RESUMO
The purpose of this study was to continuously monitor the pseudopolymorphic transition from anhydrate to monohydrate by measuring the NMR relaxation using time-domain NMR (TD-NMR). Taking advantage of the simplicity of the low-field NMR instrument configuration, which is an advantage of TD-NMR, the NMR instrument was connected to a humidity controller to monitor the pseudopolymorphic transition. First, ezetimibe (EZT) monohydrate was prepared from its anhydrate using a saturated salt solution method, and T1 relaxation of EZT monohydrate and anhydrate was measured without a humidity controller. The T1 relaxation results confirmed that EZT anhydrate and monohydrate could be distinguished using T1 relaxation measurement. Next, continuous monitoring was conducted by TD-NMR and connected to a humidity controller. Anhydrous EZT was placed in an NMR glass tube and the T1 relaxation measurement was repeated while maintaining the humidity on the side entering the NMR tube at 80% relative humidity. The T1 relaxation became gradually faster from the initial to middle monitoring phases. The final T1 relaxation was then recovered fully and these T1 relaxation times were the same as the T1 relaxation of EZT monohydrate. This study successfully monitored the pseudopolymorphic transition from EZT anhydrate to monohydrate via NMR relaxation.
Assuntos
Ezetimiba , Espectroscopia de Ressonância Magnética , Ezetimiba/química , Estrutura MolecularRESUMO
Practical training stands as a crucial component in shaping pharmacy students, bridging the gap between classroom-based theoretical knowledge and its application in real-world contexts. This study investigates the correlation between the satisfaction levels experienced during practical training and the acquisition of knowledge, particularly focusing on drug names. Drawing from the National DataBase (NDB) open data provided by Japan's Ministry of Health, Labour and Welfare, a survey centered on the top 100 dispensed drugs was crafted. A correlation analysis was conducted between the satisfaction scores gathered from students and their depth of knowledge on drug names. Intriguingly, despite observing a significantly high satisfaction level during the practical training, there was no marked correlation between this satisfaction and the proficiency in recalling drug names after the training. Furthermore, the volume of daily prescriptions handled did not significantly impact this knowledge. The findings underscore the notion that high satisfaction during training does not necessarily guarantee a thorough understanding of the subject matter. This sheds light on the importance of not solely relying on satisfaction metrics in training programs and ensuring a holistic, in-depth educational approach.
RESUMO
In this study, a public seminar on risk communication methods was conducted to raise awareness and disseminate accurate knowledge about residual pesticides to consumers. Additionally, surveys on consumer awareness were conducted on the attendees before and after the seminar to evaluate its effectiveness. Responses were obtained from 84 participants. The paired t-test was used to analyze the changes in awareness before and after the seminar. The results showed significant improvements in "trust in the government" and "understanding of residual pesticides." Furthermore, step-wise multiple regression analysis was performed to explore the factors influencing satisfaction with the risk communication seminar, and the item "understanding of the safety of residual pesticides in food" was extracted. Understanding food safety is a crucial concern in daily life for consumers. To enable consumers to have an accurate understanding of food risks and make appropriate judgments, it is essential to continue implementing risk communication and conveying information about food safety and security in the future.
Assuntos
Praguicidas , Humanos , Comunicação , Inocuidade dos AlimentosRESUMO
BACKGROUND: The method of displaying nutrition information labels on the front of food packaging (FOP: Front of Pack) has been implemented worldwide to prevent lifestyle-related diseases. This study aimed to investigate whether the use of the UK's Traffic Light Food (TLF) label, known as the FOP label, influences the dietary choices of Japanese youth and promotes healthy dietary choices. METHODS: Diet selection was performed for one week each during the baseline and intervention periods. During the intervention period, TLF labels were displayed on meal images of the intervention group. Participants chose what they would like to have for dinner of the day from 15 images. Each meal was scored based on the color of the nutrition label, and a comparison between groups was made to determine whether TLF labeling influenced meal selection for dinner. The psychological stress caused by the presence or absence of nutrition labels and nutritional components when choosing meals was also evaluated. RESULTS: A total of 69 participants were randomly assigned to two groups. Dietary choice scores indicated that the TLF-labeled group made significantly healthier dietary choices than the unlabeled group. Additionally, the TLF-labeled group showed a significant increase in the percentage of people conscious of nutritional components when choosing meals. Furthermore, a significant increase in the number of people conscious of protein, a nutritional ingredient not indicated on the TLF label, was observed. During the test period, no difference in psychological stress caused by the presence and absence of the TLF labels was observed. CONCLUSIONS: The use of TLF labels also encouraged healthy dietary choices among Japanese university students. The use of FOP nutrition labels should be considered in Japan to prevent lifestyle-related diseases through healthy dietary choices. TRIAL REGISTRATION: UMIN Clinical Trials Registry Number: UMIN000047268. Registered March 23, 2022.
