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1.
Skin Res Technol ; 30(8): e13919, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39113612

RESUMO

BACKGROUND: Diabetes mellitus (DM) presents impediment to wound healing. While ultraviolet B (UVB) exposure showed therapeutic potential in various skin conditions, its capacity to mediate diabetic wound healing remains unclear. To investigate the efficacy of UVB on wound healing and its underlying basis. MATERIALS AND METHODS: Male C57BL/6 mice were subjected to the high-fat diet followed by streptozotocin administration to establish the diabetic model. Upon confirmation of diabetes, full-thickness wounds were inflicted and the treatment group received UVB radiation at 50 mJ/cm2 for 5 min every alternate day for 2 weeks. Wound healing rate was then assessed, accompanied by evaluations of blood glucose, lipid profiles, CD31 expression, and concentrations of ghrelin and leptin. Concurrently, in vitro studies were executed to evaluate the protective role of ghrelin on human umbilical vein endothelial cells (HUVEC) under high glucose (HG) conditions. RESULTS: Post UVB exposure, there was a marked acceleration in wound healing in DM mice without alterations in hyperglycemia and lipid profiles. Compared to non-UVB-exposed mice, the UVB group showed enhanced angiogenesis manifested by a surge in CD31 expression. This trend appeared to be in harmony with the elevated ghrelin levels. In vitro experiments indicated that ghrelin significantly enhanced the migratory pace and angiogenic properties of HUVEC under HG-induced stress, potentially mediated by an upregulation in vascular endothelial growth factor expression. CONCLUSION: UVB exposure bolstered wound healing in diabetic mice, plausibly mediated through augmented angiogenesis induced by ghrelin secretion. Such findings underscore the vast potential of UVB-induced ghrelin in therapeutic strategies targeting diabetic wound healing.


Assuntos
Diabetes Mellitus Experimental , Grelina , Células Endoteliais da Veia Umbilical Humana , Camundongos Endogâmicos C57BL , Cicatrização , Animais , Humanos , Masculino , Camundongos , Glicemia/metabolismo , Grelina/metabolismo , Grelina/efeitos da radiação , Leptina/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pele/efeitos da radiação , Pele/patologia , Pele/metabolismo , Raios Ultravioleta/efeitos adversos , Terapia Ultravioleta/métodos , Cicatrização/efeitos da radiação
2.
Ren Fail ; 46(1): 2310081, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38321925

RESUMO

Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model's discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894-0.934) and 0.923 (95% CI, 0.895-0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model's favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.


Assuntos
Injúria Renal Aguda , Sepse , Humanos , Nomogramas , Estudos Retrospectivos , China
3.
Respir Res ; 22(1): 130, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910578

RESUMO

BACKGROUND: Fibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD. METHODS: 8094 patients with a fibrinogen assessment at Week 16 were included, baseline fibrinogen data were not measured. Post hoc analyses were performed by fibrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs). RESULTS: Rates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively). The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels < 3.5 g/L were 1.03 (0.95, 1.11) for moderate exacerbations, 1.08 (1.00, 1.15) for moderate/severe exacerbations, and 1.30 (1.10, 1.54) for severe exacerbations. There was an increased risk of moderate/severe exacerbation (hazard ratio [95% CI]: highest vs lowest quartile 1.16 [1.04, 1.228]; ≥ 3.5 g/L vs < 3.5 g/L: 1.09 [1.00, 1.16]) and severe exacerbation (1.35 [1.09, 1.69]; 1.27 [1.08, 1.47], respectively) with increasing fibrinogen level. Cardiovascular AESIs were highest in patients in the highest fibrinogen quartile. CONCLUSIONS: Rate and risk of exacerbations was higher in patients with higher fibrinogen levels. This supports the validity of fibrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fibrinogen as an enrichment strategy in trials examining exacerbation outcomes. TRIAL REGISTRATION: NCT02164513.


