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BACKGROUND: Doxorubicin (DXR) is an effective chemotherapeutic agent. DOX-induced cardiomyopathy (DICM), a major limitation of DXR, is a complication with limited treatment options. We previously reported that Red Ginseng (steamed and dried the root of Panax Ginseng cultivated for over six years; RGin) is beneficial for the treatment of DICM. However, the mechanism underlying the action of RGin remains unclear. In this study, we investigated the mechanism of action underlying the efficacy of RGin in the treatment of DICM. METHODS: Four-week-old DBA/2 mice were divided into: vehicle, DXR, RGin, and DXR + RGin (n = 10/group). Mice were treated with DXR (4 mg/kg, once a week, accumulated 20 mg/kg, i.p.) or RGin (0.5 g/kg, three times a week, i.p.). To evaluate efficacy, the survival rate and left ventricular ejection fraction (LVEF) were measured as a measure of cardiac function, and cardiomyocytes were subjected to Masson trichrome staining. To investigate the mechanism of action, western blotting was performed to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, transferrin receptor (TfR), and other related proteins. Data were analyzed using the Easy R software. Between-group comparisons were performed using one-way analysis of variance and analyzed using a post-hoc Tukey test. Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. P < 0.05 was considered statistically significant in all analyses. RESULTS: RGin treatment prolongs survival and protects against reduced LVEF. In the DXR group, Nrf2 was not activated and cell death was accelerated. Furthermore, there was an increase in the TfR levels, suggesting abnormal iron metabolism. However, the DXR + RGin group showed activation of the Nrf2 pathway and suppression of myocardial cell death. Furthermore, there was no increase in TfR expression, suggesting that there were no abnormalities in iron metabolism. Therefore, the mechanism of action of RGin in DICM involves an increase in antioxidant activity and inhibition of cell death through activation of the Nrf2 pathway. CONCLUSION: RGin is a useful therapeutic candidate for DICM. Its efficacy is supported by the activation of the Nrf2 pathway, which enhances antioxidant activity and inhibits cell death.
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Various types of small-scale wastewater treatment systems are widely used in rural areas, and life-cycle assessment (LCA) should be performed to evaluate their environmental performance. In this study, septic systems were first classified into five categories based on their wastewater treatment performance. Effluent samples from actual systems were collected, and their water qualities were determined. A model to evaluate the environmental load from the septic systems using LCA methods was then established. The water-quality values obtained were input to the model, and the life-cycle environmental costs of the classified septic systems were calculated. The mean environmental load of the effluent during the operation stage was 37.6%, confirming that evaluation of an effluent discharge inventory using LCA, inspection, and water-quality monitoring to improve operations is critical for reducing the environmental load. The operation stage accounts for over 99% of the involved eutrophication, biological toxicity, and toxic chemicals, which are strongly related to the quality of the effluent. Evaluation of the effluent discharge inventory using LCA is of great significance, even for small-scale wastewater treatment systems. The set of procedures developed in this study can be used to calculate comprehensive environmental impacts at wastewater treatment plants.
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Eliminación de Residuos Líquidos , Aguas Residuales , Eliminación de Residuos Líquidos/métodos , Agua , Japón , AmbienteRESUMEN
Doxorubicin-induced cardiomyopathy (DICM) is associated with a poor prognosis, and effective therapeutic drug candidates have yet to be identified. Furthermore, whether basic animal models reflect the clinical pathogenesis of DICM should be carefully examined. Although the exact mechanisms underlying the development of DICM are complex and remain unclear, oxidative stress is strongly implicated as a contributing factor. Therefore, we investigated the effects of ginseng (the root of Panax ginseng: Gin), an inexpensive and safe drug with antioxidant properties. We previously conducted a meta-analysis that yielded results suggesting its efficacy in humans. However, this study did not examine the efficacy of ginseng in detail. Therefore, this study investigated the efficacy of red ginseng (steamed and dried ginseng cultivated for over six years; RGin) in a mouse model of chronic DICM to elucidate its potential therapeutic benefits. RGin prevented the decrease in left ventricular ejection fraction associated with doxorubicin (DXR) administration and prolonged survival in DBA/2 mice. In addition, RGin reduced DXR-induced cardiomyocyte damage. These findings highlight its potential as a therapeutic option for the treatment of DICM.
