RESUMO
Polyopes affinis is a red algal species commonly found on the South coast and near Jeju Island, Korea. This study aimed to determine whether P. affinis extracts can inhibit the pathogenesis of T-helper-2 (Th2)-mediated inflammation in a human keratinocyte cell line of atopic dermatitis (AD). Cells were incubated with 10 ng/mL of interferon gamma (IFN-γ) and 10 ng/mL of tumor necrosis factor-alpha (TNF-α) at various concentrations of PAB (10, 30, and 60 µg/mL) and PAA (100, 500, and 1000 µg/mL) extracts. A gene-ontology (GO)-enrichment analysis revealed that PAB significantly enriched the genes associated with biological processes such as cell adhesion, immune response, inflammation, and chemokine-mediated pathways. PAB suppressed the expression of the secretory proteins and mRNAs that are associated with the thymus and the production of activation-regulated chemokines (TARC/CCL17) and macrophage-derived chemokines (MDC/CCL22). The effect of the extract on mitogen-activated protein kinases (MAPKs) was related to its inhibition of TARC/CCL17 and MDC/CCL22 production by blocking NF-κB and STAT1 activation. These results suggest that seaweed extract may improve AD by regulating pro-inflammatory chemokines. In conclusion, we first confirmed the existence of phloroglucinol, a polyphenol formed from a precursor called phlorotannin, which is present in PAB, and this result proved the possibility of PAB being used as a treatment for AD.
Assuntos
NF-kappa B , Fator de Necrose Tumoral alfa , Regulação para Baixo , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interferon gama/metabolismo , Queratinócitos , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: Benzene is a well-known haematological toxin causing aplastic anaemia and leukaemia. Some recent studies have shown that low-level benzene exposure (<1â ppm) disturbs the haematopoietic system. However, other studies showed inconsistent results. The aim of the present study was to examine the relationship between low-level benzene exposure and blood cell counts in Korean workers. METHODS: Blood cell counts of benzene-exposed workers were extracted from a nationwide Special Health Examination Database from 2000 to 2008. If a worker did not take a blood test for benzene between 2000 and 2004, the worker was selected for analysis. In total, 8679 personal air benzene measurements were extracted from the nationwide Workplace Environment Measurement Database from 2004 to 2008. Mean benzene levels were calculated and assigned to benzene-exposed workers using various combinations of factory/industry/process codes. Mixed-effects models were used to examine dose-related associations between benzene levels and white blood cell (WBC), red blood cell (RBC), platelet, neutrophil and lymphocyte counts. RESULTS: In total, 21â 140 blood samples were tested from 10â 702 workers between 2005 and 2008; 40% of the workers had repeated blood tests (average, 3.4 times). RBC counts in male workers showed a significant negative association with low-level benzene exposure. WBC, platelet, neutrophil and lymphocyte counts did not show a consistent association with low-level benzene exposure. CONCLUSIONS: Our findings support the potential haematotoxicity of low-level benzene exposure (<1â ppm). A longitudinal study with direct benzene measurements for exposed workers is needed to confirm the toxicity of low-level benzene exposure.
Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Benzeno/toxicidade , Contagem de Células Sanguíneas , Células Sanguíneas/efeitos dos fármacos , Indústria Química , Exposição Ocupacional/efeitos adversos , Adulto , Poluição do Ar em Ambientes Fechados/análise , Benzeno/análise , Monitoramento Ambiental/métodos , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análiseRESUMO
Immediate burn wound care is a critical factor influencing the outcomes of burn treatment. In this study, we developed a spray-type alginate hydrogel dressing that promotes wound healing, reduces pain, and increases the convenience of use in a burn treatment emergency. We investigated the efficiency of newly developed spray-type alginate hydrogel dressing on the wound healing process. We investigated the efficacy of the alginate hydrogel dressing for wound healing in 30 Sprague Dawley rats. Four deep, round second-degree burn wounds (diameter, 1.5 cm) were created bilaterally on the dorsum of the rat's trunk; the rats were divided into four groups, in which different dressing materials were applied as follows: group A, gauze (control); group B, Mepilex™ (control); group C, 2.25% alginate hydrogel; and group D, 2.5% alginate hydrogel. The gross findings of each group were compared by tracing the remaining wound and performing visual and histological observations and biochemical analysis for proteins associated with wound healing at each time period. In burn wounds, groups C and D showed significantly higher contraction, epithelialization, and healing rates. Histologically, groups C and D showed an improved arrangement of collagen fibers and a thick epithelial layer 14 days after initial wound formation. Group C showed higher CD31, TGF-ß, and fibronectin expression in Western blot analyses after day 14. This study suggests that the spray-type alginate hydrogel dressing is an effective material for initial burn wound care.
