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1.
Oncogenesis ; 8(9): 47, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467265

RESUMO

Since publication of the original article, the authors have noticed that there were errors in the labelling of Figures 6D and 6E. The correct figure and its legend are reproduced here. The authors wish to apologise for any inconvenience caused.

2.
Oncogenesis ; 6(11): e391, 2017 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-29155418

RESUMO

This corrects the article DOI: 10.1038/oncsis.2017.87.

3.
Oncogenesis ; 6(10): e389, 2017 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-28991261

RESUMO

Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2), epithelial cell-specific regulators of alternative splicing, are downregulated during the epithelial-mesenchymal transition (EMT). These factors have roles in tumor progression and metastasis in some cancers; however, their expression and function in ovarian cancer (OC) remain unclear. We found that ESRP1 and ESRP2 mRNAs were expressed at higher levels in OC cells than in immortalized ovarian surface epithelial (IOSE) cells, and confirmed their overexpression in OC tissues at the protein level. The Cancer Genome Atlas (TCGA) data analysis revealed frequent gene amplification of ESRP1 in OC tissues; however, we detected no significant correlation between ESRP1 gene copy number and gene expression in OC cells. Importantly, expression of ESRP1 and ESRP2 was inversely correlated with DNA methylation in OC cells, and ESRP2 overexpression in OC tissues was significantly associated with DNA hypomethylation. Notably, survival analysis using TCGA data from 541 OC tissues revealed that high ESRP1 expression was significantly associated with shorter 5-year survival of patients. Ectopic ESRP1 expression in mesenchymal OC cells promoted cell proliferation but suppressed cell migration. Furthermore, we found that ESRP1 drives a switch from mesenchymal to epithelial phenotype characterized by reduced cell migration in association with induction of epithelial cell-specific variant of CD44 and ENAH. Taken together, our findings suggest that an epigenetic mechanism is involved in ESRP1 overexpression, and that ESRP1 has a role in OC progression.

4.
Mol Psychiatry ; 22(10): 1473-1482, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28138157

RESUMO

Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1f/f; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca2+/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1f/f; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.


Assuntos
Transtorno Bipolar/enzimologia , Transtorno Bipolar/genética , Fosfolipase C gama/metabolismo , Prosencéfalo/enzimologia , Animais , Transtorno Bipolar/parasitologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Hipocampo/enzimologia , Hipocampo/metabolismo , Camundongos , Plasticidade Neuronal/fisiologia , Neurônios/enzimologia , Neurônios/metabolismo , Fosfolipase C gama/deficiência , Fosfolipase C gama/genética , Prosencéfalo/patologia , Células Piramidais/metabolismo , Receptor trkB/metabolismo , Receptores de Dopamina D1 , Sinapses/enzimologia , Sinapses/patologia , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/metabolismo
5.
Transl Psychiatry ; 6: e721, 2016 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-26812042

RESUMO

Internet gaming disorder (IGD) leading to serious impairments in cognitive, psychological and social functions has gradually been increasing. However, very few studies conducted to date have addressed issues related to the event-related potential (ERP) patterns in IGD. Identifying the neurobiological characteristics of IGD is important to elucidate the pathophysiology of this condition. P300 is a useful ERP component for investigating electrophysiological features of the brain. The aims of the present study were to investigate differences between patients with IGD and healthy controls (HCs), with regard to the P300 component of the ERP during an auditory oddball task, and to examine the relationship of this component to the severity of IGD symptoms in identifying the relevant neurophysiological features of IGD. Twenty-six patients diagnosed with IGD and 23 age-, sex-, education- and intelligence quotient-matched HCs participated in this study. During an auditory oddball task, participants had to respond to the rare, deviant tones presented in a sequence of frequent, standard tones. The IGD group exhibited a significant reduction in response to deviant tones compared with the HC group in the P300 amplitudes at the midline centro-parietal electrode regions. We also found a negative correlation between the severity of IGD and P300 amplitudes. The reduced amplitude of the P300 component in an auditory oddball task may reflect dysfunction in auditory information processing and cognitive capabilities in IGD. These findings suggest that reduced P300 amplitudes may be candidate neurobiological marker for IGD.