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BACKGROUND: Niemann-Pick disease type C (NPC) is a fatal neurodegenerative disorder caused by abnormal intracellular cholesterol trafficking. Cyclodextrins (CDs), the most promising therapeutic candidates for NPC, but with concerns about ototoxicity, are cyclic oligosaccharides with dual functions of unesterified cholesterol (UC) shuttle and sink that catalytically enhance the bidirectional flux and net efflux of UC, respectively, between the cell membrane and the extracellular acceptors. However, the properties of CDs that regulate these functions and how they could be used to improve treatments for NPC are unclear. METHODS: We estimated CD-UC complexation for nine CD derivatives derived from native α-, ß-, and γ-CD with different cavity sizes, using solubility and molecular docking analyses. The stoichiometry and complexation ability of the resulting complexes were investigated in relation to the therapeutic effectiveness and toxicity of each CD derivative in NPC experimental models. FINDINGS: We found that shuttle and sink activities of CDs are dependent on cavity size-dependent stoichiometry and substituent-associated stability of CD-UC complexation. The ability of CD derivatives to form 1:1 and 2:1 complexes with UC were correlated with their ability to normalize intracellular cholesterol trafficking serving as shuttle and with their cytotoxicity associated with cellular UC efflux acting as sink, respectively, in NPC model cells. Notably, the ability of CD derivatives to form an inclusion complex with UC was responsible for not only efficacy but ototoxicity, while a representative derivative without this ability negligibly affected auditory function, underscoring its preventability. CONCLUSIONS: Our findings highlight the importance of strategies for optimizing the molecular structure of CDs to overcome this functional dilemma in the treatment of NPC.
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Ciclodextrinas , Enfermedad de Niemann-Pick Tipo C , Ototoxicidad , Humanos , Ciclodextrinas/farmacología , Simulación del Acoplamiento Molecular , Enfermedad de Niemann-Pick Tipo C/tratamiento farmacológico , ColesterolRESUMEN
Cationic lipid-based lipoplexes are well-known for gene delivery. To determine the relationship between physicochemical characteristics and transfection efficiency, cationic liposomes of different sizes were prepared and incubated with plasmid DNA at different temperatures to form lipoplexes. We found that the liposome diffusion coefficient during lipoplex formation strongly correlated with the physicochemical characteristics of lipoplexes, accessibility of plasmid DNA in lipoplexes, and logarithm of gene expression per metabolic activity. Clathrin-mediated endocytosis was the major route for lipoplexes comprising 100 nm-liposomes, as reported previously. As liposome size increased, the major route shifted to lipid raft-mediated endocytosis. In addition, macropinocytosis was observed for all liposome sizes. The role of reactive oxygen species might depend on liposome size and endocytosis. Information from this study would be useful for understanding cationic lipoplex-mediated transfection.
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ADN , Liposomas , Humanos , Células Hep G2 , Transfección , Plásmidos , ADN/genética , CationesRESUMEN
Niemann-Pick disease type C (NPC) is a fatal disorder with abnormal intracellular cholesterol trafficking resulting in neurodegeneration and hepatosplenomegaly. A cyclic heptasaccharide with different degrees of substitution of 2-hydroxypropyl groups, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), acts as a strong cholesterol solubilizer and is under investigation for treating this disease in clinical trials, but its physicochemical properties and ototoxicity remain a concern. Here, we evaluated the potential of mono-6-O-α-maltosyl-γ-CD (G2-γ-CD), a single-maltose-branched cyclic octasaccharide with a larger cavity than HP-ß-CD, for treating NPC. We identified that G2-γ-CD ameliorated NPC manifestations in model mice and showed lower ototoxicity in mice than HP-ß-CD. To investigate the molecular mechanisms of action behind the differential ototoxicity of these CDs, we performed cholesterol solubility analysis, proton nuclear magnetic resonance spectroscopy, and molecular modeling, and estimated that the cholesterol inclusion mode of G2-γ-CD maintained solely the 1:1 inclusion complex, whereas that of HP-ß-CD shifted to the highly-soluble 2:1 complex at higher concentrations. We predicted the associations of these differential complexations of CDs with cholesterol with the profile of disease attenuation and of the auditory cell toxicity using specific cell models. We proposed that G2-γ-CD can serve as a fine-tuned cholesterol solubilizer for treating NPC, being highly biocompatible and physicochemically suitable for clinical application.
