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1.
Physiother Theory Pract ; 37(6): 719-728, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31294667

RESUMO

Background: Assistive use of short-acting ß2 agonists (SABAs) reportedly improves exercise tolerance, activities of daily living, and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD). However, the effect of SABA on physical activity (PA) is unclear.Objective: This study aimed to determine whether assistive use of SABA increases PA and whether additional pulmonary rehabilitation (PR) can aid further improvement.Methods: Twelve outpatients with COPD and dyspnea during daily activities despite regular use of long-acting bronchodilators were enrolled. This study comprised a 2-week pre-intervention investigation, a 12-week investigation of SABA effects, and an 8-week investigation of the additional effects of PR. Assistive use of SABA was allowed up to 4 times per day after the pre-intervention period. PA was measured for 14 consecutive days using an accelerometer sensor. Dyspnea, exercise tolerance, and HRQOL were evaluated at entry, at 4 and 12 weeks after initiating SABA use, and after completing PR.Results: Assistive use of SABA improved breathlessness during daily activities and increased PA (p < .001). PA and HRQOL were also improved following PR (p < .001 and p = .013, respectively).Conclusions: Combined therapy of SABA and PR can increase PA and HRQOL in COPD patients.


Assuntos
Terapia por Exercício/métodos , Exercício Físico/fisiologia , Procaterol/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/reabilitação , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Terapia Combinada , Humanos , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Testes de Função Respiratória , Teste de Caminhada
2.
Theranostics ; 10(14): 6201-6215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483448

RESUMO

Background: Gastric cancer remains the second leading cause of cancer-related death, and the third in mortality due to lack of effective therapeutic targets for late stage cancer patients. This study aims to identify potential druggable target biomarkers as potential therapeutic options for patients with gastric cancer. Methods: Immunohistochemistry of human gastric tumor tissues was conducted to determine the expression level of cyclin-dependent kinase 12 (CDK12). Multiple in vitro and in vivo assays such as RNAi, mass spectrometry, computer docking models, kinase assays, cell xenograft NU/NU mouse models (CDXs) and patient-derived xenograft NOD/SCID mouse models (PDXs) were conducted to study the function and molecular interaction of CDK12 with p21 activated kinase 2 (PAK2), as well as to find CDK12 inhibitors as potential treatment options for human gastric cancer. Results: Here we identified that CDK12 is a driver gene in human gastric cancer growth. Mechanistically, CDK12 directly binds to and phosphorylates PAK2 at T134/T169 to activate MAPK signaling pathway. We further identified FDA approved clinical drug procaterol can serve as an effective CDK12 inhibitor, leading to dramatic restriction of cancer cell proliferation and tumor growth in human gastric cancer cells and PDXs. Conclusions: Our data highlight the potential of CDK12/PAK2 as therapeutic targets for patients with gastric cancer, and we propose procaterol treatment as a novel therapeutic strategy for human gastric cancer.


Assuntos
Quinases Ciclina-Dependentes/antagonistas & inibidores , Procaterol/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Quinases Ativadas por p21/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Broncodilatadores/farmacologia , Linhagem Celular Tumoral , Quinases Ciclina-Dependentes/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Fosforilação , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases Ativadas por p21/metabolismo
5.
Respir Investig ; 57(2): 133-139, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30612948

