RESUMO
Histone deacetylase 6 (HDAC6) is known to deacetylate amino acid lysine in alpha-tubulin. However, the functional role of HDAC6 in the progression of cardiac disease remains uncertain. The functional role of HDAC6 in the hearts was examined using transgenic (TG) mice expressing either human wild-type HDAC6, deacetylase inactive HDAC6 (HDAC6H216A, H611A), and human HDAC6 replaced all serine or threonine residues with aspartic acid at N-terminal 1- 43 amino acids (HDAC6NT-allD) specifically in the hearts. Overexpression of wild-type HDAC6 significantly reduced acetylated tubulin levels, and overexpression of HDAC6H216A, H611A significantly increased it in the mouse hearts. Detectable acetylated tubulin disappeared in HDAC6NT-allD TG mouse hearts. Neither histological alteration nor alteration of cardiac function was observed in the HDAC6 TG mouse hearts. To analyze the role of HDAC6 and acetylated tubulin in disease conditions, we examined HDAC6 in isoprenaline-induced hypertrophy or pressure-overload hypertrophy (TAC). No obvious alteration in the heart weight/body weight ratio or gene expressions of hypertrophic markers between NTG and HDAC6NT-allD mice was observed following treatment with isoprenaline. In contrast, a marked reduction in the shortening fraction and dilated chamber dilatation was detected in the HDAC6NT-allD TG mouse hearts 2 weeks after TAC. A sustained low level of acetylated tubulin and acetylated cortactin was observed in the TAC HDAC6NT-allD TG mouse hearts. Cardiac HDAC6 activity that can regulate acetylated levels of tubulin and cortactin may be critical factors involved in cardiac disease such as pressure-overload hypertrophy.
Assuntos
Cardiopatias , Desacetilase 6 de Histona/metabolismo , Tubulina (Proteína) , Acetilação , Animais , Ácido Aspártico/metabolismo , Cortactina/metabolismo , Desacetilase 6 de Histona/genética , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Hipertrofia , Isoproterenol , Lisina/metabolismo , Camundongos , Camundongos Transgênicos , Serina/metabolismo , Treonina/metabolismo , Tubulina (Proteína)/metabolismoRESUMO
Since the Coronavirus Disease 2019 (COVID-19) pandemic began, people have been wearing face masks for many hours every day. As these face masks are in contact with the skin, it is important to pay more attention to their quality and safety. This study examined the concentration of free formaldehyde in 90 non-medical face masks and related products (33 nonwoven, 30 woven cloth, 12 polyurethane, and 15 related products) because formaldehyde is a common contact allergen in textile products. For products consisting of mixed materials, each material was sampled, resulting in 103 samples for analysis. Free formaldehyde (34-239 µg/g) was found in three cloth masks, which consisted of cotton and polyester, with antibacterial and antiviral labeling. It was confirmed that the detected formaldehyde originated from the mask-finishing treatment by a hydrochloric acid extraction discrimination test. These masks may elicit contact dermatitis if the consumers have already been sensitized to formaldehyde. However, the risk of contact dermatitis caused by formaldehyde in masks may be considered low since the frequency of formaldehyde detection in masks in Japan is low.
