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1.
Curr Opin Neurobiol ; 61: 65-72, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32092528

RESUMO

Nearly half (45%) of the human genome is composed of transposable elements, or 'jumping genes'. Since Barbara McClintock's original discovery of transposable elements in 1950, we have come to appreciate that transposable element mobilization is a major driver of evolution that transposons are active in the germline and the soma, and that transposable element dysregulation is causally associated with many human disorders. In the present review, we highlight recent studies investigating transposable element activation in the adult brain and in the context of neurodegeneration. Collectively, these studies contribute to a greater understanding of the frequency of complete retrotransposition in the adult brain as well as the presence of transposable element-derived RNA and protein in brain and fluids of patients with neurodegenerative disorders. We discuss therapeutic opportunities and speculate on the larger implications of transposable element activation in regard to current hot topics in the field of neurodegeneration.

2.
Pediatr Nephrol ; 35(3): 441-446, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31811538

RESUMO

BACKGROUND: The prevalence of hyperuricemia is increasing in adults, while the prevalence among adolescents is seldom reported. METHODS: A cross-sectional survey by multistage, stratified sampling method was carried out in Shandong Province during 2017-2018. A total of 9371 adolescents aged from 13 to 19 years were randomly sampled and analyzed in this survey. RESULTS: The overall mean serum uric acid (sUA) concentration was 6.08 ± 1.57 mg/dL and overall hyperuricemia prevalence was 25.4% and 60.5% (when hyperuricemia was defined as sUA ≥ 7 mg/dL or ≥ 5.5 mg/dL). Prevalence were 42.3% (male) and 8.0% (female) when limit was 7 mg/dL and prevalence were 82.1% (male) and 38.4% (female) when limit was 5.5 mg/dL. Male gender, increased body mass index, increased waist circumstance, increased triglycerides, increased fasting blood glucose, increased systolic blood pressure, decreased estimated glomerular filtration rate, and positive family gout history were associated with the enhanced risk of hyperuricemia according to univariate and/or multivariate logistic regression analysis. Food intake frequency of carbonate beverage, mutton, and other kinds varied between hyperuricemia adolescents and normal sUA ones. CONCLUSIONS: The studied adolescent population showed sUA level and hyperuricemia prevalence which are even higher than those of adults in China. The epidemic of youth hyperuricemia may pose a future threat of gout attacks and other hyperuricemia-related diseases, which alarms the public, health professionals and health policy makers to prepare the future health challenges.

3.
Biomed Pharmacother ; 121: 109660, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31733581

RESUMO

Topiroxostat is a selective xanthine oxidoreductase (XOR) inhibitor for the management of hyperuricemia in patients with or without gout. In this work, we aim to employ the physiologically based pharmacokinetic (PBPK) model with the drug-target residence time model to predict and characterize both the pharmacokinetics (PK) and pharmacodynamics (PD) of topiroxostat in humans. The plasma concentration-time profile of topiroxostat was simulated based on drug properties and human physiology parameters. The predictive power of this PBPK model was then demonstrated by comparison of stimulated to observed pharmacokinetic parameters. The utility of the model was further demonstrated through predicting the oral absorption and disposition characteristics of topiroxostat in humans. Finally, by combining the PBPK model and the drug-target residence time model, we successfully predicted the target occupancy and built the relationship between PK and PD using in vitro, in vivo and in silico information. The results showed that topiroxostat exhibited significant in vivo pharmacological activity even after the complete clearance of this drug from the liver (target site), which may be due to the long residence time of the binary topiroxostat-XOR complex. This work may be helpful to guide future investigations of topiroxostat and also provides a novel strategy for PK/PD studies.

4.
Medicine (Baltimore) ; 98(38): e16988, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567935

RESUMO

RATIONALE: Peripherally inserted central catheters (PICC), normally located at the lower 1/3rd of the superior vena cava (SVC) and cavo-atrial junction, are commonly used in cancer patients. Persistent left superior vena cava (PLSVC) is a vascular anomaly, in patients with which seldom research was reported about PICC implanted. After obtaining written informed consent, we present a case where two successful insertions of PICC were performed in a 50-year-old female patient with PLSVC and right SVC. PATIENTS CONCERNS: The patient had ovarian cancer and was admitted for chemotherapy using PICC. DIAGNOSES: Ovarian cancer and PLSVC. INTERVENTIONS AND OUTCOMES: Following insertion of PICC in PLSVC, thrombosis developed. PICC was removed after routine anticoagulation therapy. Owing to tumor recurrence, a second PICC was inserted in the right SVC without any complications. LESSONS: PICC insertion in PLSVC for chemotherapy may be associated with an increased risk of deep venous thrombosis of the upper extremity. A right catheter insertion in patient with PLSVC was preferred.