RESUMO

BACKGROUND: Assist use of inhaled short-acting beta 2 agonists (SABAs) is reportedly effective for preventing shortness of breath on exertion in chronic obstructive pulmonary disease (COPD) patients. However, it is unclear what strategy would be useful for improving physical activity in such patients. The aim is to investigate the effects of assisted use of SABA (procaterol) on physical activity in Japanese COPD patients targeting patient-specific restrictions in daily behavior. METHODS: Fourteen patients with stable COPD (age: 72.1±1.5, %FEV1: 55.6±4.5%) were asked to inhale 20 µg of procaterol 15 minutes before patient-specific daily physical activity that had been identified as limited by a questionnaire and document their usage in a diary. Physical activity was measured using a triaxial accelerometer and the results were collected every month for 2 months. In the first month, a clinician assessed whether inhalation of SABA was appropriate based on a usage diary and coached patients to conduct adequate assist use of SABA for limited physical activity. RESULTS: The strategy significantly improved the physical activity level, assessed using the values of the metabolic equivalents (METs) multiplied by physical activity endurance, at ≥3.0 METs (p<0.05), and physical activity endurance at ≥2.5 and ≥3.0 METs, (p<0.05, p<0.05, respectively). The degree of improvement of physical activity level was significantly positively correlated with the baseline %FVC and %FEV1 (p<0.05, p<0.05, respectively). CONCLUSIONS: Assist use of SABA targeting patient-specific restrictions, particularly when better lung function is still preserved, could be a useful approach for improving physical activity in patients with COPD.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Exercício Físico , Tutoria , Procaterol/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Administração por Inalação , Idoso , Grupo com Ancestrais do Continente Asiático , Dispneia/etiologia , Dispneia/prevenção & controle , Feminino , Humanos , Masculino , Resistência Física , Doença Pulmonar Obstrutiva Crônica/complicações , Resultado do Tratamento
6.
Pediatr Int ; 60(11): 1014-1019, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30246320

RESUMO

BACKGROUND: Transient tachypnea of the newborn (TTN) is a respiratory disorder that results from inadequate or delayed clearance of fetal lung fluid following delivery. At present, supportive care is generally practiced for the treatment of TTN. In this study, we focused on inhaled beta-agonists for the treatment of TTN, and the aim was to verify the efficacy and the safety of inhaled procaterol for the treatment of TTN. METHODS: Inhaled procaterol or normal saline solution was administered to infants. Respiratory rate and mixed venous carbon dioxide (PvCO2 ) were evaluated as the primary outcomes. The duration of hospitalization, duration of oxygen therapy, and changes in respiratory support were evaluated as secondary outcomes. RESULTS: Thirty-seven neonates diagnosed with TTN were randomly assigned to the procaterol group (n = 18) or the placebo group (n = 19). There were no differences in PvCO2 or respiratory rate between the two groups before and after intervention. Median duration of oxygen therapy (3 days; IQR, 3-6.5 days vs 2 days, IQR, 2-4.75 days; P = 0.13) and of hospitalization (15 days; IQR, 11.25-20 days vs 11 days, IQR, 8-15.5 days; P = 0.14) were not significantly different. CONCLUSIONS: Inhaled procaterol was not effective for the treatment of TTN.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Procaterol/uso terapêutico , Taquipneia Transitória do Recém-Nascido/tratamento farmacológico , Administração por Inalação , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Método Simples-Cego
7.
AAPS J ; 20(5): 84, 2018 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-30003443

RESUMO

Although high-speed laser imaging is the current standard to characterize the plume angle of suspension-based pressurized metered dose inhalers (pMDIs), this method is limited by the inability to identify the drug content in a droplet and simulate inhalation flow. The Plume Induction Port Evaluator (PIPE) is a modified induction port for cascade impactors that allows for the calculation of the angle of a plume based on direct drug mass quantification rather than indirect droplet illumination under airflow conditions. The objective of this study was to investigate the use of the PIPE apparatus to evaluate the effect of airflow on the Mass Median Plume Angle (MMPA) of commercially available suspension-based pMDIs (Ventolin® HFA, ProAir® HFA, and Proventil® HFA). Deposition patterns within PIPE were log-normally distributed allowing for the calculation of the MMPA for the three suspension products. Mass-based plume angles were significantly smaller (narrower angle) when inhalation airflow was used compared to no flow conditions (reduction of MMPA was 8, 16, and 13% for Ventolin® HFA, ProAir® HFA, and Proventil® HFA, respectively). Additionally, new parameters for characterizing plume geometry were calculated (MMPA ex-actuator and plume orientation). Mass-based plume angles of the suspension-based pMDI formulations were highly reproducible and demonstrated the effect of inhalation flow rate. These results suggest that plume geometry tests should be evaluated under flow conditions which is not possible using current methodologies. Graphical Abstract ᅟ.


