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1.
J Nutr Health Aging ; 27(11): 987-995, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37997720

RESUMO

OBJECTIVES: We aimed to evaluate the effect of frailty on lung function and disease outcomes in older adults with chronic obstructive pulmonary disease (COPD). DESIGN: Retrospective observational cohort. SETTING AND PARTICIPANTS: At baseline, comprehensive geriatric assessment and pulmonary function tests were extracted from the case management care system of the geriatric department of a tertiary medical center. MEASUREMENTS: Frailty was assessed by the modified Rockwood frailty index. Kaplan-Meier survival and Cox proportional hazard analyses were used to analyze the primary outcome. Both the Friedman test and generalized estimating equations were used to evaluate the rate of decline in lung function. RESULTS: Among 151 enrolled older patients, comprising 69 non-COPD and 82 COPD subjects, the mean age was 80.9±8.3 years. After a median follow-up of 2.87 years, the serial forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), and forced expiratory flow at 25-75% of FVC (FEF25-75%) showed significantly different slope changes between older COPD patients with and without frailty. The mortality hazard ratio (HR) was 2.53 for COPD without frailty and 3.62 for COPD with frailty, versus those without COPD. Among COPD patients, the factors most strongly associated with mortality were timed up-and-go, activities of daily living (ADLs), instrumental ADLs, FEV1/FVC, and serum HCO3-. After adjustment for potential confounders, ADLs and FEV1/FVC remained independent mortality predictors. CONCLUSION: Among older patients with COPD, frailty was common and associated with pulmonary function decline, and mortality risk was higher in frail than in non-frail subjects.


Assuntos
Fragilidade , Doença Pulmonar Obstrutiva Crônica , Idoso , Idoso de 80 Anos ou mais , Humanos , Atividades Cotidianas , Fragilidade/complicações , Pulmão , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos Retrospectivos
2.
Rev Sci Instrum ; 92(4): 043521, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243453

RESUMO

Microwave reflectometry diagnostics have been widely used to measure density profiles in fusion plasma. However, the high sensitivity of the diagnostics to plasma turbulence often results in large radial deviations in the edge density profile and causes difficulty in profile evaluation. To improve the performance of profile evaluation, a modified RANdom SAmple Consensus (RANSAC) method has been applied to fit the density profiles measured by reflectometry on the experimental advanced superconducting tokamak. Compared with the traditional least-squares method, the modified RANSAC method is much more efficient and robust in fitting the experimental profiles. Furthermore, a combination of RANSAC and a genetic algorithm (GA-RANSAC) is used to further optimize the profile evaluation procedure. The results show that this GA-RANSAC method yields better performance and stabler convergence than the modified RANSAC alone.

3.
Cardiovasc Drugs Ther ; 33(6): 739-748, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31655942

RESUMO

PURPOSE: To review current knowledge of elevated lipoprotein(a) [Lp(a)] levels in relation to atherosclerotic cardiovascular disease (ASCVD) and discuss their potential use as biomarkers and therapeutic approaches in clinical practice. METHODS: We summarized the current understanding and recent advances in the structure, metabolism, atherogenic mechanisms, standardized laboratory measurement, recommended screening populations, and prognostic value of Lp(a), with a special focus on the current potential treatment approaches for hyperlipoprotein(a)emia in patients with ASCVD. RESULTS: Lp(a) is composed of LDL-like particle and characteristic apolipoprotein(a) [apo(a)] connected by a disulfide bond. Substantial evidence shows that elevated plasma Lp(a) level is a heritable, independent, and possibly causal risk factor for ASCVD through its proatherogenic, proinflammatory, and potentially prothrombotic properties. Current guidelines recommend Lp(a) measurement for patients with an intermediate-high risk of ASCVD, familial hypercholesterolemia, a family history of early ASCVD or elevated Lp(a), and progressive ASCVD despite receiving optimal therapy. Traditional Lp(a)-lowering approaches such as niacin, PCSK9 inhibitors, mipomersen, lomitapide, and lipoprotein apheresis were associated with a non-specific and limited reduction of Lp(a), intolerable side effects, invasive procedure, and high expense. The phase 2 randomized controlled trial of antisense oligonucleotide against the apo(a) encoding gene LPA mRNA showed that IONIS-APO(a)-LRX could specifically reduce the level of Lp(a) by 90% with good tolerance, which may become a promising candidate for the prevention and treatment of ASCVD in the future. CONCLUSIONS: It is reasonable to measure Lp(a) levels to reclassify ASCVD risk and manage individuals with elevated Lp(a) to further reduce the residual risk of ASCVD, especially with IONIS-APO(a)-LRX.


