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The retina is the only organ projecting external light to the suprachiasmatic nucleus. Cholecystokinin receptor type A (Cckar/Cckar) is one of the essential factors for light reception in retinal cells. As there was a lack of literature on the matter, we aimed to elucidate the cause of the time-dependent phase change in clock gene expression. We found that Cckar mRNA expression in retinal cells exhibited diurnal variations. The rhythm of expression of the clock gene Per1/Per2 in retinal cells was altered in Cckar -/- mice. The light sensitivity of retinal cells was evaluated in wild-type mice, which showed c-Fos was activated in the ganglion cell layer more than in the inner granular layer. This increase in the number of c-Fos-positive cells was suppressed by lorglumide, a Cckar antagonist. Treatment of rat retina primary cells with lorglumide suppressed Per2 transcription, which was altered in a time-dependent manner relative to the Per2 expression. Light irradiation studies in Cckar -/- mice did not exhibit an increase in Period expression in the suprachiasmatic nucleus. These results indicate that Cckar is among the factors that regulate the cycle of clock genes on the retina. Cckar knockout attenuates the light responsiveness of suprachiasmatic nucleus and reduces the expression amplitude of Period genes in the retina. Thus, Cckar may contribute to entrainment of the light environment and maintenance of the expression cycle of Period gene, which is one of the core clock genes.
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Cachexia is a common cancer complication and is associated with weight loss and anorexia. In this study, we investigated the ameliorating effects of cystine and theanine on cancer cachexia using a mouse model. In mice carrying the colon cancer cell line C-26, there was a suppression of body weight increase and reduction in both internal fat and lower limb muscles. Repeated cystine and theanine administration significantly prevented weight loss, internal fat loss, lower limb muscle loss, and serum IL-6 increase in the cachexia model. These results suggested that cystine and theanine may be effective in ameliorating cancer cachexia.
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Caquexia , Neoplasias , Humanos , Caquexia/tratamiento farmacológico , Caquexia/etiología , Cistina/farmacología , Neoplasias/complicaciones , Pérdida de PesoRESUMEN
Medical expenses are increasing year by year in Japan. However, the quantity of disposed medical opioids is not well known. In this study, we assessed disposed medical opioids in community pharmacies of Fukuoka city and in all of medical organizations of Kumamoto cities for 3 and 2 years, respectively. We collected official opioid disposal reports in Kumamoto city and Fukuoka City Pharmaceutical Association (FCPA) disposal information sheet in Fukuoka city. The total amount of disposed opioids was worth 7.1 million Yen from 2017 to 2019 in Fukuoka city, and 8.9 million Yen in for 2 years (2018 and 2019) in Kumamoto city. In Fukuoka city, the most disposed opioid was 20 mg Oxycontin®, worth approximately 940000 Yen. In Kumamoto city we assessed data in different organizations. The most disposed opioid was 5 mg Oxinorm® at a cost of 600000 Yen at the medical institutions over the 2-year study period. The most disposed opioid was 40 mg Oxycontin®, at a cost of 640000 Yen in community pharmacies. Two hundred micrograms E-fen® buccal tablet was the most disposed of opioid, was amounting to 960000 Yen in wholesalers. On the whole in Kumamoto city, non-dispensing was the most common reason of disposal. These results indicate that the amount of disposed opioids is huge. Small package simulation studies suggest that smaller package units of MS-Contin®, Anpec® suppository, and Abstral® sublingual tablet may be able to reduce the amount of disposed opioids.
