Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biol Pharm Bull ; 47(3): 708-712, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38538324

RESUMO

In 2020, the coronavirus disease 2019 (COVID-19) pandemic made social distancing compulsory. In patient lectures by hepatitis B patients (Patient Lectures)-a humanity education initiative that had traditionally been delivered face-to-face to assembled students-it was necessary to divide the students into two groups, one that attended the Patient Lectures in person (face-to-face group) and another that assembled in a separate room to view the delivered lecture simultaneously and remotely via a teleconferencing platform (remote group). To investigate possible changes in students' awareness of hepatitis B patients before (pre-) and after (post-) the lecture that year, the face-to-face and remote-attendance groups were analyzed separately. The participants were 203 fourth-year students belonging to the Faculty of Pharmaceutical Sciences at Japan's Setsunan University, whose pre-clinical education curriculum prior to pharmacy practice experience included a Patient Lecture. The students were divided into two groups based on their student-ID numbers. Survey questionnaires were completed anonymously before and after the Patient Lecture. The students' awareness of hepatitis B patients' experience changed significantly after attending the Patient Lectures; this change was similar in both the face-to-face and remote-attendance groups. Regarding the possibility of hepatitis B virus infection, the remote group selected fewer answers implying strong convictions than did the face-to-face group, and both groups perceived several issues incorrectly. Although slight differences were observed between the two groups, the changes before and after the lectures were similar, indicating that humanity-education lectures are worthwhile not only when delivered in face-to-face contexts but also when delivered and viewed remotely within a class setting.


Assuntos
Hepatite B , Estudantes de Farmácia , Humanos , Currículo , Inquéritos e Questionários
2.
Yakugaku Zasshi ; 144(3): 329-338, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38432942

RESUMO

Although the issue of home medical care and pharmacists remains widespread, much of the discussion has concentrated on its state in urban areas. We believe that it is necessary to consider the state of home health care in medium-sized regions, that is separate from its urban form, with a population of approximately 100000. Thus, we conducted a qualitative study in Hikone City, Shiga Prefecture, to identify factors that impede pharmacists involved in home medical care. We conducted a questionnaire-based survey in an area of the same size to verify the generality of the concepts obtained from the qualitative study and validate the concepts using quantitative analyses. Two questionnaires on the role of community health care and home health care practice based on the concepts obtained from the qualitative study was sent to 342 pharmacies located in five regions. The number of valid responses was 170, and the data collection rate was 49.4%. We identified nine factors from the former and five from the latter. The current status of pharmacists in home health care in a medium-sized region, as identified by the quantitative study, was similar to that of the conceptual picture obtained from the qualitative study. Furthermore, the high versatility of the extracted concepts was verified.


Assuntos
Serviços de Assistência Domiciliar , Medicina , Farmácias , Humanos , Farmacêuticos , Serviços de Saúde Comunitária
3.
Yakugaku Zasshi ; 142(10): 1115-1123, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36184445

RESUMO

There is a need for pharmacists to be actively involved in home healthcare through a wide range of collaboration in healthcare and welfare. However, insufficient evidence is available to search for factors that prevent pharmacists from being proactive in home healthcare. In this study, we conducted an extensive questionnaire survey among pharmacists engaged in home pharmacy work who belong to the Hyogo Pharmaceutical Society regarding the current status of pharmacists' work in home medical care and their psychological burden; we also explored the factors that may hinder the future development of home medical care. As a result, 925 (44%) valid responses were obtained, and seven factors- "current multidisciplinary cooperation", "relationships with patients and their families", "emotional burden for home healthcare", "attitude toward patients", "ideal of multidisciplinary cooperation", "anxiety about aggressive intervention", and "anxiety about talking to and dealing with patients"- were extracted. Furthermore, it was suggested that pharmacists' mental burden and anxiety are closely related to their successful experiences in building relationships with patients and patients' families as well as with multidisciplinary cooperation in home healthcare. Therefore, to train pharmacists to be actively involved in home healthcare, it is important not only to impart knowledge and skills but also for them to gain experience practicing their contributions as pharmacists in the field of home healthcare with multiple professions, patients, and patients' families.