Assuntos
Aterosclerose/sangue , Hiperlipoproteinemia Tipo II/sangue , Lipoproteína(a)/sangue , Animais , Anticolesterolemiantes/uso terapêutico , Aterosclerose/etiologia , Aterosclerose/genética , Aterosclerose/prevenção & controle , Biomarcadores/sangue , Remoção de Componentes Sanguíneos , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Lipoproteína(a)/genética , Oligonucleotídeos Antissenso/uso terapêutico , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Regulação para Cima
4.
Rev Sci Instrum ; 89(10): 10H103, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30399842

RESUMO

An ordinary-mode polarized multi-channel correlation reflectometer has been developed on the Experimental Advanced Superconducting Tokamak (EAST). The system with four different probing frequencies (i.e., 20.4 GHz, 24.8 GHz, 33 GHz, and 40 GHz) and two poloidally spaced receiving antennas can realize both the radial correlation measurement and the poloidal correlation measurement. These diagnostics focus on the measurement of density fluctuation in the pedestal region to investigate the turbulence transport and H-mode physics on EAST. In this article, the system hardware design, the key component tests, and the system performance are shown in detail.

5.
Eur Rev Med Pharmacol Sci ; 22(18): 5797-5803, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30280758

RESUMO

OBJECTIVE: To explore the role of hsa-miR-203 in fracture healing and its underlying mechanism. PATIENTS AND METHODS: Expression levels of hsa-miR-203 and PBOV1 in patients with hand fractures and intra-articular fractures after treatment were detected by quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR). Viability and apoptosis of osteoblast cell line hFOB1.19 after hsa-miR-203 overexpression or knockdown were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The target gene of hsa-miR-203 was predicted by bioinformatics and verified by dual-luciferase reporter gene assay. Rescue experiments were conducted to further verify whether hsa-miR-203 could participate in fracture healing via PBOV1. RESULTS: No significant hsa-miR-203 expression was found in patients with hand fractures and intra-articular fractures after treatment for 7 days, which was remarkably upregulated on the 14th day. PBOV1 expression was gradually downregulated as treatment time prolongation. Overexpression of hsa-miR-203 decreased cell viability, but induced apoptosis of hFOB1.19 cells. Bioinformatics predicted that PBOV1 might be the target gene of hsa-miR-203, which was further verified by dual-luciferase reporter gene assay. The effect of hsa-miR-203 on viability and apoptosis of hFOB1.19 cells was reversed after the PBOV1 knockdown. CONCLUSIONS: Hsa-miR-203 inhibits fracture healing by regulating osteoblast viability and apoptosis via targeting PBOV1.


Assuntos
Consolidação da Fratura/fisiologia , MicroRNAs/fisiologia , Proteínas de Neoplasias/biossíntese , Apoptose/fisiologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Regulação para Baixo , Humanos , MicroRNAs/biossíntese , MicroRNAs/sangue , Proteínas de Neoplasias/sangue , Osteoblastos/metabolismo , Osteoblastos/fisiologia , Fatores de Tempo , Regulação para Cima
6.
Eur Rev Med Pharmacol Sci ; 22(15): 4792-4799, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30070309