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Analgésicos Opioides , Trastornos Relacionados con Opioides , Humanos , Oxicodona , Trastornos Relacionados con Opioides/tratamiento farmacológico , Ciudades , FentaniloRESUMEN
The anticancer drug, paclitaxel, is widely used for ovarian, breast, non-small cell lung, and gastric cancers; however, it induces peripheral neuropathy as a side effect. There is insufficient evidence-based prophylaxis, and new prophylaxis and treatment methods are required. We examined the effect of α1-receptor antagonists on paclitaxel-induced peripheral neuropathy using Sprague-Dawley rats and a large adverse event database. The repeated administration of doxazosin or tamsulosin significantly reduced the response threshold to paclitaxel administration in animal models. In the sciatic nerve tissue, axonal degeneration and myelopathy were significantly suppressed. Furthermore, an analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database suggested that the group using α1 inhibitors showed a lower reporting rate for paclitaxel-related peripheral neuropathy than the group that did not use these inhibitors (odds ratio (95% confidence interval): tamsulosin 0.21 (0.08−0.56), p < 0.01, doxazosin 0.41 (0.10−1.65), p = 0.195; any α1 receptor antagonist 0.54 (0.38−0.76), p < 0.01). Thus, doxazosin and tamsulosin may inhibit the development of paclitaxel-induced peripheral neuropathy by suppressing neurodegeneration, particularly axonal degeneration and myelopathy.
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OBJECTIVE: To develop versatile and interactive model classes by generating the contents of Kampo classroom sessions that can be taught by instructors who are not familiar with Kampo medicine. METHODS: In 2018, we conducted Kampo classroom sessions among fourth-year medical students at Kyushu University in which we incorporated new content. A videotaped digest edition of the classes was sent to Kampo medicine instructors in medical schools throughout Japan. An online questionnaire was given to the instructors regarding effectiveness of the class content (Q1) and whether they would introduce the content in their classes (Q2). We modified the curriculum according to survey responses and conducted revised classroom sessions again in 2019. A second online survey was given and we finalized the model classes. We compared survey responses between staff and instructors (group A) and non-specialists in Kampo medicine (group B). RESULTS: In 2018, there were significant differences between groups A (44) and B (52) regarding a patient's story and case report (Q1). In 2019, there were significant differences between groups A (42) and B (54) regarding the case report using e-learning(Q1) and an instructor's experience (Q2). CONCLUSIONS: We propose that Kampo medicine classes should incorporate an instructor's experience and interactive case report presentation using e-learning.
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Medicina Kampo , Estudiantes de Medicina , Humanos , Curriculum , Facultades de Medicina , AprendizajeRESUMEN
(1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The effects of omeprazole, a proton pump inhibitor (PPI), on oxaliplatin-induced peripheral neuropathy (OIPN) was investigated using an in vivo model and a real-world database. (3) Results: In a rat model, oxaliplatin (4 mg/kg, i.p., twice a week for 4 weeks) caused mechanical hypersensitivity accompanied by sciatic nerve axonal degeneration and myelin sheath disorder. Repeated injection of omeprazole (5−20 mg/kg, i.p., five times per week for 4 weeks) ameliorated these behavioral and pathological abnormalities. Moreover, omeprazole did not affect the tumor growth inhibition of oxaliplatin in tumor bearing mice. Furthermore, clinical database analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) suggests that the group using omeprazole has a lower reporting rate of peripheral neuropathy of oxaliplatin-treated patients than the group not using (3.06% vs. 6.48%, p < 0.001, reporting odds ratio 0.44, 95% confidence interval 0.32−0.61). (4) Conclusions: These results show the preventing effect of omeprazole on OIPN.
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Antineoplásicos , Neoplasias , Enfermedades del Sistema Nervioso Periférico , Animales , Antineoplásicos/efectos adversos , Ratones , Neoplasias/tratamiento farmacológico , Omeprazol/farmacología , Omeprazol/uso terapéutico , Oxaliplatino/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/prevención & control , Ratas , RoedoresRESUMEN
BACKGROUND: Drug repositioning is a cost-effective method to identify novel disease indications for approved drugs; it requires a shorter developmental period than conventional drug discovery methods. We aimed to identify prophylactic drugs for oxaliplatin-induced peripheral neuropathy by drug repositioning using data from large-scale medical information and life science information databases. METHODS: Herein, we analyzed the reported data between 2007 and 2017 retrieved from the FDA's database of spontaneous adverse event reports (FAERS) and the LINCS database provided by the National Institute of Health. The efficacy of the drug candidates for oxaliplatin-induced peripheral neuropathy obtained from the database analysis was examined using a rat model of peripheral neuropathy. Additionally, we compared the incidence of peripheral neuropathy in patients who received oxaliplatin at the Tokushima University Hospital, Japan. The effects of statins on the animal model were examined in six-week-old male Sprague-Dawley rats and seven or eight-week-old male BALB/C mice. Retrospective medical chart review included clinical data from Tokushima University Hospital from April 2009 to March 2018. RESULTS: Simvastatin, indicated for dyslipidemia, significantly reduced the severity of peripheral neuropathy and oxaliplatin-induced hyperalgesia. In the nerve tissue of model rats, the mRNA expression of Gstm1 increased with statin administration. A retrospective medical chart review using clinical data revealed that the incidence of peripheral neuropathy decreased with statin use. CONCLUSION AND RELEVANCE: Thus, drug repositioning using data from large-scale basic and clinical databases enables the discovery of new indications for approved drugs with a high probability of success.
