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1.
Integr Cancer Ther ; 22: 15347354231198090, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37750513

RESUMO

Erlotinib is a necessary anticancer treatment for non-small cell lung cancer (NSCLC) patients yet it causes severe side effects such as skin rash. In this study, researchers compared the untargeted compound profiles before and after erlotinib administration to observe changes in blood metabolites in NSCLC patients. The levels of 1005 substances changed after taking erlotinib. The levels of 306 and 699 metabolites were found to have increased and decreased, respectively. We found 5539 substances with peak area differences based on the presence of skin rash. Carbohydrate, amino acid, and vitamin metabolic pathways were altered in response to the onset of erlotinib-induced skin rash. Finally, this study proposed using plasma metabolites to identify biomarker(s) induced by erlotinib, as well as target molecule(s), for the treatment of dermatological toxic effects.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Exantema , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Exantema/induzido quimicamente , Exantema/tratamento farmacológico , Antineoplásicos/efeitos adversos
2.
Medicine (Baltimore) ; 101(3): e28629, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35060543

RESUMO

BACKGROUND: Pulmonary rehabilitation (PR) is a management modality that improves the quality of life of patients with chronic obstructive pulmonary disease (COPD); however, PR is not readily accessible. Therefore, we developed lung-conduction exercises (LCE) that can be performed easily without any limitations. The purpose of this randomized, assessor-blind, multicenter pilot trial was to compare the effects of LCE with PR and standard care (SC) in COPD patients. METHODS: Twenty-five participants who met the eligibility criteria were randomly allocated to the SC group (only medication, n = 9), LCE group (medication + LCE, 5 times a week, n = 8), or PR group (medication + PR, 5 times a week, n = 8). The 6-minute walk distance (6WMD), pulmonary function test, modified Medical Research Council dyspnea scale, COPD assessment test (CAT), and St. George Respiratory Questionnaire (SGRQ) survey were carried out before starting the trial and after 4 and 8 weeks to determine motor performance, lung function, and dyspnea. RESULTS: After 8 weeks, the pulmonary function test scores were the same. The 6MWD (PR, 28.3 ±â€Š38.5; LCE, 14.5 ±â€Š53.1; SC, 11.5 ±â€Š20.5; P = .984), modified Medical Research Council dyspnea scale (PR, 0.8 ±â€Š1.0; LCE, 0.8 ±â€Š0.8; SC, 0.3 ±â€Š0.5; P = .772), CAT (PR, 7.3 ±â€Š6.2; LCE, 4.2 ±â€Š5.2; SC, 1.0 ±â€Š2.2; P = .232), and SGRQ scores (PR, 11.5 ±â€Š15.4; LCE, 5.5 ±â€Š13.1; SC, 4.8 ±â€Š5.1; P = .358 [PR vs LCE], P = .795 [PR vs SC]) had improved in order of PR, LCE, and SC group. Although there were no statistically significant differences in the outcome measures between the groups, there were clinically significant improvements in the CAT and SGRQ scores. CONCLUSIONS: In this trial, PR showed more improvement in symptoms and quality of life than SC alone. To seek a more precise use of LCE, further full-sized studies with a long duration and additional outcome measures such as psychological assessment tools and cost-effectiveness ratio should be conducted. TRIAL REGISTRATION: KCT0004724.


Assuntos
Exercícios Respiratórios/métodos , Dispneia/etiologia , Terapia por Exercício/métodos , Doença Pulmonar Obstrutiva Crônica/terapia , Terapia Respiratória/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Dispneia/terapia , Tolerância ao Exercício , Feminino , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Testes de Função Respiratória , Inquéritos e Questionários , Resultado do Tratamento
3.
Integr Cancer Ther ; 20: 15347354211037917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34409891