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Pérdida Auditiva , Enfermedad de Niemann-Pick Tipo C , Ototoxicidad , gamma-Ciclodextrinas , Ratones , Animales , Enfermedad de Niemann-Pick Tipo C/tratamiento farmacológico , 2-Hidroxipropil-beta-Ciclodextrina/farmacología , 2-Hidroxipropil-beta-Ciclodextrina/uso terapéutico , 2-Hidroxipropil-beta-Ciclodextrina/química , Maltosa/uso terapéutico , Protones , Colesterol/uso terapéutico , Excipientes/uso terapéutico , Pérdida Auditiva/tratamiento farmacológicoRESUMEN
Aberrant activation of hepatocyte growth factor (HGF) and its receptor c-Met axis promotes tumor growth. Therefore, many clinical trials have been conducted. A phase 3 trial investigating a monoclonal antibody targeting HGF in combination with fluoropyrimidine-based chemotherapy had to be terminated prematurely; however, the reason behind the failure remains poorly defined. In this study, we investigated the influence of HGF on the antineoplastic effects of 5-fluorouracil (5-FU), a fluoropyrimidine, in HepG2 cells. HGF suppressed the proliferative activity of cells concomitantly treated with 5-FU more robustly as compared to that of cells treated with 5-FU alone, and markedly increased the expression of uridine phosphorylase 1 (UPP1). Intracellular concentration of 5-fluorouridine, an initial anabolite of 5-FU catalyzed by UPP1, was increased by HGF. Interestingly, erlotinib enhanced HGF-induced increase in UPP1 mRNA; in contrast, gefitinib suppressed it. Furthermore, erlotinib suppressed HGF-increased phosphorylation of the epidermal growth factor receptor at the Tyr1173 site involved in downregulation of extracellular signal-regulated kinase (Erk) activation, and enhanced the HGF-increased phosphorylation of Erk. Collectively, these findings suggest that inhibition of the HGF/c-Met axis diminishes the effects of fluoropyrimidine through downregulation of UPP1 expression. Therefore, extreme caution must be exercised in terms of patient safety while offering chemotherapy comprising fluoropyrimidine concomitantly with inhibitors of the HGF/c-Met axis.
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Antineoplásicos , Factor de Crecimiento de Hepatocito , Antineoplásicos/farmacología , Proliferación Celular , Clorhidrato de Erlotinib/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fluorouracilo/farmacología , Células Hep G2 , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Proteínas Proto-Oncogénicas c-met/metabolismoRESUMEN
It is essential for oncology pharmacists to update their knowledge, skills, and ethical attitudes. The Japanese Society of Pharmaceutical Oncology is an academic society for healthcare professionals involved in cancer treatment. It has conducted in-person seminars every year to cultivate the knowledge necessary for practicing advanced cancer medicine. Owing to the coronavirus disease (COVID-19) pandemic, the society was obligated to conduct a web-based seminar this year. A questionnaire survey was conducted before and after the webinar to explain how it works and to assess the learning attitudes of beginner and moderately skilled pharmacists in the field of oncology. Questionnaire surveys were conducted with the participants before and after watching the webinar. The questionnaires sought to determine participants' perspectives on the webinar and their knowledge of the seven modules. Of the 1756 webinar attendees, 1661 (94.6%) answered the pre-webinar survey and 1586 (90.3%) answered the post-webinar survey. Results indicate that the median post-webinar knowledge score was significantly higher than the median pre-webinar score (p < 0.001) in all modules. Principal component analysis of the degree of knowledge of seven modules revealed that the improved score group consisted of those from younger age groups, with less experience as pharmacists, non-society members, and those with less experience in past society seminars. Moreover, the web-based seminar provided a uniform learning effect throughout the country without distinguishing between urban and rural learners. The web-based educational program was an acceptable educational tool for Japanese oncology pharmacists.