Assuntos
Fibrinogênio/metabolismo , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/sangue , Idoso , Biomarcadores/sangue , Broncodilatadores/uso terapêutico , Progressão da Doença , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
4.
Opt Express ; 28(8): 11609-11617, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32403668

RESUMO

Using a Dazzler system and tilting a compressor grating, we provide an effective way of using the laser group delay dispersion to continuously steer the electron beam accelerated by an asymmetric laser wakefield. The deviation angle of the electron beam was the same as that of the angularly chirped laser pulse from its initial optical axis, which is determined by the laser pulse-front-tilt (PFT). This method can be utilized to continuously control over the pointing direction of electron bunches to the requisite trajectories, especially for practical applications in highly sensitive alignment devices such as electron-positron colliders or undulators. Additionally, we investigate the effect of PFT on the properties of the electron beam.

5.
Respir Res ; 21(1): 131, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32471423

RESUMO

BACKGROUND: The comparative efficacy of inhaled corticosteroid/long-acting muscarinic antagonist/long-acting ß2-agonist (ICS/LAMA/LABA) triple therapy administered via single or multiple inhalers in patients with chronic obstructive pulmonary disease (COPD) has not been evaluated comprehensively. We conducted two replicate trials comparing single- with multiple-inhaler ICS/LAMA/LABA combination in COPD. METHODS: 207608 and 207609 were Phase IV, 12-week, randomized, double-blind, triple-dummy non-inferiority trials comparing once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg via Ellipta inhaler, with twice-daily budesonide/formoterol (BUD/FOR) 400/12 µg via metered-dose inhaler plus once-daily tiotropium (TIO) 18 µg via HandiHaler. Patients had symptomatic COPD and forced expiratory volume in 1 s (FEV1) < 50% predicted, or FEV1 < 80% predicted and ≥ 2 moderate or 1 severe exacerbations in the prior year. The primary endpoint in both trials was weighted mean change from baseline (wmCFB) in 0-24-h FEV1 at Week 12. Secondary endpoints included CFB in trough FEV1 at Day 84 and 85. Other endpoints included serial FEV1 and health status outcomes at Week 12. Safety was evaluated descriptively. RESULTS: The modified per-protocol population included 720 and 711 patients in studies 207608 and 207609 (intent-to-treat population: 728 and 732). FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0-24-h FEV1 at Week 12 (Study 207608 treatment difference [95% confidence interval]: 15 mL [- 13, 43]; Study 207609: 11 mL [- 20, 41]). FF/UMEC/VI improved trough FEV1 CFB versus BUD/FOR+TIO at Day 84 and 85 (Day 85 treatment difference: Study 207608: 38 mL [10, 66]; Study 207609: 51 mL [21, 82]) and FEV1 at 12 and 24 h post-morning dose at Week 12 in both studies. No treatment differences were seen in health status outcomes. Safety profiles were similar between treatments; pneumonia occurred in 7 (< 1%) patients with FF/UMEC/VI and 9 (1%) patients with BUD/FOR+TIO, across both studies. CONCLUSIONS: FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0-24-h FEV1 at Week 12 in patients with COPD. Greater improvements in trough and serial FEV1 measurements at Week 12 with FF/UMEC/VI versus BUD/FOR+TIO, together with similar health status improvements and safety outcomes including the incidence of pneumonia, suggest that once-daily single-inhaler FF/UMEC/VI triple therapy is a viable option for patients looking to simplify their treatment regimen. TRIAL REGISTRATION: GSK (207608/207609; NCT03478683/NCT03478696).


Assuntos
Broncodilatadores/administração & dosagem , Nível de Saúde , Pulmão/fisiologia , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Idoso , Androstadienos/administração & dosagem , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do Tratamento
6.
Opt Express ; 27(21): 29676-29684, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684225

RESUMO

Laser wakefield accelerators have emerged as a promising candidate for compact synchrotron radiation and even x-ray free electron lasers. Today, to make the electrons emit electromagnetic radiation, the trajectories of laser wakefield accelerated electrons are deflected by transverse wakefield, counter-propagating laser field or external permanent magnet insertion device. Here, we propose a novel type of undulator that has a period of a few hundred microns and a magnetic field of tens of Tesla. The undulator consists of a bifilar capacitor-coil target that sustains a strong discharge current that generates a helical magnetic field around the coil axis when irradiated by a high-energy laser. Coupling this undulator with state-of-the-art laser wakefield accelerators can, simultaneously, produce ultra-bright quasi-monochromatic x-rays with tunable energy ranging 5-250 keV and optimize the free electron laser parameter and gain length compared with a permanent magnet-based undulator. This concept may pave a path toward ultra-compact synchrotron radiation and even x-ray free electron lasers.