RESUMO

Afatinib is a target anticancer drug of the second-generation EGFR TKI type, showing an advantage in treatment effect compared to conventional chemotherapy. However, patients on EGFR-TKI drugs also usually progress after 9 to 13 months according to secondary resistance. HAD-B1 is composed of drugs that are effective against lung cancer. This study is an exploratory study to evaluate the efficacy and safety between dosage groups by conducting a clinical trial in subjects requiring afatinib drug treatment in non-small cell lung cancer with EGFR mutation positive to determine the optimal dosage for HAD-B1 administration. At the final visit compared to before administration, each change in the disease control rate was measured according to the HAD-B1 doses of the test group 1 (972 mg), the test group 2 (1944 mg), and the control group. The efficacy and safety of HAD-B1 were compared and evaluated through sub-evaluation variables. As a result of the study, there was no statistically significant difference in the disease control rate at 12 weeks after dosing, but complete and partial remission were evaluated as 1 patient each in the test group 1, and none in the other groups. There was no statistically significant difference between groups in the sub-evaluation variable. In addition, there was no problem of safety from taking the test drug. However, the initially planned number of subjects was 66, but the number of enrolled subjects was only 14, which may limit the results of this study.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Afatinib , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/efeitos adversos
4.
Life Sci ; 278: 119578, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33965379

RESUMO

Hepatic fibrosis is a common liver disease caused by excessive collagen deposition in the liver. Since liver transplantation is the only current treatment for cirrhosis with worsened fibrosis, a new strategy to develop anti-fibrosis drugs with no adverse effects is necessary. In recent studies, amino acids have been applied as a type of therapy in various fields. l-serine plays a major role in antioxidant production via the maintenance of nicotinamide adenine dinucleotide phosphate hydride production in the mitochondria. l-serine may reduce fibrotic lesions in a mouse model of chronic liver injury. This study used 27 six-week-old C57BL/6 mice and injected them three times a week for eight weeks with carbon tetrachloride (CCl4) (1.5 mg/kg, 10% v/v CCl4 in olive oil) to create a hepatic fibrosis mouse model. The mice, which weighed approximately 20-30 g, were randomly classified into four groups: 1) the olive oil group, which received intraperitoneal injection of olive oil (1.5 mg/kg, 3 times per week for 8 weeks); 2) the CCl4-only group; 3) the CCl4 + losartan (10 mg/kg, PO, 5 days on, weekend off for 8 weeks) group; and 4) the CCl4 + l-serine (100 g/L, free access for 8 weeks) group. Hematoxylin and eosin staining and Masson's trichrome staining showed reduced inflammatory cell deposition and collagen deposition in the liver tissue in the l-serine supplemented group. l-serine was found to reduce the spread of hepatic fibrosis and has potential use in clinical settings. Based on these histopathological observations, l-serine is a potential anti-fibrosis drug.


Assuntos
Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Losartan/farmacologia , Serina/farmacologia , Animais , Peso Corporal , Tetracloreto de Carbono/química , Colágeno/química , Modelos Animais de Doenças , Inflamação , Cirrose Hepática/patologia , Cirrose Hepática Experimental/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio
5.
Medicine (Baltimore) ; 99(49): e23455, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285743

RESUMO

BACKGROUND: Afatinib is an epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) with proven efficacy for treating patients with advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, responses are limited by acquired resistance. Because traditional Korean medicine may have synergistic effects when combined with chemotherapy or radiotherapy, the aim of our study is to elucidate the efficacy and safety of afatinib plus HangAmDan-B1 (HAD-B1) combination therapy in the treatment of patients with NSCLC, as well as EGFR mutations, who need afatinib therapy. METHODS/DESIGN: This study is a randomized, multi-center, open clinical trial. A total of 178 eligible subjects, recruited at 8 centers, are randomly assigned to take Afatinib (20-40 mg) ±â€ŠHAD-B1 (0.972 g/day) for 48 weeks. In the test group, HAD-B1 and afatinib will be used in combination. The primary outcome is a comparison of progression-free survival (PFS) between afatinib monotherapy and afatinib plus HAD-B1 combination therapy in patients with local advanced or metastatic (Stage IIIA, B, C/IV) NSCLC. Secondary outcomes are the overall survival rates, clinical responses, tumor size reductions, health-related qualities of life, and safety. DISCUSSION: The result of this clinical trial will provide evidence for the efficacy and safety of using HAD-B1 in the treatment of EGFR-positive patients with locally advanced or metastatic NSCLC who require afatinib therapy. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea (ID: KCT0005414), on September 23, 2020.


