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1.
BMC Med Educ ; 24(1): 706, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943114

RESUMO

BACKGROUND: Patient care ownership (PCO) among medical students is a growing area in the field of medical education. While PCO has received increasing attention, there are no instruments to assess PCO in the context of Japanese undergraduate medical education. This study aimed to translate, culturally adapt, and validate the PCO Scale - Medical students (PCOS-S) in the Japanese context. METHODS: We collected survey data from fifth- and sixth-grade medical students from five different universities varying in location and type. Structural validity, convergent validity, and internal consistency reliability were examined. RESULTS: Data from 122 respondents were analyzed. Factor analysis of the Japanese PCOS-S revealed three factors with Cronbach's alpha values exceeding the satisfactory criterion (0.70). A positive correlation was observed between the total Japanese PCOS-S scores and the global rating scores for the clinical department as a learning environment (Pearson's correlation coefficient = 0.61). CONCLUSIONS: We conducted the translation of the PCOS-S into Japanese and assessed its psychometric properties. The Japanese version has good reliability and validity. This instrument has potential value in assessing the development of medical students' PCO.


Assuntos
Psicometria , Estudantes de Medicina , Traduções , Humanos , Estudantes de Medicina/psicologia , Japão , Reprodutibilidade dos Testes , Feminino , Masculino , Inquéritos e Questionários , Educação de Graduação em Medicina , Propriedade , Assistência ao Paciente/normas , Tradução , Análise Fatorial
2.
Med Teach ; 45(5): 524-531, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36322956

RESUMO

INTRODUCTION: The concept of social accountability in medical schools is globally accepted, but data regarding Japanese medical schools are lacking and unclear. This study aimed to elucidate the perception of social accountability of medical schools in Japan and compare this to global frameworks. METHODS: A document on Japanese medical accreditation standards (Basic Medical Education: Japanese Specifications WFME Global Standards for Quality Improvement) was used for this study. We included 45 medical schools in a qualitative content analysis done via inductive category formation. The documents were also assessed using the social obligation scale. RESULTS: Three main categories and 15 categories were identified. The three main categories were as follows: Issues in society, Quality assurance of medical school, and Improvement of individual quality. Most categories were common to those in global frameworks, but some were characteristic of the Japanese context. The distribution of schools on the social obligation scale in six elements varied mainly 'from responsibility to responsiveness' or equal unless the elements were promoted by national policy. CONCLUSIONS: The social accountability of Japanese medical schools is mostly common with the global frameworks. Our findings will help the social accountability of medical schools to become better understood and developed beyond contextual borders.


Assuntos
Educação Médica , Faculdades de Medicina , Humanos , Japão , Responsabilidade Social , Percepção , Currículo
3.
Med Teach ; : 1-6, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065689

RESUMO

As medical schools embrace diversity, it is increasingly acknowledged that medical students with disabilities must be welcome and supported in becoming physicians. Students should be able to ask for and receive reasonable accommodations to support their education. However, a practical shared approach to supporting medical students with disabilities is needed. The 12 tips in this article use sense-making theory as a framework to guide medical school faculty in supporting medical students with disabilities. The tips center on perceiving cues, creating interpretations, taking action, and communicating with students. The 12 tips can be utilized by faculty members across universities to take a proactive role in implementing support for medical students with disabilities and, in turn, nurturing an inclusive educational environment.

4.
Med Teach ; : 1-7, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37734453

RESUMO

PURPOSE: Physicians' empathy and ambiguity tolerance have recently become a focus of medical education. However, the association between the two concepts remains unclear. This study examined the association between empathy and ambiguity tolerance in the clinical context among medical trainees. METHODS: We conducted a multicenter cross-sectional study in 12 institutions: 2 universities for medical students and 10 hospitals for residents. We assessed ambiguity tolerance using the Japanese version of the Tolerance of Ambiguity in Medical Students and Doctors scale. The outcome variable was empathy, measured using the Japanese translation of the Jefferson Scales of Empathy (JSE). RESULTS: Data from 100 medical students and 135 residents were analyzed. After adjustment for possible confounders, the factor scores of 'tolerance for things that are not black or white in medicine' showed a dose-dependent association with the JSE. There was no clear trend in the association between the total scores or other factor scores and empathy. CONCLUSION: This nationwide multicenter study showed that the factor scores of 'tolerance for things that are not black or white in medicine' were associated with empathy among medical trainees. Our findings may be helpful for developing interventions in the field of medical education to nurture empathy.