Assuntos
Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Química Farmacêutica/métodos , Inaladores Dosimetrados , Procaterol/administração & dosagem , Administração por Inalação , Aerossóis , Química Farmacêutica/instrumentação , Desenho de Equipamento , Humanos , Tamanho da Partícula , Pressão
8.
Talanta ; 185: 203-212, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29759190

RESUMO

In the present study, procaterol hydrochloride (ProH) was successfully electropolymerized onto a glass carbon electrode (GCE) with simply cyclic voltammetry scans to construct a poly(procaterol hydrochloride) (p-ProH) membrane modified electrode. Compared with the bare GCE, much higher oxidation peak current responses and better peak potentials separation could be obtained for the simultaneous oxidation of dopamine (DA) and uric acid (UA), owning to the excellent electrocatalytic ability of the p-ProH membrane. And it's based on that a square wave voltammetry (SWV) method was developed to selective and simultaneous measurement of DA and UA. Under the optimum conditions, the linear dependence of oxidation peak current on analyte concentrations were found to be 1.0-100 µmol/L and 2-100 µmol/L, giving detection limits of 0.3 µmol/L and 0.5 µmol/L for DA and UA, separately. The as prepared modified electrode shows simplicity in construction with the merits of good reproducibility, high stability, passable selectivity and nice sensitivity. Finally, the proposed p-ProH membrane modified electrode was successfully devoted to the detection of DA and UA in biological fluids such as human serum and urine with acceptable results.


Assuntos
Técnicas Biossensoriais , Carbono/química , Dopamina/análise , Técnicas Eletroquímicas , Polímeros/química , Procaterol/análogos & derivados , Procaterol/química , Ácido Úrico/análise , Eletrodos , Vidro/química , Humanos
9.
Med Princ Pract ; 27(4): 350-355, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29772569

RESUMO

OBJECTIVES: International guidelines recommend the use of long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease (COPD), but the usefulness of short-acting bronchodilator assist use for stable COPD remains uncertain. The purpose of the present study was to objectively demonstrate the effects of assist use of procaterol, a short-acting ß2-agonist, on the respiratory mechanics of stable COPD patients treated with a long-acting bronchodilator using forced oscillation technique (FOT) and conventional spirometry. We also confirmed the length of time for which procaterol assist could significantly improve the pulmonary function. METHODS: We enrolled 28 outpatients with mild to severe COPD (Global Initiative for Obstructive Lung Disease stages I-III), who had used the same long-acting bronchodilator for longer than 3 months and who were in stable condition. All measures were performed using both FOT and spirometry sequentially from 15 min to 2 h after inhalation. RESULTS: Compared to baseline, inhaled procaterol assist use modestly but significantly improved spirometric and FOT measurements within 2 h after inhalation. These significant effects continued for at least 2 h. -Significant correlations were found between parameters -measured by spirometry and those measured by FOT. CONCLUSIONS: Procaterol assist use modestly but significantly improved pulmonary function determined by spirometry and respiratory mechanics in patients with stable COPD treated with long-acting bronchodilators. Thus, inhaled procaterol has the potential for assist use for COPD.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Procaterol/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Japão , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Procaterol/administração & dosagem , Testes de Função Respiratória , Espirometria
10.
Int J Mol Sci ; 19(3)2018 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-29495403