Assuntos
COVID-19 , Dermatite de Contato , COVID-19/epidemiologia , COVID-19/prevenção & controle , Dermatite de Contato/epidemiologia , Formaldeído/toxicidade , Humanos , Japão , Máscaras , Pandemias , SARS-CoV-2RESUMO
AIM: The present study clarified the outbreak situation and background risk factors for drug-resistant bacteria infection in nursing homes. METHODS: Subjects were 48 elderly individuals with urinary tract infections in 3 nursing homes during the 12-month period from January to December 2020. We analyzed the drug resistance of cultured bacteria using medical records. RESULTS: Escherichia coli was the most frequently cultured bacteria (37.1%), and extended-spectrum ß-lactamase (ESBL) -producing E. coli accounted for 26.1% of specimens. E. coli susceptibility to levofloxacin (LVFX) was seen in 47.8%, resistance in 47.8%, and intermediate response in 4.4%. E. coli susceptibility to ceftriaxone (CTRX) was seen in 73.9%, and resistance in 26.1%. E. coli susceptibility to sulfamethoxazole trimethoprim (ST) mixture was seen 81.8%, while resistance was seen in 18.2%. In addition, among ESBL-producing E. coli, susceptibility to LVFX was seen in 0% and resistance in 83.3%, and an intermediate response was seen in 16.7%, while susceptibility to ST mixture was seen in 83.3% and resistance in 16.7%. No marked differences in background risk factors were seen between the groups with LVFX-resistant and LVFX-susceptible E. coli. However, the body mass index was significantly lower (p=0.0389), and significantly more patients were treated with antimicrobial agents during the 1-year period preceding the sample acquisition and analysis (p=0.0418) in the group with CTRX-resistant E. coli than in the group with CTRX-susceptible E. coli. CONCLUSION: In the nursing homes examined, LVFX-resistant E. coli were highly prevalent, and ESBL-producing bacteria were also common. When we treat urinary tract infections, refraining from the use of LVFX is desirable, and antimicrobials should be chosen with care.
Assuntos
Escherichia coli , Infecções Urinárias , Humanos , Idoso , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Casas de Saúde , Fatores de RiscoRESUMO
PURPOSE: Green tea is a traditional beverage that has been enjoyed by the Japanese to this day. Recently, there has been an increase in the consumption of green tea beverage having high concentrations of catechins, such as (-)-epigallocatechin-3-O-gallate (EGCG). Many people tend to ingest large amounts of catechins through the frequent consumption of green tea beverage, and this dietary habit may lead to unwanted interactions between the catechins in green tea and medicinal drug. METHODS: The inhibitory effects of eight green tea catechins on drug metabolizing enzymes, cytochrome P450 (CYP) 1A2, 2C9, 2D6, and 3A4, were investigated in human liver microsomes. Incubation was initiated by the addition of cocktail probe drugs that served as specific substrates for each CYP, and the resulting metabolites were analyzed by LC-MS. RESULTS: From a comparison of the fifty percent inhibitory concentration (IC50) values of the eight green tea catechins, it was found that non-gallated catechins did not inhibit CYPs, whereas gallated catechins inhibited all CYPs except CYP2D6. Among them, CYP2C9 was most strongly inhibited by (-)-catechin-3-O-gallate (CG) (7.60 µM), and CYP1A2 was most strongly inhibited by EGCG (8.93 µM). Catechin gallate exhibited non-competitive inhibition of CYP2C9, and its Ki value was 9.76 ± 0.47µM. The present study is the first to report the inhibitory effect of CG on CYP2C9. In contrast, EGCG showed competitive inhibition of CYP1A2, and its Ki value was 14.3 ± 0.09 µM. CONCLUSION: Previous reports had predicted that plasma EGCG concentration reached 7.4 µM after ingesting green tea having high concentrations of catechins. That concentration of EGCG is equivalent to one-half to one-third of its Ki value for CYP1A2 and CYP3A4 in this study. The ingestion of beverages containing large amounts of green tea catechins together with drugs that are metabolized by CYP1A2, CYP2C9, and CYP3A4 should be avoided. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Assuntos
Catequina/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Chá/química , Catequina/análogos & derivados , Catequina/química , Inibidores das Enzimas do Citocromo P-450/química , HumanosRESUMO
OBJECTIVE: To describe a technique and its clinical applications of three-dimensional ultrasonography to type VI and VII radial polydactyly for identification of potential muscular anomalies. MATERIALS AND METHODS: Ultrasonographic examinations were performed at an out-patient department without sedation or an operative room prior to surgery. The palm was scanned in the transverse direction using a 18-MHz linear transducer under speed regulation at 3 mm/s. Sequential images acquired at 0.2 mm intervals were converted into volume data. After validation of the technique, patients with a radial polydactyly in association with triphalangism (type VII) or with polydactylies of metacarpal duplication (type VI) were included for the examination. RESULTS: Five hands of five patients, one with type VI and four with type VII, were included the study. All the patients were male and the ages at examination ranged from 7 months to 2 years. Of the five patients, four examinations were performed at an out-patient department without sedation and one was under anesthesia just prior to surgery. The muscular abnormalities identified were mal-positions of the thenar muscles in a type VI case and a deficiency of the abductor pollicis brevis muscle in a type VII case with a delta phalanx in the ulnar part. CONCLUSION: Three-dimensional ultrasound technique could be an aid to plan strategies in radial polydactyly if intrinsic muscular anomalies are suspected to be involved.