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Reposicionamiento de Medicamentos/métodos , Oxaliplatino/efectos adversos , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Profilaxis Pre-Exposición/métodos , Animales , Anticolesterolemiantes/uso terapéutico , Antineoplásicos/efectos adversos , Macrodatos , Bases de Datos Factuales , Humanos , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Japón , Masculino , Ratones , Ratones Endogámicos BALB C , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Ratas , Ratas Sprague-Dawley , Estudios Retrospectivos , Simvastatina/uso terapéuticoRESUMEN
Nutmeg, a dried seed kernel of a tall evergreen Myristicaceae tree, is widely used as a spice and herbal medicine and is known to have antidepressant-like effects. This study evaluates the mechanisms underlying this antidepressant-like effect and safety of nutmeg n-hexane extract (NNE) in mice. Tail suspension and open field tests showed that NNE (10 mg/kg, per OS (p.o.)) significantly decreased the immobility time of mice without effecting their spontaneous locomotor activity. The reduction of immobility time of mice elicited by NNE was significantly inhibited by ketanserin (5-hydroxytryptamine (5-HT)2A/2C receptor antagonist), ondansetron (5-HT3 receptor antagonist), and yohimbine (α2 receptor antagonist). WAY100635 (5-HT1A receptor antagonist) tended to inhibit the effect of NNE but without significance. Testing according to the Organisation for Economic Co-operation and Development Guidelines, no mice died due to administrated NNE (2000 mg/kg, p.o.), and behavioral and weight changes were not seen in the acute toxicity test. In the Ames test, no increase in the number of revertant colonies for each bacterial strain test strains TA98 and TA100 by nutmeg powder was observed either with or without metabolic activity by S9 mix. These results suggest that NNE shows an antidepressant-like effect involving various serotonergic and noradrenergic nervous systems and maybe a highly safe natural preparation.
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Myristica , Animales , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Suspensión Trasera/métodos , Ratones , Myristica/metabolismo , Serotonina/metabolismo , Antagonistas de la Serotonina/farmacología , NataciónRESUMEN
PURPOSE: As the prognosis of cancer patients deteriorates, secondary carcinogenesis after chemotherapy, especially secondary hematological malignancies, becomes a serious problem. However, information on the frequency and time of onset of secondary hematological malignancies and the risk of hematological malignancy with different drugs is scarce. This study aimed to evaluate the incidence of leukemia and myelodysplastic syndrome in patients with solid tumors, including breast, colon, gastric, pancreatic, small cell lung, non-small cell lung, esophageal, ovarian, cervical, and endometrial cancers. METHODS: Using the United States Food and Drug Administration Adverse Event Reporting System, we analyzed the reporting rates, reporting odds ratios, and the reporting onset times of secondary leukemia and myelodysplastic syndrome for each drug used. RESULTS: The leukemia reporting rates were higher in breast, small cell lung, ovarian, and endometrial cancers than in other cancers, and the myelodysplastic syndrome reporting rates were higher in ovarian and endometrial cancers than in other cancers. For each cancer type, the reporting odds ratios of cytocidal anticancer agents, such as taxanes, anthracyclines, alkylating agents, platinum, and topoisomerase inhibitors, were higher than those of other drugs. Alternatively, the reporting odds ratios of molecular targeted drugs and immune checkpoint inhibitors were not higher than those of other drugs. Approximately half of the cases of leukemia and myelodysplastic syndrome were reported within 1 to 4 years after chemotherapy. CONCLUSIONS: Our study clarified the risks of leukemia and myelodysplastic syndrome for several anticancer drugs in patients with solid tumors. Our data may aid in the assessment of the risks of secondary leukemia and myelodysplastic syndrome when medical oncologists, clinical pharmacists, and patients select chemotherapy regimens.