Assuntos
Rotulagem de Alimentos , Comportamentos Relacionados com a Saúde , Adolescente , Humanos , Rotulagem de Alimentos/métodos , Japão , Universidades , Valor Nutritivo , Comportamento de Escolha , Comportamento do Consumidor , Dieta , Preferências Alimentares/psicologia , EstudantesRESUMO
During the COVID-19 pandemic, face masks on patients and healthy people have been recommended to prevent airborne transmission of the virus. This increased the number of people who felt stressed while wearing masks. In this study, we investigated the stress-relieving effects of attaching aroma seals to masks. A double-blind, randomized controlled trial was conducted involving 62 university students. The participants were randomly assigned to two groups and instructed to apply a seal to their masks once a day throughout the study period. The primary measure used was the Depression, Anxiety, and Stress Scale-21 (DASS-21), while the secondary measures included the assessment of breathlessness associated with mask-wearing and the World Health Organization Five Well-Being Index (WHO-5). The intervention group, referred to as the aroma-seal use group, utilized aroma seals infused with orange-lime essential oil with the expectation of experiencing the healing effects of citrus. On the other hand, the non-intervention group, known as the placebo-seal use group, utilized identical seals without any aroma. Results indicated that the aroma-seal use group exhibited significant improvements in both the total DASS-21 scores and depression scores compared to their baseline values by the second week of the intervention. Furthermore, the aroma-seal use group demonstrated a reduced occurrence of breathlessness while wearing masks compared to the placebo-seal group. Additionally, when assessing the item "I have felt calm and relaxed" from the WHO-5 questionnaire, the aroma-seal use group displayed significantly higher scores than the placebo group. Therefore, using aroma seals containing orange-lime essential oil could be beneficial in relieving mental stress and reducing breathlessness while wearing a mask, thus improving mental health.
Assuntos
COVID-19 , Caniformia , Óleos Voláteis , Focas Verdadeiras , Humanos , Animais , Odorantes , Pandemias/prevenção & controle , COVID-19/prevenção & controle , Óleos Voláteis/uso terapêutico , Dispneia/tratamento farmacológicoRESUMO
OBJECTIVES: The COVID-19 pandemic increased psychological stress and decreased sleep quality, especially among young people. Aromatherapy alleviates psychological stress, and bergamot essential oil helps improve depression. This study aimed to verify whether bergamot essential oil use alleviates psychological stress due to the COVID-19 pandemic and improves sleep quality and morning wakefulness. DESIGN: A placebo-controlled, randomized, open-label, two-arm, two-period crossover trial. INTERVENTIONS: Each intervention period was 1 week, with a 1-week washout period between the two periods. Participants used a bergamot or placebo spray before bedtime and upon awakening in each period. MAIN OUTCOME MEASURES: The primary outcome measures were sleep quality and morning wakefulness, assessed using the Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). The secondary outcome measures were depression, anxiety, and stress, assessed using the Depression Anxiety Stress Scales-21 (DASS-21). RESULTS: A total of 48 university students participated in the study. A significant improvement was observed in "sleepiness on rising," "refreshing on rising," and "sleep length" in the bergamot group. Additionally, a significant improvement was observed in depression, anxiety, and stress. CONCLUSION: Using bergamot essential oil before bedtime helps relax the mind and body and provides sound sleep. It also improves mood and wakefulness when used upon awakening. Using aromatic essential oils is expected to relieve psychological stress and improve sleep quality and morning wakefulness.