Assuntos
Dedos/anormalidades , Imageamento Tridimensional/métodos , Músculo Esquelético/diagnóstico por imagem , Polidactilia/diagnóstico por imagem , Ultrassonografia/métodos , Humanos , Interpretação de Imagem Assistida por Computador , Lactente , MasculinoRESUMO
Loxoprofen, a propionate non-steroidal anti-inflammatory drug (NSAID), is used widely in East Asian countries. However, little is known about the transport mechanisms contributing to its intestinal absorption. The objectives of this study were to characterize the intestinal transport of loxoprofen using the human intestinal Caco-2 cell model. The transport of loxoprofen was investigated in cellular uptake studies. The uptake of loxoprofen into Caco-2 cells was pH- and concentration-dependent, and was described by a Michaelis-Menten equation with passive diffusion (Km : 4.8 mm, Vmax : 142 nmol/mg protein/30 s, and Kd : 2.2 µl/mg protein/30 s). Moreover, the uptake of loxoprofen was inhibited by a typical monocarboxylate transporter (MCT) inhibitor as well as by various monocarboxylates. The uptake of [14 C] l-lactic acid, a typical MCT substrate, in Caco-2 cells was saturable with relatively high affinity for MCT. Because loxoprofen inhibited the uptake of [14 C] l-lactic acid in a noncompetitive manner, it was unlikely that loxoprofen uptake was mediated by high-affinity MCT(s). Our results suggest that transport of loxoprofen in Caco-2 cells is, at least in part, mediated by a proton-dependent transport system. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Anti-Inflamatórios não Esteroides/metabolismo , Absorção Intestinal/fisiologia , Transportadores de Ácidos Monocarboxílicos/metabolismo , Fenilpropionatos/metabolismo , Prótons , Anti-Inflamatórios não Esteroides/farmacologia , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/fisiologia , Células CACO-2 , Relação Dose-Resposta a Droga , Humanos , Absorção Intestinal/efeitos dos fármacos , Ácido Láctico/metabolismo , Ácido Láctico/farmacologia , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Fenilpropionatos/farmacologiaRESUMO
The aim of this study was to determine the effect of interaction between tegafur (FT) and epigallocatechin-3-gallate (EGCG) on the expression of α-defensins (HD-5: human α-defensin 5, HD-6: human α-defensin 6) by using a Caco-2 cell line as a model of human intestinal epithelial cells. This is the first study in which the effect of interaction of an oral anticancer drug and functional food on the innate immune system was examined. α-Defensins are abundant constituents of mouse and human paneth cells and play a role in the innate immune system in intestine. We detected HD-5 and HD-6 mRNA in Caco-2 cells and evaluated the effects of FT and EGCG on these mRNA levels. HD-5 and HD-6 mRNA levels were decreased by exposure to FT. Production of reactive oxygen species (ROS) was induced by exposure to FT as well as H2O2 exposure, and EGCG suppressed FT-induced production of ROS. Furthermore, FT-induced decrease in HD-5 and HD-6 mRNA levels was almost completely suppressed by EGCG. These results indicate that EGCG restored the decrease of α-defensins induced by FT at the transcriptional level in Caco-2 cells, suggesting that EGCG can be used as adjunctive therapy in chemotherapy.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Catequina/análogos & derivados , Mucosa Intestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tegafur/efeitos adversos , alfa-Defensinas/metabolismo , Células CACO-2 , Catequina/farmacologia , Interações Ervas-Drogas , Humanos , Peróxido de Hidrogênio/metabolismo , Mucosa Intestinal/imunologia , Neoplasias/tratamento farmacológico , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , alfa-Defensinas/genéticaRESUMO