RESUMO

Sei-hai-to (TJ-90, Qing Fei Tang), a Chinese traditional medicine, increases ciliary beat frequency (CBF) and ciliary bend angle (CBA) mediated via cAMP (3',5'-cyclic adenosine monophosphate) accumulation modulated by Ca2+-activated phosphodiesterase 1 (PDE1A). A high concentration of TJ-90 (≥40 µg/mL) induced two types of CBF increases, a transient increase (an initial increase, followed by a decrease) and a sustained increase without any decline, while it only sustained the CBA increase. Upon inhibiting increases in intracellular Ca2+ concentration ([Ca2+]i) by 10 µM BAPTA-AM (Ca2+-chelator, 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) or Ca2+/calmodulin-dependent PDE1 by 8MmIBMX (a selective PDE1 inhibitor), TJ-90 (400 µg/mL) induced only the sustained CBF increase without any transient CBF increase. The two types of the CBF increase (the transient increase and the sustained increase) induced by TJ-90 (≥40 µg/mL) were mimicked by the stimulation with both procaterol (100 pM) and ionomycin (500 nM). Thus, TJ-90 stimulates small increases in the intracellular cAMP concentration ([cAMP]i) and [Ca2+]i in airway ciliary cells of mice. These small increases in [cAMP]i and [Ca2+]i cause inducing a transient CBF increase or a sustained CBF increase in an airway ciliary cells, depending on the dominant signal, Ca2+-signal, or cAMP-signal.


Assuntos
Cálcio/metabolismo , Cílios/efeitos dos fármacos , AMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Animais , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Feminino , Camundongos , Nigericina/análogos & derivados , Nigericina/farmacologia , Procaterol/farmacologia
11.
Clin Pharmacol Drug Dev ; 7(4): 392-399, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28884969

RESUMO

Procaterol hydrochloride hydrate (procaterol) is a ß2 -adrenergic receptor agonist that induces a strong bronchodilatory effect. The procaterol dry powder inhaler (DPI) has been frequently used in patients with bronchial asthma or chronic obstructive pulmonary disease. We evaluated the bioequivalence and safety between the new procaterol DPI (new DPI) and the approved procaterol DPI (approved DPI). This study was a randomized, double-blind, double-dummy, crossover comparison to evaluate the pharmacodynamic equivalence of the new DPI and the approved DPI in patients with bronchial asthma. Primary efficacy variables were area under the concentration-time curve (AUC) forced expiratory volume in the first second (FEV1 )/h and maximum FEV1 during the 480-minute measurement period. Patients were divided into 2 groups, New-DPI-First (n = 8) and Approved-DPI-First (n = 8), according to the investigational medical product that was administered first. Patients inhaled 20 µg of procaterol in each period. FEV1 was measured by a spirometer at predose and at 15, 30, 60, 90, 120, 180, 240, 360, and 480 minutes after each investigational medical product administration. Equivalence was evaluated by confirming that the 2-sided 90%CIs for the difference between the new and the approved DPI in means of AUC (FEV1 )/h and maximum FEV1 were within the acceptance criteria of -0.15 to 0.15 L. The difference in means of AUC (FEV1 )/h and maximum FEV1 was 0.041 L and 0.033 L, respectively, and the 90%CI was 0.004 to 0.078 L and -0.008 to 0.074 L, respectively. These CIs were both within the acceptance criteria. The new DPI was assessed as being bioequivalent to the approved DPI.


Assuntos
Asma/tratamento farmacológico , Inaladores de Pó Seco , Procaterol/farmacocinética , Adulto , Área Sob a Curva , Estudos Cross-Over , Aprovação de Equipamentos , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Procaterol/administração & dosagem , Equivalência Terapêutica , Resultado do Tratamento
12.
Pulm Pharmacol Ther ; 48: 80-87, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28964817

