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1.
Rhinology ; 61(4): 338-347, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37083114

RESUMO

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by chronic eosinophilic inflammation and new bone formation (NBF). These processes may be associated with each other in the pathogenesis and influence the severity and prognosis of the disease. However, it is still unclear how eosinophilic inflammation is involved in the NBF. METHODOLOGY: Sinus bone cells were isolated from ethmoid bone tissues of patients with CRSwNP and controls. Transforming growth factor beta 1 (TGFß1) and alkaline phosphatase (ALP) expression in sinus bone cells was determined using quantitative RT-PCR, immunoblotting, and immunohistochemistry. The co-localization of TGFß1 with eosinophils was assessed by immunofluorescence staining. Sinus bone cells were co-cultured with eosinophils (Eol-1 cell line), which were differentiated with butyrate, to measure the osteoblast differentiation activity of sinus bone cells. RESULTS: TGFß1 expression was increased in sinus bone tissues and correlated with CT scores in CRSwNP. TGFß1 was also increased in the submucosa of CRSwNP and co-localized predominantly with eosinophils compared with neutrophils Differentiated Eol-1 cells-derived TGFß1 increased ALP expression in sinus bone cells. Treatment with a TGFß inhibitor attenuated TGFß1-induced ALP expression and staining in sinus bone cells of CRSwNP, leading to loss of bone formation. CONCLUSIONS: Eosinophil-derived TGFß1 was enriched in the submucosa of CRSwNP, which induced ALP expression in sinus bone cells and NBF. Therefore, eosinophil-derived TGFß1 may mediate aberrant bone remodeling in CRSwNP.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Eosinófilos , Rinite/complicações , Rinite/patologia , Fator de Crescimento Transformador beta , Pólipos Nasais/complicações , Pólipos Nasais/patologia , Osteogênese , Sinusite/complicações , Sinusite/patologia , Inflamação/patologia , Doença Crônica
2.
Nature ; 569(7757): 546-550, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31118523

RESUMO

The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons1. The atmospheric concentration of trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s2. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased3,4. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown3. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 ± 3.0 (±1 standard deviation) gigagrams per year higher in 2014-2017 than in 2008-2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010.

3.
Sci Rep ; 8(1): 4669, 2018 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-29549350

RESUMO

The East Asian Summer Monsoon driven by temperature and moisture gradients between the Asian continent and the Pacific Ocean, leads to approximately 50% of the annual rainfall in the region across 20-40°N. Due to its increasing scientific and social importance, there have been several previous studies on identification of moisture sources for summer monsoon rainfall over East Asia mainly using Lagrangian or Eulerian atmospheric water vapor models. The major source regions for EASM previously proposed include the North Indian Ocean, South China Sea and North western Pacific. Based on high-precision and high-frequency 6-year measurement records of hydrofluorocarbons (HFCs), here we report a direct evidence of rapid intrusion of warm and moist tropical air mass from the Southern Hemisphere (SH) reaching within a couple of days up to 33°N into East Asia. We further suggest that the combination of direct chemical tracer record and a back-trajectory model with physical meteorological variables helps pave the way to identify moisture sources for monsoon rainfall. A case study for Gosan station (33.25°N, 126.19°E) indicates that the meridional transport of precipitable water from the SH accompanying the southerly/southwesterly flow contributes most significantly to its summer rainfall.