RESUMO
The title salt, (C8H20N)[Ni(NCS)3(C10H10N6)], consists of a tetra-ethyl-ammonium cation and an anion comprising an octa-hedral Ni(II) atom surrounded by three N atoms from a tripodal tris-(pyrazol-1-yl)methane ligand, and three thio-cyanate ligands, each bound at the N-atom end. The ligand Ni-N distances range from 2.097â (2) to 2.127â (2)â Å for the tripodal ligand and from 2.045â (2) to 2.075â (2)â Å for the thio-cyanate ligands. The dihedral angles between the three pyrazole rings are 59.03â (12), 53.09â (10) and 67.90â (10)°.
RESUMO
Sunscreens containing UV filters are recommended to reduce damage caused by solar UV radiation. Recently, benzophenone (BP)-type UV filters have become widely used as UV stabilizers in skin-moisturizing products and sunscreen lotions; however, very little information is available regarding the potential harmful effects of prolonged exposure to these compounds. Therefore, we investigated the toxicokinetics and metabolism of BP-type UV filters in rats using gas chromatography-mass spectrometry (GC-MS). To examine the metabolism of BP-type UV filters, we analyzed the parent compounds BP and 2-hydroxy-4-methoxybenzophenone (HMB). In rats, BP was mainly converted to benzhydrol (BH) and 4-hydroxybenzophenone (HBP) (i.e., type A UV filters). In contrast, HMB was converted into at least three intermediates, including 2,4-dihydroxybenzophenone (DHB), which was formed via o-demethylation and subsequently converted into 2,3,4-trihydroxybenzophenone (THB), and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB), which formed via the aromatic hydroxylation of HMB (i.e., type B UV filters). Next, the toxicokinetic curve for BP showed a peak concentration (Cmax) of 2.06+/-0.46 microg/ml at approximately 4h after BP administration. After a single oral dose of HMB, the Cmax of HMB reached 21.21+/-11.61 microg/ml within 3h (Tmax), and then declined rapidly compared to the kinetic curve of BP. The concentration of these metabolites in rat blood decreased much more slowly over time compared to the parent compounds. Thus, our results indicate that such metabolites might have more significant adverse effects than the parent compounds over the long term.
Assuntos
Benzofenonas/farmacocinética , Fármacos Fotossensibilizantes/farmacocinética , Protetores Solares/farmacocinética , Administração Oral , Animais , Área Sob a Curva , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Raios UltravioletaRESUMO
A novel method has been developed to simultaneously determine and quantify seven organic UV filters employing liquid (solid)-liquid extraction, derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA) and gas chromatography with mass spectrometric detection in various environmental matrices. The UV filters determined were: benzophenone (BP), benzhydrol (BH), 4-hydroxybenzophenone (HBP), 2-hydroxy-4-methoxybenzophenone (HMB), 2,4-dihydroxybenzophenone (DHB), 2,2'-dihydroxy-4-methoxybenzophenone (DHMB) and 2,3,4-trihydroxylbenzophenone (THB). Under optimal conditions, the analysis required 23 min and good linearity over the range of 10-2,500 ng/L in water and 100-25,000 ng/kg in soil for each UV filter obtained. The high recovery (62-114% and 60-125% for water and soil samples, respectively) and the low RSD values (less than 13.9 and 17.2% for water and soil samples, respectively) indicated the high performance of this method. The method detection limits (MDLs) were relatively low, ranging from 5 to 100 ng/L or kg and quantification limits ranged between 25 and 500 ng/L or kg for all test compounds. This validated method was applied in the analysis of seven BP-type UV filters collecting water and soil samples in Korea, between April and May 2003. The overall concentration of UV filters in the soil sample (500-18,380 ng/kg) was highly distributed in water sample (27-204 ng/L). The established method was successfully applied to monitor the residue measurement of the BP-type UV filters in environmental water and soil samples.