Assuntos
Afatinib/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Afatinib/administração & dosagem , Afatinib/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Qualidade de Vida , Análise de Sobrevida
6.
Medicine (Baltimore) ; 99(18): e19826, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358353

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an irreversible disease characterized by cough, sputum production, and dyspnea, and has a high prevalence and mortality. Pulmonary rehabilitation (PR) is a management that improves the quality of life for COPD patients; however, PR is not readily accessible. Therefore, we developed lung-conduction exercises (LCE) that can be performed without any limitations. LCE consists of breathing, stretching, and tapping to relieve dyspnea in COPD patients. METHODS/DESIGN: This randomized, assessor-blind, multicenter trial aims to recruit 54 patients with moderate and severe COPD. Subjects will be randomly allocated to a control group (only medication), an LCE group (medication + LCE, 5 times a week), or a PR group (medication + PR, 5 times a week). The 6-minute walk distance, pulmonary function tests (forced expiratory volume at 1 second, forced vital capacity, and forced expiratory volume at 1 second/forced vital capacity), modified Borg scale, modified medical research council dyspnea scale, COPD assessment test, and St. George respiratory questionnaire will be measured before starting the trial and after the 4th and 8th weeks to determine motor performance, lung function, and dyspnea. CONCLUSION: We aim to demonstrate that LCE is effective in improving symptoms and psychosomatic stability in COPD patients. Therefore, this trial will play an important role in fortifying the foundation of clinical application.


Assuntos
Exercícios Respiratórios/métodos , Terapia por Exercício/métodos , Doença Pulmonar Obstrutiva Crônica/terapia , Terapia Respiratória/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes de Função Respiratória , Método Simples-Cego , Resultado do Tratamento
7.
Technol Health Care ; 28(S1): 509-519, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32364183

RESUMO

BACKGROUND: This study focused on developing an upper limb rehabilitation program. In this regard, a steady state visual evoked potential (SSVEP) triggered brain computer interface (BCI)-functional electrical stimulation (FES) based action observation game featuring a flickering action video was designed. OBJECTIVE: In particular, the synergetic effect of the game was investigated by combining the action observation paradigm with BCI based FES. METHODS: The BCI-FES system was contrasted under two conditions: with flickering action video and flickering noise video. In this regard, 11 right-handed subjects aged between 22-27 years were recruited. The differences in brain activation in response to the two conditions were examined. RESULTS: The results indicate that T3 and P3 channels exhibited greater Mu suppression in 8-13 Hz for the action video than the noise video. Furthermore, T4, C4, and P4 channels indicated augmented high beta (21-30 Hz) for the action in contrast to the noise video. Finally, T4 indicated suppressed low beta (14-20 Hz) for the action video in contrast to the noise video. CONCLUSION: The flickering action video based BCI-FES system induced a more synergetic effect on cortical activation than the flickering noise based system.


Assuntos
Interfaces Cérebro-Computador , Terapia por Estimulação Elétrica/métodos , Potenciais Evocados Visuais/fisiologia , Reabilitação/instrumentação , Jogos de Vídeo , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Adulto Jovem
8.
Cancer Med ; 7(10): 5083-5095, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30160042

RESUMO

Current clinical trials of new anticancer therapies against metastatic renal cell carcinoma (RCC), including molecular-targeted therapies, have not shown promise. The purpose of this study was to preclinically assess the antitumor effects of MC-4, a partially purified material of Artemisia annua L., as a monotherapy or in combination with the known mechanistic target of rapamycin complex 1 (mTORC1) inhibitor, everolimus, against Caki-1 (Von Hippel-Lindau (VHL)+/+) and 786-O (VHL-/-) human RCC cells. MC-4 monotherapy significantly increased tumor growth inhibition and autophagic cell death in RCC cells in vitro and in vivo. Everolimus led to compensatory Akt activation by inhibiting only mTORC1 signaling pathway. In contrast to everolimus, MC-4 enhanced phosphatase and tensin homolog expression and reduced its downstream effector, Akt/pyruvate kinase muscle isozyme M2 (PKM2), leading to decreased expression of glucose transporter 1, which is associated with cancer cell metabolism. The synergistic antitumor and anti-metastatic effects induced by co-administration of MC-4 and everolimus involve cell growth inhibition and autophagic cell death via dual targeting of phosphatidylinositol 3-kinase (PI3K)/Akt/PKM2 and mTORC1. These findings suggest that MC-4 is a novel Akt/PKM2 inhibitor that can overcome the limitation of existing mTOR inhibitors and can be considered a novel strategy to treat patients with rapidly progressing advanced RCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Artemisia annua/química , Carcinoma de Células Renais/tratamento farmacológico , Everolimo/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Renais/metabolismo , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Everolimo/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Renais/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Ligação a Hormônio da Tireoide
9.
Anticancer Res ; 37(8): 4139-4146, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28739698