Assuntos
Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Malformações Vasculares/complicações , Veia Cava Superior/anormalidades , Trombose Venosa/diagnóstico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Braço , Cateterismo Periférico/efeitos adversos , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Neoplasias Ovarianas/complicações , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia
5.
Eur J Pharmacol ; 865: 172663, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31539553

RESUMO

Rheumatoid arthritis (RA) is a common immune-mediated chronic inflammatory joint disease of unknown etiology. While tumor necrosis factor-α(TNF-α) blockers have proven to be a beneficial treatment option for many patients, not all respond to such treatments. In the present study, we investigate the role of the recently discovered zinc-sensing G protein-couple receptor GPR39. To our knowledge, this study is the first to investigate the role of GPR39 in the context of RA using human fibroblast-like synoviocytes (FLS). We found that agonism of GPR39 using its specific agonist TC-G 1008 significantly ameliorated important markers of RA, including oxidative stress, mitochondrial dysfunction, expression of proinflammatory cytokines including interleukin-1ß (IL-1ß), IL-6, and monocyte chemoattractant protein 1 (MCP-1), and secretion of key matrix metalloproteinases (MMPs) including MMP-1, MMP-3 and MMP-13. Furthermore, we demonstrate that these may be mediated via the Janus-kinase (JNK), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) cellular signaling pathways. Our findings demonstrate for the first time the potential of GPR39 to mediate synovial inflammation, pannus invasion, and enzymatic degradation of articular extracellular matrix.

6.
Arthritis Res Ther ; 21(1): 200, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477161

RESUMO

BACKGROUND: Low doses of febuxostat or benzbromarone are widely used in Asian countries, but lacking studies to compare the efficacy and safety of the two urate-lowering drugs. METHODS: To compare the efficacy and safety of low-dose febuxostat with low-dose benzbromarone in patients with primary gout, a randomized controlled, open-label trial was performed among male patients with primary gout for urate-lowering therapy (ULT) in a dedicated gout clinic in China. Randomization was carried out by a third-party institution according to random number table. Patients were randomly assigned 1:1 to febuxostat group (Feb group) (20 mg daily) or benzbromarone group (Ben group) (25 mg daily) and treated for 12 weeks. General information and biochemical data were collected at baseline and at every visit monthly. Clinical characteristics before and after the ULT were analyzed in the two groups by SPSS and EmpowerStats software. RESULTS: Two hundred forty patients were enrolled and randomized in the two groups, with 214 patients completing 12 weeks' ULT (105 in the Feb group and 109 in the Ben group). After 12 weeks, substantial percentages of patients in both Feb and Ben group achieved the target serum uric acid (sUA) (< 360 µmol/L) and serum urate levels were reduced significantly for both groups (Feb 39.5% and 156.83 µmol/L vs. Ben 35.7% and 163.99 µmol/L). Multivariate analysis suggests baseline sUA level and renal function were associated with the outcome of the rate of achieving target sUA (RAT). Sub-group analysis suggests low doses of febuxostat and benzbromarone rendered better RAT for patients with sUA < 540 µmol/L and creatinine clearance rate (Ccr) ≤ 110 mL min-1 1.73 m-2 at baseline. The drugs were well tolerated, and the incidence of gout flares in Feb group was similar with that in Ben group (22.85% vs. 33.94%). CONCLUSION: Overall, febuxostat 20 mg daily and benzbromarone 25 mg daily reduced sUA, and gout patients with sUA level < 540 µmol/L or Ccr ≤ 110 mL min-1 1.73 m-2 at baseline had better chance to achieve target uric acid levels. The current study suggests sUA level and renal function are key factors to consider when recommending low doses of febuxostat and benzbromarone to gout patients. TRIAL REGISTRATION: Registered with ChiCTR, No. ChiCTR1800019352 (retrospectively registered).