Assuntos
Serviços Comunitários de Farmácia , Serviços de Assistência Domiciliar , Assistência Farmacêutica , Farmácias , Atitude do Pessoal de Saúde , Humanos , Farmacêuticos/psicologia , Papel Profissional , Inquéritos e Questionários
4.
Curr Pharm Teach Learn ; 14(8): 998-1003, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36055709

RESUMO

INTRODUCTION: Various reports have been published regarding adoption of team-based learning (TBL) in pharmacy education. However, there is insufficient published evidence on the effect of student characteristics on student learning outcomes in a TBL curriculum. The purpose of this research was to evaluate the effects of pre-study examination results and peer evaluation ratings on learning outcomes. METHODS: The TBL strategy was adopted for a basic chemistry exercise for first-year students at a private pharmacy school in Japan (2012-2019). For the analysis, students were divided into four analytical groups according to quartiles of pre-study examination results. The students were further divided into the high-peer evaluation rating group and low-peer evaluation rating group. We compared the final exam performance results between these groups. RESULTS: In all four groups by quartiles of pre-study examination results, the course final exam performance was higher for the high-peer evaluation rating students than for the low-peer evaluation rating students. CONCLUSIONS: Within the TBL framework, students with higher peer evaluation scores performed better on the final exam, regardless of the pre-study examination results.


Assuntos
Educação em Farmácia , Avaliação Educacional , Currículo , Educação em Farmácia/métodos , Avaliação Educacional/métodos , Humanos , Aprendizagem , Grupo Associado
5.
Yakugaku Zasshi ; 140(10): 1275-1284, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32999206

RESUMO

In April 2018, as part of their fifth-year pre-clinical education curriculum, pharmacy students at Setsunan University attended a lecture presented by hepatitis B patients and their lawyer entitled "Lecture by Hepatitis B Patients". This lecture was intended to help the students to understand the circumstances and difficulties encountered by hepatitis B patients on a daily basis. For this study, we conducted questionnaire surveys of the pharmacy students before and after the lecture. The survey items pertained to students' knowledge about hepatitis B (e.g., its spread and infection possibility in daily life). Students' responses before and after the lecture varied depending on the survey topic. Hepatitis B knowledge acquired by the students in their junior year increased after the lecture; moreover, attitudes to hepatitis B patients and understanding of the difficulties and prejudice that they experienced showed a significant change. For example, responses to the items, "Feel sympathy for patients suffering from discrimination and prejudice" and "Hard to work…" were much more sympathetic after the lecture; additionally, students were less likely to "Fear infection when near patients" and more likely "… to associate with patients". Thus, the "Lecture by Hepatitis B Patients" had a significant impact on the pharmacy students' perceptions of these patients, allowing them to cultivate greater empathy. From an educational standpoint, it is of the utmost importance for pharmacy/medical students to develop their humanity as members of healthcare teams. Educational real-world experiences, such as the "Lecture by Hepatitis B Patients", provide opportunities for this development.


Assuntos
Atividades Cotidianas , Educação em Farmácia/métodos , Empatia , Hepatite B/psicologia , Participação do Paciente/métodos , Pacientes/psicologia , Aprendizagem Baseada em Problemas/métodos , Relações Profissional-Paciente , Estudantes de Farmácia/psicologia , Atitude Frente a Saúde , Currículo , Humanos , Conhecimento , Inquéritos e Questionários
6.
Yakugaku Zasshi ; 140(2): 289-300, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32009048

RESUMO

In this paper, as a program targeting school pharmacists engaged in health counseling and health guidance at elementary and junior high schools, which are often evacuation centers, we have rebuilt the disaster evacuation shelter support chart program for community pharmacists. As a result of the questionnaire survey, there were seen 4 groups. There were a group that was conscious of shelter support, a group who felt that they did not have aptitude for disaster relief, a group that was conscious of general support and logistical support, and a group that showed a negative attitude towards disaster relief. From this, it was suggested that this training program worked enlighteningly to support affected area by school pharmacists, and at the same time participants themselves could lead to consideration of aptitude for support at the time of disaster.