5.
BMC Med Educ ; 23(1): 405, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37277759

RESUMO

BACKGROUND: Ambiguity is inherent to the medical field; hence, assessing and educating medical trainees regarding ambiguity tolerance is essential. The Tolerance of Ambiguity in Medical Students and Doctors (TAMSAD) scale-a novel instrument that assesses ambiguity tolerance in clinical settings-has been widely used for medical education research in Western countries. However, a version of this scale applicable to the intricate clinical contexts of Japan has not yet been developed. In this study, we developed the Japanese version of the TAMSAD (J-TAMSAD) scale and tested its psychometric properties. METHODS: In this multicenter study, we collected data through a cross-sectional survey in two universities (medical students) and ten hospitals (residents) across Japan, and evaluated the structural validity, criterion-related validity, and internal consistency reliability of the J-TAMSAD scale. RESULTS: We analyzed the data of 247 participants. The sample was randomly divided in half, with exploratory factor analysis (EFA) performed on one half and confirmatory factor analysis (CFA) on the other. EFA led to an 18-item J-TAMSAD scale comprising five factors. CFA showed acceptable fit for this five-factor model (comparative fit index = 0.900, root mean square error of approximation = 0.050, standardized root mean square residual = 0.069, goodness of fit index = 0.987). There was a positive correlation between the J-TAMSAD scale scores and total reverse scores on the Japanese version of the Short Intolerance of Uncertainty Scale (Pearson correlation coefficient 0.41). The internal consistency was found to be satisfactory (Cronbach's alpha 0.70). CONCLUSIONS: The J-TAMSAD scale was developed, and its psychometric properties were confirmed. The instrument can be useful for assessing tolerance of ambiguity among medical trainees in Japan. With further validation, it could be used to verify the educational effectiveness of curricula that foster ambiguity tolerance in medical trainees, or even in research assessing the relationship with other variables.


Assuntos
Estudantes de Medicina , Humanos , Japão , Reprodutibilidade dos Testes , Estudos Transversais , Inquéritos e Questionários , Psicometria
6.
BMC Med Educ ; 23(1): 408, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37277728

RESUMO

BACKGROUND: Formative feedback plays a critical role in guiding learners to gain competence, serving as an opportunity for reflection and feedback on their learning progress and needs. Medical education in Japan has historically been dominated by a summative paradigm within assessment, as opposed to countries such as the UK where there are greater opportunities for formative feedback. How this difference affects students' interaction with feedback has not been studied. We aim to explore the difference in students' perception of feedback in Japan and the UK. METHODS: The study is designed and analysed with a constructivist grounded theory lens. Medical students in Japan and the UK were interviewed on the topic of formative assessment and feedback they received during clinical placements. We undertook purposeful sampling and concurrent data collection. Data analysis through open and axial coding with iterative discussion among research group members was conducted to develop a theoretical framework. RESULTS: Japanese students perceived feedback as a model answer provided by tutors which they should not critically question, which contrasted with the views of UK students. Japanese students viewed formative assessment as an opportunity to gauge whether they are achieving the pass mark, while UK students used the experience for reflective learning. CONCLUSIONS: The Japanese student experience of formative assessment and feedback supports the view that medical education and examination systems in Japan are focused on summative assessment, which operates alongside culturally derived social pressures including the expectation to correct mistakes. These findings provide new insights in supporting students to learn from formative feedback in both Japanese and UK contexts.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Feedback Formativo , Japão , Competência Clínica , Retroalimentação , Reino Unido
7.
BMC Geriatr ; 22(1): 107, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130868