PURPOSE: Patients with type 2 diabetes are generally treated with various pharmacological compounds and are exposed to a high risk of drug-drug interactions. However, alterations of pharmacokinetics in a type 2 diabetes model have been obscure. The present study was undertaken to investigate the effects of type 2 diabetes on the pharmacokinetics of the fluoroquinolone grepafloxacin (GPFX) and the expression level of P-glycoprotein (P-gp), one of the drug efflux transporters. METHODS: We used Goto-Kakizaki (GK) rats, a lean model of type 2 diabetes. Plasma concentration and intestinal, renal, and biliary clearance of GPFX were measured after intravenous and intraintestinal administration in Wistar and GK rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. RESULTS: We found a significant increase in the plasma concentrations of GPFX at 90, 120 and 240 minutes after intraintestinal administration in GK rats compared with the concentrations in Wistar rats but not after intravenous administration. The increase in plasma GPFX concentration was associated with reduction in jejunal clearance of GPFX caused by a decrease in secretory transport of GPFX. However, there was no correlation between the decrease in secretory transport of GPFX and P-gp expression level. CONCLUSION: Type 2 diabetic conditions alter P-gp function as well as expression level and correlate poorly with each other.
Assuntos
Antibacterianos/farmacocinética , Diabetes Mellitus Tipo 2/metabolismo , Fluoroquinolonas/farmacocinética , Piperazinas/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Administração Intravenosa , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Modelos Animais de Doenças , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/sangue , Íleo/química , Jejuno/química , Masculino , Piperazinas/administração & dosagem , Piperazinas/sangue , Ratos , Ratos WistarRESUMO
Protein kinase C (PKC) modulators are very attractive therapeutic targets in cancer. Since most cancer cells display increased glycolysis, elucidations of the effects of PKC activation on glycolysis is necessary for the development of effective medicine. In the present study, to clarify the role of PKC in the regulation of glycolysis, we examined the effect of phorbol 12-myristate 13-acetate (PMA), a PKC activator, on the expression and activity of glucose and lactic acid metabolism-related genes in human rhabdomyosarcoma cells (RD cells). In parallel to increases in glucose uptake and mRNA levels of glucose transporters (GLUTs) induced by PMA treatment for 6 h, the hexokinase (HK) mRNA level and activity were also significantly increased in RD cells. On the other hand, a significant increase in lactate dehydrogenase (LDH) mRNA level and activity was seen when the cells were incubated with PMA for 24 h, but not for 6 or 12 h, and was associated with lactic acid production. These effects by PMA treatment were markedly suppressed by Bisindolylmaleimide (BIM), a PKC inhibitor. Furthermore, chetomin, a hypoxia-inducible factor 1 (HIF-1) inhibitor, completely abrogated the increment of LDH mRNA level and activity as well as monocarboxylate transporter (MCT) 4, a lactic acid efflux transporter. In conclusion, we found that HK and LDH activity induced by PKC activation was associated with the glucose uptake and lactic acid level and that LDH and MCT4 are modulated by a common factor, HIF-1.