RESUMO

BACKGROUND/AIM: Eribulin mesylate, also called Halaven® (HAL), was recently developed as a microtubule-targeting drug and is used in the clinic for resistant or metastatic cancer. Previously, we showed that P-glycoprotein (P-gp)-overexpressing KBV20C oral cancer cells are highly resistant to HAL compared to sensitive KB cells. This qualitative study was designed to identify specific P-gp inhibitors that increase the sensitivity of highly resistant cancer cells to HAL. MATERIALS AND METHODS: In order to identify functional P-gp inhibitors, HAL-treated KBV20C cells were co-treated with P-gp inhibitors, verapamil, elacridar, cyclosporine A, mitotane, piperine, fumagillin, curcumin, indomethacin, probenecid, sulindac, tesmilifene, and C-4. We then evaluated which P-gp inhibitors required a low dose to sensitize KBV20C cells to HAL. We also determined whether a low dose of a P-gp inhibitor could inhibit P-gp efflux pumping. RESULTS: We found that cyclosporine A sensitized HAL-treated KBV20C cells at a low dose, whereas verapamil, another first-generation P-gp inhibitor, required a dose that was nearly 10-fold higher. We also found that the natural products, piperine and mitotane, sensitized KBV20C cells to HAL co-treatment. Interestingly, we found that elacridar, a third-generation P-gp inhibitor, sensitized HAL-treated cells at a low dose. Elacridar required approximately a 500-fold lower dose than that of verapamil to exert a similar effect. All inhibitors showed P-gp inhibitory activity that correlated with sensitivity to HAL. CONCLUSION: These results suggest that highly HAL-resistant cancer cells can be sensitized with cyclosporine A or elacridar, specific P-gp inhibitors that exert their effects at a low dose. These findings provide important information regarding the sensitization of highly HAL-resistant cells with selective P-gp inhibitors and indicate that elacridar may be used to treat such highly HAL-resistant cancer cells.


Assuntos
Acridinas/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/genética , Furanos/administração & dosagem , Cetonas/administração & dosagem , Neoplasias Bucais/tratamento farmacológico , Tetra-Hidroisoquinolinas/administração & dosagem , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/patologia
10.
Arch Toxicol ; 91(4): 1635-1648, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27578022

RESUMO

Identifying novel biomarkers to detect nephrotoxicity is clinically important. Here, we attempted to identify new biomarkers for mercury-induced nephrotoxicity and compared their sensitivity to that of traditional biomarkers in animal models. Comparative proteomics analysis was performed in kidney tissues of Sprague-Dawley rats after oral treatment with HgCl2 (0.1, 1, or 5 mg/kg/day) for 21 days. Kidney cortex tissues were analyzed by two-dimensional gel electrophoresis/matrix-assisted laser desorption/ionization, and differentially expressed proteins were identified. The corresponding spots were quantitated by RT-PCR. Selenium-binding protein 1 (SBP1) was found to be the most markedly upregulated protein in the kidney cortex of rats after HgCl2 administration. However, blood urea nitrogen, serum creatinine, and glucose levels increased significantly only in the 1 or 5 mg/kg HgCl2-treated groups. A number of urinary excretion proteins, including kidney injury molecule-1, clusterin, monocyte chemoattractant protein-1, and ß-microglobulin, increased dose-dependently. Histopathological examination revealed severe proximal tubular damage in high-dose (5 mg/kg) HgCl2-exposed groups. In addition, urinary excretion of SBP1 significantly increased in a dose-dependent manner. To confirm the critical role of SBP1 as a biomarker for nephrotoxicity, normal kidney proximal tubular cells were treated with HgCl2, CdCl2, or cisplatin for 24 h. SBP1 levels significantly increased in conditioned media exposed to nephrotoxicants, but decreased in cell lysates. Our investigations suggest that SBP1 may play a critical role in the pathological processes underlying chemical-induced nephrotoxicity. Thus, urinary excretion of SBP1 might be a sensitive and specific biomarker to detect early stages of kidney injury.