RESUMO

BACKGROUND: Little is known about the actual impact of COVID-19 on caregivers of older people with dementia and resultant collaborations among them to provide continued person-centered care while undertaking infection control measures. In this study, we explored the impact of providing dementia care during COVID-19 on caregivers involved in dementia care. METHODS: This is an exploratory qualitative case study. The participants were family members living with older people with dementia, care managers, and the medical and long-term care facility staff. Data were collected from 46 caregivers via face-to-face and semi-structured interviews and analyzed using thematic analysis. RESULTS: The interviews identified 22 themes related to the impact of COVID-19 on different positions of the caregivers involved in dementia care and their collaboration, and we categorized them into six categories. The core themes were "re-acknowledgement of care priorities" and "rebuilding of relationships." When caregivers' perceptions were aligned in the decision-making processes regarding care priorities, "reaffirmation of trust" and "strengthening of intimate relationships" emerged as positive changes in their relationships. Furthermore, the differences in the ability of each caregiver to access and select correct and appropriate information about COVID-19, and the extent of infection spread in the region were related to "anxiety during COVID-19 pandemic" and caused a "gap in perception" regarding infection control. CONCLUSIONS: The present study clarified that the process of aligning the perceptions of caregivers to the objectives and priorities of care for older people with dementia during COVID-19 pandemic strengthened the relationships among caregivers. The findings of this study are useful for caregivers involved in person-centered dementia care.


Assuntos
COVID-19 , Demência , Idoso , Cuidadores , Demência/epidemiologia , Demência/terapia , Humanos , Pandemias , SARS-CoV-2
8.
BMC Med Educ ; 22(1): 501, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761249

RESUMO

BACKGROUND: Supporting professional identity development in medical students undergoing remediation in the first few years of their studies is an important topic. However, there is a lack of research on developing an effective and individualised process for successful remediation that targets learner identities. This study examined the identities of Generation Z remedial medical students through the lens of professional identity formation, focusing on the difficulties they faced and the support they sought. METHODS: An exploratory qualitative case study was conducted within a constructivist paradigm. Twenty-two medical students (14 males and 8 females) who had experienced remediation in their first few years of medical university participated in this study. All participants were members of Generation Z. Qualitative data were collected through face-to-face, semi-structured interviews and analysed using thematic analysis. RESULTS: Medical students undergoing remediation in the first few years experienced resistance to the medical profession and conflict due to the gap between the ideal and the reality they experienced after entering medical university. Students' professional identities were closely intertwined with their pre-university identities; this affected the process of professional identity formation after entering medical university. They preferred assurances of confidentiality as a prerequisite and immediately sought advice through social networks to support their professional identity development. CONCLUSIONS: When planning professional identity development support for Generation Z medical students undergoing remediation in the first few years, it is necessary to carefully select integrative interaction methods, focus on the context of individual learners, and collaboratively discuss specific responses between students and faculty. The results of this study could be useful to faculty in developing support systems for future remedial medical students that focuses on professional identity development and mentoring of remedial medical students.


Assuntos
Educação de Graduação em Medicina , Tutoria , Estudantes de Medicina , Educação de Graduação em Medicina/métodos , Feminino , Humanos , Masculino , Mentores , Pesquisa Qualitativa , Identificação Social
9.
BMC Med Educ ; 22(1): 144, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246125