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COVID-19 , Pandemias , Humanos , Japón , Aprendizaje , FarmacéuticosRESUMEN
Background: Cardiac troponin-T (TNNT2) is exclusively present in cardiac muscle. Measurement of TNNT2 is used for diagnosing acute coronary syndrome. However, its expression may not be limited in myocardium. This study aimed at evaluating the expression of TNNT2 in neoplastic tissues. Methods and Results: We used paraffin-embedded blocks of 68 patients with lung cancer (age, 68 ± 11 years old; early-stage, 33; advance-stage, 35) at Miyazaki University Hospital, Japan between January 1, 2017, and March 31, 2019. We stained the slide sections with primary monoclonal antibody against TNNT2 protein, and assessed the frequency of positive staining, and its association with pathological severity. In addition, we examined whether TNNT2 gene is detected in lung cancer tissues of four patients using reverse transcription-polymerase chain reaction. Immunoreactivity for TNNT2 protein was present in the cytoplasm and nucleus of lung cancer cells. The frequency was 37% (25 of 68) in all patients and was irrespective of histologic type (six of 13, squamous cell carcinoma; 18 of 50, adenocarcinoma; 0 of 4, neuroendocrine cell carcinoma; 1 of 1, large cell carcinoma). The prevalence increased with pathological staging [9% (3 of 33) at early-stage (Stage 0-I); 63% (22 of 35) at advance-stage (Stage II-IV and recurrence)]. In addition, frequency of positive staining for TNNT2 increased with pleural (χ2 = 5.877, P = 0.015) and vascular (χ2 = 2.449, P = 0.118) invasions but decreased with lymphatic invasion (χ2 = 3.288, P = 0.070) in specimens performed surgical resection. Furthermore, TNNT2 mRNA was detected in the resected squamous cell carcinoma and adenocarcinoma tissues. Conclusions: Our data suggest the aberrant expression of TNNT2 in lung cancer and its prevalence increases with pathological severity.
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Varicocele is a common cause of male infertility. It is reported that low sperm concentration, motility and morphology are indicative of increased sperm DNA fragmentation index (DFI) in men with varicocele. Although research has been conducted into the relationship between varicocele and DFI, little is known about seminal oxidation-reduction potential (ORP) in varicocele patients. We assessed the relationship between varicocele with seminal ORP and sperm DFI in both fertile and infertile men. This prospective case-control study compared the findings from infertile men with varicocele to those of men with normal spermatogenesis without varicocele. Semen samples were collected and assessed using the WHO (2010) guidelines. ORP was measured (mV) and normalized to sperm concentration (mV/106 sperm/mL). DFI was measured using the sperm chromatin structure assay (SCSA) method. For group comparisons, only samples with a concentration >1 × 106 sperm/mL were included. Infertile men with varicocele had significantly lower mean sperm concentration, motility and total sperm count. Conversely, infertile men with varicocele had a significantly higher mean serum FSH level, and higher ORP and DFI values than fertile controls. ORP was higher in patients with varicocele and positively correlated with DFI (p < 0.01). ORP and DFI showed significant negative correlations with semen parameters (sperm concentration, motility and total sperm count) in infertile men with a varicocele.
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Infertilidad Masculina , Varicocele , Estudios de Casos y Controles , Fragmentación del ADN , Humanos , Infertilidad Masculina/genética , Masculino , Oxidación-Reducción , Semen , Recuento de Espermatozoides , Motilidad Espermática , Espermatozoides/metabolismo , Varicocele/complicacionesRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Cyclosporine A (CyA) causes intrahepatic biliary stasis via inhibition of bile acid excretion through the bile salt export pump. We report a case of a patient in whom ursodeoxycholic acid (UDCA) markedly promoted the absorption of microemulsion-formulated CyA. CASE SUMMARY: The patient was a 22-year-old Japanese man diagnosed with stage 3 aplastic anaemia. He was treated with CyA, and 2 h post-dose (C2) was increased by UDCA. WHAT IS NEW AND CONCLUSION: A remarkable interaction was observed between CyA and UDCA. This is a valuable finding for improving the treatment strategies for haematological disorders.
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Anemia Aplásica/tratamiento farmacológico , Ciclosporina/farmacocinética , Emulsiones/química , Inmunosupresores/farmacocinética , Ácido Ursodesoxicólico/farmacología , Ciclosporina/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Pruebas de Función Hepática , Masculino , Adulto JovenRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Continuing education is essential for pharmacists to acquire and maintain the knowledge, skills, and ethical attitudes necessary for clinical practice. However, with the emergence of COVID-19, the social circumstances and face-to-face learning environments have changed. The objectives of this study were to determine Japanese pharmacists' perception of a web-based educational programme in oncology, and assess changes in their understanding of pharmaceutical care in oncology before and after their participation in the webinar. METHODS: Questionnaire-based surveys were conducted for the participants of the web-based educational programme to determine their perspectives on the webinar, and their degree of comprehension of the five cancer types covered before and after watching the webinar. RESULTS AND DISCUSSION: Of the 1936 pharmacists taking the programme, all participated in the pre-webinar survey, and 1861 (96.1%) in the post-webinar survey. Compared with previous seminars that were held in the offline mode before the COVID-19 pandemic, 76.8% of respondents were significantly satisfied with the web-based educational programme. The median post-webinar comprehension scores in all modules were significantly higher than the median pre-webinar scores (p < 0.0001). A majority of the participants agreed that a web-based educational programme was satisfactory in acquiring knowledge. WHAT IS NEW AND CONCLUSION: This web-based educational programme was effective for Japanese pharmacists for postgraduate education in pharmaceutical care in oncology. To the best of our knowledge, our study is the first to report the effectiveness of a web-based educational programme for oncology pharmacists using a large population.