Assuntos
Glucose/metabolismo , Ácido Láctico/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Proteína Quinase C/metabolismo , Linhagem Celular Tumoral , Dissulfetos/farmacologia , Regulação da Expressão Gênica , Proteínas Facilitadoras de Transporte de Glucose/genética , Hexoquinase/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Alcaloides Indólicos/farmacologia , L-Lactato Desidrogenase/genética , Transportadores de Ácidos Monocarboxílicos/genética , Proteínas Musculares/genética , RNA Mensageiro/metabolismo , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
A column-switching liquid chromatography/electrospray ionization tandem mass spectrometry to determine paclitaxel and its metabolites, 6α-hydroxypaclitaxel and p-3'-hydroxypaclitaxel, in human plasma was developed. The analytical system had a Shim-Pack MAYI-ODS (10 × 4.6 mm i.d.) trapping column with deproteinization ability that concentrates analytes and removes water-soluble components. This method covered a linearity range of 5-5000 ng/mL of concentrations in plasma for paclitaxel, a range of 0.87-870 ng/mL for 6α-hydroxypaclitaxel and a range of 0.87-435 ng/mL for p-3'-hydroxypaclitaxel. The intra-day precision and inter-day precision of analysis were less than 11.1%, and the accuracy was within ±14.4% at concentrations of 5, 50, 500 and 5000 ng/mL for paclitaxel, 0.87, 8.7, 87 and 870 ng/mL for 6α-hydroxypaclitaxel, and 0.87, 8.7, 87 and 435 ng/mL for p-3'-hydroxypaclitaxel. The total run time was 30 min. Our method was successfully applied to clinical pharmacokinetic investigation.
Assuntos
Antineoplásicos Fitogênicos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Paclitaxel/sangue , Espectrometria de Massas em Tandem/métodos , Taxoides/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/instrumentação , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/métodos , Desenho de Equipamento , Humanos , Limite de Detecção , Neoplasias Pulmonares/tratamento farmacológico , Espectrometria de Massas em Tandem/instrumentaçãoRESUMO
AIMS AND OBJECTIVES: To understand the psychological aspects in patients undergoing post-operative wound care and to gain insights for improving nursing practice. BACKGROUND: Very few studies have examined education on or practice of wound care with a view towards the patient's psychology. DESIGN: Descriptive exploratory qualitative study. METHODS: Four patients who had undergone open surgery of the upper gastrointestinal tract were interviewed using a semi-structured format to gain an understanding of their feelings and opinions with regard to wound care. Interview transcripts were analysed using an inductive coding approach. RESULTS: Fifteen categories of responses were finally identified from the data. Patients wanted nursing staff to observe their wound more often so that patients could recognise improvement, to have better knowledge of the patient's disease and condition, to explain the patient's situation more completely and to appropriately answer questions. Patients also said that they felt more comfortable in posing questions or concerns regarding their condition to nursing staff than to their surgeons and did so while the wounds were being taken care of by nurses. CONCLUSIONS: These findings suggested the importance of nursing staff to fully understand and to be ready to share feelings regarding a patient's postoperative condition and to have skills in properly explaining the importance of each procedure or steps in treatments that a patient must undergo. The present study also indicates that it is imperative for nursing staff to learn methods to build relationships with patients so that they can express their feelings of fear or anxiety freely to nurses. RELEVANCE TO CLINICAL PRACTICE: It is not possible to develop nursing practice without understanding psychological aspects of patients undergoing postoperative wound care.