Assuntos
Cloreto de Cádmio/toxicidade , Nefropatias/induzido quimicamente , Cloreto de Mercúrio/toxicidade , Proteínas de Ligação a Selênio/metabolismo , Animais , Biomarcadores/metabolismo , Nitrogênio da Ureia Sanguínea , Cloreto de Cádmio/administração & dosagem , Cisplatino/administração & dosagem , Cisplatino/toxicidade , Creatinina/sangue , Relação Dose-Resposta a Droga , Eletroforese em Gel Bidimensional , Córtex Renal/efeitos dos fármacos , Córtex Renal/patologia , Nefropatias/patologia , Masculino , Cloreto de Mercúrio/administração & dosagem , Metais Pesados/administração & dosagem , Metais Pesados/toxicidade , Proteínas/efeitos dos fármacos , Proteínas/metabolismo , Proteômica/métodos , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
11.
Brain Res Bull ; 119(Pt A): 93-100, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26434709

RESUMO

Although sigma-1 receptor (Sig-1R) antagonists have a potential antinociceptive effect in inflammatory diseases, the precise mechanism is not fully understood. The present study was aimed to elucidate the role of spinal neurons and microglia in the anti-nociceptive mechanism of BD1047 (a prototypical Sig-1R antagonist) using an inflammatory pain model based on intraplantar injection of zymosan. Oral pretreatment with BD1047 dose-dependently reduced zymosan-induced thermal and mechanical hyperalgesia as well as spinal neuronal activation including increased immunoreactivity of Fos, protein kinase C (PKC) and 'PKC-dependent phosphorylation of the NMDA receptor subunit 1' (pNR1). Zymosan also led to increased CD11b immunoreactivity (a marker of microglia) accompanied by 'phosphorylated p38 mitogen activated protein kinase' (p-p38MAPK) and interleukin-1ßimmunoreactivity in the spinal dorsal horn. Intrathecal injection of a microglia modulator (minocycline), p38MAPK inhibitor (SB203580) or interleukin-1ßneutralizing antibody significantly attenuated zymosan-induced hyperalgesia. Specifically, oral pretreatment with BD1047 reduced the immunoreactivity of CD11b, p-p38MAPK and interleukin-1ß. In the spinal cord section, Sig-1R immunoreactivity was exclusively distributed in both spinal dorsal horn neurons and central endings of unmyelinated primary afferent fibers but not in glia. Intrathecal injection of BD1047 alleviated zymosan-induced hyperalgesia up to the level of oral administration. Taken together, our data imply that antinociceptive effect induced by oral treatment with BD1047 may be mediated, at least in part, by the inhibition of neuronal and microglial activation in the spinal cord triggered by inflammatory conditions.


Assuntos
Analgésicos/farmacologia , Etilenodiaminas/farmacologia , Dor/tratamento farmacológico , Dor/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Dor/patologia , Células do Corno Posterior/efeitos dos fármacos , Células do Corno Posterior/metabolismo , Células do Corno Posterior/patologia , Ratos Sprague-Dawley , Receptores sigma/antagonistas & inibidores , Receptores sigma/metabolismo , Medula Espinal/patologia , Zimosan
12.
Water Environ Res ; 87(2): 169-78, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25790519

RESUMO

The objectives of this study were to monitor total phosphorus concentrations and loads along the Cache la Poudre River in Northern Colorado as it flows from a pristine area through urban regions and, finally, through mixed land uses. The study attempted to evaluate the sources and influences of total phosphorus under different hydrologic conditions. Nine sampling events were completed from April 2010 to May 2011 to assess the influence of various hydrologic conditions on aqueous and riverbed sediment total phosphorus concentrations. Total phosphorus concentrations and loads exceeded the in-stream limits proposed by the Colorado Department of Public Health and Environment in all observed hydrologic conditions, and nonpoint sources were significant in high-flow conditions. Reducing nutrients only at water resource recovery facilities (WRRFs) could not achieve the in-stream limits without substantial reduction of non-point-source loads. The study exposed a need for flexibility in WRRF discharge limits based on the overall total phosphorus load in the river from other sources.


