NPR-B) and then synthesizes intracellular cGMP. GC-A receptor stimulation has natriuretic, vasodilatory, cardiorenal protective and anti-renin-angiotensin-aldosterone system actions, and GC-B receptor stimulation can suppress myocardial fibrosis and can activate bone growth before epiphyseal plate closure. These physiological effects are useful as therapeutics for some disease states, such as heart failure, hypertension, and dwarfism. To optimize the therapeutics for each disease state, we must consider drug metabolism, delivery systems, and target receptor(s). We review the cardiac NP system; new designer NPs, such as modified/combined NPs and modified peptides that can bind to not only NP receptors but receptors for other systems; and oral drugs that enhance endogenous NP activity. Finally, we discuss prospective drug discoveries and the development of novel NP therapeutics.
Language	English
Publishing date	2022-06-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology11060859
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Article: Natriuretic Peptide-Based Novel Therapeutics: Long Journeys of Drug Developments Optimized for Disease States

Ichiki, Tomoko / Jinno, Atsushi / Tsuji, Yoshihisa

Biology. 2022 June 03, v. 11, no. 6

2022

Abstract	The field of natriuretic peptides (NPs) as an endocrine hormone has been developing since 1979. There are three peptides in humans: atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which bind to the guanylyl cyclase-A (GC-A) receptor (also called natriuretic peptide receptor-A (NPR-A)), and C-type natriuretic peptide (CNP), which binds to the GC-B receptor (also called the NPR-B) and then synthesizes intracellular cGMP. GC-A receptor stimulation has natriuretic, vasodilatory, cardiorenal protective and anti-renin–angiotensin–aldosterone system actions, and GC-B receptor stimulation can suppress myocardial fibrosis and can activate bone growth before epiphyseal plate closure. These physiological effects are useful as therapeutics for some disease states, such as heart failure, hypertension, and dwarfism. To optimize the therapeutics for each disease state, we must consider drug metabolism, delivery systems, and target receptor(s). We review the cardiac NP system; new designer NPs, such as modified/combined NPs and modified peptides that can bind to not only NP receptors but receptors for other systems; and oral drugs that enhance endogenous NP activity. Finally, we discuss prospective drug discoveries and the development of novel NP therapeutics.
Keywords	atrial natriuretic peptide ; drugs ; dwarfing ; fibrosis ; growth plate ; heart failure ; hypertension ; pharmacokinetics ; therapeutics
Language	English
Dates of publication	2022-0603
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology11060859
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Self-assessment scale for the community-based and emergency practice.

Wakabayashi, Takao / Tsuji, Yoshihisa / Yamamoto, Takeshi / Sohma, Hitoshi / Yamamoto, Wari

BMC medical education

2022 Volume 22, Issue 1, Page(s) 799

Abstract: Background: For current medical education, community-based primary care for the elderly is an essential topic. This study aimed to establish a scale of community-based assessment for clinical and emergency practice (C-CEP).: Methods: A self- ... ...

Abstract	Background: For current medical education, community-based primary care for the elderly is an essential topic. This study aimed to establish a scale of community-based assessment for clinical and emergency practice (C-CEP). Methods: A self-assessment scale for C-CEP was developed according to four steps. Initially, we reviewed publications from the societies of the United States, British, and Japan regarding educational goals. In addition, we searched MEDLINE for educational goals regarding attitude, skills, and knowledge. Getting together, we established 23 items as the educational goals of the C-CEP. Second, we collected responses for these 23 items from 5th-grade medical students (n = 195). Third, we conducted an exploratory factor analysis (EFA) using their responses to determine the fundamental structure of the self-assessment scale. Finally, a confirmatory factor analysis (CFA) was performed to assess the fitness of the self-assessment scale developing the EFA, resulting in modification of the items. Results: In EFA and CFA results, C-CEP Scale consisted of four factors with 15 items: "Attitude and communication in emergency care," Basic clinical skills," "Knowledge of community healthcare," and "Knowledge of evidence-based medicine perseverance." The model fit indices were acceptable (Goodness of Fix Index = 0.928, Adjusted Goodness of Fit Index = 0.900, Comparative Fit Index = 0.979, and Root Mean Square Error of Approximation = 0.045). The values of McDonald's omega as an estimate of scale reliability were more than 0.7 in all four factors. As for test-retest reliability, the intraclass correlation coefficients were ≥ 0.58 for all factors. All four factors of the C-CEP Scale correlated positively with the Medical Professionalism Evaluation Scale subscales. Conclusions: We developed a valid and reliable self-assessment scale to assess student competence.
MeSH term(s)	Humans ; Aged ; Reproducibility of Results ; Self-Assessment ; Psychometrics ; Factor Analysis, Statistical ; Students
Language	English
Publishing date	2022-11-17
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	2044473-4
ISSN	1472-6920 ; 1472-6920
ISSN (online)	1472-6920
ISSN	1472-6920
DOI	10.1186/s12909-022-03848-z
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Article ; Online: Blue Foreign Body in the Esophagus.