Assuntos
Recursos Humanos de Enfermagem/normas , Cuidados Pós-Operatórios , Ferimentos e Lesões/enfermagem , Humanos , Pessoa de Meia-Idade , Pesquisa Qualitativa , Ferimentos e Lesões/psicologiaAssuntos
Doenças Autoimunes , Implantes de Mama/efeitos adversos , Remoção de Dispositivo/métodos , Pericardite , Pleurisia , Géis de Silicone/efeitos adversos , Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/etiologia , Doenças Autoimunes/terapia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Pericardite/diagnóstico por imagem , Pericardite/etiologia , Pericardite/fisiopatologia , Pericardite/cirurgia , Pleurisia/diagnóstico por imagem , Pleurisia/fisiopatologia , Pleurisia/cirurgia , Radiografia Torácica/métodos , Cintilografia/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
PURPOSE: Intestinal ischemia-reperfusion (I/R) damages remote organs, including the liver, and promotes multi-organ failure (MOF). However, the molecular mechanisms underlying acute liver injury after intestinal I/R have not been completely elucidated. Farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR) regulate metabolizing enzymes and transporters, and coordinately prevent hepatotoxicity reflecting an inability of appropriate excretion of endogenous toxic compounds. In this study, we assessed FXR, PXR and CAR expression levels and their localization levels in nuclei in the liver after intestinal I/R. We also investigated the effect of IL-6 on FXR, PXR and CAR expression levels and their localization levels in nuclei in in vitro experiments. METHODS: We used intestinal I/R model rats. Moreover, HepG2 cells were used in in vitro study. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Nuclear receptor localization in nuclei was analyzed by Western blotting using nuclear extracts. RESULTS: FXR and PXR expression levels began to be decreased at 3 h, and FXR, PXR and CAR expression levels were decreased at 6 h after intestinal I/R. The localization levels of FXR, PXR and CAR in nuclei began to be decreased at 3 h, and all of them were decreased at 6 h after intestinal I/R. In HepG2 cells, FXR, PXR and CAR expression levels were decreased by 0.5-1 ng/mL, 0.5-100 ng/mL and 100 ng/mL IL-6 treatment for 24 h, respectively. FXR, PXR and CAR localization levels in nuclei were suppressed by 0.5-10 ng/mL, 10-100 ng/mL and 10-100 ng/mL IL-6 treatment for 24 h, respectively. CONCLUSIONS: FXR, PXR and CAR expression levels are decreased in the liver after intestinal I/R. IL-6 is one of main causes the decreases in expressions of these receptors.
Assuntos
Fígado/patologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Esteroides/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Animais , Western Blotting , Núcleo Celular/metabolismo , Receptor Constitutivo de Androstano , Regulação da Expressão Gênica , Células Hep G2 , Humanos , Interleucina-6/administração & dosagem , Interleucina-6/metabolismo , Intestinos/irrigação sanguínea , Intestinos/patologia , Masculino , Receptor de Pregnano X , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Receptores Citoplasmáticos e Nucleares/genética , Receptores de Esteroides/genética , Fatores de TempoRESUMO
PURPOSE: Uric acid is thought to be one of the most important antioxidants in human biological fluids. Intestinal ischemia-reperfusion (I/R) is an important factor associated with high rates of morbidity and mortality. Reactive oxygen species (ROS) are responsible for intestinal I/R injury. The aim of this study was to clarify the efflux for uric acid from the intestine after intestinal I/R. METHODS: We used intestinal ischemia-reperfusion (I/R) model rats. Serosal to mucosal flux for [¹4C]-uric acid was assessed by using Ussing-type diffusion chambers. BCRP/Bcrp expression was assessed by Western blot analysis. Caco-2 cells were used for a model of the intestinal epithelium, and rotenone was used as a mitochondrial dysfunction inducer. RESULTS: Serosal to mucosal flux for uric acid was increased after intestinal I/R, and that for mannitol was also increased. Ko143, which is a BCRP inhibitor, did not affect the uric acid transport. The decreasing uric acid transport mediated by Bcrp was caused by decrease in the level of Bcrp homodimer, bridged by an S-S bond. The suppression of Bcrp S-S bond formation was associated with mitochondrial dysfunction. Moreover, BCRP S-S bond formation activity was decreased by rotenone in Caco-2 cells. CONCLUSIONS: Serosal to mucosal flux for uric acid is significantly increased via the paracelluler route, but that via the transcellular route mediated by Bcrp is decreased after intestinal I/R. The decreasing uric acid flux mediated by Bcrp is caused by suppression of Bcrp S-S bond formation. This suppression of Bcrp S-S bond formation may be related to mitochondrial dysfunction.
