RESUMO
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.
Assuntos
Caquexia , Neoplasias , Humanos , Caquexia/tratamento farmacológico , Caquexia/etiologia , Cistina/farmacologia , Neoplasias/complicações , Redução de PesoRESUMO
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.
Assuntos
Myristica , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Elevação dos Membros Posteriores/métodos , Camundongos , Myristica/metabolismo , Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , NataçãoRESUMO
(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.
Assuntos
Antineoplásicos , Neoplasias , Doenças do Sistema Nervoso Periférico , Animais , Antineoplásicos/efeitos adversos , Camundongos , Neoplasias/tratamento farmacológico , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/prevenção & controle , Ratos , RoedoresRESUMO
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.
Assuntos
Analgésicos/farmacologia , Antineoplásicos/efeitos adversos , Temperatura Baixa/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Hiperalgesia/tratamento farmacológico , Analgésicos/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Cloridrato de Duloxetina/farmacologia , Cloridrato de Duloxetina/uso terapêutico , Humanos , Hiperalgesia/induzido quimicamente , Hiperalgesia/diagnóstico , Masculino , Medicina Kampo/métodos , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Medição da Dor , Ratos , Ratos Sprague-DawleyRESUMO
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.
Assuntos
Antineoplásicos/efeitos adversos , Leucemia/induzido quimicamente , Síndromes Mielodisplásicas/induzido quimicamente , Neoplasias/tratamento farmacológico , Sistemas de Notificação de Reações Adversas a Medicamentos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológicoRESUMO
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.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Fármacos Neuroprotetores/uso terapêutico , Oxaliplatina/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Resultado do TratamentoRESUMO
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.
Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Humanos , Estresse Oxidativo/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/prevenção & controle , Profilaxia Pré-Exposição , Pesquisa Translacional BiomédicaRESUMO
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.
Assuntos
Alendronato/farmacologia , Antineoplásicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Ácido Zoledrônico/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Humanos , GencitabinaRESUMO
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.
Assuntos
Donepezila/farmacologia , Fármacos Neuroprotetores/farmacologia , Oxaliplatina/farmacologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Masculino , Camundongos , Células PC12 , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacosRESUMO
Oxaliplatin has been used as a first choice for colorectal, gastric and pancreatic cancer, but it induces peripheral neuropathies. Dimethyl fumarate (DMF) is an oral drug for multiple sclerosis with neuroprotective effects on oxidative stress. Using both in vivo and in vitro models, we investigated the effects of DMF on oxaliplatin-induced peripheral neuropathy and other side effects, as well as on the anti-tumor activity of oxaliplatin. Repeated intraperitoneal injection of 4 mg/kg oxaliplatin (twice per week for 4 weeks) caused mechanical allodynia (as revealed by the von Frey tests), cold hyperalgesia (as revealed by the acetone tests), and axonal degeneration in the sciatic nerve of rats. Co-administration of oral DMF (200 mg/kg, five times per week for 4 weeks) relieved oxaliplatin-induced mechanical allodynia but not cold hyperalgesia, and ameliorated axonal degeneration. In addition, DMF did not exacerbate oxaliplatin-induced body weight loss or bone marrow suppression, such as reduction in red blood cells, white blood cells, neutrophils and lymphocytes. Furthermore, DMF did not inhibit the anti-tumor activity of oxaliplatin in any cultured cancer cell line (C26, mouse colon carcinoma; HCT116, human colon carcinoma; MKN45, human gastric adenocarcinoma; MIA PaCa-2, human pancreatic carcinoma) or C26-bearing mice. These results suggest that DMF prevents oxaliplatin-induced mechanical allodynia and axonal degeneration without affecting the anti-tumor activity of oxaliplatin. Therefore, DMF may be useful for managing oxaliplatin-induced chronic peripheral neuropathy.
Assuntos
Antineoplásicos , Fumarato de Dimetilo/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Oxaliplatina , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Fumarato de Dimetilo/farmacologia , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fármacos Neuroprotetores/farmacologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Carga Tumoral/efeitos dos fármacosRESUMO
Chemotherapy agents such as oxaliplatin, cisplatin, paclitaxel, and bortezomib frequently cause severe peripheral neuropathy and there is currently no effective strategy to prevent this. Dimethyl fumarate (DMF) is a new oral drug for the treatment of multiple sclerosis, and has neuroprotective effects via up-regulation of the nuclear factor-erythroid-2-related factor 2 (Nrf2)-dependent antioxidant response. In this study, we investigated the effect of DMF on chemotherapy agent-induced neurodegenerations in cultured cells. We found that DMF and its metabolite monomethyl fumarate (MMF) attenuated oxaliplatin-, cisplatin-, and bortezomib- (but not paclitaxel-) induced inhibition of neurite outgrowth, but had no effect on cell death as a result of these agents in cultured PC12 cells and primary cultured rat dorsal root ganglion (DRG) neurons. Furthermore, Nrf2 DNA binding activity was increased by DMF and MMF in PC12 cells. These findings suggest that DMF, which activates Nrf2 pathway, has a potential protective action against chemotherapy-induced neurotoxicity, particularly neurite impairments.