Assuntos
COVID-19 , Óleos Voláteis , Humanos , Adolescente , Óleos Voláteis/uso terapêutico , Qualidade do Sono , Estudos Cross-Over , Pandemias , Estresse Psicológico/tratamento farmacológicoRESUMO
Nutrition labeling on the front of food packages has been implemented worldwide to help improve public health awareness. In this randomized double-blind controlled trial, we used a Google Forms questionnaire to evaluate the effectiveness of nutrition labeling on food packages in university students. The questionnaire, ultimately completed by 247 students, included 15 dietary images from which they were asked to choose what they wanted to eat for breakfast, lunch, and dinner the following day. For the interventional (traffic light food [TLF]) group only, TLF labels were displayed on dietary images. This group had a significantly higher proportion of people conscious of healthy eating during all meals than the control group, and the effect of TLF labeling on choosing meals was the highest for lunch. In addition to the indicated nutritional components, the TLF group had a significantly higher proportion of people who were conscious of the ones of protein and dietary fiber that were not indicated on the label. The use of TLF labels resulted in an increase in the proportion of people choosing a healthy diet as well as being conscious of their nutritional components. Therefore, the use of TLF labels may help promote healthy dietary choices in Japan.
Assuntos
Rotulagem de Alimentos , Comportamentos Relacionados com a Saúde , Humanos , Comportamento de Escolha , Comportamento do Consumidor , População do Leste Asiático , Rotulagem de Alimentos/métodos , Preferências Alimentares , Refeições , Valor Nutritivo , Estudantes , UniversidadesRESUMO
BACKGROUND: Chimpi, the dried peel of Citrus unshiu or Citrus reticulata, has various pharmacological effects. Chimpi extract was recently shown to affect the skin, including its inhibitory effect against atopic dermatitis. In this study, we analyzed the effects of Chimpi extract on the functional molecule aquaporin-3 (AQP3), which is involved in water transport and cell migration in the skin. METHODS AND RESULTS: Chimpi extract was added to HaCaT human skin keratinocytes, and the AQP3 expression level was analyzed. A wound healing assay was performed to evaluate the effect of Chimpi extract on cell migration. The components of Chimpi extract and fractions obtained by liquid-liquid distribution studies were added to HaCaT cells, and AQP3 expression was analyzed. Chimpi extract significantly increased AQP3 expression in HaCaT cells at both the mRNA and protein levels. Immunocytochemical staining revealed that Chimpi extract also promoted the transfer of AQP3 to the cell membrane. Furthermore, Chimpi extract enhanced cell migration. Hesperidin, narirutin, and nobiletin did not increase AQP3 levels. Although the components contained in the fractions obtained from the chloroform, butanol, and water layer increased AQP3, the active components could not be identified. CONCLUSIONS: These results reveal that Chimpi extract may increase AQP3 levels in keratinocytes and increase the dermal water content. Therefore, Chimpi extract may be effective for the management of dry skin.
Assuntos
Aquaporina 3 , Citrus , Humanos , Aquaporina 3/genética , Aquaporina 3/metabolismo , Células Cultivadas , Queratinócitos/metabolismo , Água/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismoRESUMO
Vaccination is crucial for preventing the spread of COVID-19. Vaccination for COVID-19 was implemented in Japan in community units, and community pharmacists were engaged in vaccine preparation. Capturing the knowledge, attitudes, and practices (KAP) of pharmacists regarding COVID-19 infection control is important for developing future community health action strategies and plans. We conducted a cross-sectional study among 141 pharmacists who were members of a pharmacist association in the Shinagawa Ward of Tokyo (1-31 July 2021) using a Google online questionnaire. The questionnaire included demographic information and KAP questions regarding COVID-19. A correlation test was used for analyzing KAP scores. Significant correlations were found among all KAP scores. Stepwise logistic regression analysis showed "age" as a significant knowledge factor and "marriage", "pharmacist careers", "information source: official government website", and "information source: word of mouth from family and friends" as significant attitude factors. Good KAP scores were recorded in this study, indicating increased comprehension of infection control measures and increased knowledge scores, as pharmacy pharmacists were practically involved in COVID-19 infection control measures through vaccine preparation. Policymakers should understand the value of pharmacists as healthcare professionals and should enhance public health through the effective use of pharmacists.