7.
Opt Express ; 26(6): 7107-7116, 2018 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-29609397

RESUMO

We demonstrate generation of 0.2 mJ terahertz (THz) pulses in lithium niobate driven by Ti:sapphire laser pulses at room temperature. Employing tilted pulse front technique, the 800 nm-to-THz energy conversion efficiency has been optimized to 0.3% through chirping the sub-50 fs pump laser pulses to overcome multi-photon absorption and to extend effective interaction length for phase matching. Our approach paves the way for mJ-level THz generation via optical rectification using existing Ti:sapphire laser systems which can deliver Joule-level pulse energy with sub-50 fs pulse duration.

8.
Respir Res ; 19(1): 19, 2018 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-29370819

RESUMO

BACKGROUND: Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg has been shown to improve lung function and health status, and reduce exacerbations, versus budesonide/formoterol in patients with chronic obstructive pulmonary disease (COPD). We evaluated the non-inferiority of single-inhaler FF/UMEC/VI versus FF/VI + UMEC using two inhalers. METHODS: Eligible patients with COPD (aged ≥40 years; ≥1 moderate/severe exacerbation in the 12 months before screening) were randomized (1:1; stratified by the number of long-acting bronchodilators [0, 1 or 2] per day during run-in) to receive 24-week FF/UMEC/VI 100/62.5/25 µg and placebo or FF/VI 100/25 µg + UMEC 62.5 µg; all treatments/placebo were delivered using the ELLIPTA inhaler once-daily in the morning. Primary endpoint: change from baseline in trough forced expiratory volume in 1 s (FEV1) at Week 24. The non-inferiority margin for the lower 95% confidence limit was set at - 50 mL. RESULTS: A total of 1055 patients (844 [80%] of whom were enrolled on combination maintenance therapy) were randomized to receive FF/UMEC/VI (n = 527) or FF/VI + UMEC (n = 528). Mean change from baseline in trough FEV1 at Week 24 was 113 mL (95% CI 91, 135) for FF/UMEC/VI and 95 mL (95% CI 72, 117) for FF/VI + UMEC; the between-treatment difference of 18 mL (95% CI -13, 50) confirmed FF/UMEC/VI's was considered non-inferior to FF/VI + UMEC. At Week 24, the proportion of responders based on St George's Respiratory Questionnaire Total score was 50% (FF/UMEC/VI) and 51% (FF/VI + UMEC); the proportion of responders based on the Transitional Dyspnea Index focal score was similar (56% both groups). A similar proportion of patients experienced a moderate/severe exacerbation in the FF/UMEC/VI (24%) and FF/VI + UMEC (27%) groups; the hazard ratio for time to first moderate/severe exacerbation with FF/UMEC/VI versus FF/VI + UMEC was 0.87 (95% CI 0.68, 1.12). The incidence of adverse events was comparable in both groups (48%); the incidence of serious adverse events was 10% (FF/UMEC/VI) and 11% (FF/VI + UMEC). CONCLUSIONS: Single-inhaler triple therapy (FF/UMEC/VI) is non-inferior to two inhalers (FF/VI + UMEC) on trough FEV1 change from baseline at 24 weeks. Results were similar on all other measures of efficacy, health-related quality of life, and safety. TRIAL REGISTRATION: GSK study CTT200812; ClinicalTrials.gov NCT02729051 (submitted 31 March 2016).