RESUMO

BACKGROUND: Genetic variation in the ß2-adrenergic receptor (ADRB2) gene has been thought to have an important role in the differential response to ß2-agonist therapy for asthma. However, previous studies have shown little evidence for an association between these ADRB2 variants and the bronchial dilator response (BDR) in chronic obstructive pulmonary disease (COPD) patients. This discrepancy could be explained by differences in the distribution and heterogeneity of pulmonary emphysema in COPD patients, since emphysema distribution and heterogeneity are thought to have a role in pulmonary function in COPD patients. We hypothesized that differences in emphysema distribution and heterogeneity may have masked significant alterations of the bronchodilator response among ADRB2 genotypes in COPD patients in previous studies. METHODS: The BDR (induced by 20 µg of procaterol) was measured in 211 patients who had a smoking history of more than 10 pack/years and had undergone chest high resolution computed tomography examination. A low attenuations area (<960 Hounsfield Units) was identified and the emphysema heterogeneity index (EHI%) was calculated with a range in value from -100% to 100%. ADRB2 Arg16Gly genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The BDR was augmented in patients with homogenous emphysema compared with those with upper-dominant emphysema. In patients carrying the AA genotype of ADRB2, the BDR was significantly increased in patients with upper-dominant emphysema, but not in patients with lower-dominant emphysema. CONCLUSION: Combination analysis of ADRB2 Arg16Gly polymorphism and EHI% may predict the effectiveness of ß2-adrenergic receptor agonist treatment in patients with COPD and emphysema.


Assuntos
Broncodilatadores/farmacologia , Procaterol/farmacologia , Enfisema Pulmonar/tratamento farmacológico , Receptores Adrenérgicos beta 2/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Enfisema Pulmonar/fisiopatologia , Tomografia Computadorizada por Raios X
13.
Intern Med ; 56(15): 1949-1955, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28768962

RESUMO

Objective The 6-min walk test (6MWT) is a simple test that is used to examine the exercise tolerance and outcomes in patients with chronic obstructive pulmonary disease (COPD). Although the 6MWT is useful for assessing exercise tolerance, it is difficult to evaluate time-dependent parameters such as the walking pattern. A modified 6MWT has been devised to assess the walking pattern by calculating the number of steps per second (NSPS). This study was performed to investigate walking pattern of COPD patients in the modified 6MWT before and after a single inhalation of the short-acting ß2-agonist procaterol. Methods Nine male COPD patients participated in this study. The 6MWT was performed before and after the inhalation of procaterol hydrochloride. A digital video recording of the 6MWT was made. After the 6MWT, the number of steps walked by the subject in each 5-s period was counted manually with a hand counter while viewing the walking test on the video monitor. Results After the inhalation of procaterol, the 6-min walking distance increased significantly in comparison to baseline (p<0.01). The mean NSPS was also significantly increased after the inhalation of procaterol in comparison to baseline (p<0.01). The walking pattern was displayed on a graph of time versus NSPS, and the walking pace was shown by a graph of time versus cumulative steps. Conclusion The analysis of the COPD patients' walking test performance and their walking pattern and pace in the 6MWT may help to evaluate the effects of drug treatment.


Assuntos
Broncodilatadores/uso terapêutico , Procaterol/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Teste de Caminhada/métodos , Administração por Inalação , Idoso , Idoso de 80 Anos ou mais , Broncodilatadores/administração & dosagem , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procaterol/administração & dosagem , Fatores de Tempo
14.
Talanta ; 174: 436-443, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28738604

RESUMO

Poly(glutamic acid) (P-GLU)/carboxyl functionalized multiwalled carbon nanotubes (MWCNTs-COOH)/polyvinyl alcohol (PVA) modified glassy carbon electrode (GCE) has been successfully prepared and the electrochemical behavior of procaterol hydrochloride (ProH) was studied. The results show that the as-prepared modified electrode exhibits a good electrocatalytic property towards the oxidation of ProH in 0.2M phosphate buffer solution (PBS) (pH 6.0) due to the enhanced oxidation peak current at ~+0.59V. Under optimal reaction conditions, the oxidation peak current of ProH is proportional to its concentration in the linear dynamic ranges of 0.060 - 8.0µM (R = 0.9974), with a detection limit of 8.0 × 10-9M. Finally, this method was efficiently used for the determination of ProH in tablets and human urine with recoveries of 88.5~98.7% and 89.2 ~ 108.0%, respectively.