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Antineoplásicos/efectos adversos , Leucemia/inducido químicamente , Síndromes Mielodisplásicos/inducido químicamente , Neoplasias/tratamiento farmacológico , Sistemas de Registro de Reacción Adversa a Medicamentos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológicoRESUMEN
Paclitaxel is an essential drug in the chemotherapy of ovarian, non-small cell lung, breast, gastric, endometrial, and pancreatic cancers. However, it frequently causes peripheral neuropathy as a dose-limiting factor. Animal models of paclitaxel-induced peripheral neuropathy (PIPN) have been established. The mechanisms of PIPN development have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory PIPN effects. This review summarizes the basic and clinical evidence for therapeutic or prophylactic effects for PIPN. In pre-clinical research, many reports exist of neuropathy inhibitors that target oxidative stress, inflammatory response, ion channels, transient receptor potential (TRP) channels, cannabinoid receptors, and the monoamine nervous system. Alternatively, very few drugs have demonstrated PIPN efficacy in clinical trials. Thus, enhancing translational research to translate pre-clinical research into clinical research is important.
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Antineoplásicos Fitogénicos/efectos adversos , Paclitaxel/efectos adversos , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Animales , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Humanos , Estrés Oxidativo/efectos de los fármacos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/metabolismo , Enfermedades del Sistema Nervioso Periférico/prevención & control , Profilaxis Pre-Exposición , Investigación Biomédica TraslacionalRESUMEN
Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia (PPE), is a major side effect of capecitabine. Although the pathogenesis of HFS remains unknown, some studies suggested a potential involvement of inflammation in its pathogenesis. Proton pump inhibitors (PPIs) have been reported to have anti-inflammatory effects. In this study, we investigated the ameliorative effects of omeprazole, a PPI on capecitabine-related HFS in mice model, and a real-world database. Repeated administration of capecitabine (200 mg/kg, p.o., five times a week for 3 weeks) increased fluid content, redness, and tumor necrosis factor (TNF)-α substance of the mice hind paw. Co-administration of omeprazole (20 mg/kg, p.o., at the same schedule) significantly inhibited these changes induced by capecitabine. Moreover, based on the clinical database analysis of the Food and Drug Administration Adverse Event Reporting System, the group that has used any PPIs had a lower reporting rate of capecitabine-related PPE than the group that has not used any PPIs. (6.25% vs. 8.31%, p < 0.0001, reporting odds ratio (ROR) 0.74, 95% confidence interval (CI) 0.65-0.83). Our results suggest that omeprazole may be a potential prophylactic agent for capecitabine-induced HFS.
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Capecitabina/efectos adversos , Síndrome Mano-Pie/tratamiento farmacológico , Omeprazol/farmacología , Inhibidores de la Bomba de Protones/farmacología , Animales , Capecitabina/farmacología , Modelos Animales de Enfermedad , Síndrome Mano-Pie/metabolismo , Síndrome Mano-Pie/patología , Ratones , Ratones Endogámicos ICRRESUMEN
The anticancer agents including oxaliplatin, paclitaxel, and bortezomib cause severe peripheral neuropathy. The Kampo medicine Sokeikakketsuto (SOKT) has been widely used to treat several types of pain. In this study, the analgesic effects of SOKT on oxaliplatin-, paclitaxel-, and bortezomib-induced peripheral neuropathy were investigated in rat models. Rats were treated with oxaliplatin (4 mg/kg, intraperitoneally (i.p.), twice a week for four weeks), paclitaxel (4 mg/kg, i.p., twice a week for two weeks), or bortezomib (0.2 mg/kg, i.p., twice a week for two weeks). SOKT (0.3 or 1.0 g/kg) or duloxetine hydrochloride (30 mg/kg, as a positive control) was administered orally after neuropathy developed. Mechanical allodynia and cold hyperalgesia were assessed using the von Frey test and the acetone test, respectively. These tests were performed immediately before and 30, 60, 90, and 120 min after the administration of the drugs. Repeated treatment of oxaliplatin induced mechanical allodynia and cold hyperalgesia. A single administration of SOKT (1 g/kg, per os (p.o.)), as well as duloxetine, temporarily reversed both the mechanical allodynia and the cold hyperalgesia. Repeated administration of paclitaxel and bortezomib also induced the mechanical allodynia. SOKT and duloxetine reversed the mechanical allodynia caused by bortezomib, but not by paclitaxel. SOKT might have the potential to become a new drug to relieve the symptom of oxaliplatin- or bortezomib-induced peripheral neuropathy.