7.
Mol Med Rep ; 20(2): 1700-1706, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257543

RESUMO

Neuroblastoma is the fourth most common type of extracranial malignant solid tumor in children. Isatin had been demonstrated to have inhibitory effects on neuroblastoma tumors in vivo and in vitro. The aim of the present study was to investigate the molecular mechanism related to the anti­invasion effect of isatin on SH­SY5Y cells using microarray analysis. The microarray data identified a number of genes to be differentially upregulated or downregulated between isatin­treated cells and untreated controls. A large number of these genes were associated with the mTOR signaling pathway. The differentially expressed genes involved in the mTOR signaling pathway were verified further, as well as their downstream genes associated with autophagy. The results of the present study provided an insight into the potential inhibitory mechanism of isatin on neuroblastoma metastasis.


Assuntos
Antineoplásicos/farmacologia , Isatina/farmacologia , Invasividade Neoplásica/prevenção & controle , Neuroblastoma/tratamento farmacológico , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica/genética , Neuroblastoma/genética , Neuroblastoma/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
8.
Bone ; 120: 239-245, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29653292

RESUMO

The aim of the study was to investigate the association between rs5859 in Sep15, rs1139793 in TrxR2 polymorphisms with the risks of KBD and to detect the expression of AP-1 pathway in KBD subjects and in vitro. 208 KBD and 206 control subjects were included. PCR-Restriction Fragment Length Polymorphism (RFLP), Amplification Refractory Mutation Specific-PCR (ARMS-PCR) and Western Blotting were conducted. The results showed the minor A-allele frequency of rs5859 in KBD was statistically significantly higher than that in the control group (P < 0.05). The cases carrying A-allele had a 2-fold (95%CI: 1.064-3.956) increased risk of developing KBD compared with the G-allele carriers. There was no significant difference in genotype and allele distribution of rs1139793 between KBD patients and controls (P > 0.05). The frequency of the minor A allele of rs5859 was significantly different in Chinese healthy population compared with European, African and American. The frequency of the minor A allele of rs1139793 showed significant difference when compared with African and American. The levels of JunB, JunD, P65 proteins in KBD group were higher than those in control group (P < 0.0001). The expression of JunB, JunD, P65 proteins all increased in tBHP-induced C28/I2 oxidative damage model compared with control group (P < 0.05) and decreased after Se supplementation. Our finding indicated Sep15 is a possible candidate susceptibility gene for KBD. Combined with the in vitro study, our studies reveal novel insights into the mechanism of Se supplementation as an antioxidant via inhibiting the AP-1 signaling pathway in patients with KBD.


Assuntos
Predisposição Genética para Doença , Doença de Kashin-Bek/genética , Polimorfismo de Nucleotídeo Único/genética , Selenoproteínas/genética , Transdução de Sinais , Tiorredoxina Redutase 2/genética , Fator de Transcrição AP-1/metabolismo , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Linhagem Celular , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Grupos Étnicos/genética , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Selênio/farmacologia
9.
Bone ; 117: 15-22, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30153510

RESUMO

OBJECTIVE: Selenium deficiency is a risk factor for Kashin-Beck Disease (KBD), an endemic osteoarthropathy. Although promoter hypermethylation of glutathione peroxidase 3 (GPX3) (a selenoprotein) has been identified in several cancers, little is known about promoter methylation and expression of GPX3 and their relation to selenium in KBD. The present study was thus conducted to investigate this research question. METHODS: Methylation and expressions of GPX3 in whole blood drawn from 288 KBD patients and 362 healthy controls and in chondrocyte cell line were evaluated using methylation-specific PCR and qRT-PCR, respectively. The protein levels of PI3K/Akt/c-fos signaling in the whole blood and chondrocyte cell line were determined with Western blotting. Chondrocytes apoptosis were detected by Hoechst 33342 and Annexin V-FITC/PI staining. RESULTS: GPX3 methylation was increased, GPX3 mRNA was decreased, and protein levels in the PI3K/Akt/c-fos signaling pathway were up-regulated in the whole blood collected from KBD patients as compared with healthy controls. Similar results were obtained for chondrocytes injured by oxidative stress. There was a significant, decreasing trend in GPX3 expression across groups of unmethylation, partial methylation, and complete methylation for GPX3, in sequence. Compared with unmethylation group, protein levels in PI3K/Akt/c-fos pathway were enhanced in partial and complete methylation groups. Treatment of chondrocytes with sodium selenite resulted in reduced methylation and increased expression of GPX3 as well as down-regulated level of PI3K/Akt/c-fos proteins. CONCLUSIONS: The methylation and expression of GPX3 and expression of PI3K/Akt/c-fos pathway are altered in KBD and these changes are reversible by selenium supplementation.