Assuntos
Eletroquímica/instrumentação , Vidro/química , Ácido Glutâmico/química , Nanotubos de Carbono/química , Ácido Poliglutâmico/química , Álcool de Polivinil/química , Procaterol/análise , Eletrodos , Humanos , Modelos Moleculares , Conformação Molecular , Polimerização , Procaterol/urina
15.
Respir Care ; 62(9): 1123-1130, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28611228

RESUMO

BACKGROUND: Albuterol hydrofluoroalkane (HFA) either alone or with a valved holding chamber is used to treat bronchoconstriction. Delays between actuation and inhalation are common. Currently, the recommended interval between actuations of an albuterol HFA is 60 s. Using a shorter interval when multiple actuations are ordered will improve productivity in the hospital setting. METHODS: We studied aerosol characteristics of albuterol HFA (Ventolin, ProAir, and Proventil) with a cascade impactor calibrated at 30 L/min. We studied pressurized metered-dose inhalers (pMDI) alone, coupled to a nonelectrostatic valved holding chamber, and coupled to the valved holding chamber but introducing a 10-s delay between actuation and measurement. We tested intervals between actuations of 60, 30, and 15 s (not for delay scenario). The variable of most interest was fine-particle mass. Albuterol was measured by spectrophotometer (276 nm). RESULTS: Variations in fine-particle mass from 60-s values were < 15% for Ventolin and ProAir for all conditions tested and for Proventil with a valved holding chamber. Variations in fine-particle mass from 60-s values were > 15% for Proventil (pMDI alone with a 30-s interval and pMDI/valved holding chamber with delay and a 30-s interval). Adding a valved holding chamber increased fine-particle mass for all brands (ProAir 7-12%, Ventolin 26-35%, and Proventil 44-47%). The introduction of a 10-s delay reduced fine-particle mass for all brands (ProAir 34-39%, Ventolin 39-42%, and Proventil 27-32%). Comparison of fine-particle mass among brands showed that Proventil was > ProAir > Ventolin. CONCLUSIONS: Decreasing the interval between actuations from 60 to 30 and 15 s does not seem to affect the aerosol characteristics of ProAir and Ventolin. Although some changes were noticed for Proventil, the pMDI outperformed Ventolin that had the lowest fine-particle mass. The use of a valved holding chamber increased fine-particle mass, but introducing a 10-s delay between actuation and inhalation significantly reduced fine-particle mass.


Assuntos
Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Hidrocarbonetos Fluorados/administração & dosagem , Inaladores Dosimetrados , Fatores de Tempo , Administração por Inalação , Aerossóis/administração & dosagem , Esquema de Medicação , Sistemas de Liberação de Medicamentos , Humanos , Procaterol/administração & dosagem
16.
Respir Res ; 18(1): 79, 2017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28464879

RESUMO

BACKGROUND: Epithelial-mesenchymal transition is currently recognized as an important mechanism for the increased number of myofibroblasts in cancer and fibrotic diseases. We have already reported that epithelial-mesenchymal transition is involved in airway remodeling induced by eosinophils. Procaterol is a selective and full ß2 adrenergic agonist that is used as a rescue of asthmatic attack inhaler form and orally as a controller. In this study, we evaluated whether procaterol can suppress epithelial-mesenchymal transition of airway epithelial cells induced by eosinophils. METHODS: Epithelial-mesenchymal transition was assessed using a co-culture system of human bronchial epithelial cells and primary human eosinophils or an eosinophilic leukemia cell line. RESULTS: Procaterol significantly inhibited co-culture associated morphological changes of bronchial epithelial cells, decreased the expression of vimentin, and increased the expression of E-cadherin compared to control. Butoxamine, a specific ß2-adrenergic antagonist, significantly blocked changes induced by procaterol. In addition, procaterol inhibited the expression of adhesion molecules induced during the interaction between eosinophils and bronchial epithelial cells, suggesting the involvement of adhesion molecules in the process of epithelial-mesenchymal transition. Forskolin, a cyclic adenosine monophosphate-promoting agent, exhibits similar inhibitory activity of procaterol. CONCLUSIONS: Overall, these observations support the beneficial effect of procaterol on airway remodeling frequently associated with chronic obstructive pulmonary diseases.