Assuntos
COVID-19 , Vacinas , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Controle de Infecções , Farmacêuticos , Inquéritos e QuestionáriosRESUMO
This study aimed to determine psychological and physical differences in elementary and junior high school teachers during COVID-19. This questionnaire-based cross-sectional study was conducted among 427 teachers in Tokyo, Japan (between 15 and 30 October 2020). The questionnaire explored school type (elementary and middle schools), sex, age, and COVID-19 changes (psychological changes, physical changes, impact on work, and infection control issues perceived to be stressed). Post hoc tests for I cannot concentrate on work at all, found a significant difference for no change-improved and male teacher in elementary school female teacher in junior high school (p = 0.03). Regarding stress situation due to implementation of COVID-19 infection control, there were significant differences for disinfection work by teachers between male teachers in elementary school female teachers in junior high school (p = 0.04) and female teachers in elementary school female teachers in junior high school (p = 0.03). COVID-19 produced differences in psychological and physical changes between male and female teachers in elementary and junior high schools. Some experienced psychological and physical stress, whereas others showed improvement. Given that teachers' mental health also affects students' educational quality, it is important to understand and improve teachers' psychological and physical circumstances and stress.
Assuntos
COVID-19 , Professores Escolares , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , Professores Escolares/psicologia , Instituições AcadêmicasRESUMO
To promote and raise the awareness of accurate knowledge on pesticide residues, the symposium program on risk communication on pesticide residues was held by the broadcasted online style. The risk communication program was statistically evaluated using a pre- and post-program online questionnaire survey. We had the questionnaire answers of the 105 valid participants. The analysis of post-program questionnaires shows that the risk communication program was effective in terms of levels of understanding and interest. Pre-program risk perception or awareness of safety assessments was significantly and positively correlated with awareness for establishing standard values of pesticide residues by the analysis of pre-program questionnaires. Risk perception after the program was significantly higher than before the program, suggesting that risk perception increased due to the program by analysis the same question between pre- and post-program questionnaires. Multiple regression analysis suggests that the participants with higher pre-program awareness of safety assessments or pre-program awareness for establishing standard values appeared to have higher levels of understanding and post-program risk perception.
Assuntos
Resíduos de Praguicidas , Comunicação , Humanos , Resíduos de Praguicidas/análise , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Coronavirus infections are spreading rapidly worldwide, and primary and middle schools are closed in many countries. After the state of emergency was lifted in Japan, schools have reopened, and teachers are conducting face-to-face classes while maintaining safety precautions. This study aimed to assess the factors contributing to infection-related anxiety and educational anxiety among teachers conducting face-to-face classes during the COVID-19 pandemic after schools reopened. METHODS: This questionnaire-based cross-sectional study was conducted with 263 primary and middle school teachers in the Shinagawa area of Tokyo (October 10-30, 2020). The questionnaire assessed the type of school (primary or middle school), sex, age, and factors contributing to infection-related anxiety and educational anxiety that arose from the pandemic. The levels of anxiety and the factors contributing to anxiety were assessed using a 5-point Likert scale ranging from 1 (not at all) to 5 (very anxious). RESULTS: In an analysis of the data of 237 participants excluding the missing data, many teachers reported feeling infection- and education-related anxiety. A majority of the participants were women (n = 152, 64.1%), and the mean age of the participants was 39.8 ± 11.3 years. A stepwise multiple regression analysis identified six factors for infection-related anxiety as significant (R2 = 0.61, p < 0.001). Among these variables, the largest partial regression coefficient value was reported for the following reason: "I feel anxious because we cannot ensure the safety of teachers themselves or of their families" (ß = 0.37, p < 0.001). For educational anxiety, four of six reasons were identified as significant (R2 = 0.64, p < 0.001). Among these, "anxiety about the students' home situations" (ß = 0.41, p < 0.001) and "delay in education (students' side)" (ß = 0.27, p < 0.001) had stronger associations with anxiety compared to the others. CONCLUSION: In-person education during the COVID-19 pandemic has caused teachers to experience anxiety. This report provides useful information by highlighting the reasons for infection-related anxiety and educational anxiety that teachers experience in face-to-face classes during a pandemic. Even if the coverage of a COVID-19 vaccine becomes widespread worldwide, we will still be combating COVID-19 infections for at least a few years. Given concerns regarding such infections, to ensure students' right to education, it is essential to understand why teachers feel anxious and to determine appropriate measures to decrease such anxiety.