Assuntos
Comportamento Aditivo/fisiopatologia , Encéfalo/fisiopatologia , Potenciais Evocados Auditivos/fisiologia , Internet , Processos Mentais/fisiologia , Jogos de Vídeo , Adulto , Potenciais Evocados P300/fisiologia , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Índice de Gravidade de Doença , Análise e Desempenho de Tarefas , Adulto Jovem
6.
Osteoporos Int ; 27(2): 635-42, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26329100

RESUMO

UNLABELLED: This study investigated the association between lipid profiles and insulin resistance and bone mineral content (BMC) in Korean adolescents and found that BMC was inversely associated with triglyceride (TG) and homeostasis model assessment of insulin resistance (HOMA-IR). This association did not differ according to obesity status in either boys or girls. INTRODUCTION: To prevent future osteoporosis, it is important to identify factors that affect bone health in adolescents as well as adults. This study aimed to examine the association between lipid profiles and insulin resistance and BMC in Korean adolescents. METHODS: Data from 706 boys and 621 girls, who participated in the Korea National Health and Nutrition Examination Survey from 2008 to 2011, were analyzed. Lipid profiles were measured, and HOMA-IR was calculated to assess insulin resistance. BMC was measured for the total femur, femur neck, and lumbar spine by using whole-body dual-energy X-ray absorptiometry (DXA). RESULTS: TG level and HOMA-IR were negatively correlated with BMC at all three sites in boys. In girls, TG level showed a negative correlation with BMC at the femur neck and lumbar spine, and HOMA-IR was negatively associated with BMC at the femur neck only. These inverse associations did not differ according to obesity status in either sex. Adjusted means of BMC at the three sites in boys tended to decrease in the higher tertile groups of TG and HOMA-IR, and the adjusted means of BMC for the total femur in girls tended to decrease in the higher tertile groups of TG and HOMA-IR. CONCLUSIONS: BMC was inversely associated with TG and HOMA-IR in Korean adolescents, and this association was more pronounced in boys. This association did not differ according to obesity status in either sex.


Assuntos
Densidade Óssea/fisiologia , Resistência à Insulina/fisiologia , Lipídeos/sangue , Adolescente , Antropometria/métodos , Criança , Feminino , Homeostase/fisiologia , Humanos , Estilo de Vida , Masculino , Avaliação Nutricional , Inquéritos Nutricionais , Obesidade/sangue , Obesidade/fisiopatologia , Caracteres Sexuais , Triglicerídeos/sangue
7.
Transl Psychiatry ; 5: e628, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26327686

RESUMO

Despite that Internet gaming disorder (IGD) shares clinical, neuropsychological and personality characteristics with alcohol use disorder (AUD), little is known about the resting-state quantitative electroencephalography (QEEG) patterns associated with IGD and AUD. Therefore, this study compared the QEEG patterns in patients with IGD with those in patients with AUD to identify unique neurophysiological characteristics that can be used as biomarkers of IGD. A total of 76 subjects (34 with IGD, 17 with AUD and 25 healthy controls) participated in this study. Resting-state, eyes-closed QEEGs were recorded, and the absolute and relative power of brains were analyzed. The generalized estimating equation showed that the IGD group had lower absolute beta power than AUD (estimate = 5.319, P < 0.01) and the healthy control group (estimate = 2.612, P = 0.01). The AUD group showed higher absolute delta power than IGD (estimate = 7.516, P < 0.01) and the healthy control group (estimate = 7.179, P < 0.01). We found no significant correlations between the severity of IGD and QEEG activities in patients with IGD. The current findings suggest that lower absolute beta power can be used as a potential trait marker of IGD. Higher absolute power in the delta band may be a susceptibility marker for AUD. This study clarifies the unique characteristics of IGD as a behavioral addiction, which is distinct from AUD, by providing neurophysiological evidence.