Assuntos
Planejamento em Desastres , Educação Continuada em Farmácia , Abrigo de Emergência , Farmacêuticos , Instituições Acadêmicas , Análise por Conglomerados , Análise Fatorial , Humanos , Japão
7.
Yakugaku Zasshi ; 139(5): 817-826, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31061350

RESUMO

The use of medical supply vehicles (mobile pharmacies) as a disaster measure developed after the Great East Japan Earthquake in 2011 when a massive tsunami destroyed the medicine supply system. In the 2016 Kumamoto earthquake, mobile pharmacies were dispatched from Oita, Wakayama, and Hiroshima and contributed to medical treatment in the disaster area. In this study, we conducted an interview to structure the mental conflicts of the pharmacists supporting the disaster victims by means of the mobile pharmacies, a novel medical support tool. We conducted a semi-structured interview of 21 pharmacists. The modified grounded theory approach was used for data collection and analysis. As a result, 36 concepts and 13 categories were generated. The support pharmacists maintained mobile pharmacies as a method for cooperation among multiple occupations, and talked about further collaboration in the operation of mobile pharmacies.


Assuntos
Medicina de Desastres , Planejamento em Desastres , Terremotos , Saúde Mental , Unidades Móveis de Saúde , Farmácias , Farmacêuticos/psicologia , Vítimas de Desastres , Humanos , Cooperação Internacional , Entrevistas como Assunto , Japão
8.
Food Chem Toxicol ; 100: 217-224, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28007454

RESUMO

Phthalates are used in food packaging, and are transferred to foods as contaminants. In this study, we examined the hydrolytic metabolism of dimethyl phthalate (DMP), dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) by rat tissue microsomes. We found that carboxylesterase and lipase contribute differently to these activities. When DMP, DBP and DEHP were incubated with rat liver microsomes, DBP was most effectively hydrolyzed to the phthalate monoester, followed by DMP, and the activity toward DEHP was marginal. In contrast, small-intestinal microsomes exhibited relatively higher activity toward long-side-chain phthalates. Pancreatic microsomes showed high activity toward DEHP and DBP. Liver microsomal hydrolase activity toward DMP was markedly inhibited by bis(4-nitrophenyl)phosphate, and could be extracted with Triton X-100. The activity toward DBP and DEHP was partly inhibited by carboxylesterase inhibitor, and was partly solubilized with Triton X-100. Ces1e, Ces1d and Ces1f expressed in COS cells exhibited the highest hydrolase activity toward DBP, showing a similar pattern to that of liver microsomes. Ces1e showed activity towards DMP and DEHP. Pancreatic lipase also hydrolyzed DBP and DEHP. Thus, carboxylesterase and lipase contribute differently to phthalate hydrolysis: short-side-chain phthalates are mainly hydrolyzed by carboxylesterase and long-side-chain phthalates are mainly hydrolyzed by lipase.


Assuntos
Dibutilftalato/metabolismo , Dietilexilftalato/metabolismo , Microssomos Hepáticos/metabolismo , Ácidos Ftálicos/metabolismo , Animais , Carboxilesterase/metabolismo , Cromatografia Líquida , Dibutilftalato/análise , Dietilexilftalato/análise , Hidrólise , Intestino Delgado/metabolismo , Isoenzimas , Masculino , Pâncreas/metabolismo , Ratos , Ratos Sprague-Dawley
9.
Yakugaku Zasshi ; 136(10): 1415-1425, 2016 10 01.
Artigo em Japonês | MEDLINE | ID: mdl-27452082

RESUMO

In 2014, there were about 160 thousands community pharmacists in Japan. Community pharmacists are health care workers who help victims in a disaster and are potential resources who can provide disaster relief. However, currently the disaster relief activities of community pharmacists are merely a resourceful and flexible demonstration of their professional abilities and not a specifically organized activity. Therefore, disaster relief education programs for community pharmacists are being explored and studies are still in the nascent stage. In this study, pharmacists of a pharmaceutical organization in Kobe City were asked to reply to a questionnaire survey so that their hopes and ideas about the disaster relief activities that they carry out can help build effective educational programs to enhance relief activities. Finally, 8 factors (cumulative contribution rate: 90.9%) were extracted by factor analysis (maximum likelihood method, the diagonal elements: squared multiple correlation, quartimin rotation) of the 25 questions. In addition, a hierarchical cluster analysis (Ward method) by the factor scores of the extracted 8 factors resulted in 7 groups. The findings revealed the groups into which the community pharmacists were divided and their hopes and ideas about disaster relief. We expect that these results could bring awareness about the disaster relief activities suitable for each community pharmacist, provide appropriate training opportunities for those who volunteer, and motivate daily studies and preparations for disaster relief activities among community pharmacists.