Assuntos
Apoptose/genética , Condrócitos/metabolismo , Condrócitos/patologia , Metilação de DNA/genética , Glutationa Peroxidase/genética , Doença de Kashin-Bek/genética , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Linhagem Celular , Condrócitos/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Feminino , Glutationa Peroxidase/sangue , Humanos , Doença de Kashin-Bek/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Selênio/farmacologia , Transdução de Sinais
10.
Nat Neurosci ; 21(8): 1038-1048, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30038280

RESUMO

Transposable elements, known colloquially as 'jumping genes', constitute approximately 45% of the human genome. Cells utilize epigenetic defenses to limit transposable element jumping, including formation of silencing heterochromatin and generation of piwi-interacting RNAs (piRNAs), small RNAs that facilitate clearance of transposable element transcripts. Here we utilize Drosophila melanogaster and postmortem human brain samples to identify transposable element dysregulation as a key mediator of neuronal death in tauopathies, a group of neurodegenerative disorders that are pathologically characterized by deposits of tau protein in the brain. Mechanistically, we find that heterochromatin decondensation and reduction of piwi and piRNAs drive transposable element dysregulation in tauopathy. We further report a significant increase in transcripts of the endogenous retrovirus class of transposable elements in human Alzheimer's disease and progressive supranuclear palsy, suggesting that transposable element dysregulation is conserved in human tauopathy. Taken together, our data identify heterochromatin decondensation, piwi and piRNA depletion and consequent transposable element dysregulation as a pharmacologically targetable, mechanistic driver of neurodegeneration in tauopathy.


Assuntos
Morte Celular/genética , Elementos de DNA Transponíveis/genética , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Neurônios/patologia , RNA Interferente Pequeno/genética , Tauopatias/genética , Proteínas tau/genética , Doença de Alzheimer/genética , Animais , Restrição Calórica , Drosophila melanogaster , Regulação da Expressão Gênica/genética , Humanos , Atividade Motora , Paralisia Supranuclear Progressiva/genética
11.
Zhongguo Zhong Yao Za Zhi ; 42(5): 852-855, 2017 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-28994525

RESUMO

The Chinese herbal compound formula preparation was made based on theory of Chinese medicine, which was confirmed by long period clinical application, and with multi-compound and multi-target characteristics. During the exploitation process of innovation medicine of Chinese herbal compound formula, selecting and speeding up the research development of drugs with clinical value shall be paid more attention, and as request of rules involved in new drug research and development, the whole process management should be carried out, including project evaluation, manufacturing process determination, establishment of quality control standards, evaluation for pharmacological and toxic effect, as well as new drug application process. This reviews was aimed to give some proposals for pharmacodynamics research methods involved in exploration of Chinese herbal compound formula preparation, including: ①the endpoint criteria should meet the clinical attribution of new drugs; ②the pre-clinical pharmacodynamics evaluation should be carried on appropriate animal models according to the characteristics of diagnosis and therapy of Chinese medicine and observation indexes; ③during the innovation of drug for infants and children, information on drug action conforming to physiological characteristics of infants and children should be supplied, and the pharmacodynamics and toxicology research shall be conducted in immature rats according to the body weight of children. In a summary, the clinical application characteristics are the important criteria for evaluation of pharmacological effect of innovation medicine of Chinese herbal compound formula.