Tomiyama, Ryosuke / Ichiki, Tomoko / Tsuji, Yoshihisa

Gastroenterology

2021 Volume 162, Issue 7, Page(s) e14–e15

MeSH term(s)	Cyanosis ; Esophagus/diagnostic imaging ; Esophagus/surgery ; Foreign Bodies/diagnostic imaging ; Foreign Bodies/surgery ; Humans
Language	English
Publishing date	2021-11-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2021.11.025
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Article ; Online: Two Types of Immune Checkpoint Inhibitor-related Pancreatitis.

Ichiki, Tomoko / Hori, Yasuki / Tsuji, Yoshihisa

Internal medicine (Tokyo, Japan)

2021 Volume 61, Issue 10, Page(s) 1477–1478

MeSH term(s)	Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Pancreatitis/chemically induced ; Pancreatitis/drug therapy
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2021-11-06
Publishing country	Japan
Document type	Journal Article ; Comment
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.8452-21
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Article: Gut microbiota and metabolites in patients with COVID-19 are altered by the type of SARS-CoV-2 variant.

Yokoyama, Yoshihiro / Ichiki, Tomoko / Yamakawa, Tsukasa / Tsuji, Yoshihisa / Kuronuma, Koji / Takahashi, Satoshi / Narimatsu, Eichi / Katanuma, Akio / Nakase, Hiroshi

Frontiers in microbiology

2024 Volume 15, Page(s) 1358530

Abstract: Introduction: Patients with COVID-19 have dysbiosis of the intestinal microbiota with altered metabolites in the stool. However, it remains unclear whether the differences among SARS-CoV-2 variants lead to differences in intestinal microbiota and ... ...

Abstract	Introduction: Patients with COVID-19 have dysbiosis of the intestinal microbiota with altered metabolites in the stool. However, it remains unclear whether the differences among SARS-CoV-2 variants lead to differences in intestinal microbiota and metabolites. Thus, we compared the microbiome and metabolome changes for each SARS-CoV-2 variant in patients with COVID-19. Materials and methods: We conducted a multicenter observational study of patients with COVID-19 and performed fecal microbiome, metabolome, and calprotectin analyses and compared the results among the different SARS-CoV-2 variants. Results: Twenty-one patients with COVID-19 were enrolled and stratified according to the SARS-CoV-2 strain: six with the Alpha, 10 with the Delta, and five with the Omicron variant. Fecal microbiome analysis showed that α-diversity was reduced in the order of the Omicron, Delta, and Alpha variants ( Conclusion: The intestinal microbiota of patients with COVID-19 varies depending on the SARS-CoV-2 variant. Dysbiosis of the intestinal microbiota due to differences in SARS-CoV-2 variants causes a decrease in intestinal short-chain fatty acids.
Language	English
Publishing date	2024-03-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2024.1358530
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Article ; Online: The diagnostic accuracy of endoscopic ultrasound-shear wave elastography in multiple pancreatic regions for chronic pancreatitis based on the Rosemont criteria.