Assuntos
Conscientização , Planejamento em Desastres , Conhecimentos, Atitudes e Prática em Saúde , Farmácias/organização & administração , Farmacêuticos/psicologia , Feminino , Humanos , Japão , Masculino , Inquéritos e Questionários
10.
Food Chem Toxicol ; 86: 116-23, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26321725

RESUMO

Salicylates are used as fragrance and flavor ingredients for foods, as UV absorbers and as medicines. Here, we examined the hydrolytic metabolism of phenyl and benzyl salicylates by various tissue microsomes and plasma of rats, and by human liver and small-intestinal microsomes. Both salicylates were readily hydrolyzed by tissue microsomes, predominantly in small intestine, followed by liver, although phenyl salicylate was much more rapidly hydrolyzed than benzyl salicylate. The liver and small-intestinal microsomal hydrolase activities were completely inhibited by bis(4-nitrophenyl)phosphate, and could be extracted with Triton X-100. Phenyl salicylate-hydrolyzing activity was co-eluted with carboxylesterase activity by anion exchange column chromatography of the Triton X-100 extracts of liver and small-intestinal microsomes. Expression of rat liver and small-intestinal isoforms of carboxylesterase, Ces1e and Ces2c (AB010632), in COS cells resulted in significant phenyl salicylate-hydrolyzing activities with the same specific activities as those of liver and small-intestinal microsomes, respectively. Human small-intestinal microsomes also exhibited higher hydrolyzing activity than liver microsomes towards these salicylates. Human CES1 and CES2 isozymes expressed in COS cells both readily hydrolyzed phenyl salicylate, but the activity of CES2 was higher than that of CES1. These results indicate that significant amounts of salicylic acid might be formed by microsomal hydrolysis of phenyl and benzyl salicylates in vivo. The possible pharmacological and toxicological effects of salicylic acid released from salicylates present in commercial products should be considered.


Assuntos
Aromatizantes/metabolismo , Microssomos/metabolismo , Salicilatos/metabolismo , Animais , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/metabolismo , Aromatizantes/química , Humanos , Hidrólise , Intestino Delgado/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Salicilatos/química
11.
Yakugaku Zasshi ; 135(5): 753-9, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-25948313

RESUMO

The KJ method (named for developer Jiro Kawakita; also known as affinity diagramming) is widely used in participatory learning as a means to collect and organize information. In addition, the World Café (WC) has recently become popular. However, differences in the information obtained using each method have not been studied comprehensively. To determine the appropriate information selection criteria, we analyzed differences in the information generated by the WC and KJ methods. Two groups engaged in sessions to collect and organize information using either the WC or KJ method and small group discussions were held to create "proposals to improve first-year education". Both groups answered two pre- and post- session questionnaires that asked for free descriptions. Key words were extracted from the results of the two questionnaires and categorized using text mining. In the responses to questionnaire 1, which was directly related to the session theme, a significant increase in the number of key words was observed in the WC group (p=0.0050, Fisher's exact test). However, there was no significant increase in the number of key words in the responses to questionnaire 2, which was not directly related to the session theme (p=0.8347, Fisher's exact test). In the KJ method, participants extracted the most notable issues and progressed to a detailed discussion, whereas in the WC method, various information and problems were spread among the participants. The choice between the WC and KJ method should be made to reflect the educational objective and desired direction of discussion.


Assuntos
Mineração de Dados/métodos , Educação em Farmácia/métodos , Processos Grupais , Aprendizagem/fisiologia , Aprendizagem Baseada em Problemas/métodos , Aprendizagem Baseada em Problemas/tendências , Estudantes de Farmácia/psicologia , Humanos , Inquéritos e Questionários
12.
Yakugaku Zasshi ; 135(1): 99-105, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-25743905

RESUMO

  A revised core curriculum model for pharmaceutical education, developed on the basis of the principles of outcome-based education, will be introduced in 2015. Inevitably, appropriate assessments of students' academic achievements will be required. Although evaluations of the cognitive domain can be carried out by paper tests, evaluation methods for the attitude domain and problem-solving abilities need to be established. From the viewpoint of quality assurance for graduates, pharmaceutical education reforms have become vital to evaluation as well as learning strategies. To evaluate student academic achievements on problem-solving abilities, authentic assessment is required. Authentic assessment is the evaluation that mimics the context tried in work and life. Specifically, direct evaluation of performances, demonstration or the learners' own work with integrated variety knowledge and skills, is required. To clarify the process of graduate research, we obtained qualitative data through focus group interviews with six teachers and analyzed the data using the modified grounded theory approach. Based on the results, we clarify the performance students should show in graduate research and create a rubric for evaluation of performance in graduate research.