Assuntos
Androstadienos/administração & dosagem , Álcoois Benzílicos/administração & dosagem , Broncodilatadores/administração & dosagem , Clorobenzenos/administração & dosagem , Nebulizadores e Vaporizadores/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinuclidinas/administração & dosagem , Administração por Inalação , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
9.
Am J Respir Crit Care Med ; 196(4): 438-446, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28375647

RESUMO

RATIONALE: Randomized data comparing triple therapy with dual inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) are limited. OBJECTIVES: We compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy in patients with COPD. METHODS: The FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) trial was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticasone furoate/umeclidinium/vilanterol 100 µg/62.5 µg/25 µg; ELLIPTA inhaler) with twice-daily ICS/LABA therapy (budesonide/formoterol 400 µg/12 µg; Turbuhaler). A patient subgroup remained on blinded treatment for up to 52 weeks. Co-primary endpoints were change from baseline in trough FEV1 and in St. George's Respiratory Questionnaire (SGRQ) total score at Week 24. MEASUREMENTS AND MAIN RESULTS: In the intent-to-treat population (n = 1,810) at Week 24 for triple therapy (n = 911) and ICS/LABA therapy (n = 899), mean changes from baseline in FEV1 were 142 ml (95% confidence interval [CI], 126 to 158) and -29 ml (95% CI, -46 to -13), respectively, and mean changes from baseline in SGRQ scores were -6.6 units (95% CI, -7.4 to -5.7) and -4.3 units (95% CI, -5.2 to -3.4), respectively. For both endpoints, the between-group differences were statistically significant (P < 0.001). There was a statistically significant reduction in moderate/severe exacerbation rate with triple therapy versus dual ICS/LABA therapy (35% reduction; 95% CI, 14-51; P = 0.002). The safety profile of triple therapy reflected the known profiles of the components. CONCLUSIONS: These results support the benefits of single-inhaler triple therapy compared with ICS/LABA therapy in patients with advanced COPD. Clinical trial registered with www.clinicaltrials.gov (NCT02345161).


Assuntos
Androstadienos/uso terapêutico , Álcoois Benzílicos/uso terapêutico , Budesonida/uso terapêutico , Clorobenzenos/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinuclidinas/uso terapêutico , Administração por Inalação , Broncodilatadores/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Qualidade de Vida
10.
COPD ; 13(2): 167-75, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26516724

RESUMO

Patients' preference is an important factor in selecting an inhaler treatment for COPD. The DISKUS® dry powder inhaler (DPI), which has been available to deliver several COPD medications for a decade, and the ELLIPTA® DPI, developed for the delivery of newer once-daily medications for patients with COPD, were studied in terms of patient preference and inhaler-specific attributes. We conducted a randomized, open-label, crossover study in patients with COPD. Patients used placebo ELLIPTA DPI once daily and placebo DISKUS DPI twice daily, for ∼1 week each, while continuing their COPD medications. Endpoints were: inhaler preference based on size of the numbers on the dose-counter (primary); the number of steps needed and inhaler size (secondary); and based on comfort of the mouthpiece, ease of opening, overall preference, and dosing regimen preference ('other'). Safety assessments included adverse events (AEs). A total of 287 patients were randomized. A significantly (p < 0.001) larger proportion of patients preferred the ELLIPTA DPI over DISKUS DPI for each of the tested attributes and overall, and preferred once-daily over twice-daily dosing. AEs were reported for 36 patients (13%); one (dry mouth) was considered to be related to the placebo-containing DISKUS DPI. Three patients had five non-fatal serious AEs, none were deemed inhaler-related. This study demonstrated that more patients with COPD preferred five specific inhaler attributes of the ELLIPTA DPI over DISKUS DPI and overall, and preferred once-daily versus twice-daily dosing. Safety profiles were consistent with those expected for COPD.