Assuntos
Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Fósforo/análise , Rios/química , Poluentes Químicos da Água/análise , Colorado , Fenômenos Geológicos , Hidrologia , Movimentos da Água
13.
J Toxicol Environ Health A ; 77(22-24): 1384-98, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25343288

RESUMO

The aim of this study was to investigate urinary metabolomic profiles associated with cadmium (Cd)-induced nephrotoxicity and their potential mechanisms. Metabolomic profiles were measured by high-resolution (1)H-nuclear magnetic resonance (NMR) spectroscopy in the urine of rats after oral exposure to CdCl2 (1, 5, or 25 mg/kg) for 6 wk. The spectral data were further analyzed by a multivariate analysis to identify specific urinary metabolites. Urinary excretion levels of protein biomarkers were also measured and CdCl2 accumulated dose-dependently in the kidney. High-dose (25 mg/kg) CdCl2 exposure significantly increased serum blood urea nitrogen (BUN), but serum creatinine (sCr) levels were unchanged. High-dose CdCl2 (25 mg/kg) exposure also significantly elevated protein-based urinary biomarkers including osteopontin, monocyte chemoattractant protein-1 (MCP-1), kidney injury molecules-1 (Kim-1), and selenium-binding protein 1 (SBP1) in rat urine. Under these conditions, six urinary metabolites (citrate, serine, 3-hydroxyisovalerate, 4-hydroxyphenyllactate, dimethylamine, and betaine) were involved in mitochondrial energy metabolism. In addition, a few number of amino acids such as glycine, glutamate, tyrosine, proline, or phenylalanine and carbohydrate (glucose) were altered in urine after CdCl2 exposure. In particular, the metabolites involved in the glutathione biosynthesis pathway, including cysteine, serine, methionine, and glutamate, were markedly decreased compared to the control. Thus, these metabolites are potential biomarkers for detection of Cd-induced nephrotoxicity. Our results further indicate that redox metabolomics pathways may be associated with Cd-mediated chronic kidney injury. These findings provide a biochemical pathway for better understanding of cellular mechanism underlying Cd-induced renal injury in humans.


Assuntos
Biomarcadores/urina , Cádmio/toxicidade , Rim/efeitos dos fármacos , Metaboloma , Animais , Moléculas de Adesão Celular/urina , Quimiocina CCL2/urina , Rim/metabolismo , Nefropatias/induzido quimicamente , Espectroscopia de Ressonância Magnética , Masculino , Análise Multivariada , Análise de Componente Principal , Ratos , Ratos Sprague-Dawley , Proteínas de Ligação a Selênio/urina
14.
J Environ Qual ; 42(2): 497-506, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23673842

RESUMO

Excess nutrients are among the leading sources of water quality impairment in the Unites States, and the USEPA has been working with state regulatory agencies to develop nutrient criteria for wastewater treatment plants (WWTPs). The Colorado Department of Public Health and Environment is scheduled to establish nutrient regulations in 2013, and stream total P (TP) concentration standards of 0.16 mg L in warm water and 0.11 mg L in cold water have been proposed for the rivers in the state. The objectives of this study were to monitor TP concentrations and loads along the Cache La Poudre River as it flows from the pristine upstream area through urban regions and finally through a mixture of agricultural and urban land uses. The study attempts to evaluate the sources and influences of TP under different hydrologic conditions. Twelve sampling events were completed from April 2010 to August 2011 to assess the influence of various flow and precipitation conditions on aqueous TP concentrations. During midrange flows and dry conditions, WWTPs were the major sources of TP, but other sources were more significant under high-flow and wet conditions according to a load analysis. The analysis indicates that reducing the TP load from WWTPs will only marginally affect the TP load in the river, and therefore it appears that other sources (e.g., stormwater and agricultural runoff) need to be addressed before the aquatic life-based stream standard can be achieved.


Assuntos
Fósforo , Águas Residuárias , Colorado , Monitoramento Ambiental , Rios , Poluentes Químicos da Água
15.
Ann Nutr Metab ; 61(1): 47-56, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22832546

RESUMO

BACKGROUND/AIMS: To evaluate the effects of medical nutrition therapy (MNT) on body composition and metabolic syndrome (MetS) components in premenopausal Korean women with a body mass index ≥23. METHODS: Participants (n = 160) were classified into MetS (n = 44) or non-MetS (n = 116) groups based on the criteria proposed by the revised National Cholesterol Education Program-Adult Treatment Panel III and the International Diabetes Federation classification. Anthropometric and dietary assessments and blood analyses were performed for all participants prior to and following 12 weeks of MNT. RESULTS: Following MNT, body fat decreased in both groups by roughly 11% (p < 0.001), and the number of participants meeting the criteria for MetS thus decreased from 44 to 19 (56.8%). Mean waist circumference (WC), blood pressure (BP), plasma triglyceride (TG) and blood glucose levels decreased in the MetS group (p < 0.001). Body fat reduction in the MetS group was correlated with changes in WC (r = 0.584), systolic BP (r = 0.451), diastolic BP (r = 0.429) and plasma TG (r = 0.488) levels after adjusting for covariates (p < 0.05). CONCLUSIONS: Body fat reduction and MetS component improvement was achieved by MNT in overweight women. Changes in MetS components appear to be related to body fat reduction. MNT should focus on body fat reduction when used as a primary prevention for MetS.