RESUMO

OBJECTIVE: To investigate the effect and related mechanisms of miR-485-5p on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). PATIENTS AND METHODS: The expression level of miR-485-5p was detected in clinical cases and during the osteogenic differentiation. Three group were established to study the potential function between miR-485-5p and osteogenic differentiation: miR-NC group (negative control), miR-485-5p mimics (BMSCs transfected by miR-485-5p mimics), and mimics + si-Osx (BMSCs transfected by miR-485-5p mimics and si-Osx), after the induction of osteogenic differentiation, the cell viability of BMSCs and osteogenic markers were determined. RESULTS: In our work, miR-485-5p was found up-regulated in patients with osteoporosis by comparing with health cases. Besides, during osteogenic differentiation, miR-485-5p was suppressed. These results suggest miR-485-5p has a negative regulating effect. To research potential target of miR-485-5p, we checked it in three publicly available algorithms, TargetScan, miRDB and microRNA. We found that Osterix (Osx) is a direct target of miR-485-5p, and Luciferase assays confirmed our hypothesis, the subsequent experiments showed that decreased expression of Osx resulting from the up-regulation of miR-485-5p could restrain the cell viability and the expression level of osteogenic markers CONCLUSIONS: Our research revealed the promote function of miR-485-5p on osteoporosis, indicating that miR-485-5p could be a potential therapeutic strategy for the treatment of osteoporosis.


Assuntos
MicroRNAs/metabolismo , Osteoporose/patologia , Fatores de Transcrição/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Biomarcadores/metabolismo , Diferenciação Celular , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Osteogênese , Osteoporose/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/química , Fatores de Transcrição/genética
7.
J Viral Hepat ; 25(10): 1116-1120, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29660219

RESUMO

Sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for hepatitis B virus (HBV) infection. NTCP rs2296651 is believed to be an Asian-specific variant responsible for HBV susceptibility. We investigated the relationship between rs2296651 and HBV infection in Taiwan based on stratification by gender and menopausal status. We recruited 10 017 Taiwan Biobank participants aged 30-70 years with complete genetic data and sociodemographic information. Gender-stratified multivariate logistic regression models were used to determine the relationship between NTCP variant and HBV infection. Among individuals with HBV infection, the genotype frequencies of GG, AG and AA in women were 0.85, 0.15 and 0 while those in men were 0.82, 0.18 and 0, respectively. The multivariate-adjusted odds ratios (OR) of HBV infection were 0.77 (95% CI 0.59-0.99) in women and 0.98 (95% CI 0.79-1.20) in men. The adjusted OR was 0.87 (CI 0.63-1.19) in premenopausal and 0.59 (0.36-0.97) in postmenopausal women. We found that genetic variation in the HBV receptor gene (NTCP) was significantly associated with a decreased risk of HBV infection in Taiwanese women.


Assuntos
Predisposição Genética para Doença/genética , Hepatite B/genética , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Simportadores/genética , Adulto , Idoso , Feminino , Estudos de Associação Genética , Genótipo , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Humanos , Masculino , Menopausa , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Taiwan/epidemiologia
9.
Klin Monbl Augenheilkd ; 234(8): 1015-1018, 2017 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-28114694

RESUMO

Autologous serum (AS) and amniotic membrane transplantation (AMT) are used in the treatment of several ocular surface diseases. AMT is associated with a surgical intervention. Surgery could be avoided by using eye drops prepared from an amniotic membrane homogenate (AMH) or amniotic membrane suspension (AMS). EGF, bFGF, IL-6 and IL-8 were detected in AMS. However, EGF and bFGF concentrations in AMS were about 1.7-17× lower than in AMH, and IL-6 and IL-8 could not be detected in AMH. 100 % AMS, 15 and 30 % AMH significantly decreased proliferation of human corneal epithelial cells (HCECs) compared to controls (p = <0.002 for all), but 15 and 30 % AMS did not affect proliferation. Migration increased significantly compared to controls with 15 and 30 % AMS (p < 0.001), but did not change significantly with 15 or 30 % AMH (p = 0.153 and p = 0.083). Proliferation of HCECs was significantly greater with 15 % AS than with 30 % AS (p < 0.001). HCEC migration was significantly greater with 30 % AS than with 5 % AS (p < 0.01). In summary, 15 and 30 % AMS and 15 and 30 % AS exhibit the best supportive effect on human corneal epithelial cells. Nevertheless, we always have to keep in mind that individual growth factor concentrations exhibit high inter-individual fluctuations in AS or AMS eye drops.