Assuntos
Broncodilatadores/administração & dosagem , Cooperação do Paciente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Relação Dose-Resposta a Droga , Esquema de Medicação , Inaladores de Pó Seco , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
11.
Pulm Pharmacol Ther ; 31: 85-91, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25197005

RESUMO

BACKGROUND: The bronchodilator response to short-acting ß2-agonist and short-acting muscarinic antagonist monotherapies varies on a day-to-day basis within individual patients. The objective of this study was to compare daily variation in bronchodilator response to the combined use of albuterol and ipratropium with monotherapies in patients with chronic obstructive pulmonary disease (COPD). METHODS: This was a 4-week, randomized, open-label, two-period crossover study in patients with COPD. Patients were randomized 1:1 to receive albuterol via metered dose inhaler followed by ipratropium or vice versa during treatment Period 1 (10-14 days). The order of treatments was then reversed during treatment Period 2 (10-14 days). Pre-defined efficacy endpoints were: forced expiratory volume in 1 s (FEV1), derived FEV1, inspiratory capacity (IC) and daily variability of FEV1 and IC as measured by coefficient of variation (CV). RESULTS: Albuterol and ipratropium improved FEV1 when administered as the first bronchodilator, compared with pre-dose values (0.269 and 0.243 L, respectively). Administration of the second bronchodilator provided further improvements in lung function, but to a lesser magnitude than the first bronchodilator (0.094 L for both treatments). A statistically significant reduction in daily variability in FEV1 was observed for dual bronchodilator therapy compared with monotherapy (difference in CV = 0.007; p = 0.019) and pre-dose values (no treatment; difference in CV = 0.022; p < 0.001). CONCLUSIONS: The free combination of albuterol and ipratropium resulted in greater improvements and lower day-to-day variability in FEV1 compared with either monotherapy or no bronchodilator therapy. The reduced daily variability may be an important therapeutic advantage of using different classes of bronchodilators in COPD. TRIAL REGISTRATION: NCT01691482.


Assuntos
Albuterol/uso terapêutico , Broncodilatadores/uso terapêutico , Ipratrópio/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Idoso , Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Estudos Cross-Over , Esquema de Medicação , Quimioterapia Combinada , Feminino , Volume Expiratório Forçado , Humanos , Ipratrópio/administração & dosagem , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória
12.
BMC Pulm Med ; 15: 91, 2015 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-26286141

RESUMO

BACKGROUND: Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD). This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment. METHODS: Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg. Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety. RESULTS: Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001). UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL. Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George's Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks. The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common. CONCLUSIONS: Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment. TRIAL REGISTRATION: NCT01822899 Registration date: March 28, 2013.


Assuntos
Combinação Fluticasona-Salmeterol/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinuclidinas/administração & dosagem , Administração por Inalação , Adulto , Broncodilatadores/administração & dosagem , Método Duplo-Cego , Feminino , Seguimentos , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do Tratamento
17.
Pharmacol Res Perspect ; 11(2): e01054, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36846967

RESUMO

The aim of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK3772847, compared with placebo administered subcutaneously (SC) in healthy participants, including cohorts of Japanese and Chinese participants. This was a single-center, randomized, placebo-controlled, double-blind, single ascending dose study. Following a screening period of up to 28 days, eligible participants were assigned to one of four cohorts receiving a single dose of GSK3772847 70 mg (cohort 1) or 140 mg (cohorts 2, 3, and 4) or placebo SC. In cohorts 1 and 2, participants were randomly assigned to one of three injection sites (upper arm, abdomen, or thigh), while cohorts 3 and 4 included Japanese and Chinese participants, respectively, assigned to receive GSK3772847 or placebo SC (upper arm). Participants attended follow-up visits on Days 9, 15, 29, 43, 57, 71, and 85 before final analysis. GSK3772847 was generally well tolerated. Most adverse events (AEs) were mild, resolved without treatment and were considered not related to study treatment by the investigator. There were no serious AEs or deaths during the study. The PK and PD were dose dependent, with negligible differences across injection sites or ethnicities. Target engagement was demonstrated by reduced free soluble interleukin 33 (sIL-33) concentrations and substantially increased total sIL-33 concentrations compared with baseline. Subcutaneously administered GSK3772847 was well tolerated in healthy participants, including cohorts of Japanese and Chinese participants, and shows consistent PK and PD across injection sites and ethnicities.