Assuntos
Transtornos Relacionados ao Uso de Álcool/fisiopatologia , Comportamento Aditivo/fisiopatologia , Encéfalo/fisiopatologia , Eletroencefalografia , Internet , Jogos de Vídeo , Adulto , Humanos , Masculino , Descanso , Índices de Gravidade do Trauma , Adulto Jovem
8.
J Wound Care ; 24(7): 326-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26198555

RESUMO

OBJECTIVE: Infection is the second most common cause of graft loss after skin grafting. Cutimed Sorbact is a range of dressings coated with a hydrophobic fatty acid that irreversibly binds to the bacterial surface and mechanically removes bacteria from the wound. The dressing is a hydrogel-impregnated material, which prevents wounds from drying. Here, we report on cases in which we used the gel instead of the widely used petrolatum gauze or paraffin gauze in a tie-over dressing for the fixation of grafted skin. METHOD: Patients treated for skin grafting between March 2013 and July 2013 were treated with the hydrogel-impregnated dressings and a tie over dressing. The wounds were opened five days after treatment. RESULTS: In total seven patients were treated with an age range of 23-86 years old. No infections were seen and the method was effective regardless of wound size, the thickness of the skin harvested and condition of the defect. CONCLUSION: Using this hydrogel-impregnated dressings, provide antibacterial and moisturising effects simultaneously, which a petrolatum or paraffin gauze cannot provide. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest to declare.


Assuntos
Curativos Hidrocoloides , Transplante de Pele , Infecção da Ferida Cirúrgica/prevenção & controle , Cicatrização/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos Graxos , Feminino , Géis , Humanos , Masculino , Pessoa de Meia-Idade , Parafina , Vaselina , Resultado do Tratamento
9.
Dis Esophagus ; 27(8): 798-801, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24152165

RESUMO

Two recent genome-wide association studies have identified that the rs2274223 single-nucleotide polymorphism inphospholipase C epsilon 1 and the single-nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high-resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.08-3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR=0.71, 95% CI=0.52-0.97) and no significant association in the older group (OR=1.19, 95% CI=0.87-1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteínas de Membrana Transportadoras/genética , Fosfoinositídeo Fosfolipase C/genética , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Carcinoma de Células Escamosas do Esôfago , Feminino , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , República da Coreia , Risco
10.
J Obstet Gynaecol ; 33(2): 160-2, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23445139

RESUMO

The safety of domperidone in pregnancy remains unknown. Therefore, the study aimed to prospectively evaluate the fetal outcomes of women who were taking domperidone during pregnancy. In a prospective cohort study design, 120 1st- trimester pregnant women who were taking domperidone for controlling gastrointestinal tract symptoms and 212 age-matched pregnant women not exposed to any potential teratogenic agent, were followed-up until delivery. In the case group, domperidone was indicated for control of functional gastrointestinal disorders in 59.2%, the maximum dose was 30 mg/day and exposure occurred between 2(+4) and 20 weeks' gestation. Fetal outcomes including gestational age at birth, birth weight and length, head circumference at birth, and 1- and 5-min Apgar score were similar in the two study groups. There were three babies born with malformations in each group (OR = 0.6; 95% CI 0.1, 2.8). In conclusion, domperidone does not appear to be a major human teratogen. However, our findings require further confirmation in larger studies.


Assuntos
Antieméticos/efeitos adversos , Peso ao Nascer/efeitos dos fármacos , Domperidona/efeitos adversos , Desenvolvimento Fetal/efeitos dos fármacos , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos
11.
Cell Mol Biol (Noisy-le-grand) ; Suppl.58: OL1780-5, 2012 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-23046871

RESUMO

The Forkhead box O (FoxO) transcription factors, including FoxO1, FoxO3a, FoxO4, and FoxO6, are implicated in the regulation of cell apoptosis and survival. Here, we examined the role of FoxO transcription factors and the involvement of the PI3K/Akt and mitogen-activated protein kinase (MAPK) pathways in neuronal apoptosis in the brain of the silkworm Bombyx mori following starvation. Starvation inhibited cell proliferation and induced apoptosis through caspase-3 activation. The level of phosphorylated kinase Akt increased when the animals ceased feeding. Starvation conditions reduced extracellular-signal-regulated kinase phosphorylation but increased both c-Jun N-terminal kinase and p38 (MAPK) phosphorylation. FoxO1 and FoxO3a were simultaneously localized in the nuclei. These results provide new insights into the process of apoptosis of brain neurons through the involvement of FoxO transcription factors following starvation of insect species.