Assuntos
Curativos Biológicos , Doenças da Córnea/terapia , Soro , Cicatrização/fisiologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Epitélio Corneano/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Soluções Oftálmicas , Resultado do Tratamento
10.
Cardiovasc Drugs Ther ; 30(6): 623-633, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27858191

RESUMO

LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is comprised of the angiotensin receptor blocker valsartan and the neprilysin inhibitor pro-drug sacubitril (AHU377). After oral administration, AHU377 is rapidly metabolized to the active neprilysin inhibitor LBQ657. LCZ696 exerts its effects of diuresis, natriuresis, vasodilation and aldosterone secretion inhibition through simultaneous renin-angiotensin-aldosterone system (RAAS) blockade and natriuretic peptides system (NPS) enhancement. Powerful evidence including PARAMETER and PRARDIGM-HF trials have shown that LCZ696 outperforms RAAS inhibition in treating patients with hypertension and heart failure with reduced ejection fraction (HFrEF), and is well tolerated. In addition, accumulating evidence also suggests its potential use in heart failure with preserved ejection fraction (HFpEF), chronic kidney disease (CKD), post-myocardium infarction (post-MI) and stroke. Both the FDA and CHMP have approved LCZ696 for treatment of HFrEF. Despite all this, some special issues (e.g. use in specific subgroups, adverse events, contraindications and cost-effectiveness analysis) should be considered before its implementation in clinical practice.


Assuntos
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Fármacos Cardiovasculares , Tetrazóis , Aminobutiratos/efeitos adversos , Aminobutiratos/farmacologia , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Animais , Compostos de Bifenilo , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Contraindicações , Análise Custo-Benefício , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Tetrazóis/efeitos adversos , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Valsartana
11.
Leukemia ; 30(4): 800-11, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26621337

RESUMO

Natural killer (NK) cells are key components of the innate immune system, providing potent antitumor immunity. Here, we show that the tumor growth factor-ß (TGF-ß)/SMAD signaling pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia (ALL). We characterized NK cells in 50 consecutive children with B-ALL at diagnosis, end induction and during maintenance therapy compared with age-matched controls. ALL-NK cells at diagnosis had an inhibitory phenotype associated with impaired function, most notably interferon-γ production and cytotoxicity. By maintenance therapy, these phenotypic and functional abnormalities partially normalized; however, cytotoxicity against autologous blasts remained impaired. We identified ALL-derived TGF-ß1 to be an important mediator of leukemia-induced NK cell dysfunction. The TGF-ß/SMAD signaling pathway was constitutively activated in ALL-NK cells at diagnosis and end induction when compared with healthy controls and patients during maintenance therapy. Culture of ALL blasts with healthy NK cells induced NK dysfunction and an inhibitory phenotype, mediated by activation of the TGF-ß/SMAD signaling pathway, and abrogated by blocking TGF-ß. These data indicate that by regulating the TGF-ß/SMAD pathway, ALL blasts induce changes in NK cells to evade innate immune surveillance, thus highlighting the importance of developing novel therapies to target this inhibitory pathway and restore antileukemic cytotoxicity.


Assuntos
Citotoxicidade Imunológica/imunologia , Evasão da Resposta Imune/imunologia , Células Matadoras Naturais/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Lactente , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Masculino , Fosforilação , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Transdução de Sinais , Células Tumorais Cultivadas , Microambiente Tumoral/imunologia
12.
Genet Mol Res ; 14(4): 15158-68, 2015 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-26634479