RESUMO

BACKGROUND: The COVID-19 pandemic has caused medical colleges worldwide to suspend in-person classes and clinical clerkships. This fluid situation urgently required educators and learners to make a paradigm shift from traditional medical education. However, descriptions of how leaders manage policy decisions, especially considering cultural contexts, are limited. This study explores how the deans of medical colleges in Japan addressed the situations in which face-to-face contact is difficult and interacted with various stakeholders during the COVID-19 pandemic. METHODS: The study employed a nationwide online survey by sending individual e-mails to the director of medical education at each of the 82 medical colleges in Japan. Responses were collected between May 26 and June 12, 2020 from the deans or directors of medical education. The survey questions were developed based on a literature review and consultations with international research collaborators. The survey asked what difficulties and opportunities were encountered through curriculum adjustments during the COVID-19 pandemic and what lessons could be shared with medical educators worldwide. Survey responses were analyzed using thematic analysis. The themes were categorized by stakeholder and then analyzed using the domains of sensemaking theory. RESULTS: A total of 48 medical colleges in Japan completed the survey, yielding a response rate of 58.5%. The levels of participation in the study were 42.9%, 77.8%, and 74.2% among national, public, and private medical colleges, respectively, with responses from public and private medical colleges tending to be higher than those from national medical colleges. Japanese deans' decisions for actions in adapting to COVID-19 involve perceiving cues from multiple stakeholder groups, including medical students, parents of medical students, medical faculties, and government officials. Thematic analysis of survey data reveals that Japanese deans' actions in adapting to COVID-19 reflect characteristics of Japanese culture, with Japanese deans tending to emphasize in-depth introspection and collaboration with diverse stakeholders. CONCLUSIONS: Despite a lack of clear national guidelines for decision making, Japanese deans adapted to COVID-19 challenges by learning from one another and seeking the perspectives of a diverse group of stakeholders, aligned with local cultural context. Their approach offers important lessons for global medical educators.


Assuntos
COVID-19 , Educação Médica , COVID-19/epidemiologia , Humanos , Japão/epidemiologia , Pandemias , SARS-CoV-2
10.
J Allergy Clin Immunol ; 148(3): 858-866, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33609627

RESUMO

BACKGROUND: Sensory nerves regulate cutaneous local inflammation indirectly through induction of pruritus and directly by acting on local immune cells. The underlying mechanisms for how sensory nerves influence cutaneous acquired immune responses remain to be clarified. OBJECTIVE: This study aimed to explore the effect of peripheral nerves on cutaneous immune cells in cutaneous acquired immune responses. METHODS: We analyzed contact hypersensitivity (CHS) responses as a murine model of delayed-type hypersensitivity in absence or presence of resiniferatoxin-induced sensory nerve denervation. We conducted ear thickness measurements, flow cytometric analyses, and mRNA expression analyses in CHS. RESULTS: CHS responses were attenuated in mice that were denervated during the sensitization phase of CHS. By screening neuropeptides, we found that pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA expression was decreased in the dorsal root ganglia after denervation. Administration of PACAP restored attenuated CHS response in resiniferatoxin-treated mice, and pharmacological inhibition of PACAP suppressed CHS. Flow cytometric analysis of skin-draining lymph nodes showed that cutaneous dendritic cell migration and maturation were reduced in both denervated mice and PACAP antagonist-treated mice. The expression of chemokine receptors CCR7 and CXCR4 of dendritic cell s was enhanced by addition of PACAP in vitro. CONCLUSION: These findings indicate that a neuropeptide PACAP promotes the development of CHS responses by inducing cutaneous dendritic cell functions during the sensitization phase.


Assuntos
Dermatite de Contato/imunologia , Células de Langerhans/imunologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/imunologia , Animais , Denervação , Dermatite de Contato/genética , Diterpenos/administração & dosagem , Feminino , Gânglios Espinais/fisiologia , Haptenos/administração & dosagem , Linfonodos/imunologia , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Neurotoxinas/administração & dosagem , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Receptores CCR7/imunologia , Receptores CXCR4/imunologia , Canais de Cátion TRPV
11.
Medicina (Kaunas) ; 58(11)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36363571