Assuntos
Avaliação Pré-Clínica de Medicamentos/normas , Medicamentos de Ervas Chinesas/farmacologia , Animais , Modelos Animais de Doenças , Humanos , Medicina Tradicional Chinesa , Controle de Qualidade , Ratos
12.
J Vasc Access ; 18(5): 396-401, 2017 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-28777395

RESUMO

INTRODUCTION: This pilot exploratory study aimed to compare the health-related quality of life (HRQOL) among patients diagnosed with different types of cancer receiving peripherally inserted central catheters (PICCs). METHODS: A multicenter cross-section study of cancer patients with PICCs was performed from February 1, 2013 to April 24, 2014. The primary objective of this study was to compare HRQOL in different cancer type patients with PICC. HRQOL was examined based on European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30). Multiple linear regression models were conducted for coping with potential confounding variables. We also examined PICC-related quality of daily life with a self-made questionnaire. RESULTS: Three hundred and fifty-seven cancer patients with PICC completed the survey in nine teaching hospitals. Lung cancer patients with PICC reported the worst dyspnea. Digestive tract cancer patients reported the worst appetite loss. Patients with hematologic malignancy reported the worst emotional, social function, fatigue and financial impact. Breast cancer patients reported better HRQOL. Baseline variables were proven not significant predictors of EORTC QLQ-C30 global health status. In self-made survey, pain after PICC insertion was null or a little in 98.6% of cancer patients. Limitation of upper extremity activity was null or a little in 94.1% of patients. CONCLUSIONS: HRQOL varies in different types of cancer patients with PICC. PICC may have a low impact on cancer patients' HRQOL. Further large sample studies are needed.


Assuntos
Antineoplásicos/administração & dosagem , Cateterismo Venoso Central/instrumentação , Cateterismo Periférico/instrumentação , Cateteres de Demora , Cateteres Venosos Centrais , Neoplasias/tratamento farmacológico , Qualidade de Vida , Administração Intravenosa , Adulto , Idoso , China , Estudos Transversais , Feminino , Hospitais de Ensino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/psicologia , Projetos Piloto , Inquéritos e Questionários
13.
Oncol Rep ; 38(2): 735-744, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28677729

RESUMO

To investigate the role of centromere protein U (CENPU) in human bladder cancer (BCa), CENPU gene expression was evaluated in human BCa tissues. We used real-time quantitative PCR (qPCR) and found that CENPU gene expression in human BCa tissues was higher compared to that observed in cancer-adjacent normal tissues. High CENPU expression was found to be strongly correlated with tumor size and TNM stage. Kaplan-Meier survival analysis indicated that high CENPU levels were associated with reduced survival. We used a lentivirus to silence endogenous CENPU gene expression in the BCa T24 cell line. CENPU knockdown was confirmed by qPCR. Cellomic imaging and BrdU assays showed that cell proliferation was significantly reduced in the CENPU-silenced cells compared to that noted in the control cells. Flow cytometry revealed that in the CENPU-silenced cells the cell cycle was arrested at the G1 phase relative to that in the control cells. In addition, apoptosis was significantly increased in the CENPU-silenced cells. Giemsa staining showed that CENPU-silenced cells, compared to control cells, displayed a significantly lower number of cell colonies. The genome-wide effect of CENPU knockdown showed that a total of 1,274 differentially expressed genes was found, including 809 downregulated genes and 465 upregulated genes. Network analysis by Ingenuity Pathway Analysis (IPA) resulted in 25 distinct signaling pathways, including the top-ranked network: 'Cellular compromise, organismal injury and abnormalities, skeletal and muscular disorders'. In-depth IPA analysis revealed that CENPU was associated with the HMGB1 signaling pathway. qPCR and western blot analysis demonstrated that in the HMGB1 signaling pathway, CENPU knockdown downregulated expression levels of ILB, CXCL8, RAC1 and IL1A. In conclusion, our data may provide a potential pathway signature for therapeutic targets with which to treat BCa.