4.
J Hum Nutr Diet ; 31(3): 370-378, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28948659

RESUMO

BACKGROUND: We assessed the nutritional risks among children hospitalised with acute burn injuries and their associated clinical outcomes using three nutritional risk screening (NRS) tools: Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONGKIDS ), Pediatric Yorkhill Malnutrition Score (PYMS) and Screening Tool for the Assessment for Malnutrition in Pediatrics (STAMP). METHODS: This prospective cross-sectional study was conducted from October 2015 to November 2016, in a regional burn centre. Patients were screened by two independent observers, using the three NRS tools. RESULTS: A total of 100 children aged 3 months to 16.5 years were included. STRONGKIDS identified 16% of patients as having high risk, with being identified 45% by PYMS and 44% by STAMP. After adjustment for confounding factors in multivariate regression analysis, patients in the high-risk group had significantly longer median (SD) lengths of stay [medium versus high risk: STRONGKIDS , 9.5 (6.6) versus 15.0 (24.2) days; PYMS, 8.5 (4.4) versus 13.0 (16.1) days; STAMP, 9.0 (5.7) versus 11.0 (17.4) days] and greater median (SD) weight loss [medium versus high risk: STRONGKIDS, 0.15 (0.8) versus -0.35 (0.8) kg; STAMP, 0.5 (0.7) versus 0 (0.1) kg] than patients in the medium-risk group (P < 0.05). The strengths of agreement in the nutritional risk classification between the two observers were good (κ for STRONGKIDS = 0.61; PYMS = 0.79; STAMP = 0.75) (P < 0.01). CONCLUSIONS: The STRONGKIDS , PYMS and STAMP tools could be useful and practical for determining which hospitalised children with acute burn injuries will need additional nutritional intervention.


Assuntos
Queimaduras/complicações , Hospitalização/estatística & dados numéricos , Desnutrição/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Avaliação Nutricional , Doença Aguda , Adolescente , Criança , Criança Hospitalizada/estatística & dados numéricos , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Desnutrição/etiologia , Programas de Rastreamento/métodos , Estado Nutricional , Estudos Prospectivos , Fatores de Risco
5.
Oncogene ; 36(39): 5512-5521, 2017 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-28534506

RESUMO

Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis. LSD1 demethylates HIF1α at lysine (K) 391, which protects HIF1α against ubiquitin-mediated protein degradation. LSD1 also directly suppresses PHD2-induced HIF1α hydroxylation, which has a mutually dependent interplay with Set9-mediated HIF1α methylation. Moreover, the HIF1α acetylation that occurs in a HIF1α methylation-dependent manner is inhibited by the LSD1/NuRD complex. HIF1α stabilized by LSD1 cooperates with CBP and MTA1 to enhance vascular endothelial growth factor (VEGF)-induced tumor angiogenesis. Thus, LSD1 is a key regulator of HIF1α/VEGF-mediated tumor angiogenesis by antagonizing the crosstalk between PTMs involving HIF1α protein degradation.


Assuntos
Neoplasias da Mama/irrigação sanguínea , Histona Desmetilases/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Células HEK293 , Xenoenxertos , Histona Desmetilases/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Transcrição Gênica , Transfecção , Ubiquitina/metabolismo
7.
Clin Exp Dermatol ; 41(6): 595-600, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27339295

RESUMO

BACKGROUND: Filaggrin is a key protein involved in skin barrier function. Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris and have been shown to be major predisposing factors for atopic dermatitis (AD). AIM: To investigative the clinical characteristics of patients with AD with FLG mutations and determine the differences between patients with AD with and without FLG mutations. METHODS: We identified FLG mutations in patients with AD by complete sequencing and SNaPshot methods, and then analysed the data on clinical characteristics from questionnaire responses. RESULTS: We found that earlier age of AD onset (P < 0.05), tendency to respiratory atopy (P = 0.03), more severe clinical characteristics of AD (higher Eczema Area and Severity Index, P = 0.02) and decrease in skin hydration (P = 0.04) were associated with FLG-related AD. CONCLUSION: Our data demonstrate that FLG mutations are indicators of a poor prognosis in AD, and are predisposing factors that exist in early infancy and persist into adulthood.