Assuntos
COVID-19 , Pandemias , Adulto , Ansiedade/epidemiologia , Vacinas contra COVID-19 , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Instituições Acadêmicas , TóquioRESUMO
The average age of patients with type 2 diabetes in Japan is over 70 years. Elderly patients tend to have poor medication compliance, therefore, it is important to understand their individual situations to improve medication compliance, the treatment of their diabetes, and their quality of life (QOL). This study aimed to identify factors associated with medication compliance in elderly type 2 diabetic patients. A cross-sectional study based on questionnaires was conducted on type 2 diabetes patients aged 65 years or older. The participants were recruited from patients who visited three dispensing pharmacies in the Shinagawa area of Tokyo between March 1 and September 30, 2019. The questionnaire consisted of patient information (sex, age, medication compliance status, knowledge of drug effects, and side effects), 12-Item Short Form Survey quality of life rating scale (SF-12), and Diabetes Treatment Satisfaction Questionnaire (DTSQ). Factors related to medication compliance were then evaluated. In all, there were 47 respondents: 31 males and 16 females. Four factors were found to be associated with medication compliance in elderly type 2 diabetic patients: medication storage (P = 0.01), knowledge of drug effects (P < 0.001), knowledge of side effects (P = 0.026), and physical functioning: (PF) (P = 0.045), a subscale of SF-12. Furthermore, the strength of the association between these four factors and medication compliance was calculated using Cramer's V coefficient of association. Knowledge of drug effects was the most strongly associated (knowledge of drug effects: V = 0.559; knowledge of side effects: V = 0.464; medication storage: V = 0.451; PF: V = 0.334). Because diabetes mellitus has no subjective symptoms and treatment effects are not felt to a great extent, it is difficult to motivate patients to consistently adhere to medication. When pharmacists provide medication guidance to elderly patients with type 2 diabetes mellitus, it is important to provide sufficient information to ensure they fully understand the drug effects to maintain medication compliance.
Assuntos
Diabetes Mellitus Tipo 2 , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Adesão à Medicação , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
Vancomycin (VAN) is an anti-microbial agent used to treat a number of bacterial infections, which has a high incidence of nephrotoxicity. We examined the pharmacokinetics of VAN retrospectively based on trough concentrations at large scale and identified pharmacokinetic differences between Japanese patients having solid malignancy and non-malignancy patients. Data were analyzed from 162 solid malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN. We failed to detect differences in values for VAN clearance or shorter elimination half-lives between these two groups. In contrast, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to solid malignancies in each stage. We conclude that VAN clearance in solid malignancy patients is increased and that the blood concentration of VAN becomes lower than expected. These results suggest that early monitoring of VAN levels in solid malignancy patients might be essential for maintaining desired effects without side-effects.
Assuntos
Antibacterianos/sangue , Monitoramento de Medicamentos/métodos , Neoplasias/sangue , Vancomicina/sangue , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Taxa de Depuração Metabólica/fisiologia , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Vancomicina/uso terapêuticoRESUMO
The pharmacokinetics of vancomycin (VAN) was retrospectively examined based on trough concentrations at large scale to identify pharmacokinetic differences between Japanese hematologic malignancy and non-malignancy patients. Data from 261 hematologic malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN estimated by an empirical Bayesian method, were collected and analyzed. Our results showed significantly higher values for VAN clearance and shorter elimination half-lives in patients with hematologic malignancies than non-malignancy patients. In addition, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to hematologic malignancies. In conclusion, since in hematologic cancer patients VAN clearance is increased, the blood concentration of VAN becomes lower than expected and this may contribute to the survival of resistant bacteria when VAN is administered at low doses. These results suggest that early monitoring of VAN levels in hematologic cancer patients might be recommended to maintain desired effects without side-effects.