RESUMO

Background and Objectives: Clinically used concentrations of sevoflurane, an inhaled anesthetic, have been reported to significantly inhibit tumor growth. We investigated the effects of sevoflurane on sphere formation and the proliferation of human glioblastoma stem cells (GSCs) to determine whether sevoflurane exerts short- and long-term effects on human tumor cells. Materials and Methods: High-grade patient-derived GSCs (MD13 and Me83) were exposed to 2% sevoflurane. To evaluate the effect of sevoflurane on viability, proliferation, and stemness, we performed a caspase-3/7 essay, cell proliferation assay, and limiting dilution sphere formation assays. The expression of CD44, a cell surface marker of cancer stem-like cells in epithelial tumors, was evaluated using quantitative reverse transcription PCR. Differences between groups were evaluated with a one-way analysis of variance (ANOVA). Results: Sevoflurane exposure for 4 days did not significantly promote caspase 3/7 activity in MD13 and Me83, and cell proliferation was not observed after 5 days of exposure. Furthermore, prolonged exposure to sevoflurane for 6 days did not promote the sphere-forming and proliferative potential of MD13 and Me83 cells. These results suggest that sevoflurane does not promote either apoptosis, proliferative capacity, or the colony-forming ability of human mesenchymal glioblastoma stem cells in vitro. Conclusions: Sevoflurane at clinically used concentrations does not promote the colony-forming ability of human mesenchymal glioblastoma stem cells in vitro. It is very important for neurosurgeons and anesthesiologists to know that sevoflurane, a volatile anesthetic used in surgical anesthesia, would not exacerbate the disease course of GSCs.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Sevoflurano/farmacologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proliferação de Células , Apoptose , Linhagem Celular Tumoral
12.
Biol Pharm Bull ; 44(4): 528-534, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33473072

RESUMO

Psoriasis is an immune disorder-related inflammatory skin disease. Recent studies have suggested a contribution of T cell activation in the pathogenesis of psoriasis. Interleukin-2 (IL-2)-inducible T cell kinase (ITK) regulates T cell activation, including proliferation, and cytokine production. In this study, we investigated the effect of the topically administered selective ITK inhibitor BMS-509744 on imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. Topically administered BMS-509744 ameliorated IMQ-induced psoriasis-like skin inflammation as shown by decreased skin lesions, epidermal thickening, and cell infiltration into the dermis. These suppressive effects occurred with lower numbers of cluster of differentiation antigen-3+ (CD3+) T cells and T helper subset 17 (Th17)-related cytokine expression in IMQ-treated skin. IMQ-induced upregulation of proinflammatory cytokine expression was also inhibited by topical application of BMS-509744 in IMQ-treated skin. Our report showed for the first time that topical application of BMS-509744 ameliorated psoriasis-like skin inflammation in mice, which is likely mediated by the inhibition of T cell activation in the skin lesions.


Assuntos
Imiquimode/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Animais , Complexo CD3/metabolismo , Dermatite/tratamento farmacológico , Dermatite/metabolismo , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Pele/metabolismo , Pele/patologia , Células Th17/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
13.
Biol Pharm Bull ; 44(7): 910-919, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33896885

RESUMO

Glioblastoma multiforme (GBM) is the most prevalent malignant primary brain tumor with a high recurrence rate. Despite multimodal therapy including surgical resection, chemotherapy, and radiotherapy, the median survival time after the initial diagnosis of GBM is approximately 14 months. Since cancer stem cells (CSCs) are considered the leading cause of cancer recurrence, glioblastoma stem cell-targeted therapy is a promising strategy for the treatment of GBM. However, because CSC heterogeneity has been implicated in the difficulties of CSC-target therapy, more in-depth knowledge of CSC biology is still required to develop novel therapies. In this study, we established single cell-derived tumorspheres from human glioblastoma U87MG cells. One of these tumorspheres, P4E8 clone, showed CSC-like phenotypes, such as self-renewal capacity, expression of CSC markers, resistance to anti-cancer agents, and in vivo tumorigenicity. Therefore, we used P4E8 cells as a cell-based model of glioblastoma stem cells (GSCs). Gene expression analysis using microarray indicated that the most highly expressed genes in P4E8 cells compared to the parental U87MG were PC3-secreted microprotein (MSMP). Furthermore, MSMP was expressed in patient-derived GSCs and human glioma tissues at the protein level, implying that MSMP might contribute to glioma development and progression.