Assuntos
Dermatite Atópica/genética , Proteínas de Filamentos Intermediários/genética , Fenômenos Fisiológicos da Pele/genética , Pele/patologia , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Dermatite Atópica/sangue , Dermatite Atópica/epidemiologia , Eczema/genética , Proteínas Filagrinas , Predisposição Genética para Doença , Genótipo , Humanos , Ictiose Vulgar/etiologia , Ictiose Vulgar/genética , Lactente , Mutação , Prognóstico , República da Coreia/epidemiologia , Análise de Sequência de DNA , Índice de Gravidade de Doença , Pele/metabolismo , Adulto Jovem
8.
Public Health Nutr ; 19(15): 2769-80, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27194183

RESUMO

OBJECTIVE: To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study. DESIGN: Cross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995-2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion. SETTING: Twenty-seven centres across ten European countries. SUBJECTS: Women (64 %) and men (36 %) aged 35-74 years (n 36 020). RESULTS: Pronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38-43 % for women and 41-45 % for men within Mediterranean countries compared with 16-27 % for women and 20-26 % for men in central and northern European countries. Likewise, a south-north gradient was found for daily energy intake from snacks, with 13-20 % (women) and 10-17 % (men) in Mediterranean countries compared with 24-34 % (women) and 23-35 % (men) in central/northern Europe. CONCLUSIONS: We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.


Assuntos
Inquéritos sobre Dietas , Dieta , Comportamento Alimentar , Adulto , Idoso , Estudos Transversais , Ingestão de Energia , Europa (Continente) , Feminino , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Estudos Prospectivos , Lanches
9.
Parasite Immunol ; 37(4): 180-91, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25559209

RESUMO

In our previous studies, the recombinant type II macrophage migration inhibitory factor homologue (rAs-MIF) secreted from Anisakis simplex suppressed experimental inflammation mouse model through IL-10 production and CD4(+)CD25(+)Foxp3(+) T-cell recruitment. Also, TLR2 gene expression was significantly increased following rAs-MIF treatment. To know the relation between TLR2 and amelioration mechanisms of rAs-MIF, we induced allergic airway inflammation by ovalbumin and alum with or without rAs-MIF under TLR2 blocking systems [anti-TLR2-specific antibody (α-mTLR2 Ab) treatment and using TLR2 knockout mice]. As a result, the amelioration effects of rAs-MIF in allergic airway inflammation model (diminished inflammation and Th2 response in the lung, increased IL-10 secretion, CD4(+)CD25(+)Foxp3(+) T-cell recruitment) were diminished under two of the TLR2 blocking model. The expression of TLR2 on the surface of lung epithelial cell was significantly elevated by rAs-MIF treatment or Pam3CSK (TLR2-specific agonist) treatment, but they might have some competition effect on the elevation of TLR2 expression. In addition, the elevation of IL-10 gene expression by rAs-MIF treatment was significantly inhibited by α-mTLR2 Ab or Pam3CSK pretreatment. In conclusion, anti-inflammatory effects of the rAs-MIF on OVA-induced allergic airway inflammation might be closely related to TLR2.


Assuntos
Anisakis , Proteínas de Helminto/imunologia , Hipersensibilidade/imunologia , Fatores Inibidores da Migração de Macrófagos/imunologia , Receptor 2 Toll-Like/imunologia , Compostos de Alúmen , Animais , Modelos Animais de Doenças , Feminino , Hipersensibilidade/patologia , Inflamação/induzido quimicamente , Inflamação/imunologia , Interleucina-10/imunologia , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Receptor 2 Toll-Like/genética
10.
Oncogene ; 33(10): 1325-35, 2014 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-23474752

RESUMO

The epithelial-mesenchymal transition (EMT) is the pivotal mechanism underlying the initiation of cancer invasion and metastasis. Although Mel-18 has been implicated in several biological processes in cancer, its function in the EMT of human cancers has not yet been studied. Here, we demonstrate that Mel-18 negatively regulates the EMT by epigenetically modulating miR-205. We identified miR-205 as a novel target of Mel-18 using a microRNA microarray analysis and found that Mel-18 increased miR-205 transcription by the inhibition of DNA methyltransferase-mediated DNA methylation of the miR-205 promoter, thereby downregulating its target genes, ZEB1 and ZEB2. Furthermore, the loss of Mel-18 promoted ZEB1- and ZEB2-mediated downregulation of E-cadherin transcription and also enhanced the expression of mesenchymal markers, leading to increased migration and invasion in MCF-7 cells. In MDA-MB-231 cells, Mel-18 overexpression restored E-cadherin expression, resulting in reduced migration and invasion. These effects were reversed by miR-205 overexpression or inhibition. A tumor xenograft with Mel-18 knockdown MCF-7 cells consistently showed increased ZEB1 and ZEB2 expression and decreased E-cadherin expression. Taken together, these results suggest that Mel-18 functions as a tumor suppressor by its novel negative control of the EMT, achieved through regulating the expression of miR-205 and its target genes, ZEB1 and ZEB2.