Assuntos
Antibacterianos/farmacocinética , Neoplasias Hematológicas/tratamento farmacológico , Vancomicina/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Monitoramento de Medicamentos , Feminino , Humanos , Japão , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Estudos Retrospectivos , Vancomicina/administração & dosagem , Vancomicina/sangueRESUMO
We previously demonstrated that the expression levels of drug-metabolizing enzymes, cytochrome P450 (CYP) enzymes, in the liver are significantly decreased in a murine model of ulcerative colitis (UC). In this study, we investigated changes in the pharmacokinetics of phenytoin, a CYP2C substrate drug, in the presence of UC. Colitis was induced by feeding male mice 3.5% dextran sulfate sodium (DSS) dissolved in drinking water for 10 days. The messenger RNA (mRNA) expression of CYP2C29 and CYP2C37 and the protein expression of CYP2C in the liver were evaluated via real-time reverse transcription-polymerase chain reaction and Western blotting, respectively. In DSS-treated animals, both mRNA and protein expression levels of CYP2C in the liver were significantly reduced relative to those in control animals (by 20%-40%). Phenytoin (30 mg/kg) was administered orally in a single dose to mice, and plasma concentrations were measured. Plasma concentrations of phenytoin were higher in the DSS-treated group than in the control group at 12, 24, and 36 hours after administration. Animals given DSS also exhibited a higher area under the plasma concentration-time curve extrapolated to infinity (AUCinf, 315 µg·h/mL), a delayed elimination half-life ( T1/2, 8.1 hours), and a decreased body clearance (CL/F, 3.52 mL/h) compared with that of control animals (AUCinf, 215 µg·h/mL; T1/2, 3.6 h; CL/F, 5.58 mL/h). This study indicated that the presence of UC decreases CYP2C expression levels in the liver, thereby delaying the metabolism of CYP2C substrates, including phenytoin, and increasing blood concentrations of these substrates.
Assuntos
Anticonvulsivantes/farmacocinética , Colite Ulcerativa/enzimologia , Sistema Enzimático do Citocromo P-450/metabolismo , Fenitoína/farmacocinética , Administração Oral , Animais , Anticonvulsivantes/sangue , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos ICR , Fenitoína/sangue , Especificidade por SubstratoRESUMO
In previous studies, we showed that a high-dose intake of green tea polyphenol (GP) induced a hepatospecific decrease in the expression and activity of the drug-metabolizing enzyme cytochrome P450 3A (CYP3A). In this study, we examined whether this decrease in CYP3A expression is induced by epigallocatechin gallate (EGCG), which is the main component of GP. After a diet containing 1.5% EGCG was given to mice, the hepatic CYP3A expression was measured. The level of intestinal bacteria of Clostridium spp., the concentration of lithocholic acid (LCA) in the feces, and the level of the translocation of pregnane X receptor (PXR) to the nucleus in the liver were examined. A decrease in the CYP3A expression level was observed beginning on the second day of the treatment with EGCG. The level of translocation of PXR to the nucleus was significantly lower in the EGCG group. The fecal level of LCA was clearly decreased by the EGCG treatment. The level of intestinal bacteria of Clostridium spp. was also decreased by the EGCG treatment. It is clear that the hepatospecific decrease in the CYP3A expression level observed after a high-dose intake of GP was caused by EGCG. Because EGCG, which is not absorbed from the intestine, causes a decrease in the level of LCA-producing bacteria in the colon, the level of LCA in the liver decreases, resulting in a decrease in the nuclear translocation of PXR, which in turn leads to the observed decrease in the expression level of CYP3A.