Assuntos
Eosinófilos/fisiologia , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Procaterol/administração & dosagem , Mucosa Respiratória/citologia , Mucosa Respiratória/fisiologia , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Brônquios/citologia , Brônquios/diagnóstico por imagem , Brônquios/fisiologia , Linhagem Celular , Relação Dose-Resposta a Droga , Eosinófilos/citologia , Eosinófilos/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Mucosa Respiratória/efeitos dos fármacos , Resultado do Tratamento
17.
Pflugers Arch ; 469(9): 1215-1227, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28477148

RESUMO

This study demonstrated that PDE1 (phosphodiesterase 1) existing in the ciliary beat frequency (CBF)-regulating metabolon regulates CBF in procaterol-stimulated lung airway ciliary cells of mouse. Procaterol (an ß2-agonist) increased the ciliary bend angle (CBA) and CBF via cAMP accumulation in the ciliary cells of mice: interestingly, the time course of CBF increase was slower than that of CBA increase. However, IBMX (3-isobutyl-1-methylxanthine, an inhibitor of PDE) increased CBA and CBF in an identical time course. Lowering an intracellular Ca2+ concentration ([Ca2+]i) caused by switching to an EGTA-containing Ca2+-free solution from normal one elevated the procaterol-induced increasing rate of CBF. These observations suggest that Ca2+-dependent PDE1 controls cAMP-stimulated CBF increase. Either application of 8MmIBMX (8-methoxymethyl-IBMX, a selective PDE1 inhibitor), BAPTA-AM (an intracellular Ca2+ chelator), or calmidazolium (an inhibitior of calmodulin) alone increased CBA and CBF in the lung airway ciliary cells and increased cAMP contents in the isolated lung cells, and like IBMX, each application of the compound made the time courses of CBA and CBF increase stimulated by procaterol identical. The immunoelectron microscopic examinations revealed that PDE1A exists in the space between the nine doublet tubules ring and plasma membrane in the lung airway cilium, where the outer dynein arm (a molecular motor regulating CBF) functions. In conclusion, PDE1A is a key factor slowing the time course of the procaterol-induced increase in CBF via degradation of cAMP in the CBF-regulating metabolon of the mouse lung airway cilia.


Assuntos
Cálcio/farmacologia , Cílios/efeitos dos fármacos , Cílios/metabolismo , AMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 1/antagonistas & inibidores , Animais , Calmodulina/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Procaterol/farmacologia
18.
Respir Physiol Neurobiol ; 240: 41-47, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28238903

RESUMO

The aim of this retrospective study was to assess responses to a bronchodilator by forced oscillation technique (FOT) and to relate the results of respiratory impedance (Zrs) to spirometric parameters in patients with chronic obstructive pulmonary disease (COPD). Zrs was measured as a function of frequency from 4 to 36Hz before and after inhalation of procaterol, a short-acting ß2-agonist (n=60). Respiratory resistance (Rrs) and reactance (Xrs) were significantly frequency-dependent, and inspiratory and expiratory phases were different both before and after procaterol inhalation. The Rrs at 4Hz and Xrs at 4-20Hz during a whole breath were significantly improved after procaterol inhalation. The response to procaterol inhalation varied among patients, and changes in Xrs at 4Hz significantly correlated with% change in forced expiratory volume in one second and changes in forced vital capacity. Taken together, Zrs, and specifically Xrs parameters, are sensitive to acute physiological responses to a bronchodilator in COPD.