Assuntos
Neoplasias da Mama/metabolismo , Transição Epitelial-Mesenquimal , Proteínas de Homeodomínio/metabolismo , MicroRNAs/genética , Complexo Repressor Polycomb 1/fisiologia , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Animais , Antígenos CD , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Caderinas/genética , Caderinas/metabolismo , Metilação de DNA , Regulação para Baixo , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , MicroRNAs/metabolismo , Transplante de Neoplasias , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco , Homeobox 1 de Ligação a E-box em Dedo de Zinco
11.
Rev Sci Instrum ; 83(9): 093505, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23020374

RESUMO

The Thomson scattering diagnostic system is successfully installed in the Korea Superconducting Tokamak Advanced Research (KSTAR) facility. We got the electron temperature and electron density data for the first time in 2011, 4th campaign using a field programmable gate array (FPGA) based signal control board. It operates as a signal generator, a detector, a controller, and a time measuring device. This board produces two configurable trigger pulses to operate Nd:YAG laser system and receives a laser beam detection signal from a photodiode detector. It allows a trigger pulse to be delivered to a time delay module to make a scattered signal measurement, measuring an asynchronous time value between the KSTAR timing board and the laser system injection signal. All functions are controlled by the embedded processor running on operating system within a single FPGA. It provides Ethernet communication interface and is configured with standard middleware to integrate with KSTAR. This controller has operated for two experimental campaigns including commissioning and performed the reconfiguration of logic designs to accommodate varying experimental situation without hardware rebuilding.

12.
Osteoarthritis Cartilage ; 20(11): 1426-38, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22890185

RESUMO

OBJECTIVE: The objectives were to investigate the in vivo effects of treatment with rebamipide on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA) and to explore its mode of action. MATERIALS AND METHODS: OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA). Oral administration of rebamipide was initiated on the day of MIA injection, 3 or 7 days after. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. We analyzed the samples macroscopically and histomorphologically, and used immunohistochemistry to investigate the expression of matrix metalloproteinase-13 (MMP-13), interleukin-1ß (IL-1ß), hypoxia-inducible factor-2α (HIF-2α), inducible nitric oxide synthase (iNOS), and nitrotyrosine in knee joints. Real-time quantitative reverse transcription-polymerase chain reaction was used to quantify the mRNA for catabolic and anticatabolic factors in human OA chondrocytes. RESULTS: Rebamipide showed an antinociceptive property and attenuated cartilage degeneration. Rebamipide reduced the expression of MMP-13, IL-1ß, HIF-2α, iNOS, and nitrotyrosine in OA cartilage in a dose-dependent manner. Nitrotyrosine expression in the subchondral bone region was decreased in the rebamipide-treated joints. mRNA expression of MMP-1, -3, and -13, and ADAMTS5 was attenuated in IL-1ß-stimulated human OA chondrocytes. By contrast, rebamipide induced the mRNA expression of tissue inhibitor of metalloproteinase-1 and -3. CONCLUSION: The results show the inhibitory effects of rebamipide on pain production and cartilage degeneration in experimentally induced OA. The suppression of oxidative damage and the restoration of extracellular matrix homeostasis of articular chondrocyte suggest that rebamipide is a potential therapeutic strategy for OA.