Assuntos
Benzofenonas/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Solo/análise , Protetores Solares/análise , Água/análise , Acetamidas , Benzofenonas/química , Filtração , Fluoracetatos , Geografia , Coreia (Geográfico) , Estrutura Molecular , Protetores Solares/química , Ácido Trifluoracético/análise , Ácido Trifluoracético/química , Compostos de Trimetilsilil/análise , Compostos de Trimetilsilil/química , Raios Ultravioleta , Água/químicaRESUMO
The catalytic subunit of telomerase reverse transcriptase (TERT) protects dividing cells from replicative senescence in vitro. Here, we show that expression of TERT mRNA is induced in the ipsilateral cortical neurons after occlusion of the middle cerebral artery in adult mice. Transgenic mice that overexpress TERT showed significant resistance to ischemic brain injury. Among excitotoxicity, oxidative stress, and apoptosis comprising of routes of ischemic neuronal death, NMDA receptor-mediated excitotoxicity was reduced in forebrain cell cultures overexpressing TERT. NMDA-induced accumulation of cytosolic free Ca2+ ([Ca2+]c) was reduced in forebrain neurons from TERT transgenic mice, which was attributable to the rapid flow of [Ca2+]c into the mitochondria from the cytosol without change in Ca2+ influx and efflux through the plasma membrane. The present study provides evidence that TERT is inducible in postmitotic neurons after ischemic brain injury and prevents NMDA neurotoxicity through shift of the cytosolic free Ca2+ into the mitochondria, and thus plays a protective role in ameliorating ischemic neuronal cell death.
Assuntos
Lesão Encefálica Crônica/prevenção & controle , Isquemia Encefálica/terapia , N-Metilaspartato , Síndromes Neurotóxicas/prevenção & controle , Telomerase/biossíntese , Animais , Lesão Encefálica Crônica/induzido quimicamente , Lesão Encefálica Crônica/genética , Isquemia Encefálica/genética , Cálcio/metabolismo , Células Cultivadas , Técnicas de Cocultura , Proteínas de Ligação a DNA , Modelos Animais de Doenças , Agonistas de Aminoácidos Excitatórios , Corantes Fluorescentes , Regulação da Expressão Gênica , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/prevenção & controle , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/genética , Camundongos , Camundongos Transgênicos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neuroglia/citologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Síndromes Neurotóxicas/etiologia , Neurotoxinas , RNA Mensageiro/biossíntese , Telomerase/genéticaRESUMO
Mice carrying a mutation in the first intron of Unc5h3 were accidentally produced by transgenic insertion and characterized for their homozygous mutant phenotypes. Morphological and histological analysis revealed cerebellar and midbrain abnormalities, which are similar to the previously reported phenotypes of the Unc5h3 mutant. Behavioral analysis showed higher ambulatory activity and circling, and defects in habituation in a novel environment. Their body weights were 10-30% less than wildtype mice from 2-3 weeks of age to 22 months possibly due to reduced accumulation of adipose tissues. The transgenic insertion site was identified and mapped to the intron 1 of Unc5h3 gene with approximately 50 kb deletion of the intron sequence. This intronic mutation interfered with the mRNA expression of the Unc5h3 gene not in testes, but in many tissues including the brain, implying that this intronic region may play a role in regulating tissue-specific transcription of Unc5h3.