RESUMO

We measured the effect of Schwann cell transplantation and complement factor 5a (C5a) receptor antagonist on nerve function recovery in rats with spinal cord injury. Experimental spinal cord injury was induced in eighty Wistar rats and these were randomly divided into four treatment groups: culture medium and saline injection (control group), Schwann cell injection (cell transplantation group), C5a receptor antagonist injection (C5a receptor antagonist group), and both Schwann cell and C5a receptor antagonist injections (combination group). Rear limb functional recovery was assessed 1, 2, 4, 6, and 8 weeks after the spinal cord injury with the tilt table test and the Basso, Beattie, Bresnahan scale. Sex-determining region Y (SRY) gene expression was measured at week 4 and horseradish peroxidase (HRP) labeling was used at week 8 to further assess the recovery of neuroelectrophysiological functions. The rear limb functional assessment showed that the combination group had better outcomes than the cell transplantation and C5a receptor antagonist groups. All treatment groups had better outcomes than control. Only the cell transplantation and combination groups showed SRY expression. The number of HRP-positive nerve fibers in the different groups ranked as follows: combination group > cell transplantation and C5a receptor antagonist > control. The refractory period and amplitude of the induced potential in the combination group were significantly greater than in the other three groups. These results suggest that the combination of Schwann cell transplantation and the C5a receptor antagonist enhances the regeneration of injured synapses and improves limb function and electrophysiology.


Assuntos
Membro Posterior/fisiologia , Regeneração Nervosa/fisiologia , Receptor da Anafilatoxina C5a/antagonistas & inibidores , Recuperação de Função Fisiológica/fisiologia , Células de Schwann/transplante , Traumatismos da Medula Espinal/fisiopatologia , Animais , Transplante de Células/métodos , Feminino , Membro Posterior/metabolismo , Masculino , Ratos , Ratos Wistar , Traumatismos da Medula Espinal/metabolismo
13.
J Obstet Gynaecol ; 35(4): 341-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26018222

RESUMO

The aim of this study was to investigate the potential relationship between acylation-stimulating protein (ASP), insulin resistance, lipometabolism, the intrauterine metabolic environment and fetal growth in well-controlled gestational diabetes mellitus (GDM) women. A total of 55 well-controlled GDM women, 66 pregnant women with normal glucose tolerance (NGT) and their newborns, were included in this study. Fasting maternal and cord blood ASP, serum lipid profiles, glucose level, insulin level, HOMA-IR, in addition to neonatal anthropometry data, were measured. Maternal blood ASP in GDM is higher than that in NGT. In the GDM group, maternal blood ASP has a positive correlation with TG, FFA and HOMA-IR. Maternal and cord blood ASP levels of LGA fetuses correlate with elevated birth weight and SF4. Similarly, cord blood ASP levels of LGA fetuses also correlate with birth weight and SF4 in the NGT group. The maternal blood ASP level of GDM mothers is associated with lipometabolism, insulin resistance and LGA fetal growth. Nevertheless, the cord blood ASP level correlates with FFA of GDM mothers, LGA fetal growth of GDM and NGT mothers. ASP may be a biomarker for evaluating insulin resistance of GDM and LGA fetal growth.


Assuntos
Complemento C3a/metabolismo , Diabetes Gestacional , Sangue Fetal/metabolismo , Desenvolvimento Fetal , Resistência à Insulina , Metabolismo dos Lipídeos , Adulto , Anafilatoxinas/metabolismo , Peso ao Nascer , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , China , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/metabolismo , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Recém-Nascido , Gravidez , Estatística como Assunto
14.
Clin Otolaryngol ; 39(6): 352-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25117943