Assuntos
Alanina/análogos & derivados , Analgésicos/farmacologia , Artrite Experimental/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Quinolonas/farmacologia , Alanina/farmacologia , Animais , Artrite Experimental/patologia , Artrite Experimental/fisiopatologia , Biomarcadores/metabolismo , Cartilagem Articular/patologia , Células Cultivadas , Condrócitos/metabolismo , Condrócitos/patologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Metaloproteinases da Matriz Secretadas/genética , Metaloproteinases da Matriz Secretadas/metabolismo , Camundongos , Osteoartrite/complicações , Osteoartrite/patologia , Estresse Oxidativo/efeitos dos fármacos , Dor/complicações , Dor/fisiopatologia , Medição da Dor , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Joelho de Quadrúpedes/efeitos dos fármacos , Joelho de Quadrúpedes/patologia
13.
Int J Clin Pharmacol Ther ; 49(11): 672-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22011692

RESUMO

BACKGROUND: Sertraline is a naphthalenamine derivative which has the effect of selective serotonin reuptake inhibition. It has been used for major depression, and obsessive compulsive disorder. This study was performed to evaluate the pharmacokinetic (PK) characteristics after the administration of low dose sertraline for the purpose of exploring an application of microdosing methods in PK studies. METHODS: An open-label, three-period, single-sequence, dose-escalation study was performed in 6 healthy Korean male volunteers. Subjects were administered a single dose of 5 mg, 25 mg and 50 mg sertraline orally in each period, with 1 week washouts between periods. Blood samples were obtained up to 96 h after drug administration. Plasma concentrations were determined using high performance liquid chromatography-tandem mass spectrometry. PK parameters of sertraline were analyzed using non-compartmental methods. RESULTS: A total of 6 subjects completed the study. After the administration of sertraline at 5 mg, 25 mg and 50 mg, the median tmax were 6.0, 6.0 and 4.0 h and the mean (SD) elimination half-lives were 31.9 (6.5), 27.2 (6.7) and 28.0 (6.6) h, respectively. The AUC and Cmax increased dose-dependently. The dose-normalized mean (SD) AUC and Cmax were different in each dosing group (p < 0.01) with 2.0 (0.8), 5.3 (1.2) and 6.0 (1.9) mg × hr/l/mg in the 5 mg, 25 mg and 50 mg groups for dose-normalized AUC, and 0.07 (0.01), 0.18 (0.05) and 0.21 (0.08) mg/l/mg in the 5 mg, 25 mg and 50 mg groups for dose-normalized Cmax, respectively, which indicates a lack of dose proportionality. CONCLUSION: A lack of dose proportional properties was shown in the 5 mg dose relative to the 25 mg and 50 mg doses of sertraline. This shows that the PK parameters for low-dose sertraline could be different from those in clinical concentrations.


Assuntos
Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Sertralina/farmacocinética , Adulto , Área Sob a Curva , Relação Dose-Resposta a Droga , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Sertralina/efeitos adversos , Adulto Jovem
14.
Br J Dermatol ; 165(6): 1344-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21711335

RESUMO

BACKGROUND: Serotonin (5-hydroxytryptamine, 5-HT) levels are increased by light exposure but the role and mechanism of 5-HT in the pigmentation of skin cells are unclear. OBJECTIVES: To clarify the effect of 5-HT on melanogenesis and to determine the 5-HT receptor subtype involved. METHODS: B16F10, SK-MEL-2 and Melan-A cells were cultured in Dulbecco's modified Eagle's medium with low fetal bovine serum. The three cell lines were treated with various concentrations of 5-HT, and 5-HT receptor agonists and antagonists. The involvement of the 5-HT receptor 2A (5-HTR2A) was examined by gene silencing and use of 5-HTR2A antagonists. RESULTS: 5-HT and the 5-HTR2A agonist, DOI, increased melanogenesis in the three cell lines. These increased events were suppressed by 5-HTR2A antagonists or gene silencing of the HTR2A gene. CONCLUSIONS: 5-HTR2A is involved in melanogenesis. These findings highlight the role of 5-HT and suggest new ways of controlling melanogenesis.