Assuntos
Centrômero/genética , Proteína HMGB1/genética , Proteínas de Membrana/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/patologia
15.
Anticancer Drugs ; 28(6): 645-653, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28379899

RESUMO

Isatin was reported to possess anticancer activities through its effect on tumor proliferation, apoptosis, and metastasis in vitro and in vivo. This study aimed to elucidate the underlying mechanism behind isatin's ability to inhibit neuroblastoma cell metastasis. Our results demonstrated that isatin could inhibit neuroblastoma cell proliferation, invasion, and migration in a dose-dependent manner. Moreover, isatin inhibited the expression level of monoamine oxidase A as well as that of its downstream protein hypoxia-inducible factor 1α. Further study indicated that isatin inhibited reactive oxygen species production, extracellular signal-regulated kinase activation, vascular endothelial growth factor receptor-1 phosphorylation, and chemokine receptor type 4 expression. All results support the potential antimetastatic effect of isatin in neuroblatoma cells.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Isatina/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Neuroblastoma/tratamento farmacológico , Receptores CXCR4/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Monoaminoxidase/metabolismo , Metástase Neoplásica , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Espécies Reativas de Oxigênio/metabolismo , Receptores CXCR4/biossíntese , Receptores CXCR4/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
J Vasc Access ; 18(2): 153-157, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28218366

RESUMO

PURPOSE: To evaluate incidence and risk factors of peripherally inserted central catheter (PICC)-related complications in cancer patients. METHODS: A prospective, multicenter, cohort study of cancer patients with PICC insertion was performed from February 1, 2013 to April 24, 2014. All patients were monitored in clinic until PICCs were removed. The primary endpoint was PICC removal due to complications. Patient-, catheter- and insertion-related factors were analyzed in univariable and multivariable logistic regression analysis to identify significant independent risk factors for PICC-related complications. RESULTS: There were 477 cancer patients included, for a total of 50,841 catheter-days. Eighty-one patients (17.0%) developed PICC-related complications, with an incidence of 1.59 per 1000 catheter days. Thirty-six (7.5%) PICCs were removed because of complications. The most common complications were skin allergy (4.6%), catheter occlusion (3.4%) and accidental withdrawal (2.3%). Nine (1.9%) patients developed symptomatic upper extremity deep venous thrombosis (UEDVT) and central line associated bloodstream infection (CLABSI) was shown in six (1.3%) PICCs with an infection rate 0.12 per 1000 catheter days. In multivariable analysis, body mass index (BMI) >25 (odds ratio, 2.09; 95% confidence interval, 1.26-3.47, p = 0.004) was shown to be a significant risk factor for PICC complications. CONCLUSIONS: Cancer patients with BMI greater than 25 were more likely to have PICC complications.


Assuntos
Antineoplásicos/administração & dosagem , Obstrução do Cateter , Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Cateteres de Demora/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Dermatite Alérgica de Contato/epidemiologia , Neoplasias/tratamento farmacológico , Trombose Venosa Profunda de Membros Superiores/epidemiologia , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/microbiologia , Cateterismo Venoso Central/instrumentação , Cateterismo Periférico/instrumentação , China/epidemiologia , Dermatite Alérgica de Contato/diagnóstico , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/diagnóstico , Razão de Chances , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Trombose Venosa Profunda de Membros Superiores/diagnóstico , Adulto Jovem
17.
Neuropharmacology ; 113(Pt A): 556-566, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27847271

RESUMO

Hypertension is associated with increased reactive oxygen species (ROS) production in the paraventricular nucleus (PVN) of the hypothalamus. Oleuropein (OL) has a variety of biochemical roles, including antihypertensive and antioxidative functions. However, there have been few reports on the effects of OL on oxidative stress in the PVN on hypertension. In spontaneously hypertensive rats (SHR), eight-week administration of 60 mg/kg/day of OL significantly reduced blood pressure, pro-inflammatory cytokines and the expression of components of the renin-angiotensin system (RAS) compared with SHR rats treated with saline. Concomitantly, OL inhibited superoxide, and increased the antioxidant defense system in the PVN of SHR. We also found that OL increased mitochondrial biogenesis through mtDNA, PGC-1α, Complex II and Complex IV expression and regulated mitochondrial dynamics through the fusion-related protein Mfn2 and fision-related protein DRP1 to attenuate mitochondrial impairment. Furthermore, the phase II enzyme levels of Nrf2 and its downstream proteins NQO-1 and HO-1 were all markedly increased in the PVN of the OL-treated SHR group compared with the saline-treated SHR rats. Our findings demonstrate that OL administration can protect the PVN of the hypothalamus from oxidative stress by improving mitochondrial function through the activation of the Nrf2-mediated signaling pathway.