RESUMO

OBJECTIVES: To investigate the laryngopharyngeal reflux (LPR) episodes and pH values in patients with suspected obstructive sleep apnoea (OSA) using the Dx-pH oropharyngeal probe. DESIGN: Prospective cohort study. SETTING: Tertiary medical centre. PARTICIPANTS: Forty patients with complaint of snoring or suspected OSA were prospectively enrolled to receive full nocturnal polysomnography (PSG). The patients were divided into 2 groups: a simple snorers group if the Respiratory Disturbance Index (RDI) was < 5 and an OSA group if the RDI was ≥ 5. MAIN OUTCOME MEASURES: The patients simultaneously received Dx-pH oropharyngeal probe monitoring for 12 h from about 6 pm to 6 am of the next day. The number of LPR events was recorded if the nadir of rapid pH drops was below pH 5.0 and 5.5. The difference of LPR events between the two groups and the difference of LPR events between awake and sleep periods in each group were analysed, respectively. RESULTS: There were 18 (45%) patients diagnosed as OSA with a mean RDI of 28.7, and 22 patients (55%) diagnosed as simple snorers. Between 2 groups, there were no significant differences in the LPR events and pH values during the awake period, sleep period or overall recording period. Comparison of the LPR events and minimum pH values between the awake period and the sleep period revealed there were no significant differences in either group. CONCLUSION: Using the new sensitive Dx-pH oropharyngeal probe with PSG, we found that OSA does not correlate with a higher incidence of LPR episodes.


Assuntos
Orofaringe/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Idoso , Estudos de Coortes , Monitoramento Ambiental , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Polissonografia , Estudos Prospectivos
15.
Free Radic Res ; 48(7): 794-805, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24678962

RESUMO

One major pathological hallmark of Alzheimer's disease (AD) is accumulation of senile plaques in patients' brains, mainly composed of amyloid beta-peptide (Aß). Nicotinamide adenine dinucleotide (NAD) has emerged as a common mediator regulating energy metabolism, mitochondrial function, aging, and cell death, all of which are critically involved in neuronal demise observed in AD. In this work, we tested the hypothesis that NAD may attenuate Aß-induced DNA damages, thereby conferring neuronal resistance to primary rat cortical cultures. We found that co-incubation of NAD dose-dependently attenuated neurotoxicity mediated by Aß25-35 and Aß1-42 in cultured rat cortical neurons, with the optimal protective dosage at 50 mM. NAD also abolished the formation of reactive oxygen species (ROS) induced by Aß25-35. Furthermore, Aßs were capable of inducing oxidative DNA damages by increasing the extents of 8-hydroxy-2´-deoxyguanosine (8-OH-dG), numbers of apurinic/apyrimidinic (AP) sites, genomic DNA single-stranded breaks (SSBs), as well as DNA double-stranded breaks (DSBs)/fragmentation, which can all be attenuated upon co-incubation with NAD. Our results thus reveal a novel finding that NAD is protective against DNA damage induced by existing Aß, leading ultimately to neuroprotection in primary cortical culture.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Córtex Cerebral/citologia , Dano ao DNA , DNA/metabolismo , NAD/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Animais , Células Cultivadas , DNA/genética , DNA/isolamento & purificação , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos , Oxirredução/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
16.
AJNR Am J Neuroradiol ; 34(1): 115-20, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22723060

RESUMO

BACKGROUND AND PURPOSE: FUS-induced BBB opening is a promising technique for noninvasive and local delivery of drugs into the brain. Here we propose the novel use of a neuronavigation system to guide the FUS-induced BBB opening procedure and investigate its feasibility in vivo in large animals. MATERIALS AND METHODS: We developed an interface between the neuronavigator and FUS to allow guidance of the focal energy produced by the FUS transducer. The system was tested in 29 swine by more than 40 sonication procedures and evaluated by MR imaging. Gd-DTPA concentration was quantitated in vivo by MR imaging R1 relaxometry and compared with ICP-OES assay. Brain histology after FUS exposure was investigated using H&E and TUNEL staining. RESULTS: Neuronavigation could successfully guide the focal beam, with precision comparable to neurosurgical stereotactic procedures (2.3 ± 0.9 mm). A FUS pressure of 0.43 MPa resulted in consistent BBB opening. Neuronavigation-guided BBB opening increased Gd-DTPA deposition by up to 1.83 mmol/L (a 140% increase). MR relaxometry demonstrated high correlation with ICP-OES measurements (r(2) = 0.822), suggesting that Gd-DTPA deposition can be directly measured by imaging. CONCLUSIONS: Neuronavigation provides sufficient precision for guiding FUS to temporally and locally open the BBB. Gd-DTPA deposition in the brain can be quantified by MR relaxometry, providing a potential tool for the in vivo quantification of therapeutic agents in CNS disease treatment.