Assuntos
Teoria Fundamentada , Educação em Farmácia
13.
Yakugaku Zasshi ; 134(11): 1199-208, 2014.
Artigo em Japonês | MEDLINE | ID: mdl-25366917

RESUMO

The Faculty of Pharmaceutical Sciences, Setsunan University, offers the Self-improvement and Participatory Career Development Education Program: Internship and Volunteer Training Experience for Pharmacy Students to third-year students. We previously reported that the training experience was effective in cultivating important attributes among students, such as a willingness to learn the aims of pharmacists, an awareness of their own role as healthcare workers, and a desire to reflect on their future careers and lives. A follow-up survey of the participants was carried out three years after the training experience. The questionnaire verified that the training experience affected attendance at subsequent lectures and course determination after graduation. We confirmed the relationship between the participants' degree of satisfaction with the training experience and increased motivation for attending subsequent lectures. Through the training experience, participants discovered future targets and subjects of study. In addition, they became more interested in subsequent classroom lessons and their future. The greater the participants' degree of satisfaction with their training experience, the more interest they took in practical training and future courses. The present study clarified that the training experience was effective in cultivating important attributes such as a willingness to learn and an interest in future courses. Moreover, the training positively affected the course determination after graduation.


Assuntos
Educação em Farmácia , Internato e Residência , Seguimentos , Humanos , Internato e Residência/métodos , Estudantes de Farmácia , Inquéritos e Questionários
14.
Yakugaku Zasshi ; 134(2): 185-94, 2014.
Artigo em Japonês | MEDLINE | ID: mdl-24492221

RESUMO

Learning chemistry is cumulative: basic knowledge and chemical calculation skills are required to gain understanding of higher content. However, we often suffer from students' lack of learning skills to acquire these concepts. One of the reasons is the lack of adequate training in the knowledge and skills of chemistry, and one of the reasons for this lack is the lack of adequate evaluation of training procedures and content. Team-based learning (TBL) is a strong method for providing training in the knowledge and skills of chemistry and reaffirms the knowledge and skills of students of various levels. In our faculty, TBL exercises are provided for first-year students concurrently with lectures in physical chemistry and analytical chemistry. In this study, we researched the adoption of a peer evaluation process for this participatory learning model. Questionnaires taken after TBL exercises in the previous year showed a positive response to TBL. Further, a questionnaire taken after TBL exercises in the spring semester of the current year also yielded a positive response not only to TBL but also to peer evaluation. In addition, a significant correlation was observed between the improvement of students' grades in chemistry classes and the feeling the percentage (20%) of peer evaluation in overall evaluation low (logistic regression analysis, p=0.022). On the basis of the findings, we argue that TBL provides a generic, practical learning environment including an effective focus on learning strategy and evaluation of knowledge, skills, and attitudes, and studies on the educational effects of TBL and peer evaluation.


Assuntos
Química/educação , Comportamento Cooperativo , Educação em Farmácia/métodos , Avaliação Educacional , Processos Grupais , Aprendizagem , Estudantes de Farmácia/psicologia , Humanos , Inquéritos e Questionários
15.
Xenobiotica ; 43(12): 1064-72, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23742084