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COVID-19/prevención & control , Educación Continua/métodos , Educación a Distancia/métodos , Educación en Farmacia/métodos , Internet , Farmacéuticos/estadística & datos numéricos , Evaluación de Programas y Proyectos de Salud/métodos , Adulto , Femenino , Encuestas de Atención de la Salud/métodos , Humanos , Japón , Masculino , Persona de Mediana Edad , Pandemias , Rol Profesional , SARS-CoV-2 , Adulto JovenRESUMEN
Intrathecal administration of anticancer drugs is an effective dosage strategy, but the elimination of intraventricular drugs is not uniform in all patients. For safety, a system to evaluate local pharmacokinetics in the ventricles after administration is desired. In this study, we developed a simple and reproducible method to measure topotecan concentration in the cerebrospinal fluid (CSF) and confirmed its clinical applicability. High-performance liquid chromatography (HPLC) analysis was performed using a C18 column to measure the total topotecan concentration in the CSF. Clinical CSF samples were obtained from a 1-year old child with poor CSF absorption and stagnation. The patient received topotecan via an intraventricular subcutaneous reservoir. The HPLC method complied with the validation criteria. The lower limit of quantitation of this method was 0.04 µM. Using the developed method, we could determine the difference in topotecan CSF concentrations at 24 and 48 h after administration. The patient's topotecan elimination rate was extremely low, and signs of adverse effects were observed at high CSF concentration of topotecan. The developed method could detect the delay in topotecan elimination after intrathecal injection. The findings of this study are valuable for the development of personalized treatments for the intrathecal administration of anticancer drugs.
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BACKGROUND: A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted. METHODS: A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE. RESULTS: Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified. CONCLUSIONS: Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.
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WHAT IS KNOWN AND OBJECTIVE: Methotrexate (MTX) is an important agent for the treatment of primary central nervous system lymphomas (PCNSL) but needs to be given in big doses by intravenous infusions to achieve therapeutic concentrations in the cerebrospinal fluid. However, co-administration with many drugs may delay the excretion of MTX which may cause serious adverse effects if the serum concentration exceeds 0.1 µmol/L 72 h after an intravenous infusion. CASE SUMMARY: A 67-year-old Japanese female with PCNSL was treated with high-dose MTX-based chemotherapy. The serum MTX concentration 72 h post-infusion was 0.153 µmol/L when she was taking levofloxacin (LVFX) but <0.1 µmol/L 72 h after 4 subsequent infusions when she was not taking LVFX. She was given many other drugs but the timing of the short course of LVFX and the fact that ciprofloxacin also delays MTX excretion suggests that LVFX was the cause. WHAT IS NEW AND CONCLUSION: Co-administration of LVFX may delay the excretion of MTX. Therefore, serum concentrations of MTX should be monitored to help prevent and improve the management of potentially serious MTX drug-drug interaction.
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Antibacterianos/farmacología , Antimetabolitos Antineoplásicos/farmacocinética , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Levofloxacino/farmacología , Linfoma/tratamiento farmacológico , Metotrexato/farmacocinética , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/sangre , Antimetabolitos Antineoplásicos/uso terapéutico , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Femenino , Humanos , Metotrexato/administración & dosificación , Metotrexato/sangre , Metotrexato/uso terapéuticoRESUMEN
Previous studies have shown that viewing cute pictures leads to performance improvement in a subsequent fine motor task. We examined the beneficial effects of viewing cute pictures in a more complex sporting skill (i.e., basketball free throws) by comparing three conditions (viewing baby animal pictures, adult animal pictures, and no pictures) and two tests (no-pressure and pressure). The participants, all of whom were college basketball players, performed 16 free throws in each condition. In the no-pressure test, male participants improved performance after viewing pictures of baby animals but not after adult animals and no pictures. In the pressure test, no significant improvement was observed. For female participants, the cuteness-viewing effect was not observed in both tests. The results suggest that viewing cute pictures may improve performance during basketball free throws in a low-pressure situation by narrowing the breadth of attentional focus and inducing approach motivation and caregiving behaviors.