Assuntos
Glioma/fisiopatologia , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica , Glioblastoma/fisiopatologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Recidiva Local de Neoplasia/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Transplante Heterólogo
14.
Angew Chem Int Ed Engl ; 60(17): 9316-9320, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33481308

RESUMO

Vapor-phase treatment of ZIF-8 membranes with manganese(II) acetylacetonate (Mn(acac)2 ) allows permselectivity tuning. Propylene/propane selectivity increases from 31 to 210 after the Mn(acac)2 treatment at 165 °C for 30 min, while selectivities increase from 14.6 to 242 for H2 /CH4 , from 2.9 to 38 for CO2 /CH4 , from 2.4 to 29 for CO2 /N2 , and from 2.9 to 7.5 for O2 /N2 , after Mn(acac)2 treatment at 175 °C for 30 min. Stable equimolar propylene/propane mixture selectivity of 165 at ambient temperature and 4 bar equimolar feed with a propylene flux of 8.3×10-4  mol m-2 s-1 is established. A control experiment excludes thermal treatment alone causing these changes. XPS analysis reveals the presence of Mn(acac)2 on the outer surface of the vapor-treated ZIF-8 membranes while no other changes are detectable by X-ray diffraction and infrared spectroscopy.

15.
Pflugers Arch ; 471(2): 313-327, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30250967

RESUMO

Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are synthesized from dietary carbohydrates by colonic bacterial fermentation. These SCFAs supply energy, suppress cancer, and affect ion transport. However, their roles in ion transport and regulation in the intracellular environment remain unknown. In order to elucidate the roles of SCFAs, we measured short-circuit currents (ISC) and performed RT-PCR and immunohistochemical analyses of ion transporters in rat rectal colon. The application of 30 mM butyrate shifted ISC in a negative direction, but did not attenuate the activity of epithelial Na+ channels (ENaC). The application of bumetanide, a Na+-K+-2Cl- cotransporter inhibitor, to the basolateral side reduced the negative ISC shift induced by butyrate. The application of XE991, a KCNQ-type K+ channel inhibitor, to the apical side decreased the ISC shift induced by butyrate in a dose-dependent manner. The ISC shift was independent of HCO3- and insensitive to ibuprofen, an SMCT1 inhibitor. The mucosa from rat rectal colon expressed mRNAs of H+-coupled monocarboxylate transporters (MCT1, MCT4, and MCT5, also referred to as SLC16A1, SLC16A3, and SLC16A4, respectively). RT-PCR and immunofluorescence analyses demonstrated that KCNQ2 and KCNQ4 localized to the apical membrane of surface cells in rat rectal colon. These results indicate that butyrate, which may be transported by H+-coupled monocarboxylate transporters, activates K+ secretion through KCNQ-type K+ channels on the apical membrane in rat rectal colon. KCNQ-type K+ channels may play a role in intestinal secretion and defense mechanisms in the gastrointestinal tract.


Assuntos
Butiratos/metabolismo , Colo/metabolismo , Secreções Intestinais/metabolismo , Potássio/metabolismo , Reto/metabolismo , Animais , Antracenos/farmacologia , Bumetanida/farmacologia , Cloretos/metabolismo , Colo/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Secreções Intestinais/efeitos dos fármacos , Transporte de Íons/efeitos dos fármacos , Transporte de Íons/fisiologia , Canais de Potássio KCNQ/metabolismo , Masculino , Transportadores de Ácidos Monocarboxílicos/metabolismo , Propionatos/farmacologia , Ratos , Ratos Sprague-Dawley , Sódio/metabolismo , Canais de Sódio/metabolismo
16.
Int J Mol Sci ; 20(21)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31717704

RESUMO

Adenosine regulates exocrine and endocrine secretions in the pancreas. Adenosine is considered to play a role in acini-to-duct signaling in the exocrine pancreas. To identify the molecular basis of functional adenosine receptors in the exocrine pancreas, immunohistochemical analysis was performed in the rat, mouse, and guinea pig pancreas, and the secretory rate and concentration of HCO3- in pancreatic juice from the rat pancreas were measured. The A2A adenosine receptor colocalized with ezrin, an A-kinase anchoring protein, in the luminal membrane of duct cells in the mouse and guinea pig pancreas. However, a strong signal ascribed to A2B adenosine receptors was detected in insulin-positive ß cells in islets of Langerhans. The A2A adenosine receptor agonist 4-[2-[[6-Amino-9-(N-ethyl-ß-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid (CGS 21680) stimulated HCO3--rich fluid secretion from the rat pancreas. These results indicate that A2A adenosine receptors may be, at least in part, involved in the exocrine secretion of pancreatic duct cells via acini-to-duct signaling. The adenosine receptors may be a potential therapeutic target for cancer as well as exocrine dysfunctions of the pancreas.