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Analgésicos/farmacología , Antineoplásicos/efectos adversos , Frío/efectos adversos , Medicamentos Herbarios Chinos/farmacología , Hiperalgesia/tratamiento farmacológico , Analgésicos/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Clorhidrato de Duloxetina/farmacología , Clorhidrato de Duloxetina/uso terapéutico , Humanos , Hiperalgesia/inducido químicamente , Hiperalgesia/diagnóstico , Masculino , Medicina Kampo/métodos , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Dimensión del Dolor , Ratas , Ratas Sprague-DawleyRESUMEN
Oxaliplatin is an essential drug in the chemotherapy of colorectal, gastric, and pancreatic cancers, but it frequently causes peripheral neuropathy as a dose-limiting factor. So far, animal models of oxaliplatin-induced peripheral neuropathy have been established. The mechanisms of development of neuropathy induced by oxaliplatin have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory effects on neuropathy. In this review, we summarize the basic and clinical evidence for the therapeutic effects of oxaliplatin. In basic research, there are many reports of neuropathy inhibitors that target oxidative stress, inflammatory response, sodium channel, transient receptor potential (TRP) channel, glutamate nervous system, and monoamine nervous system. Alternatively, very few drugs have clearly demonstrated the efficacy for oxaliplatin-induced peripheral neuropathy in clinical trials. It is important to activate translational research in order to translate basic research into clinical research.
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Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Oxaliplatino/efectos adversos , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Animales , Antineoplásicos/administración & dosificación , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Fármacos Neuroprotectores/uso terapéutico , Oxaliplatino/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Resultado del TratamientoRESUMEN
Additional fees for ward pharmacists' services have been valued for hospitals in Japan. However, the calculation period for services provided to inpatients in the psychiatric ward is limited to 8 weeks. This study aimed to reveal the need for the services of pharmacists in the hospital ward for inpatients hospitalized for >8 weeks in the psychiatric ward. Patients who were hospitalized in the psychiatric ward from September 2016 to February 2017 were analyzed retrospectively. The pharmacists suggested prescriptions for inpatients admitted for >8 weeks, similar to those admitted for <9 weeks, and this supported pharmacotherapy without exacerbating patient outcomes. Moreover, significant decreases in benzodiazepine doses were found between the prior and post prescription suggestions of the pharmacist for inpatients >8 weeks of admission. Healthcare expenditures were also reduced. These results suggest that the prescriptions suggested by pharmacists for inpatients admitted for >8 weeks in the psychiatric ward were useful. In conclusion, our findings show that ward pharmacists' services were necessary not only for the inpatients hospitalized for <9 weeks, but also for those hospitalized for >8 weeks.