Assuntos
Antineoplásicos/efeitos adversos , Antioxidantes , Fumarato de Dimetilo/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Degeneração Neural/induzido quimicamente , Degeneração Neural/prevenção & controle , Crescimento Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores , Animais , DNA/metabolismo , Gânglios Espinais/efeitos dos fármacos , Células PC12 , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Ligação Proteica/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
Bisphosphonates and statins are known to have antitumor activities against different types of cancer cell lines. In the present study, we investigated the antiproliferative effects of the combination of zoledronic acid (ZOL), a bisphophosphonate, and fluvastatin (FLU), a statin, in vitro on two types of human pancreatic cancer cell lines, Mia PaCa-2 and Suit-2. The pancreatic cancer cell lines were treated with ZOL and FLU both individually and in combination to evaluate their antiproliferative effects using WST-8 cell proliferation assay. In this study, we demonstrated a potent synergistic antiproliferative effect of both drugs when used in combination in both cell lines. Moreover, we studied the molecular mechanism behind this synergistic effect, which was inhibited by the addition of the mevalonate pathway products, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Furthermore, we aimed to determine the effect of ZOL and FLU combination on RhoA and Ras guanosine 5'-triphosphate (GTP)-proteins. The combination induced a marked accumulation in RhoA and unprenylated Ras. GGPP and FPP reversed the increase in the amount of both proteins. These results indicated that the combination treatment impaired RhoA and Ras signaling pathway by the inhibition of geranylgeranylation and/or farnesylation. This study provides a potentially effective approach for the treatment of pancreatic cancer using a combination treatment of ZOL and FLU.
Assuntos
Antineoplásicos/farmacologia , Difosfonatos/farmacologia , Ácidos Graxos Monoinsaturados/farmacologia , Imidazóis/farmacologia , Indóis/farmacologia , Anticolesterolemiantes/farmacologia , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fluvastatina , Humanos , Ácido Mevalônico/metabolismo , Neoplasias Pancreáticas/metabolismo , Fosfatos de Poli-Isoprenil/metabolismo , Ácido Zoledrônico , Proteínas ras/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: In Japanese Kampo medical practice, suidoku (fluid disturbance) is one of the most important concepts for selecting the proper medication. Suidoku is an excessive or uneven distribution of fluid that is indicated by splashing sounds and pitting edema. However, few objective reports about suidoku have been published. Bioelectrical impedance analysis (BIA) uses resistance values obtained from weak electrical currents to estimate body composition, including intracellular and extracellular water and muscle and fat mass. In this study, we used BIA to search for objective factors that can discriminate the various types of suidoku. METHODS: Two hundred twenty-nine patients who visited the Kampo Medicine Clinic of Kyushu University Hospital from June 2010 to August 2015 were divided into non-suidoku (n = 180, 80 male and 100 female), splashing sound (n = 32, 8 male and 24 female) and edema groups (n = 17, 5 male and 12 female). Body composition values were taken from the electronic medical records of InBody730 (a vertical, segmental, multi-frequency analyzer by InBody, Tokyo Japan) testing done at the initial visit. Various parameters of the body composition values of female in the non-suidoku and suidoku groups (splashing sound and edema groups) were compared: there were too few male patients to provide significance. RESULTS: The age and body weight were significantly lower in the splashing sound group than in the non-suidoku group (p < 0.05). In contrast, the body weight of the edema group was significantly heavier than that of the non-suidoku group (p < 0.05). In ROC analysis, the percent Body Fat ≤ 27.8 %, Muscle Mass Index of the Trunk ≤ 6.5 kg/m2, VFA (Visceral fat area) ≤ 5.4 and BMI ≤ 19.2 kg/m2 were associated with splashing sound, and Muscle Mass Index of Legs ≥ 4.8 kg/m2 and BMI ≥ 21.4 kg/m2 were associated with edema. CONCLUSION: Our data suggest that the use of this type of BIA to estimate body composition would be a useful tool for the diagnosis of suidoku for women.