Assuntos
Apoptose , Bombyx/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Caspase 3/metabolismo , Núcleo Celular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neurônios/enzimologia , Neurônios/metabolismo , Fosforilação , Transdução de Sinais , Inanição , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Water Sci Technol ; 65(10): 1789-94, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22546793

RESUMO

Pressure retarded osmosis (PRO) is a novel membrane process to produce energy. PRO has the potential to convert the osmotic pressure difference between fresh water (i.e. river water) and seawater to electricity. Moreover, it can recover energy from highly concentrated brine in seawater desalination. Nevertheless, relatively little research has been undertaken for fundamental understanding of the PRO process. In this study, the characteristics of the PRO process were examined using a proof-of-concept device. Forward osmosis (FO), reverse osmosis (RO), and nanofiltration (NF) membranes were compared in terms of flux rate and concentration polarization ratio. The results indicated that the theoretical energy production by PRO depends on the membrane type as well as operating conditions (i.e. back pressure). The FO membrane had the highest energy efficiency while the NF membrane had the lowest efficiency. However, the energy production rate was low due to high internal concentration polarization (ICP) in the PRO membrane. This finding suggests that the control of the ICP is essential for practical application of PRO for energy production.


Assuntos
Água Doce/química , Membranas Artificiais , Modelos Químicos , Centrais Elétricas/instrumentação , Água do Mar/química , Eletricidade , Hidrodinâmica , Osmose , Pressão Osmótica , Energia Renovável
13.
Histol Histopathol ; 26(10): 1231-41, 2011 10.
Artigo em Inglês | MEDLINE | ID: mdl-21870327

RESUMO

Recently, the clonal integration of a new human polyomavirus (Merkel cell polyomavirus or MCPyV) has been reported in Merkel cell carcinoma (MCC). In order to investigate the presence of MCPyV in small cell carcinomas (SCCs) and small round cell tumors (SRCTs), we collected formalin-fixed paraffin-embedded tissue specimens including 14 MCCs, 24 SCCs, 7 Ewing sarcoma/primitive neuroectodermal tumors (ES/PNETs) and 5 neuroblastomas. We also collected specimens of other cancers including 12 malignant melanomas, 10 breast, 10 ovarian and 20 gastric cancers. We used 3 primer sets for which the sequences were previously published (LT1, LT3, and VP1) and 3 newly designed primer sets (LT1-1, LT1-1a, and LT3a). Quantitative real-time PCR was also performed with the LTq primer set. Nested PCR using the LT3a primer set detected more cases of MCPyV infection in MCC. In total, 12 of 14 (85.7%) MCC cases were positive for MCPyV by PCR, which was consistent with published data. Some SCC specimens were also positive for MCPyV (37.5%) by PCR. PCR products from MCC and SCC cases showed premature truncation and frameshift mutation. Furthermore, one case of ES/PNET and one gastric carcinoma showed MCPyV DNA. However, MCPyV DNA and transcript were only detected in MCCs with quantitative real-time PCR analysis. In addition, 11 of 13 (84.6%) MCC cases and 6 of 23 (26.1%) SCC cases showed immunoreactivity with monoclonal antibodies against MCPyV large T-antigen. Considering both PCR and IHC results, MCPyV was detected in all MCCs tested. The presence of MCPyV in all MCC cases tested and in some SCC cases suggests that MCPyV may be involved in the malignant transformation.