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Mucosa Intestinal/metabolismo , Proteínas de Neoplasias/metabolismo , Traumatismo por Reperfusão/metabolismo , Ácido Úrico/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Adenosina/análogos & derivados , Adenosina/farmacologia , Animais , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Dicetopiperazinas , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Intestinos/lesões , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Ratos , Ratos Wistar , Rotenona/farmacologia , Desacopladores/farmacologiaRESUMO
An 83-year-old Japanese man who had been aware of a tumor near his anus for 2 years underwent tumor resection. Although he was diagnosed with basal cell carcinoma (BCC), extramammary Paget disease (EMPD) was also accidentally found in the same specimen. In the pathological histology of EMPD, there were large round cells with ample cytoplasm spread in the epidermis; these cells were positive for cytokeratin 7 and gross cystic disease fluid protein 15. No signs that are typically associated with EMPD, such as erythema or leukoderma, were observed near the anus. There have been only 4 reports in which BCC and EMPD developed in the same area, and the authors present the fifth case. In the reported case, no clear evidence was found for the corelative development of BCC and EMPD.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Immunoglobulin A (IgA) secretion and alpha-defensins play a role in the innate immune system to protect against infection. Ganoderma lucidum (W.Curt.: Fr.) P. Karst. (Reishi) is a well-known mushroom in traditional Chinese medicine. This study aimed to determine the effects of Reishi on IgA secretion from Peyer's patch (PP) cells and alpha-defensin-5 (RD-5) and RD-6 expression in the rat small intestine. MATERIALS AND METHODS: The rats received an oral injection of 0.5-5mg/kg of Reishi powder (1mL/kg) by sonde. All animals were euthanized 24h after Reishi administration. We examined RD-5, RD-6, and Toll-like receptor (TLR) 4 mRNA levels in the jejunum, ileum, and in Peyer's patches (PP) through quantitative real-time PCR analysis. IgA secretion from PP was measured through enzyme-linked immunosorbent assay of the supernatant after primary culture. RESULTS: Reishi increased IgA secretion in the presence of lipopolysaccharide (LPS) and increased TLR4 mRNA levels, but had no effect on the viability of PP cells. Moreover, Reishi increased RD-5, RD-6, and TLR4 mRNA levels significantly in the ileum in a concentration-dependent manner. CONCLUSIONS: Reishi can induce IgA secretion and increase the mRNA levels of RD-5 and RD-6 in the rat small intestine, through a TLR4-dependent pathway. The present results indicate that Reishi might reduce the risk of intestinal infection.
Assuntos
Íleo/efeitos dos fármacos , Imunoglobulina A Secretora/metabolismo , Fatores Imunológicos/farmacologia , Jejuno/efeitos dos fármacos , Nódulos Linfáticos Agregados/efeitos dos fármacos , Reishi , alfa-Defensinas/metabolismo , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Íleo/imunologia , Íleo/metabolismo , Imunoglobulina A Secretora/imunologia , Fatores Imunológicos/isolamento & purificação , Jejuno/imunologia , Jejuno/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos Endogâmicos C3H , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Reishi/química , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , Regulação para Cima , alfa-Defensinas/genética , alfa-Defensinas/imunologiaRESUMO
Organic anion transporting polypeptide 2B1 (OATP2B1) is the major uptake transporter in the intestine, and transports various clinically used therapeutic agents. Insulin acts through the insulin receptor in targeted cells, and Rab8A is one of the insulin signaling pathways. The small intestine in humans also expresses insulin receptor and Rab8A. It has been reported that insulin stimulates peptide transporter 1 (PEPT1) expression at the apical membrane and increases uptake of PEPT1 substrates in small intestine epithelial model cells (Caco-2 cells). However, the effect of insulin on OATP2B1 in the small intestine has not been fully investigated. We found that Rab8A was associated with OATP2B1-mediated estrone-3-sulfate (E3S) uptake. Insulin stimulated the uptake of E3S by Caco-2 cells and the enhancement was sustained for 120 min. The Vmax value of E3S uptake significantly increased upon insulin exposure. Caco-2 cells treated with insulin showed increased OATP2B1 expression at the cell surface. The apical-to-basal transport of E3S was also increased by insulin. The increase of E3S transport was inhibited by the cold condition (4 °C) or the OATP2B1 inhibitor, taurocholate. These results indicate that insulin acts on the small intestine to increase OATP2B1-mediated absorption.
