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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.

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.

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.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.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.

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.

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.

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.

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.

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.

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.

Objectives: Patients' adherence to enteral administration of nutrients is influenced by their feeling during administration. The present study compared the taste of commercially prepared ice cream with that of enteral nutrient ice cream, using a sensory test. Additionally, the factors influencing the comprehensive evaluation of enteral nutrient ice cream and commercially prepared ice cream were identified. Methods: A sensory test was performed by 30 pharmacists, on commercially prepared ice cream and enteral nutrient ice cream using the Semantic Differential Method. The factors related to comprehensive evaluation were extracted, and those influencing the comprehensive evaluation of ice cream were analyzed by Covariance structure analysis. Results: No significant differences were observed in the comprehensive evaluation of enteral nutrient ice cream and commercially prepared ice cream (p = 0.08, 95% CI = −0.78 to 0.04). Covariance structure analysis identified five factors related to Easy-to-intake (i.e., Taste, Ease to ingest, Continuity, Peculiar flavor, and Familiarity), which strongly influenced Comprehensive evaluation (standardized estimated value: 0.88). In addition, four factors related to discomfort factor (i.e., Feeling of heaviness, Concentration of taste, Greasiness, and Milky smell) were found not to influence Comprehensive evaluation directly but were correlated with Ease-to-intake (standardized estimate: 0.64). Conclusion: It is important for healthcare professionals to understand the factors involved in the comprehensive evaluation of enteral nutrients, and they should provide appropriate information about it.

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.

Aims: It is necessary for medical staff to fully understand disparities in the comprehensive evaluation of enteral nutrients due to differences in their physical form. In this study, we compared the overall rating of each enteral nutrient with respect to form and examined the factors that influence their overall evaluation. Methods: Sensory tests were conducted on 261 pharmaceutical students using the Sematic Differential method. Comparison of comprehensive evaluations for each form of enteral nutrient was carried out for liquids (room temperature, warm, cold), jelly (solid), and mousse (semi-solid) forms. Additionally, factors influencing the comprehensive evaluation of enteral nutrients were investigated using covariance structure analysis. Results: Overall evaluation of each enteral nutrient form showed the jelly was rated highest (2.57 ± 1.49), followed by the warm liquid (2.53 ± 1.29), cold liquid (2.42 ± 1.20), room temperature liquid (2.26 ± 1.20), and the mousse (1.93 ± 1.07). From the result of factor analysis, four factors (flavor, richness, presence, and texture) were extracted. Covariance structure analysis of factors affecting the overall rating revealed that flavor had a significant influence (fitness index: GFI=0.908, AGFI=0.878, RMSEA=0.074, AIC=912.742). Conclusion: Differences in the form of enteral nutrients affected the overall satisfaction of patients. It is important for medical staff, including pharmacists, to deepen their understanding of factors related to the overall rating of enteral nutrients in order to meet the needs of patients.

Objectives: To determine cyclophosphamide exposure to preparers during tablet crushing and subsequent handling by analyzing indoor air collected using a high-performance volatile organic compounds-solvent desorption (VOC-SD) passive air sampler. Methods: The passive sampler was taped to the mask over the mouth of the preparer and indoor air was collected during crushing and preparation of cyclophosphamide tablets (Endoxan®). After collection, the carbon molecular sieve adsorbent of the passive sampler was placed in a centrifuge tube, and 1 mL of carbon disulfide was used to elute cyclophosphamide from the adsorbent. Liquid–liquid extraction with 1 mL of water was performed, and the aqueous phase was used as the test solution. Cyclophosphamide concentration was determined by liquid chromatography with ultraviolet and tandem mass spectrometry detection. Results: Cyclophosphamide concentration was detected in the range of 7.6–157.7 ng/sampler. Our results showed that low-level exposure occurred near the mouth of the preparer, which could present risks for long-term exposure, especially if combined with multiple toxic drug exposures. Conclusion: The anticancer drug monitoring methodology described here is a simple exposure assessment that can be used to ensure the safety of hospital pharmacy tablet preparers. Furthermore, since the anticancer drug exposure risk is very high for preparers, preparation should be in hood or with face mask.

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.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.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.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.

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.

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.

The risk assessment of di(2-ethylhexyl)phthalate (DEHP) migration from polyvinyl chloride (PVC) medical devices is an important issue for patients. The aim of this study was to determine DEHP degradation and migration from PVC sheets. To this end, the method for the simultaneous determination of DEHP and its breakdown products (mono(2-ethylhexyl)phthalate (MEHP) and phthalic acid (PA)) was improved. Their migration levels from 0 to 50 kGy gamma-ray irradiated PVC sheets were determined. DEHP migration level decreased in proportion to the dose of gamma-ray irradiation, while MEHP and PA migration levels increased. The hardness and the elastic modulus of PVC sheets were examined, but no clear relationship between DEHP migration and these parameters was observed.

Tris(2-ethylhexyl)trimellitate (TOTM) is used as an alternative plasticizer of polyvinyl chloride (PVC) medical devices. A method for the determination of TOTM released from PVC medical devices into intravenous preparations was developed, which uses liquid chromatography-tandem mass spectrometry (LC–MS/MS). A PVC tube was filled with an intravenous preparation and extraction was carried out by shaking for 1 h at room temperature. LC was performed with an Inertsil ® -C8 (50 mm × 2.1 mm, 5 μm) column. The isocratic mobile phase was acetonitrile:purified water (90:10, v/v) at a flow rate of 0.2 ml/min. MS detection was accomplished with an MS/MS detector equipped with a turbo ionspray ionization source in the positive ion mode. The limit of detection and the limit of quantification for the standard solution of TOTM was 0.5 ng/ml (S/N = 3) and 1.0 ng/ml (S/N ≥ 10), respectively. When Prograf ® (tacrolimus) was used, the average recovery of TOTM was 101.1% (R.S.D. = 4.72%; n = 3). When our method was applied to the determination of TOTM released from unsterilized and gamma-ray-sterilized PVC tubes, we found that a higher concentration of TOTM was released from the unsterilized PVC tube than from the gamma-ray-sterilized one.