Assuntos
Carcinoma de Célula de Merkel/virologia , Carcinoma de Células Pequenas/virologia , Poliomavírus das Células de Merkel/isolamento & purificação , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/patologia , Carcinoma de Células Pequenas/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/patologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/patologia
14.
Dis Esophagus ; 24(8): 596-600, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21595775

RESUMO

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of esophageal cancer (EC) in South Korea. We conducted a case-control study including 340 patients with EC, and 1700 controls. P53 codon 72 polymorphism was determined by real-time polymerase chain reaction. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in EC were 39.4%, 45.6%, and 15.0%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively. Compared with the Arg/Arg genotype, the OR of the Arg/Pro genotype was 1.09 (95% CI = 0.85-1.41) and that of the Pro/Pro genotype was 1.47 (95% CI = 1.02-2.11) for EC overall. When adjusted by age, gender, and smoking status, the OR of the Arg/Pro genotype was 1.24 (95% CI = 0.92-1.67) and that of the Pro/Pro genotype was 1.77 (95% CI = 1.15-2.74) for EC overall. In never-smokers and ever-smokers, the OR of the Arg/Pro genotype was 0.59 (95% CI = 0.37-0.95) and 1.39 (95% CI = 1.00-1.91), respectively, and there was a significant difference in the homogeneity test (P= 0.011). We observed that the p53 codon 72 polymorphism was associated with an increased risk of EC in this Korean case-control study, and smoking status modified the association between the p53 codon 72 polymorphism and the risk of EC.


Assuntos
Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Genes p53 , Polimorfismo Genético , Fumar , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia/epidemiologia , Fatores de Risco
15.
Acta Psychiatr Scand ; 123(5): 376-86, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21175552

RESUMO

OBJECTIVE: Obsessive-compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD. METHOD: Twenty unmedicated patients with OCD and 20 age-, sex-, and IQ-matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task. RESULTS: Compared with controls, patients with OCD showed increased ventral striatal activation in the no-loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no-gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation. CONCLUSION: These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.


Assuntos
Gânglios da Base , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo , Córtex Pré-Frontal , Adulto , Antecipação Psicológica , Atenção , Gânglios da Base/patologia , Gânglios da Base/fisiopatologia , Mapeamento Encefálico , Emoções , Feminino , Humanos , Masculino , Motivação , Transtorno Obsessivo-Compulsivo/patologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Recompensa
16.
Phytomedicine ; 17(10): 800-10, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20382513

RESUMO

Diabetic nephropathy (DN) characterized as nephrotic syndrome and diffuse glomerulosclerosis can cause renal failure and end-stage kidney disease. Expansion of mesangial matrix around capillaries in the kidney glomeruli is a prominent feature of DN. This study investigated whether licorice extracts inhibited mesangial cell (MC) proliferation and matrix accumulation induced by high glucose (HG). Human renal MC were cultured in media containing 5.5 mM glucose plus 27.5 mM mannitol as an osmotic control or 33 mM glucose for 3 d in the presence of water or ethanol extracts from raw licorice (LW, LE) or roasted licorice (RLW, RLE). Non-polar components including glycyrrhetic acid were elevated during licorice roasting, whereas polar components soluble in water extracts were diminished. Exposure of cells to HG caused significant increases in collagen IV secretion and connective tissue growth factor (CTGF) expression, which was appeased by RLW and RLE at transcriptional levels. The inhibitory potency was high in the order of RLE > or = RLW > or = LE > > LW. Non-polar glycyrrhetic acid but not glycyrrhizin retarded HG-stimulated mesangial matrix deposition through diminishing CTGF expression. In addition, RLW and RLE but not LW modulated membrane type matrix metalloproteinase-1 (MT-1 MMP) expression, MMP-2 activity and tissue inhibitor of MMP-2 (TIMP-2), which facilitated the degradation of mesangial matrix. Furthermore, the augmented expression of CTGF and TIMP-2 in HG-exposed cells was mediated by Akt activation and TGF-beta/Smad signaling through PKCbeta2-responsive signaling pathways. However, HG-down-regulated MT-1 MMP expression was independent of activation of ERK1/2 and Akt when using their inhibitors of DB98059 (ERK1/2) and LY294002 (Akt) alone or in combination. These results demonstrate that extracts from roasted licorice may be highly potent therapeutic agents for the prevention and treatment of mesangial fibrosis and glomerulosclerosis leading to diabetes nephropathy due to longstanding diabetes mellitus.