Assuntos
Síndrome Metabólica/dietoterapia , Sobrepeso/dietoterapia , Pré-Menopausa , Adulto , Glicemia/análise , Pressão Sanguínea , Composição Corporal , Índice de Massa Corporal , Ingestão de Energia , Feminino , Seguimentos , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Sobrepeso/fisiopatologia , Cooperação do Paciente , República da Coreia , Fatores de Risco , Inquéritos e Questionários , Triglicerídeos/sangue , Circunferência da Cintura
16.
Opt Express ; 19(14): 12919-24, 2011 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-21747444

RESUMO

We report on orange a-plane light-emitting diodes (LEDs) with InGaN single quantum well (SQW) grown on r-plane sapphire substrates by metal organic chemical vapor deposition (MOCVD). The peak wavelength and the full-width at half maximum (FWHM) at a drive current of 20mA were 612.2 nm and 72 nm, respectively. The device demonstrated a blue shift in emission wavelength from 614.6 nm at 10 mA to 607.5 nm at 100 mA, representing a net shift of 7.1 nm over a 90 mA range, which is the longest wavelength compared with reported values in nonpolar LEDs. The polarization ratio values obtained from the orange LED varied between 0.36 and 0.44 from 10 to 100mA and a weak dependence of the polarization ratio on the injection current was observed.


Assuntos
Óxido de Alumínio/química , Cor , Gálio/química , Índio/química , Iluminação/instrumentação , Semicondutores , Cristalização/métodos , Desenho de Equipamento , Análise de Falha de Equipamento
17.
Artigo em Inglês | MEDLINE | ID: mdl-21096379

RESUMO

A complete glove-based master-slave tactile feedback system was developed to provide users with a remote sense of touch. The system features a force-sensing master glove with piezoresistive force sensors mounted at each finger tip, and a pressure-transmitting slave glove with silicone-based pneumatically controlled balloon actuators, mounted at each finger tip on another hand. A control system translates forces detected on the master glove, either worn by a user or mounted on a robotic hand, to discrete pressure levels at the fingers of another user. System tests demonstrated that users could accurately identify the correct finger and detect three simultaneous finger stimuli with 99.3% and 90.2% accuracy, respectively, when the subjects were located in separate rooms. The glove-based tactile feedback system may have application to virtual reality, rehabilitation, remote surgery, medical simulation, robotic assembly, and military robotics.


Assuntos
Biorretroalimentação Psicológica/instrumentação , Luvas Cirúrgicas , Sistemas Microeletromecânicos/instrumentação , Estimulação Física/instrumentação , Tato/fisiologia , Transdutores , Interface Usuário-Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Retroalimentação , Humanos , Estresse Mecânico
18.
Clin Biochem ; 38(1): 84-7, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15607322

RESUMO

OBJECTIVES: Smoking is a risk factor for coronary artery disease and triggers vascular injury by platelet aggregation and induces atherosclerosis through induction of oxidative stress. Green tea is known to have antioxidant capacity and anti-platelet activity. DESIGN AND METHODS: Twenty adult male smokers ingested 600 mL of green tea for 4 weeks. Their lipid profile, C-reactive protein (CRP), total antioxidant capacity, oxidized LDL, soluble VCAM-1, soluble ICAM-1, and soluble P-selectin were measured at baseline and 2 and 4 weeks after green tea ingestion. RESULTS: Plasma soluble P-selectin (sP-selectin) levels decreased significantly after 2 and 4 weeks of green tea ingestion compared with those before green tea ingestion (P < 0.001). Plasma concentrations of oxidized LDL decreased significantly after green tea ingestion (P < 0.05). CONCLUSIONS: The results of this study suggest the effect of green tea on sP-selectin and oxidized LDL.


Assuntos
Arteriosclerose/metabolismo , Fumar/metabolismo , Chá/metabolismo , Adulto , Biomarcadores , Humanos , Lipoproteínas LDL/sangue , Selectina-P/sangue , Fatores de Tempo
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