Assuntos
Catequina/análogos & derivados , Citocromo P-450 CYP3A/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Catequina/sangue , Catequina/farmacocinética , Catequina/farmacologia , Linhagem Celular Tumoral , Clostridium/efeitos dos fármacos , Clostridium/genética , Fezes/química , Humanos , Intestinos/microbiologia , Ácido Litocólico/metabolismo , Fígado/metabolismo , Masculino , Camundongos Endogâmicos ICR , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND AND AIM: The expression levels of cytochrome P450 (CYP) in the liver were analyzed over time in dextran sulfate sodium (DSS)-induced ulcerative colitis mouse model, from the initial active stage to the remission stage, to investigate the relationship between the changes in pathological conditions and CYP expression levels. METHODS: DSS solution was given to mice for 10 days, after which water without DSS was provided for 40 days. Pathological conditions and CYP expression levels were examined over time. The mechanism for variation in CYP expression was also analyzed. RESULTS: The mRNA expression levels of CYP (CYP3A11, CYP1A2, CYP2C29, CYP2D9, and CYP2E1) decreased as pathological conditions worsened and reached their lowest levels on day 10 of DSS treatment. Pathological conditions improved following the discontinuation of DSS, and CYP expression levels normalized by day 50. Blood lipopolysaccharide levels, the hepatic expression of inflammatory cytokines, and the nuclear translocation of pregnane X receptor and constitutive androstane receptor in the liver exhibited patterns similar to the observed variations in CYP expression levels. CONCLUSION: The capacity for metabolizing drugs that are substrates of CYP decreases during the active stage of ulcerative colitis but subsequently improves during the remission stage. This decrease in CYP expression was likely caused by the observed reduction in the levels of nuclearly localized pregnane X receptor and constitutive androstane receptor, and the increase in the production of inflammatory cytokines triggered by lipopolysaccharides.
Assuntos
Colite Ulcerativa/enzimologia , Colite Ulcerativa/patologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Expressão Gênica/genética , Fígado/enzimologia , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Receptor Constitutivo de Androstano , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos ICR , Receptor de Pregnano X , RNA Mensageiro/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Esteroides/metabolismoRESUMO
Recently, it was reported that the anticoagulant effect of warfarin was reduced when patients receiving warfarin also took menthol. The purpose of this study is to reveal the mechanism of this reduced anticoagulant effect of warfarin from the pharmacokinetic point of view. Warfarin was orally administered to mice 24h after the administration of menthol for 2 days, and the plasma warfarin concentration was measured. In the menthol administration group, the area under the blood concentration time curve of warfarin was decreased by approximately 25%, while total clearance was increased to 1.3-fold compared to the control group. The hepatic cytochrome P450 (CYP) 2C protein expression level in the menthol administration group was significantly increased compared to that in the control group. An increase in the nuclear translocation of constitutive androstane receptor (CAR) was also observed. The addition of menthol to human hepatic cells, HepaRG cells, caused an increase in the mRNA expression level of CYP2C9. The results of this study revealed that menthol causes an increase in CYP2C expression levels in the liver, which leads to an enhancement of warfarin metabolism, resulting in a decreased anticoagulant effect of warfarin. It was also suggested that menthol acted directly on the liver and increased the expression level of CYP2C by enhancing the nuclear translocation of CAR.
Assuntos
Anticoagulantes/farmacologia , Indutores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Mentol/farmacologia , Varfarina/farmacologia , Animais , Anticoagulantes/sangue , Anticoagulantes/farmacocinética , Linhagem Celular Tumoral , Sistema Enzimático do Citocromo P-450/genética , Humanos , Coeficiente Internacional Normatizado , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos ICR , Varfarina/sangue , Varfarina/farmacocinéticaRESUMO
The objective of this article is to reduce the preparation time for oral anticancer drugs, reduce the exposure to drug preparations, and develop drug preparation equipment without external drug leaks in a closed state. In the newly developed closed oral drug preparation device, a 10 mL disposable syringe that was replaced with one projection for crushing tablets and a no-processing 30 mL disposable syringe were connected to a three-way stopcock. Using this instrument, Endoxan(®) tablets (principal components: cyclophosphamide) were crushed and suspended in water in a closed state. The drug was prepared to suspension and flowed out via a feeding tube by switching the handle of the three-way stopcock. To assess human exposure to cyclophosphamide, a high-performance volatile organic compound-solvent desorption passive sampler was attached to the preparer's mouth to collect air drifting in the vicinity, and cyclophosphamide levels were subsequently measured by liquid chromatography with tandem mass spectrometry. Using the developed drug preparation equipment, Endoxan(®) tablets were suspended in a closed state. According to liquid chromatography with tandem mass spectrometry analysis, the exposure of the preparer to cyclophosphamide was greatly reduced when using the developed device; cyclophosphamide was detected in only two of the five samples, though only at trace levels. The closed oral drug preparation device may permit the preparation and administration of toxic drugs to patients while greatly reducing the risk of occupational exposure among health-care workers and caregivers.