RESUMO

Hydrolytic metabolism of methyl-, ethyl-, propyl-, butyl-, heptyl- and dodecylparaben by various tissue microsomes and plasma of rats, as well as human liver and small-intestinal microsomes, was investigated and the structure-metabolic activity relationship was examined. Rat liver microsomes showed the highest activity toward parabens, followed by small-intestinal and lung microsomes. Butylparaben was most effectively hydrolyzed by the liver microsomes, which showed relatively low hydrolytic activity towards parabens with shorter and longer alkyl side chains. In contrast, small-intestinal microsomes exhibited relatively higher activity toward longer-side-chain parabens, and showed the highest activity towards heptylparaben. Rat lung and skin microsomes showed liver-type substrate specificity. Kidney and pancreas microsomes and plasma of rats showed small-intestinal-type substrate specificity. Liver and small-intestinal microsomal hydrolase activity was completely inhibited by bis(4-nitrophenyl)phosphate, and could be extracted with Triton X-100. Ces1e and Ces1d isoforms were identified as carboxylesterase isozymes catalyzing paraben hydrolysis by anion exchange column chromatography of Triton X-100 extract from liver microsomes. Ces1e and Ces1d expressed in COS cells exhibited significant hydrolase activities with the same substrate specificity pattern as that of liver microsomes. Small-intestinal carboxylesterase isozymes Ces2a and Ces2c expressed in COS cells showed the same substrate specificity as small-intestinal microsomes, being more active toward longer-alkyl-side-chain parabens. Human liver microsomes showed the highest hydrolytic activity toward methylparaben, while human small-intestinal microsomes showed a broadly similar substrate specificity to rat small-intestinal microsomes. Human CES1 and CES2 isozymes showed the same substrate specificity patterns as human liver and small-intestinal microsomes, respectively.


Assuntos
Microssomos/metabolismo , Especificidade de Órgãos , Parabenos/metabolismo , Animais , Biocatálise , Células COS , Carboxilesterase/metabolismo , Chlorocebus aethiops , Humanos , Hidrólise , Isoenzimas/metabolismo , Masculino , Redes e Vias Metabólicas , Microssomos/enzimologia , Parabenos/química , Ratos , Ratos Sprague-Dawley , Solubilidade , Especificidade por Substrato
16.
Yakugaku Zasshi ; 132(10): 1179-88, 2012.
Artigo em Japonês | MEDLINE | ID: mdl-23037704

RESUMO

We adopted peer evaluation (mutual evaluation between students) for small group discussion (SGD) among first graders. The peer evaluation criteria were 5 grade scales for 5 fields: "preparation," "remark," "listening," "activeness," and "role." A comparison with tutor evaluation clarified the validity of peer evaluation for summative evaluation. Although the average of peer evaluation (4.2 (4.0-4.4)) was higher than that of tutor evaluation (3.8 (3.7-4.1)) (p=0.0601, Mann-Whitney U test), the value of the correlation coefficient between peer evaluation and summative evaluation of SGD (average 0.35 (0.12-0.54)) was almost the same as that of the coefficient between tutor evaluation and summative evaluation of SGD (average 0.36 (0.24-0.42)) (p=0.6761, Mann-Whitney U test). Principal component analysis showed that the tutor could not evaluate "remark" and "listening" independently, while students evaluate "listening" independently from other evaluation criteria. The combination of peer and tutor evaluation may be multilateral evaluation for SGD. The questionnaire about peer evaluation for students showed that they recognized the value of peer evaluation and favorably accepted its use.


Assuntos
Grupo Associado , Farmacologia/educação , Ensino/métodos
18.
Drug Metab Dispos ; 38(12): 2210-7, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20823294

RESUMO

Mycophenolate mofetil (MMF) is the ester prodrug of the immunosuppressant agent mycophenolic acid (MPA) and is rapidly activated by esterases after oral administration. However, the role of isoenzymes in MMF hydrolysis remains unclear. Although human plasma, erythrocytes, and whole blood contain MMF hydrolytic activities, the mean half-lives of MMF in vitro were 15.1, 1.58, and 3.20 h, respectively. Thus, blood esterases seemed to contribute little to the rapid MMF disappearance in vivo. In vitro analyses showed that human intestinal microsomes exposed to 5 and 10 µM MMF exhibited hydrolytic activities of 2.38 and 4.62 nmol/(min · mg protein), respectively. Human liver microsomes exhibited hydrolytic activities of 14.0 and 26.1 nmol/(min · mg protein), respectively, approximately 6-fold higher than those observed for intestinal microsomes. MMF hydrolytic activities in human liver cytosols were 1.40 and 3.04 nmol/(min · mg protein), respectively. Because hepatic cytosols generally contain 5-fold more protein than microsomes, MMF hydrolysis in human liver cytosols corresponded to approximately 50% of that observed in microsomes. Fractions obtained by 9000g centrifugation of supernatants from COS-1 cells expressing human carboxylesterase (CES) 1 or 2 exhibited MMF hydrolytic activity, with CES1-containing fractions showing higher catalytic efficiency than CES2-containing fractions. The CES inhibitor bis-p-nitrophenylphosphate inhibited MMF hydrolysis in human liver microsomes and cytosols with IC(50) values of 0.51 and 0.36 µM, respectively. In conclusion, both intestinal and hepatic CESs and in particular CES1 may be involved in MMF hydrolysis and play important roles in MMF bioactivation. Hepatic CES1 activity levels may help explain the between-subject variability observed for MMF usage.