Assuntos
Insulina/farmacologia , Transportadores de Ânions Orgânicos/metabolismo , Transporte Biológico/efeitos dos fármacos , Células Cultivadas , Humanos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Transportadores de Ânions Orgânicos/genética , Ácido Taurocólico/farmacologia , TemperaturaRESUMO
OBJECTIVE: To evaluate validity and reliability of the Japanese version of the Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). DESIGN: Observational study; cross-sectional, longitudinal. METHODS: Seventy-five adults with growth hormone deficiency completed the SF-36 (a generic health-related QOL scale) and the QoL-AGHDA before growth hormone replacement therapy and approximately 3 weeks later (when the therapy began). A sample (n=1000) of controls from the general population was also studied. We computed rates of missing data, measured reproducibility and internal consistency reliability, and tested for known-groups validity, concurrent validity, unidimensionality (by principle component analysis), and content validity. RESULTS: Rates of missing data were low (0-1.4%). The mean of QoL-AGHDA scores in the patients was 8.2 (SD, 6.4). The scores were reproducible (k=0.41-0.78), and internally consistent (alpha=0.91) and the scale was unidimensional. QoL-AGHDA scores were associated with SF-36 scores as hypothesized. Scores were significantly higher in the patients than in controls (8.1+/-0.7, and 5.6+/-0.2, P<0.001). Discrimination between patients and controls was slightly better using scores on the "General Health" and "Role Physical" subscale of the SF-36 as explanatory variables than using QoL-AGHDA scores. CONCLUSIONS: The QoL-AGHDA's reliability, validity, and rates of missing data were satisfactory, and the scale was confirmed to be unidimensional. However, because some subscales of the SF-36 were better for discriminating patients from controls, the content validity of the QoL-AGHDA may need to be re-evaluated.
Assuntos
Hormônio do Crescimento Humano/deficiência , Qualidade de Vida , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Nível de Saúde , Indicadores Básicos de Saúde , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Japão , Idioma , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Proteínas Recombinantes/uso terapêutico , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Patient-reported quality of life is strongly affected by some dermatologic conditions. We developed a Japanese version of the Dermatology Life Quality Index (DLQI-J) and used psychometric methods to examine its validity and reliability. METHODS: The Japanese version of the DLQI was created from the original (English) version, using a standard method. The DLQI-J was then completed by 197 people, to examine its validity and reliability. Some participants completed the DLQI-J a second time, 3 days later, to examine the reproducibility of their responses. In addition to the DLQI-J, the participants completed parts of the SF-36 and gave data on their demographic and clinical characteristics. Their physicians provided information on the location and clinical severity of the skin disease. RESULTS: The participants reported no difficulties in answering the DLQI-J items. Their mean age was 24.8 years, 77.2% were female, and 78.7% had acne vulgaris. The mean score of DLQI was 3.99(SD: 3.99). The responses were found to be reproducible and stable. Results of principal-component and factor analysis suggested that this scale measured one construct. The correlations of DLQI-J scores with sex or age were very poor, but those with SF-36 scores and with clinical severity were high. CONCLUSION: The DLQI-J provides valid and reliable data despite having only a small number of items.
Assuntos
Acne Vulgar/psicologia , Psicometria/instrumentação , Qualidade de Vida , Perfil de Impacto da Doença , Inquéritos e Questionários , Acne Vulgar/classificação , Acne Vulgar/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Relações Interpessoais , Japão , Idioma , Masculino , Projetos Piloto , Instituições Acadêmicas , Terminologia como Assunto , Traduções , Local de Trabalho/psicologiaRESUMO
As for Isehara City Visiting Nursing Liaison Congress, we investigated and analyzed the actual conditions of visiting nursing care development at Isehara city by using the NADA nursing diagnosis. It is desirable that a visiting nurse should have skills in evacuation, suction of the respiratory tract, rehabilitation, prevention of complications and an early detection of a poor condition of the patient. In addition, we found that it is also desirable that a visiting nurse fulfill a leadership function in coordinating to support home-care, have a communication skill to anticipate potential problems of patients and counsel his or her family concerns in a short period of time.