Assuntos
Matriz Extracelular , Mesângio Glomerular/efeitos dos fármacos , Glucose/farmacologia , Glycyrrhiza/química , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Sequência de Bases , Western Blotting , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Primers do DNA , Ativação Enzimática , Mesângio Glomerular/enzimologia , Mesângio Glomerular/patologia , Humanos , Hiperplasia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Allergol. immunopatol ; 35(6): 239-242, nov. 2007. tab
Artigo em En | IBECS | ID: ibc-058247

RESUMO

Background: The aim of the study was to report the maternal and fetal outcomes of women with respiratory illnesses who were treated with inhaled fluticasone during pregnancy. Material and methods: We identified 12 cases treated with inhaled fluticasone during pregnancy out of women who received obstetric and teratogen-risk evaluation at the Korean Motherisk Program. A detailed medical and obstetric history was obtained and cases were followed-up until either spontaneous or voluntary pregnancy termination or delivery occurred. Results: None of the participants had any obstetric complication. However, in addition to fluticasone, most of the 12 cases were simultaneously exposed to a variety of medications. There were 3 abortions (one spontaneous and 2 requested by the patients arguing personal reasons). Live born babies without any evidence of major congenital malformations included 8 singleton babies and 2 twins. Of them, 3 babies were born prematurely. Conclusions: Our results are in agreement with previous large studies where no increased rate of adverse outcomes was reported with the use of inhaled corticosteroids during pregnancy


Objetivo: la finalidad de este estudio fue conocer la evolución de la madre y el feto de aquellas mujeres afectas de enfermedad respiratoria que fueron tratadas con fluticasona inhalada durante el embarazo. Material y métodos: se estudiaron 12 mujeres que durante el embarazo estaban en tratamiento con fluticasona inhalada, a las que se evaluó el riesgo teratógeno de acuerdo con el Programa Coreano de Riesgo Materno. Se obtuvo una historia clínica y obstétrica detallada y los casos se siguieron hasta la terminación espontánea o voluntaria del embarazo. Resultados: ninguna de las pacientes tuvo complicaciones obstétricas. Sin embargo, además de la fluticasona, la mayoría de las pacientes estuvieron expuestas simultáneamente a una variedad de medicamentos. Hubo 3 abortos (uno espontáneo y 2 a requerimiento de las pacientes que arguyeron razonas personales). Los recién nacidos vivos (de ellos, dos fueron gemelos y tres prematuros) no mostraron ninguna evidencia de malformaciones congénitas. Conclusiones: estos resultados están de acuerdo con estudios previos amplios en los que no se observó un incremento de efectos adversos por el uso de corticosteroides inhalados durante el embarazo


Assuntos
Feminino , Gravidez , Adulto , Humanos , Beclometasona/efeitos adversos , Nebulizadores e Vaporizadores , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/imunologia , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Teratologia/métodos , Asma/complicações , Asma/diagnóstico , Desenvolvimento Embrionário e Fetal , Desenvolvimento Embrionário e Fetal/fisiologia
18.
Neuroscience ; 133(4): 1007-19, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15964489

RESUMO

The action of riluzole, a neuroprotective drug, on cloned delayed rectifier K+ channels (Kv1.5 and Kv3.1) was examined using the whole-cell patch-clamp technique. Riluzole reversibly inhibited Kv1.5 currents in a concentration-dependent manner with an IC50 of 39.69+/-2.37 microM. G-protein inhibitors (pertussis toxin and GDPbetaS) did not prevent this inhibition of riluzole on Kv1.5. No voltage-dependent inhibition by riluzole was found over the voltage range in which channels are fully activated. Riluzole shifted the steady-state inactivation curves of Kv1.5 in a hyperpolarizing direction in a concentration-dependent manner. It accelerated the deactivation kinetics of Kv1.5 in a concentration dependent-manner, but had no effect on the steady-state activation curve. Riluzole exhibited a use-independent inhibition of Kv1.5. The effects of riluzole on Kv3.1, the Shaw-type K+ channel were also examined. Riluzole caused a concentration-dependent inhibition of Kv3.1 currents with an IC50 of 120.98+/-9.74 microM and also shifted the steady-state inactivation curve of Kv3.1 in the hyperpolarizing direction. Thus, riluzole inhibits both Kv1.5 and Kv3.1 currents in a concentration-dependent manner and interacts directly with Kv1.5 by preferentially binding to the inactivated and to the closed states of the channel.