Assuntos
Broncodilatadores/uso terapêutico , Volume Expiratório Forçado/efeitos dos fármacos , Procaterol/farmacologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Resistência das Vias Respiratórias/efeitos dos fármacos , Análise de Variância , Broncodilatadores/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oscilometria , Procaterol/uso terapêutico , Testes de Função Respiratória , Estudos Retrospectivos , Espirometria , Volume de Ventilação Pulmonar/efeitos dos fármacos
19.
J Asthma ; 54(5): 479-487, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27880056

RESUMO

OBJECTIVE: It has been hypothesized that some patients with chest tightness of unknown origin can be successfully treated with a bronchodilator and that they should be diagnosed with chest pain variant asthma. We conducted a prospective study to characterize newly diagnosed patients with chest tightness relieved with bronchodilator use and without characteristic bronchial asthma attacks. METHODS: Eleven patients were registered following recurrent positive responses of chest tightness to inhalation of a ß2-agonist. These patients underwent assessments of airway responsiveness to methacholine, bronchial biopsy and bronchial lavage under fiber-optic bronchoscopy before receiving treatment. RESULTS: For the patients with chest tightness relieved with bronchodilator use, the bronchial biopsy specimens exhibited significant increases in lymphocyte and macrophage infiltration (p < 0.05) and no significant increase in eosinophils (p = 0.2918) compared with the control subjects. The bronchial responsiveness to methacholine was increased in two of the patients with chest tightness, and it was not increased in seven; in addition, increased percentages of eosinophils were detected in bronchial lavage fluid (5% or more) from two patients, but no increase was detected in eight patients. CONCLUSIONS: We suspect that the chest tightness was induced by airway constriction in these patients, but further study is necessary to validate this hypothesis. We propose that the chest tightness relieved with bronchodilator use was attributed to airway constriction resulting from inflammation with lymphocytes and macrophages and/or that the chest tightness was directly attributed to airway inflammation. This clinical trial is registered at www.umin.ac.jp (UMIN13994 and UMIN 16741).


Assuntos
Broncodilatadores/farmacologia , Broncodilatadores/uso terapêutico , Dor no Peito/tratamento farmacológico , Dor no Peito/imunologia , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Idoso , Obstrução das Vias Respiratórias/tratamento farmacológico , Obstrução das Vias Respiratórias/imunologia , Asma/tratamento farmacológico , Asma/imunologia , Hiper-Reatividade Brônquica , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/citologia , Broncoscopia , Doença Crônica , Eosinófilos/metabolismo , Feminino , Fluticasona/farmacologia , Fluticasona/uso terapêutico , Humanos , Linfócitos/metabolismo , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Procaterol/farmacologia , Procaterol/uso terapêutico , Estudos Prospectivos , Testes de Função Respiratória
20.
Luminescence ; 32(5): 745-750, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27862870

RESUMO

Based on the strong enhancement effect of procaterol hydrochloride on the electrochemiluminescence (ECL) of Ru(bpy)32+ (bpy = 2,2'-bipyridine) in an alkaline H3 PO4 -NaOH buffer solution on a bare Pt electrode, a simple, rapid and sensitive method was developed for the determination of procaterol hydrochloride. The optimum conditions for the enhanced ECL have been developed in detail in this work. Under optimum conditions, the logarithmic ECL enhancement vs. the logarithmic concentration of procaterol hydrochloride is linear over a wide concentration range of 2.0 × 10-7 to 2.0 × 10-4  M (r = 0.9976), with a limit of detection of 1.1 × 10-8  M (S/N = 3), and a relative standard deviation of 2.1% (n = 7, c = 5.0 × 10-6  M). The proposed method was applied to the determination of this drug in tablets with recoveries of 89.7%-98.5%. In addition, a possible mechanism for the enhanced ECL of Ru(bpy)32+ , which is caused by ProH, has also been proposed.


Assuntos
Medições Luminescentes/métodos , Compostos Organometálicos/química , Procaterol/análise , Procaterol/química , 2,2'-Dipiridil/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Concentração de Íons de Hidrogênio , Limite de Detecção , Rutênio/química , Comprimidos/análise , Comprimidos/química
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