Shintani, Shuhei / Inatomi, Osamu / Hiroe, Kosuke / Tomozawa, Yuki / Inoue, Akitoshi / Kimura, Hidenori / Nishida, Atsushi / Tsuji, Yoshihisa / Watanabe, Yoshiyuki / Andoh, Akira

Journal of medical ultrasonics (2001)

2023 Volume 50, Issue 4, Page(s) 485–492

Abstract: Purpose: Although endoscopic ultrasound (EUS) has been widely used for diagnosing chronic pancreatitis (CP), the assessment of fibrosis using the Rosemont criteria (RC) is generally subjective. Shear wave elastography using EUS (EUS-SWE) has been ... ...

Abstract	Purpose: Although endoscopic ultrasound (EUS) has been widely used for diagnosing chronic pancreatitis (CP), the assessment of fibrosis using the Rosemont criteria (RC) is generally subjective. Shear wave elastography using EUS (EUS-SWE) has been advocated as an objective approach to evaluating pancreatic fibrosis; however, it is unknown which pancreatic region should be selected for measurement. This study aims to compare the diagnostic accuracy in diagnosing CP by measurement site. Methods: Fifty patients with CP or suspected CP who underwent EUS-SWE were retrospectively analyzed. As per the RC, they were classified into two groups: CP and non-CP. Pancreatic stiffness was evaluated by measuring the velocities of the shear wave (Vs) in addition to determining the relevant cutoff value of Vs for diagnosing CP. The correlation between Vs and RC, and the RC factors affecting pancreatic stiffness were evaluated. Results: In the CP group, the Vs were notably higher in all regions (P < 0.001). The Vs for diagnostic accuracy of CP were highest in the body [area under the curve (AUC): 0.87]. A significant correlation was seen between the number of RC and Vs in all regions, with the correlation coefficient being highest in the pancreatic body (rs = 0.55). Multivariate analysis revealed that lobularity with honeycombing was an independent factor for pancreatic stiffness (P = 0.02). Conclusion: The pancreatic body is a suitable region for assessing pancreatic stiffness using EUS-SWE. Additionally, quantifying Vs is a valuable objective indicator for diagnosing CP.
MeSH term(s)	Humans ; Elasticity Imaging Techniques ; Retrospective Studies ; Pancreas/diagnostic imaging ; Pancreatitis, Chronic/diagnostic imaging ; Endosonography ; Fibrosis
Language	English
Publishing date	2023-08-16
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1396630-3
ISSN	1613-2254 ; 0287-0592 ; 1346-4523
ISSN (online)	1613-2254
ISSN	0287-0592 ; 1346-4523
DOI	10.1007/s10396-023-01350-7
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Article ; Online: Fatal Immune Checkpoint Inhibitor-related Pancreatitis.

Ueno, Masayuki / Tsuji, Yoshihisa / Yokoyama, Toshihide / Koyama, Takashi / Uenishi, Yosuke / Ishida, Etsuji / Mizuno, Motowo

Internal medicine (Tokyo, Japan)

2021 Volume 60, Issue 24, Page(s) 3905–3911

Abstract: We herein report a case of fatal pancreatitis induced by an immune checkpoint inhibitor. A 62-year-old man with cancer of unknown primary was treated with pembrolizumab. After 12 cycles, immune-related pneumonitis developed and was treated with ... ...

Abstract	We herein report a case of fatal pancreatitis induced by an immune checkpoint inhibitor. A 62-year-old man with cancer of unknown primary was treated with pembrolizumab. After 12 cycles, immune-related pneumonitis developed and was treated with prednisolone. Three months later, pancreatitis developed, which was successfully treated with hydration and protease inhibitors. Eight months later, another attack of pancreatitis occurred, which did not respond to therapy, including high-dose corticosteroids, and he eventually died. This is the first report describing fatal immune checkpoint inhibitor-related pancreatitis. Despite the rarity of this complication, attention should be paid to its potential severity and treatment.
MeSH term(s)	Adrenal Cortex Hormones/therapeutic use ; Humans ; Immune Checkpoint Inhibitors ; Male ; Middle Aged ; Pancreatitis/chemically induced ; Pancreatitis/diagnosis ; Pancreatitis/drug therapy ; Pneumonia/drug therapy ; Prednisolone/therapeutic use
Chemical Substances	Adrenal Cortex Hormones ; Immune Checkpoint Inhibitors ; Prednisolone (9PHQ9Y1OLM)
Language	English
Publishing date	2021-06-12
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.7366-21
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Article ; Online: Non-compliance to practice guidelines still exist in the early management of acute pancreatitis: Time for reappraisal?