Assuntos
Ataxia/genética , Hipercinese/genética , Íntrons/genética , Camundongos Mutantes , Mutagênese Insercional/genética , Receptores de Superfície Celular/genética , Magreza/genética , Animais , Camundongos , Camundongos Transgênicos , Receptores de Netrina , FenótipoRESUMO
BACKGROUND/AIMS: This study was designed to evaluate the dose-effect relationship of statins in patients with ischemic congestive heart failure (CHF), since the role of statins in CHF remains unclear. METHODS: The South koreAn Pitavastatin Heart FaIluRE (SAPHIRE) study was designed to randomize patients with ischemic CHF into daily treatments of 10 mg pravastatin or 4 mg pitavastatin. RESULTS: The low density lipoprotein cholesterol level decreased by 30% in the pitavastatin group compared with 12% in the pravastatin (p < 0.05) group. Left ventricular systolic dimensions decreased significantly by 9% in the pitavastatin group and by 5% in the pravastatin group. Left ventricular ejection fraction (EF) improved significantly from 37% to 42% in the pitavastatin group and from 35% to 39% in the pravastatin group. Although the extent of the EF change was greater in the pitavastatin group (16% vs. 11%) than that in the pravastatin group, no significant difference was observed between the groups (p = 0.386). Exercise capacity, evaluated by the 6-min walking test, improved significantly in the pravastatin group (p < 0.001), but no change was observed in the pitavastatin group (p = 0.371). CONCLUSIONS: Very low dose/low potency pravastatin and high dose/high potency pitavastatin had a beneficial effect on cardiac reverse remodeling and improved systolic function in patients with ischemic CHF. However, only pravastatin significantly improved exercise capacity. These findings suggest that lowering cholesterol too much may not be beneficial for patients with CHF.
Assuntos
LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Isquemia Miocárdica/tratamento farmacológico , Pravastatina/administração & dosagem , Quinolinas/administração & dosagem , Idoso , Biomarcadores/sangue , Regulação para Baixo , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/fisiopatologia , Pravastatina/efeitos adversos , Estudos Prospectivos , Quinolinas/efeitos adversos , Recuperação de Função Fisiológica , República da Coreia , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
BACKGROUND: Immature platelet fraction (IPF, %) is a measure of reticulated platelets (RPs), which represents the state of thrombopoiesis. The IPF is obtained from an automated hematology analyzer as one of the platelet parameters. This study was performed to establish reference intervals of IPF and its cut-off values for the differential diagnosis of thrombocytopenia. METHODS: Blood samples from 2,039 healthy individuals (1,161 males, 878 females) were obtained to establish reference intervals. The patient group included patients with idiopathic thrombocytopenic purpura (ITP) (N=150) and aplastic anemia (AA) (N=51) with platelet counts of less than 100×10(9)/L. We evaluated the reliability of the IPF measurements, the reference intervals, and cut-off value for the diagnosis of ITP. RESULTS: The reference intervals of IPF were 0.5-3.2% in males and 0.4-3.0% in females (95% confidence interval). The median IPF% of ITP and AA were 7.7% (range, 1.0-33.8%) and 3.5% (range, 0.6-12.9%), respectively. Statistical analysis revealed a significant difference between the IPF% of ITP and AA (P<0.0001). The cut-off value of IPF for differentiating ITP from AA was 7.3% with a sensitivity and specificity of 54.0% and 92.2%, respectively. CONCLUSIONS: A rapid and inexpensive automated measurement of IPF can be integrated as a standard parameter to evaluate the thrombopoietic state of the bone marrow. This study determined the reference intervals of IPF from a large population of healthy individuals, including children. Further studies are needed to establish the clinical utility of IPF.
Assuntos
Anemia Aplástica/diagnóstico , Contagem de Plaquetas/normas , Púrpura Trombocitopênica Idiopática/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Fatores SexuaisRESUMO
BACKGROUND: The study objective was to assess the efficacy of 16-slice multidetector row computed tomography (MDCT) in estimating residual stenosis and successful reperfusion after thrombolysis in patients with ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 31 patients with STEMI underwent MDCT scanning within 6 h (mean 4.6+/-1.1) after thrombolysis and the results for detection of significant residual stenosis and distal flow of the infarct-related artery were compared with those from conventional coronary angiography (CCAG) performed within 24 h (mean 12.1+/-5.6) after the MDCT scan. Successful reperfusion was defined as Thrombolysis In Myocardial Infarction flow 2 or 3 on CCAG and full contrast enhancement of the distal artery landmarks on MDCT. A final analysis was performed using 24 patients (312 segments). MDCT had a positive predictive value of 73.3% and a negative predictive value of 95.1% for detecting significant residual stenosis. It accurately estimated 17 of 18 patients (94.4%) with successful reperfusion and 5 of 6 (83.3%) with failed reperfusion on the basis of comparison with CCAG. CONCLUSIONS: MDCT demonstrated high accuracy not only for the detecting residual stenosis, but also for assessing successful reperfusion after thrombolytic therapy in patients with STEMI.