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A polymorphism in the gene encoding the metabolic enzyme cytochrome P450 family 3 subfamily A member 5 (CYP3A5) is a particularly influential factor in the use of tacrolimus in Japanese patients. Those who are homozygotic for the *3 mutation lack CYP3A5 activity, which results in substantial individual differences in tacrolimus metabolism. The aim of this study was to analyze the relationship between individual differences in tacrolimus blood concentration changes and CYP3A5 polymorphisms in allogeneic hematopoietic stem cell transplantation recipients during the period of increasing blood concentration of the drug following treatment onset. This was a prospective observational cohort study, involving 20 patients administered tacrolimus by continuous infusion. The subjects were divided into the *1/*3 and *3/*3 groups based on CYP3A5 polymorphism analysis. The tacrolimus blood concentration/dose (C/D) ratio increased from day 1 and was largely stable on day 5, and a significant difference was observed between the *1/*3 and *3/*3 groups in the time course of the C/D ratio during this period (p < 0.05). This study reveals the effects of CYP3A5 polymorphism on continuous changes in tacrolimus blood concentration.
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We herein report the cytokine expression at different stages for three patients who developed cardiac complications after immune checkpoint inhibitor (ICI) therapy. Case 1 with biopsy-proven myocarditis showed increased levels of interleukin (IL)-8, monocyte chemotactic and activating factor, and granulocyte macrophage colony-stimulating factor (GM-CSF) when he developed Takotsubo cardiomyopathy. Case 2 with subclinical myocarditis showed predominant activation of IL-8 during the progressive clinical course. Case 3 with cytokine-releasing syndrome showed substantial activations of IL-6, IL-8, GM-CSF, and interferon-γ. Our data suggest the development of unique cytokine activation in individual patients with cardiac complications after ICI therapy.
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Citocinas , Inhibidores de Puntos de Control Inmunológico , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Humanos , Interferón gamma , Masculino , MonocitosRESUMEN
OBJECTIVE: To assess the effect of green tea intake on the pharmacokinetics of the ß-blocker celiprolol. MATERIALS AND METHOD: In an open-label crossover study, 3 healthy subjects were given water or a green tea beverage daily for 3 days. On day 4, each subject received a single oral dose of 200 mg celiprolol with water or green tea. Serum and urinary concentrations of celiprolol were measured for up to 24 hours. RESULTS: Green tea intake decreased the area under the serum concentration-time curve and urinary excretion of celiprolol by 98.6 and 98.0%, respectively. CONCLUSION: Green tea intake might have a negative impact on the clinical effectiveness of celiprolol.
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Celiprolol , Té , Antagonistas Adrenérgicos beta , Estudios Cruzados , Voluntarios Sanos , HumanosRESUMEN
BACKGROUND: The concentration of MTX in blood is often measured quickly and easily by immunoassays. Thus, immunoassays may facilitate the easy determination of the concentration of MTX in the cerebrospinal fluid (CSF). In this study, we measured methotrexate (MTX) concentrations in the CSF using a high-performance liquid chromatography (HPLC) method intended for analyzing CSF matrices and a chemiluminescence immunoassay (CLIA) method intended for assessing serum and plasma matrices and verified the differences in the results of the two methods. METHODS: HPLC analysis for MTX in the CSF was performed using a Prominence UFLC system with a C18 column. The HPLC method was validated in accordance with the 2018 FDA guideline. The CLIA method was performed using an ARCHITECT i1000SR system intended for serum and plasma matrices. A total of 47 CSF samples (14 clinical and 33 spiked specimens) were analyzed using the two methods. RESULTS: The HPLC method passed the validation criteria. The concentration of MTX in the same sample, determined using the HPLC and CLIA methods, differed proportionally; the percent difference in the concentrations averaged -23.0% (95% confidence interval: -36.9% to -9.1%) as revealed by the Bland-Altman plot. The relationship between the measured values, evaluated using the Passing-Bablok regression, was as follows: HPLC = 1.205 × CLIA - 0.024. CONCLUSION: The equation deduced in this study can be used to correct the concentration of MTX measured using the CLIA method.