Assuntos
Voluntários Saudáveis , Humanos , Método Duplo-Cego
18.
Am J Bot ; 99(12): e501-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23196392

RESUMO

PREMISE OF THE STUDY: In Chinese bayberry (Myrica rubra), the available simple sequence repeat (SSR) markers are insufficient to meet the developing demand for genetic and molecular breeding research. This study was aimed at developing a large number of polymorphic expressed sequence tag (EST)-SSRs from the transcriptome of Chinese bayberry. • METHODS AND RESULTS: Five hundred ninety-four compound EST-SSRs and 5557 noncompound ones were identified from 41239 unigene sequences generated from the transcriptome of M. rubra cv. Biqi. Using 10 Chinese bayberry cultivars, 109 polymorphic EST-SSRs were screened from 412 selected. In total, they generated 389 alleles, with a polymorphism ratio of 93.8%. In addition, it was observed that the polymorphism levels of compound EST-SSRs were somewhat lower than those of noncompound ones. • CONCLUSIONS: The 109 polymorphic EST-SSRs developed from the Chinese bayberry transcriptome should greatly promote the development of genetic and molecular breeding studies in this as well as other Myricaceae species.


Assuntos
Primers do DNA/genética , DNA de Plantas/genética , Etiquetas de Sequências Expressas , Repetições de Microssatélites , Myrica/genética , Polimorfismo Genético , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Transcriptoma
19.
Plant Sci ; 314: 111115, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34895544

RESUMO

Kiwifruit plants have a fleshy, shallow root system which is sensitive to waterlogging stress, which results in a decrease in crop yield or even plants death. Although the waterlogging stress responses in kiwifruit have attracted much attention, the underlying molecular mechanism remains unclear. In this study, waterlogging led to drastic inhibition of root growth of 'Donghong' kiwifruit (Actinidia chinensis) plants grown in vitro, which was accompanied by significant elevation of endogenous acetaldehyde and ethanol contents. RNA-seq of roots of plants waterlogged for 0, 1 and 2 days revealed that a total of 149 genes were up- or down-regulated, including seven biosynthetic genes related to the glycolysis/gluconeogenesis pathway and 10 transcription factors. Analyses with real-time PCR, dual-luciferase assays and EMSA demonstrated that AcERF74 and AcERF75, two members of the ERF-VII subfamily, directly upregulated AcADH1 (alcohol dehydrogenase). Moreover, the overexpression of AcERF74/75 in transgenic calli resulted in dramatic increase of endogenous ethanol contents through the triggering of AcADH1 and AcADH2 expression. Although the AcPDC2 (pyruvate decarboxylase) expression was also enhanced in transgenic lines, the endogenous acetaldehyde contents showed no significant changes. These results illustrated that AcERF74/75 are two transcriptional activators on alcoholic fermentation related genes and are responsive to waterlogging stress in kiwifruit.


Assuntos
Actinidia/crescimento & desenvolvimento , Actinidia/genética , Actinidia/metabolismo , Fermentação/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Fatores de Transcrição/metabolismo , Adaptação Fisiológica/genética , Adaptação Fisiológica/fisiologia , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Desidratação/fisiopatologia , Fermentação/fisiologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Fatores de Transcrição/genética
20.
Rev Sci Instrum ; 93(4): 043104, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35489950

RESUMO

The uncertainties of spot size and position need to be clarified for x-ray sources as they can affect the detecting precision of the x-ray probe beam in applications such as radiography. In particular, for laser-driven x-ray sources, they would be more significant as they influence the inevitable fluctuation of the driving laser pulses. Here, we have employed the penumberal coded aperture imaging technique to diagnose the two-dimensional spatial distribution of an x-ray emission source spot generated from a Cu solid target irradiated by an intense laser pulse. Taking advantage of the high detection efficiency and high spatial resolution of this technique, the x-ray source spot is characterized with a relative error of ∼5% in the full width at half maximum of the intensity profile in a single-shot mode for general laser parameters, which makes it possible to reveal the information of the unfixed spot size and position precisely. Our results show the necessity and feasibility of monitoring the spot of these novel laser-driven x-ray sources via the penumbral coded aperture imaging technique.

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