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Pacientes Internos , Trastornos Mentales/tratamiento farmacológico , Farmacéuticos , Servicio de Farmacia en Hospital , Prescripciones , Sugestión , Benzodiazepinas/administración & dosificación , Benzodiazepinas/economía , Costos de la Atención en Salud , Japón , Trastornos Mentales/economía , Prescripciones/estadística & datos numéricos , Estudios Retrospectivos , Factores de TiempoRESUMEN
Oxaliplatin frequently causes severe peripheral neuropathy as a dose-limiting toxicity. However, this toxicity lacks a strategy for prevention. Cystine/Theanine is a supplement, which includes precursors for the biosynthesis of glutathione. In this study, we investigated the effects of Cystine/Theanine on oxaliplatin-induced peripheral neuropathy using an in vivo model. Repeated injection of oxaliplatin (4 mg/kg intraperitoneally twice a week for 2 weeks) caused mechanical allodynia, cold hyperalgesia and axonal degeneration of the sciatic nerve in rats. Mechanical allodynia and axonal degeneration, but not cold hyperalgesia, were ameliorated by daily co-administration of Cystine [200 mg/kg orally (p.o.)] and Theanine (80 mg/kg p.o.). Moreover, co-administration of Cystine and Theanine to rats significantly increased the glutathione level in the sciatic nerve compared with the oxaliplatin group. Furthermore, Cystine and Theanine did not attenuate the tumour cytotoxicity of oxaliplatin in C-26 tumour cell-bearing mice. These findings suggest that Cystine and Theanine may be beneficial for preventing oxaliplatin-induced peripheral neuropathy.
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Cistina/administración & dosificación , Glutamatos/administración & dosificación , Hiperalgesia/tratamiento farmacológico , Oxaliplatino/efectos adversos , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Administración Oral , Animales , Frío , Cistina/farmacología , Modelos Animales de Enfermedad , Quimioterapia Combinada , Glutamatos/farmacología , Glutatión/metabolismo , Hiperalgesia/inducido químicamente , Hiperalgesia/metabolismo , Masculino , Ratones , Neoplasias , Células PC12 , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/metabolismo , Ratas , Ratas Sprague-Dawley , Nervio Ciático/metabolismoRESUMEN
Oxaliplatin is a platinum-based antineoplastic drug commonly used for treating colorectal, gastric, and pancreatic cancer. However, it frequently causes peripheral neuropathy as dose-limiting toxicity and is lacking a strategy for prevention. Alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, is an oral antidiabetic drug. Previous studies have shown that DPP-4 inhibitors have pleiotropic effects, including neuroprotection. In this study, we investigated the effects of alogliptin on oxaliplatin-induced peripheral neuropathy using in vitro and in vivo models. In PC12 cells, alogliptin attenuated neurite disorders induced by oxaliplatin and cisplatin. The repeated injection of oxaliplatin caused mechanical allodynia and axonal degeneration of the sciatic nerve in rats. These neuropathies were ameliorated by co-administration of alogliptin. Moreover, alogliptin did not attenuate tumor cytotoxicity of oxaliplatin in the cultured colon, gastric, or pancreatic cancer cell lines and tumor-bearing mice. These findings suggest that alogliptin may be beneficial for preventing oxaliplatin-induced peripheral neuropathy.
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Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Hiperalgesia/prevención & control , Fármacos Neuroprotectores/farmacología , Oxaliplatino/efectos adversos , Enfermedades del Sistema Nervioso Periférico/prevención & control , Piperidinas/farmacología , Uracilo/análogos & derivados , Aloinjertos , Animales , Axones/efectos de los fármacos , Axones/patología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Relación Dosis-Respuesta a Droga , Células HCT116 , Humanos , Hiperalgesia/inducido químicamente , Hiperalgesia/fisiopatología , Masculino , Ratones , Ratones Endogámicos BALB C , Neuritas/efectos de los fármacos , Neuritas/patología , Células PC12 , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Ratas , Ratas Sprague-Dawley , Nervio Ciático/efectos de los fármacos , Nervio Ciático/fisiopatología , Carga Tumoral/efectos de los fármacos , Uracilo/farmacologíaRESUMEN
Few therapeutic options exist for gemcitabine-resistant pancreatic cancer. In this study, we investigated the anti-cancer effects of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors and bisphosphonates in pancreatic cancer cell lines (SUIT-2 and MIA PaCa-2) which show poor responses to gemcitabine, established through long-term culture in nutrient-deprived or gemcitabine-containing media. Under the nutrient-deprived condition, IC50s for statins and bisphosphonates decreased and those for gemcitabine increased compared with those under normal conditions. In cells cultured long-term with gemcitabine, although IC50s for gemcitabine increased, those for statins and bisphosphonates either slightly increased or remained unchanged. Thus, these drugs may be effective against pancreatic cancer cells which show poor responses to gemcitabine.