Assuntos
Composição Corporal/fisiologia , Líquidos Corporais/fisiologia , Impedância Elétrica , Medicina Kampo , Adulto , Idoso , Edema/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Deaf people often experience difficulty in understanding medication information provided by pharmacists due to communication barriers. We held medication education lectures for deaf and hard of hearing (HH) individuals and examined the extent to which deaf participants understood medication-related information as well as their attitude about medication. We used two questionnaires to compare the results from the deaf participants with those from the HH and hearing participants. We found that before the lecture, the deaf participants' understanding of medication use was lower than that of the HH and hearing participants. The deaf participants' knowledge increased after the lecture, but did not improve to the level exhibited by the HH participants. However, the deaf participants felt confident using medication despite their low comprehension levels. In conclusion, adjusting the medication information provided by pharmacists according to the recipient's reading level could help improve deaf patients' knowledge; however, such measures might not increase deaf patients' comprehension levels sufficiently.
Assuntos
Surdez , Educação de Pacientes como Assunto , Pessoas com Deficiência Auditiva , Farmacêuticos , Compreensão , Educação em Saúde , Perda Auditiva , HumanosRESUMO
Our previous studies have shown that treatment of pregnant rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 1 µg/kg) at gestational day (GD) 15 reduces the pituitary synthesis of luteinizing hormone (LH) during the late fetal and early postnatal period, leading to the imprinting of defects in sexual behaviors at adulthood. However, it remains unclear how the attenuation of pituitary LH is linked to sexual immaturity. To address this issue, we performed a DNA microarray analysis to identify the gene(s) responsible for dioxin-induced sexual immaturity on the pituitary and hypothalamus of male pups, born of TCDD-treated dams, at the age of postnatal day (PND) 70. Among the reduced genes, we focused on gonadotropin-releasing hormone (GnRH) in the hypothalamus because of published evidence that it has a role in sexual behaviors. An attenuation by TCDD of GnRH expression emerged at PND4, and no subsequent return to the control level was seen. A change in neither DNA methylation nor histone acetylation accounted for the reduced expression of GnRH. Intracerebroventricular infusion of GnRH to the TCDD-exposed pups after reaching maturity restored the impairment of sexual behaviors. Supplying equine chorionic gonadotropin, an LH-mimicking hormone, to the TCDD-exposed fetuses at GD15 resulted in a recovery from the reduced expression of GnRH, as well as from the defects in sexual behavior. These results strongly suggest that maternal exposure to TCDD fixes the status of the lowered expression of GnRH in the offspring by reducing the LH-assisted steroidogenesis at the perinatal stage, and this mechanism imprints defects in sexual behaviors at adulthood.
Assuntos
Poluentes Ambientais/toxicidade , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Exposição Materna/efeitos adversos , Dibenzodioxinas Policloradas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/psicologia , Comportamento Sexual Animal , Animais , Animais Recém-Nascidos , Gonadotropina Coriônica/uso terapêutico , Metilação de DNA , Embrião de Mamíferos , Feminino , Impressão Genômica , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/uso terapêutico , Cavalos , Masculino , Troca Materno-Fetal , Hipófise/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ratos , Ratos Wistar , Comportamento Sexual Animal/efeitos dos fármacos , Testículo/metabolismo , Fatores de TempoRESUMO
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.
RESUMO
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.
Assuntos
Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Humanos , Oxicodona , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Cidades , FentanilaRESUMO
Cancer patients have greater physical and mental anxiety than non-cancer patients because of the severity of their disease and the strong side effects of anticancer drugs. In this study, therefore, we sent out questionnaires to both cancer and noncancer patients to investigate the specific patient education for reducing anxiety of cancer patients, and compared the results in detail in Miyazaki Prefectural Miyazaki Hospital. The number of days of patient education was significantly more in cancer patients than in non-cancer patients. However, regardless of the number of days of patient education, understanding the level of side effects was significantly higher in cancer patients than in non-cancer patients. A significant correlation was shown between the relief level of patients and the listening level of pharmacists in both patient groups. Regarding the level of patient understanding, a significant correlation was shown between treatment methods and all of the other factors(effects of drugs, patients' degree of relief, pharmacists' degree of attentiveness). On the other hand, a significant correlation was shown only between treatment methods and effects of drugs on the level of understanding in non-cancer patients. These results suggest that characteristic patient education should be conducted for cancer patients, and that it would be best if it is done early on.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Assistência Farmacêutica , Idoso , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Educação de Pacientes como Assunto , Inquéritos e QuestionáriosRESUMO
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.
Assuntos
Medicina Kampo , Estudantes de Medicina , Humanos , Currículo , Faculdades de Medicina , AprendizagemRESUMO
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.