Talukdar, Rupjyoti / Tsuji, Yoshihisa / Jagtap, Nitin / Pradeep, R / Rao, G V / Reddy, D Nageshwar

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.

2021

Abstract: Introduction: Earlier national surveys on the management of acute pancreatitis (AP) had reported non-compliance to practice guidelines. In the past decade, several guidelines were revised based on new evidence. In this multicenter international survey, ... ...

Abstract	Introduction: Earlier national surveys on the management of acute pancreatitis (AP) had reported non-compliance to practice guidelines. In the past decade, several guidelines were revised based on new evidence. In this multicenter international survey, we aimed to evaluate the practice patterns of early management of AP and compliance to the revised treatment guidelines across different disciplines and practice environments. Methods: A structured questionnaire was sent via email to a target population of 654 that constituted of medical and surgical gastroenterologists, physicians and general surgeons, paediatricians from academic and non-academic centres across 30 countries. Other than demographic variables, the questionnaire contained items pertaining to early management of AP, such as, assessment at admissions and within first 72 h s, details regarding analgesics, IV hydration, oral/enteral feeding and antibiotic use. Results: The response rate was 46.2% and after exclusions, a total of 297 participant's responses were analysed. Majority of the participants were from Asia, followed by Europe and the Americas. 181 (60.9%) claimed to follow practice guidelines, out of which 59 (32.6%) followed more than one. On further probing, only 41.9% were actually compliant to feeding and 59.7% to antibiotic guidelines. Even though participants opted for aggressive hydration, early feeding and avoidance of prophylactic antibiotics, there were non-compliance and discrepancies in titration of fluid therapy, indications of feeding and antibiotic use. Discussion: Discrepancies and non-compliance still appear to exist in the early management of AP due to lack of strong evidence. We discuss ways that could improve compliance to the existing guidelines until stronger evidence comes to the fore.
Language	English
Publishing date	2021-05-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2056680-3
ISSN	1424-3911 ; 1424-3903
ISSN (online)	1424-3911
ISSN	1424-3903
DOI	10.1016/j.pan.2021.05.301
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Article: Impaired tryptophan metabolism in the gastrointestinal tract of patients with critical coronavirus disease 2019.

Yokoyama, Yoshihiro / Ichiki, Tomoko / Yamakawa, Tsukasa / Tsuji, Yoshihisa / Kuronuma, Koji / Takahashi, Satoshi / Narimatsu, Eichi / Nakase, Hiroshi

Frontiers in medicine

2022 Volume 9, Page(s) 941422

Abstract: Introduction: Coronavirus disease 2019 (COVID-19) is still causing a global pandemic. But the mechanism of COVID-19 severity is not well elucidated.: Materials and methods: We conducted two single-center observational studies of patients with COVID- ... ...

Abstract	Introduction: Coronavirus disease 2019 (COVID-19) is still causing a global pandemic. But the mechanism of COVID-19 severity is not well elucidated. Materials and methods: We conducted two single-center observational studies of patients with COVID-19. In the first study, the enrolled patients were distinguished based on critical vs. non-critical COVID-19. We collected blood samples from the patients at admission to measure markers related to inflammation and thrombosis and stool samples to analyze the fecal microbiome, metabolome, and calprotectin level. In the second study, we collected ileum and colon tissue samples from patients with critical COVID-19 who required colonoscopy due to severe gastrointestinal symptoms and analyzed mucosal gene expression. Results: A total of 19 blood samples and 10 stool samples were collected. Interleukin (IL)-6 was the only serum inflammatory marker with significantly higher levels in the critical group than in the non-critical group. The fecal calprotectin level in the critical group was significantly higher than that in the non-critical group ( Discussion: Critical COVID-19 patients have gastrointestinal inflammation potentially caused by impaired tryptophan metabolism in the small intestine due to decreased expression of genes involved in tryptophan metabolism.
Language	English
Publishing date	2022-08-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.941422
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