Assuntos
Pâncreas/metabolismo , Receptores Purinérgicos P1/metabolismo , Roedores/metabolismo , Animais , Bicarbonatos/análise , Proteínas do Citoesqueleto/metabolismo , Feminino , Cobaias , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Pâncreas/química , Ductos Pancreáticos/metabolismo , Ratos
17.
Angew Chem Int Ed Engl ; 58(46): 16390-16394, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31568623

RESUMO

Vapor phase ligand treatment (VPLT) of 2-aminobenzimidazole (2abIm) for 2-methylimidazole (2mIm) in ZIF-8 membranes prepared by two different methods (LIPS: ligand induced permselectivation and RTD: rapid thermal deposition) results in a notable shift of the molecular level cut-off to smaller molecules establishing selectivity improvements from ca. 1.8 to 5 for O2 /N2 ; 2.2 to 32 for CO2 /CH4 ; 2.4 to 24 for CO2 /N2 ; 4.8 to 140 for H2 /CH4 and 5.2 to 126 for H2 /N2 . Stable (based on a one-week test) oxygen-selective air separation performance at ambient temperature, 7 bar(a) feed, and 1 bar(a) sweep-free permeate with a mixture separation factor of 4.5 and oxygen flux of 2.6×10-3  mol m-2 s-1 is established. LIPS and RTD membranes exhibit fast and gradual evolution upon a 2abIm-VPLT, respectively, reflecting differences in their thickness and microstructure. Functional reversibility is demonstrated by showing that the original permeation properties of the VPLT-LIPS membranes can be recovered upon 2mIm-VPLT.

18.
Exp Dermatol ; 27(1): 22-29, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28423239

RESUMO

Janus kinases (JAKs) are required for several inflammatory cytokine signalling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis. JTE-052 inhibited the Th1-, Th2- and Th17-type inflammatory responses of human T cells and mast cells in vitro. Oral administration of JTE-052 inhibited skin inflammation in hapten-induced chronic dermatitis in mice, associated with reduced levels of inflammatory cytokines in the skin and immunoglobulin (Ig) E in serum. In contrast, although ciclosporin partly inhibited skin inflammation, it did not reduce interleukin (IL)-4 production in skin, and enhanced IgE production in serum. Oral administration of JTE-052 also inhibited skin inflammation in mouse models of atopic dermatitis and psoriasis induced by a mite extract, thymic stromal lymphopoietin or IL-23. The maximal efficacy of JTE-052 in these dermatitis models was superior to the conventional therapeutic agents, ciclosporin and methotrexate. Topical application of JTE-052 ointment ameliorated hapten-induced chronic dermatitis in rats more effectively than tacrolimus ointment. Furthermore, JTE-052 ointment did not cause the thinning of normal skin associated with topical corticosteroids. These results indicate that JTE-052 is a promising candidate as an anti-inflammatory drug for various types of chronic dermatitis, with a distinctly different profile from conventional therapy following either oral or topical application.


Assuntos
Dermatite Atópica/tratamento farmacológico , Inflamação/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Pirróis/uso terapêutico , Animais , Ciclosporina/uso terapêutico , Citocinas/metabolismo , Dermatite Atópica/metabolismo , Feminino , Haptenos/química , Humanos , Imunoglobulina E/sangue , Inflamação/metabolismo , Interleucina-23/metabolismo , Subunidade p19 da Interleucina-23/metabolismo , Masculino , Metotrexato/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ratos , Ratos Endogâmicos BN , Pele/fisiopatologia , Linfopoietina do Estroma do Timo
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