Assuntos
Melaninas/biossíntese , Melanose/etiologia , Receptor 5-HT2A de Serotonina/fisiologia , Serotonina/fisiologia , Animais , Western Blotting , Movimento Celular/efeitos dos fármacos , Inativação Gênica , Humanos , Melanócitos/metabolismo , Melanoma/fisiopatologia , Melanose/metabolismo , Camundongos , RNA Interferente Pequeno/farmacologia , Receptor 5-HT2A de Serotonina/genética , Serotonina/farmacologia , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Neoplasias Cutâneas/fisiopatologia , Células Tumorais Cultivadas
15.
Neuroscience ; 160(3): 587-95, 2009 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-19272429

RESUMO

ATP acts as a neurotransmitter or co-neurotransmitter in many areas of the CNS and peripheral nervous systems; however, little is known about the expression and functional role of purinoceptors (P2) in midbrain dopaminergic neurons. Therefore, we investigated P2X receptor expression and regulation of spontaneous firing activity in dopaminergic neurons of the substantia nigra pars compacta (SNc) in rats using patch-clamp and Ca(2+)-imaging techniques. In most neurons, application of ATP (1 microM-1 mM) increased firing rate dose-dependently (EC(50)=1.26+/-0.26 microM, n=45). When the P2-receptor agonists such as 2-methylthio-adenosine 5'-triphosphate (2-MeSATP) or ATPgammaS were applied or pressure-applied to the neuron, the firing activity increased together with a rise in cytosolic Ca(2+) concentration ([Ca(2+)]c), but application of beta,gamma-methylene ATP (P2X(1, 3) agonist) or methylthio-adenosine 5'-diphosphate (P2Y(1) agonist) had no effect. In many neurons, the effect of ATP was abolished by the application of the P2-receptor antagonists, suramin or pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). When ATP was applied in a Ca(2+)-free solution, there was no detectable change in [Ca(2+)]c, suggesting that ATP does not release Ca(2+) from intracellular stores. In the single-cell reverse transcription polymerase chain reaction (RT-PCR), we found that 65% of dopaminergic neurons expressed mRNAs for P2X receptors; positive amplifications of P2X(6) (57.1%), P2X(2/6) (25.0%), and P2X(4) mRNA (17.9%), respectively. From the above results, we could conclude that ATP modulates firing activities in the rat SNc dopaminergic neurons, possibly via P2X(2), P2X(2/6), and/or P2X(4) receptors.


Assuntos
Potenciais de Ação/fisiologia , Trifosfato de Adenosina/metabolismo , Dopamina/metabolismo , Neurônios/fisiologia , Receptores Purinérgicos P2/metabolismo , Substância Negra/fisiologia , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Animais , Cálcio/metabolismo , Fármacos do Sistema Nervoso Central/farmacologia , Citoplasma/metabolismo , Técnicas In Vitro , Técnicas de Patch-Clamp , Agonistas do Receptor Purinérgico P2 , Antagonistas do Receptor Purinérgico P2 , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Suramina/farmacologia , Tionucleotídeos/farmacologia
16.
Sarcoidosis Vasc Diffuse Lung Dis ; 26(2): 121-31, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20560292