Assuntos
Carboxilesterase/fisiologia , Hidrolases de Éster Carboxílico/fisiologia , Imunossupressores/metabolismo , Ácido Micofenólico/análogos & derivados , Adulto , Animais , Células COS , Chlorocebus aethiops , Feminino , Humanos , Hidrólise , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/metabolismo , Proteínas Recombinantes/metabolismo
19.
Toxicol Lett ; 185(2): 110-5, 2009 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-19133322

RESUMO

Glutamate-cysteine ligase is a rate-limiting enzyme in the de novo synthesis of glutathione, a known scavenger of electrophiles and reactive oxygen species. Glutamate-cysteine ligase catalytic subunit (GCLC) is regulated transcriptionally by nuclear factor erythroid 2-related factor 2 (Nrf2). It has been reported that ethanol induces human GCLC production via Nrf2-mediated transactivation of the antioxidant-responsive element (ARE). Here, the luciferase reporter assay revealed the presence of an ethanol-responsive element in the human GCLC promoter; it spanned bases -1432 to -832 in hepatocytes and HepG2 cells transfected with cytochrome P450 2E1 (CYP2E1). The region lacked an ARE but had a putative nuclear factor-kappaB (NF-kappaB) element. NF-kappaB DNA-binding activity was activated in response to ethanol treatment. CYP2E1 expression was required for GCLC promoter-driven gene expression and the activation of NF-kappaB. Thus ethanol-induced GCLC transcription is mediated by not only Nrf2 but also NF-kappaB.


Assuntos
Domínio Catalítico/genética , Etanol/farmacologia , Expressão Gênica/efeitos dos fármacos , Glutamato-Cisteína Ligase/genética , NF-kappa B/metabolismo , Northern Blotting , Linhagem Celular Tumoral , Ensaio de Desvio de Mobilidade Eletroforética , Expressão Gênica/fisiologia , Glutationa/metabolismo , Humanos , Luciferases/genética , Regiões Promotoras Genéticas , Ligação Proteica , RNA/metabolismo , Transcrição Gênica , Transfecção
20.
Biochem J ; 415(3): 477-82, 2008 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-18605988

RESUMO

Mouse MT-I (metallothionein-I) transcription is regulated by MTF-1 (metal-response-element-binding transcription factor-1) which is recruited to the promoter in response to zinc. Cr(VI) [chromium(VI)] pretreatment blocks zinc-activation of the endogenous MT-I gene and attenuates zinc-activation of MT-I-promoter-driven luciferase reporter genes in transient transfection assays. Chromatin immunoprecipitation assays revealed that Cr(VI) only modestly reduces recruitment of MTF-1 to the MT-I promoter in response to zinc, but drastically reduces the recruitment of RNA polymerase II. These results suggest that Cr(VI) inhibits the ability of MTF-1 to transactivate this gene in response to zinc. Zinc has recently been shown to induce the formation of a co-activator complex containing MTF-1 and the histone acetyltransferase p300 which plays an essential role in the activation of MT-I transcription. In the present study, co-immunoprecipitation assays demonstrated that Cr(VI) pretreatment blocks the zinc-induced formation of this co-activator complex. Thus Cr(VI) inhibits mouse MT-I gene expression in response to zinc by interfering with the ability of MTF-1 to form a co-activator complex containing p300 and recruiting RNA polymerase II to the promoter.


Assuntos
Cromo/farmacologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteína p300 Associada a E1A/antagonistas & inibidores , Metalotioneína/genética , Fatores de Transcrição/antagonistas & inibidores , Transcrição Gênica , Zinco/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteína p300 Associada a E1A/genética , Proteína p300 Associada a E1A/metabolismo , Metalotioneína/metabolismo , Camundongos , Regiões Promotoras Genéticas , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Elementos de Resposta , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transfecção
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...