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Alendronato/farmacología , Antineoplásicos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Ácido Zoledrónico/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Humanos , GemcitabinaRESUMEN
Benzodiazepine receptor agonists (BZDs) should be appropriately used owing to the associated risks of delirium and falls. Since January 2018, the liaison team pharmacist at Iizuka Hospital has been applying digital labels with recommendations for the reduction of use and changes in the medication orders and prescriptions of BZDs on electronic medical records of patients in the surgical ward. This study aimed to verify the effectiveness of reducing the use of BZDs via the implementation of digital labels. Patients in the surgical ward were retrospectively assessed for changes in medication orders and prescription ratios of BZDs before and after the implementation of digital labels. The ratio of the number of digital labels implemented to the number of confirmations of medication orders and prescriptions of BZDs was 15.0% at the start of implementation; however, the ratio gradually and significantly decreased to 3.6%. The medication order ratio of BZDs was 52.2% before the implementation of digital labels; however, this ratio decreased to 2.7% and 5.6% immediately and 4 months after the implementation of digital labels, respectively. The present study showed that medication orders for BZDs were reduced after the implementation of digital labels and that the reduction effect was maintained for a certain period of time. Thus, the liaison team pharmacist-led approach can contribute to the proper use of BZDs.
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Utilización de Medicamentos/estadística & datos numéricos , Registros Electrónicos de Salud , Agonistas de Receptores de GABA-A , Prescripción Inadecuada/prevención & control , Accidentes por Caídas , Anciano , Anciano de 80 o más Años , Delirio/inducido químicamente , Femenino , Agonistas de Receptores de GABA-A/administración & dosificación , Agonistas de Receptores de GABA-A/efectos adversos , Humanos , Prescripción Inadecuada/estadística & datos numéricos , Masculino , Prescripciones/estadística & datos numéricosRESUMEN
Oxaliplatin induces severe peripheral neuropathy. The effect of donepezil, a drug used for treatment of Alzheimer's disease, on oxaliplatin-induced peripheral neuropathy was investigated using both in vivo and in vitro models. Donepezil effectively attenuated oxaliplatin- and cisplatin-induced inhibition of neurite outgrowth in cultured PC12 cells. In a rat model, repeated oral administration of donepezil (5 times/week for 4 weeks) ameliorated oxaliplatin-induced mechanical allodynia (von Frey test) and sciatic nerve axonal degeneration. Moreover, donepezil did not inhibit the anti-tumor activity of oxaliplatin in any cultured cancer cell line. Therefore, donepezil may be useful for managing oxaliplatin-induced peripheral neuropathy.
Asunto(s)
Donepezilo/farmacología , Fármacos Neuroprotectores/farmacología , Oxaliplatino/farmacología , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Masculino , Ratones , Células PC12 , Ratas , Ratas Sprague-Dawley , Nervio Ciático/efectos de los fármacosRESUMEN
Objective. The purpose of this study was to teach communication skills for patient care to pre-clerkship students and observe changes in student perspectives towards communication from pre- to post-training. Methods. Two cohorts of fourth-year pharmacy students completed an eight-week pre-clerkship training course designed to improve their communication skills. The course involved class discussions and in-class research of medications, practicing communication skills, learning to give science-based responses, and developing an awareness of patient education for lifestyle, self-medication, quality of life, and medication adherence. A comparison of students' pre- and post-training responses to a questionnaire were used to assess changes in students' ability and confidence in communicating with patients. An exploratory factor analysis was used to analyze and compare the data results. Results. Students' mean post-training scores for perceived ability to make small talk and confidence to communicate with patients increased compared to pre-training scores. Based on the results of the exploratory factor analysis, the greatest increase in students' scores was in the area of patient education skills. Conclusion. The pre-clerkship communication training improved student understanding of the pharmacy communication skills needed to conduct effective patient education and pharmacist-patient interaction beyond dispensing, affirming the theory that specialized communication training before students' begin a clerkship may be essential.