RESUMO

BACKGROUND: Agents that target pro-inflammatory cytokines may be useful in pulmonary sarcoidosis. OBJECTIVE: To determine effectiveness of a non-selective cyclic nucleotide phosphodiesterase (PDE) inhibitor, pentoxifylline (POF). DESIGN: Randomized, double-blind, placebo-controlled trial, SETTING: Clinical Research Center, National Institutes of Health. PATIENTS: 27 patients with biopsy-confirmed pulmonary sarcoidosis receiving prednisone. INTERVENTION: Placebo or POF (1200-2000 mg/day) for 10 months, as prednisone was tapered. MEASUREMENTS: Primary endpoints: sustained improvement in two or more pulmonary function parameters, or a combination of one pulmonary function parameter and dyspnea. RESULTS: Except for one patient, primary endpoints were not reached in POF-treated patients. Therefore, a post hoc analysis was performed. The observed relative risk reduction for flares associated with POF treatment was 54.9% (95% CI 0.21, 0.89) and the absolute risk reduction was 50.6% (95% CI 0.22, 0.80). Compared to placebo treatment, in the POF group, the mean prednisone dose was lower at 8 and 10 months (p = 0.007 and 0.01 respectively), and there was a trend towards less prednisone usage over the entire study period (p = 0.053), as determined by cumulative change analysis. CONCLUSIONS: Although our exploratory post hoc analysis suggested that POF reduced flares and had steroid-sparing effects, given the study limitations, definitive conclusions cannot be drawn regarding the efficacy of POF in pulmonary sarcoidosis. In addition, gastrointestinal side-effects, at the doses used, would seem to limit the use of POF in treating pulmonary sarcoidosis. Overall, however, this trial may provide a basis for using more specific, better-tolerated, PDE inhibitors in future clinical trials.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Pentoxifilina/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Adolescente , Adulto , Idoso , Biópsia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Fluxo Expiratório Forçado/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pentoxifilina/administração & dosagem , Inibidores de Fosfodiesterase/administração & dosagem , Testes de Função Respiratória , Resultado do Tratamento , Adulto Jovem
17.
J Food Sci ; 72(7): S497-502, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17995663

RESUMO

Volatile components in regular and decaffeinated green teas were isolated by simultaneous steam distillation and solvent extraction (SDE), and then analyzed by GC-MS. A total of 41 compounds, including 8 alcohols, 15 terpene-type compounds, 10 carbonyls, 4 N-containing compounds, and 4 miscellaneous compounds, were found in regular and decaffeinated green teas. Among them, linalool and phenylacetaldehyde were quantitatively dominant in both regular and decaffeinated green teas. By a decaffeination process using supercritical carbon dioxide, most volatile components decreased. The more caffeine was removed, the more volatile components were reduced in green teas. In particular, relatively nonpolar components such as terpene-type compounds gradually decreased according to the decaffeination process. Aroma-active compounds in regular and decaffeinated green teas were also determined and compared by aroma extract dilution analysis (AEDA). Most greenish and floral flavor compounds such as hexanal, (E)-2-hexenal, and some unknown compounds disappeared or decreased after the decaffeination process.


Assuntos
Cafeína/análise , Dióxido de Carbono/farmacologia , Manipulação de Alimentos/métodos , Chá/química , Volatilização/efeitos dos fármacos , Cromatografia com Fluido Supercrítico/métodos , Precipitação Fracionada , Cromatografia Gasosa-Espectrometria de Massas , Humanos
18.
Scand J Rheumatol ; 36(4): 259-64, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17763202

RESUMO

OBJECTIVE: To determine the clinical implications of the over-expression of synovial and circulating interleukin (IL)-23p19 and the correlation between IL-23p19 and other cytokines such as IL-17, tumour necrosis factor (TNF)alpha, and IL-1beta in rheumatoid arthritis (RA). METHODS: Synovial fluid (SF) and sera of 22 patients with RA were obtained during knee arthrocentesis and stored at -20 degrees C. Tender/swollen joint counts, 100-mm visual analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and antibodies to cyclic citrullinated peptide (anti-CCP Ab) were measured. Bony erosions were determined by X-rays. Serum and SF IL-23p19, IL-17, TNFalpha, and IL-1beta concentrations were measured by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The concentration of IL-23p19 correlated with the concentration of IL-17 in SF and sera, and with the concentrations of TNFalpha and IL-1beta in sera. SF IL-23p19 concentration was higher in patients who had bony erosions than those who had not. However, there was no correlation between IL-23p19 concentrations and other clinical parameters of RA. CONCLUSION: Upregulated IL-23p19 in SF might be involved in joint destruction in RA through interplay with other cytokines such as IL-17, TNFalpha, and IL-1beta.