Assuntos
Barreira Hematoencefálica/anatomia & histologia , Barreira Hematoencefálica/cirurgia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Imageamento por Ressonância Magnética/métodos , Neuronavegação/métodos , Animais , Barreira Hematoencefálica/efeitos da radiação , Estudos de Viabilidade , Projetos Piloto , Suínos
17.
Pediatr Hematol Oncol ; 29(5): 415-23, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22632168

RESUMO

Despite the favorable outcome of most pediatric patients with Hodgkin lymphoma (HL), there is rising concern about risks of carcinogenesis from both diagnostic and therapeutic radiation exposure for patients treated on study protocols. Although previous studies have investigated radiation exposure during treatment, radiation from post-treatment surveillance imaging may also increase the likelihood of secondary malignancies. All diagnostic imaging examinations involving ionizing radiation exposure performed for surveillance following completion of therapy were recorded for 99 consecutive pediatric patients diagnosed with HL from 2000 to 2010. Cumulative radiation dosage from these examinations and the frequency of relapse detection by these examinations were recorded. In the first 2 years following completion of therapy, patients in remission received a median of 11 examinations (range 0-26). Only 13 of 99 patients relapsed, 11 within 5 months of treatment completion. No relapse was detected by 1- or 2-view chest radiographs (n = 38 and 296, respectively), abdomen/pelvis computed tomography (CT) scans (n = 211), or positron emission tomography (PET) scans alone (n = 11). However, 10/391 (2.6%) of chest CT scans, 4/364 (1.1%) of neck CT scans, and 3/47 (6.4%) of PET/CT scans detected relapsed disease. Thus, only 17 scans (1.3%) detected relapse in a total of 1358 scans. Mean radiation dosages were 31.97 mSv for Stage 1, 37.76 mSv for Stage 2, 48.08 mSv for Stage 3, and 51.35 mSv for Stage 4 HL. Approximately 1% of surveillance imaging examinations identified relapsed disease. Given the very low rate of relapse detection by surveillance imaging stipulated by current protocols for pediatric HL patients, the financial burden of the tests themselves, the high cure rate, and risks of second malignancy from ionizing radiation exposure, modification of the surveillance strategy is recommended.


Assuntos
Doença de Hodgkin/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/efeitos adversos , Doses de Radiação , Tomografia Computadorizada por Raios X/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença de Hodgkin/terapia , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
18.
J Hosp Infect ; 80(2): 162-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22188630

RESUMO

BACKGROUND: Varicella zoster infection can be spread by infected healthcare workers (HCWs) to coworkers and patients. A self-reported history of chickenpox infection is sometimes taken as proof of immunity. AIM: To establish the relationship between positive recall history and serological immunity against varicella zoster virus (VZV) amongst healthcare workers in a tertiary hospital in Taiwan. METHODS: Between May 2008 and April 2009, all HCWs in a Taiwanese tertiary care hospital were tested for VZV immunoglobulin G (IgG), and completed a self-administered questionnaire to determine their history of varicella infection or vaccination. Those who were seronegative were vaccinated. FINDINGS: All HCWs (N=3733) at the hospital participated in this study. Their mean age was 34.6 years, and the seroprevalence of VZV was 91.1%. Sensitivity, specificity, and positive and negative predictive values of a self-reported history of varicella infection were 82.3%, 48.6%, 96.3% and 14.4%, respectively. Corresponding figures for a history of varicella vaccination were 23.4%, 69.4%, 90.9% and 6.5%, respectively. The recall history of younger HCWs and medical professionals (doctors, nurses and paramedical staff) to varicella had higher sensitivity. However, only the recall history of medical professionals had a significantly higher positive predictive value. CONCLUSION: A positive recall history of varicella infection and vaccination did not ensure the presence of protective VZV IgG, and a negative history was not predictive of a lack of immunity. For effective prevention of nosocomial infection, VZV IgG status should be documented for all HCWs, and susceptible HCWs should be vaccinated.