Assuntos
Potenciais da Membrana/efeitos dos fármacos , Inibição Neural/efeitos dos fármacos , Neuropeptídeos/fisiologia , Fármacos Neuroprotetores/farmacologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/fisiologia , Riluzol/farmacologia , Animais , Células CHO , Cricetinae , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Interações Medicamentosas , Estimulação Elétrica/métodos , Guanosina Difosfato/análogos & derivados , Guanosina Difosfato/farmacologia , Concentração Inibidora 50 , Cinética , Canal de Potássio Kv1.5 , Potenciais da Membrana/fisiologia , Potenciais da Membrana/efeitos da radiação , Técnicas de Patch-Clamp/métodos , Toxina Pertussis/farmacologia , Canais de Potássio Shaw , Tionucleotídeos/farmacologia
19.
Eur J Cancer Prev ; 14(2): 175-9, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15785322

RESUMO

It is still unclear whether the exposure to electromagnetic fields (EMFs) generated by mobile phone radiation is directly linked to cancer. We examined the biological effects of an EMF at 835 MHz, the most widely used communication frequency band in Korean CDMA mobile phone networks, on bacterial reverse mutation (Ames assay) and DNA stability (in vitro DNA degradation). In the Ames assay, tester strains alone or combined with positive mutagen were applied in an artificial mobile phone frequency EMF generator with continuous waveform at a specific absorption rate (SAR) of 4 W/kg for 48 h. In the presence of the 835-MHz EMF radiation, incubation with positive mutagen 4-nitroquinoline-1-oxide and cumene hydroxide further increased the mutation rate in Escherichia coli WP2 and TA102, respectively, while the contrary results in Salmonella typhimurium TA98 and TA1535 treated with 4-nitroquinoline-1-oxide and sodium azide, respectively, were shown as antimutagenic. However, these mutagenic or co-mutagenic effects of 835-MHz radiation were not significantly repeated in other relevant strains with same mutation type. In the DNA degradation test, the exposure to 835-MHz EMF did not change the rate of degradation observed using plasmid pBluescript SK(+) as an indicator. Thus, we suggest that 835-MHz EMF under the conditions of our study neither affected the reverse mutation frequency nor accelerated DNA degradation in vitro.


Assuntos
Telefone Celular , Dano ao DNA , Campos Eletromagnéticos/efeitos adversos , 4-Nitroquinolina-1-Óxido/toxicidade , Derivados de Benzeno/toxicidade , DNA Bacteriano , Escherichia coli/genética , Testes de Mutagenicidade , Mutagênicos/toxicidade , Mutação , Plasmídeos , Salmonella typhimurium/genética , Azida Sódica/toxicidade
20.
Oral Microbiol Immunol ; 20(1): 51-5, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15612947

RESUMO

The present study has been performed to evaluate Porphyromonas gingivalis heat shock protein (HSP) 60 as a candidate vaccine to protect against multiple putative periodontopathic bacteria. Mouse anti-P. gingivalis HSP antisera demonstrated the elevated IgG antibody titers against the multiple bacteria tested and cross-reacted with heat-induced bacterial proteins of the target bacteria. The antisera also demonstrated a significantly higher opsonophagocytosis function against all the target bacteria than the control sera (P<0.01). We concluded that P. gingivalis HSP 60 could potentially be developed as a vaccine against multiple periodontopathic bacteria.


Assuntos
Vacinas Bacterianas/imunologia , Chaperonina 60/imunologia , Soros Imunes/imunologia , Doenças Periodontais/prevenção & controle , Porphyromonas gingivalis/imunologia , Animais , Especificidade de Anticorpos/imunologia , Western Blotting , Reações Cruzadas/imunologia , Avaliação Pré-Clínica de Medicamentos , Camundongos , Doenças Periodontais/microbiologia
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