Assuntos
Artrite Reumatoide/fisiopatologia , Interleucina-23/fisiologia , Artrite Reumatoide/diagnóstico por imagem , Humanos , Inflamação/fisiopatologia , Interleucina-17/análise , Interleucina-1beta/análise , Articulação do Joelho/fisiopatologia , Subunidades Proteicas , Radiografia , Líquido Sinovial/química , Fator de Necrose Tumoral alfa/análise
19.
J Neuroendocrinol ; 19(6): 475-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17504441

RESUMO

Gonadotophin-releasing hormone (GnRH) peptide released from the terminal nerve (TN)-GnRH neurones of the dwarf gourami primarily modifies the electrical properties of various neurones, including the TN-GnRH neurones themselves. However, our knowledge on the expression of GnRH receptors (GnRHRs) in the TN-GnRH neurones is still limited. Here, we used the single-cell reverse transcriptase-polymerase chain reaction after whole-cell patch-clamp recording to study the distribution of various GnRHR types expressed in the individual TN-GnRH neurones. We found that TN-GnRH neurones express two of the three types of GnRHRs cloned in the dwarf gourami: GnRHR1-2 and -R2, but not -R1-1. Furthermore, in agreement with our previous findings, all TN-GnRH neurones contained mRNAs of salmon GnRH but not chicken GnRH-II.


Assuntos
Nervos Cranianos/metabolismo , Proteínas de Peixes/classificação , Hormônio Liberador de Gonadotropina/metabolismo , Perciformes/fisiologia , Receptores LHRH/classificação , Animais , Nervos Cranianos/citologia , Feminino , Proteínas de Peixes/metabolismo , Masculino , Receptores LHRH/metabolismo , Fatores Sexuais
20.
Eur J Clin Nutr ; 61(12): 1435-41, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17299477

RESUMO

OBJECTIVE: To evaluate validity and reliability of the food-frequency questionnaire (FFQ) developed for the Korean Genome Epidemiologic Study (KoGES). METHODS: FFQ was administered twice at 1-year interval (first FFQ (FFQ1) at the beginning and second FFQ (FFQ2) at the end of the study) and diet records (DRs) were collected for 3 days during each of the four seasons from December 2002 to May 2004 for those who attended the health examination center. At the end of the study period, we collected the 12-day DRs of 124 participants. The nutrient intakes from the DRs were compared with both FFQ1 and FFQ2. RESULTS: The intakes of energy and some nutrients estimated from FFQ1 and FFQ2 were different from those assessed by the DRs. Especially, the consumption of carbohydrates was higher in FFQ1 and FFQ2 than in the DRs. The de-attenuated, age, sex and energy intake adjusted correlation coefficients between the FFQ2 and the 12-day DRs in Korean population ranged between 0.23 (Vitamin A) and 0.64 (carbohydrate). The median for all nutrients was 0.39. The correlations were similar when we compared nutrient densities of both methods. Joint classification of calorie-adjusted nutrient intakes assessed by FFQ2 and 12-day DRs by quartile ranged from 25.8% (vitamin A) to 39.5% (carbohydrate, iron) for exact concordance. Except vitamin A, the proportion of subjects classified into distant quartile was less than 7% in all nutrients. The median of correlations between the two FFQs 1 year apart were 0.45 for all nutrient intakes and 0.39 for nutrient densities. CONCLUSIONS: We conclude that the FFQ we have developed appears to be an acceptable tool for assessing the nutrient intakes in this population. Further studies for calibration of the FFQ collected from multicenters participating in the KoGES are needed. SPONSORSHIP: This study was supported by the budget of the National Genome Research Institute, Korea National Institute of Health (2002-347-6111-221).


Assuntos
Dieta , Ingestão de Energia/fisiologia , Comportamento Alimentar , Inquéritos e Questionários/normas , Adulto , Idoso , Estudos de Coortes , Registros de Dieta , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Feminino , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Minerais/administração & dosagem , Reprodutibilidade dos Testes , Estações do Ano , Sensibilidade e Especificidade , Vitaminas/administração & dosagem
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