Assuntos
Hipertensão/metabolismo , Iridoides/farmacologia , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Iridoides/uso terapêutico , Masculino , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
18.
J Vasc Access ; 18(1): e1-e2, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-27911464

RESUMO

Peripherally inserted central catheters (PICCs) have been placed through the peripheral veins, and the best location for the tip of the PICCs is the lower third of the superior vena cava (SVC) and cavo-atrial junction. PICCs are commonly used in intravenous administration, parenteral nutrition therapy, chemotherapy, as well as in critical care units. The success rates in venipuncture are enhanced when ultrasonographic guides are used by the bedside PICC teams. There have been few reports of PICCs placed in super elderly patients with permanent cardiac pacemakers. We share a case of two successful PICC insertions in a 97-year-old patient with bilateral pacemaker placement, that have not been reported previously.


Assuntos
Cateterismo Cardíaco , Estimulação Cardíaca Artificial , Cateterismo Venoso Central , Cateterismo Periférico , Marca-Passo Artificial , Veia Subclávia , Extremidade Superior/irrigação sanguínea , Idoso de 80 Anos ou mais , Cateterismo Venoso Central/instrumentação , Cateterismo Periférico/instrumentação , Cateteres de Demora , Cateteres Venosos Centrais , Humanos , Masculino , Veia Subclávia/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia de Intervenção
19.
Medicine (Baltimore) ; 96(51): e9222, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29390472

RESUMO

INTRODUCTION: Peripherally inserted central venous catheters (PICC) are widely used in cancer patients and ultrasound-guided PICC insertion could improve success rate. The tip position of the catheter should be located at the border of lower one-third of the superior vena cava (SVC) and cavo-atrial junction. The migration is malposition at the late stage after PICCs were inserted, and catheter malposition was associated with thrombosis and other complications.After patient's informed consent, we report a case of a 66-year-old male with twice catheter migrations resulting in thrombosis after being diagnosed with cardiac cancer. CONCLUSION: The correct position of the catheter tip can ensure the normal use of PICC and reduce the complications. For the migrated catheter, it should be removed as soon as possible, and when thrombosis has been developed, standard anticoagulant therapy should be given.


Assuntos
Anticoagulantes/administração & dosagem , Cateterismo Periférico/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Migração de Corpo Estranho/complicações , Trombose Venosa Profunda de Membros Superiores/etiologia , Trombose Venosa Profunda de Membros Superiores/terapia , Idoso , Cateterismo Periférico/métodos , Remoção de Dispositivo , Falha de Equipamento , Seguimentos , Migração de Corpo Estranho/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/tratamento farmacológico , Humanos , Masculino , Medição de Risco , Resultado do Tratamento , Ultrassonografia Doppler em Cores/métodos , Trombose Venosa Profunda de Membros Superiores/diagnóstico por imagem
20.
Medicine (Baltimore) ; 96(51): e9225, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29390474

RESUMO

INTRODUCTION: Primary cardiac angiosarcoma is a rare tumor and the common treatment is surgical resection followed by chemotherapy. Peripherally inserted central venous catheters (PICCs) are widely used in cancer patients and ultrasound-guided PICC insertion could improve success rate especially in patient with abnormal anatomy structure. Reports about PICCs being placed in patient who had suffered from the cardiac angiosarcoma and neoplasty of right atrium with an ipsilateral cardiac permanent pacemaker are rarely.After patient's informed consent, we present a case of the successful insertion of PICC into a patient with the ipsilateral cardiac disease with a pacemaker placement, which has not been previously reported. CONCLUSIONS: This report highlights PICC could be used in patient with cardiac disease with a pacemaker placement for chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cateterismo Periférico/métodos , Cateteres Venosos Centrais , Neoplasias Cardíacas/terapia , Hemangiossarcoma/terapia , Marca-Passo Artificial , Terapia Combinada , Feminino , Seguimentos , Átrios do Coração/efeitos dos fármacos , Neoplasias Cardíacas/diagnóstico , Hemangiossarcoma/diagnóstico , Humanos , Infusões Intralesionais , Pessoa de Meia-Idade , Doenças Raras , Resultado do Tratamento
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