Assuntos
Anticorpos Antivirais/sangue , Varicela/epidemiologia , Pessoal de Saúde , Herpesvirus Humano 3/imunologia , Anamnese/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Soroepidemiológicos , Inquéritos e Questionários , Taiwan/epidemiologia , Adulto Jovem
19.
Arch Ital Biol ; 149(4): 492-8, 2011 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-22205595

RESUMO

Hypocretin (Hcrt) has been implicated in the control of motor activity and in respiration and cardiovascular changes. Loss of Hcrt in narcolepsy is linked to sleepiness and to cataplexy, a sudden loss of muscle tone which is triggered by sudden strong emotions. In the current study we have compared the effects of treadmill running, to yard play on cerebrospinal fluid (CSF) Hcrt level in normal dogs. We find that treadmill locomotion, at a wide range of speeds, does not increase Hcrt level beyond baseline, whereas yard play produces a substantial increase in Hcrt, even though both activities produce comparable increases in heart rate, respiration and body temperature. We conclude that motor and cardiovascular changes are not sufficient to elevate CSF levels of Hcrt and we hypothesize that the emotional aspects of yard play account for the observed increase in Hcrt.


Assuntos
Pressão Sanguínea/fisiologia , Temperatura Corporal/fisiologia , Perileno/análogos & derivados , Condicionamento Físico Animal/fisiologia , Jogos e Brinquedos , Quinonas/líquido cefalorraquidiano , Respiração , Análise de Variância , Animais , Cães , Teste de Esforço , Masculino , Perileno/líquido cefalorraquidiano , Fenol , Radioimunoensaio
20.
Int J Tuberc Lung Dis ; 15(10): 1415-20, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22283904

RESUMO

BACKGROUND: Serum biomarkers are rarely studied in patients with non-tuberculous mycobacterial lung disease (NTM-LD). OBJECTIVE: To investigate the role of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and other inflammatory markers in NTM-LD. DESIGN: From April 2009 to March 2010, patients with NTM culture-positive respiratory specimens who were clinically and radiographically suspected of NTM-LD were evaluated for serum levels of sTREM-1, C-reactive protein, procalcitonin and interferon-gamma. RESULTS: Of the 86 patients enrolled, 60 fulfilled the diagnosis of NTM-LD. Using the receiver-operating characteristics curve analysis, serum sTREM-1 had the highest discriminative power for NTM-LD and colonisation (area under the curve = 0.714). Using a cut-off value of 180 pg/ml, the sensitivity and specificity of sTREM-1 were respectively 58% and 89%. Logistic regression analysis revealed that Mycobacterium avium complex, M. kansasii, positive sputum acid-fast smear and higher serum sTREM-1 level were independent risk factors for NTM-LD. Age >65 years and higher serum sTREM-1 level were associated with worse 6-month survival. CONCLUSION: In patients with respiratory specimens that are culture-positive for NTM with clinical suspicion of NTM-LD, serum sTREM-1 level measurements may be helpful in diagnosing and predicting outcome for NTM-LD.


Assuntos
Pneumopatias/diagnóstico , Glicoproteínas de Membrana/sangue , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Receptores Imunológicos/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/análise , Calcitonina/sangue , Peptídeo Relacionado com Gene de Calcitonina , Distribuição de Qui-Quadrado , Humanos , Interferon gama/sangue , Estimativa de Kaplan-Meier , Modelos Logísticos , Pneumopatias/sangue , Pneumopatias/microbiologia , Pessoa de Meia-Idade , Análise Multivariada , Infecções por Mycobacterium não Tuberculosas/sangue , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium avium/isolamento & purificação , Mycobacterium kansasii/isolamento & purificação , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Precursores de Proteínas/sangue , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Escarro/microbiologia , Taiwan , Receptor Gatilho 1 Expresso em Células Mieloides , Regulação para Cima
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