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1.
Respir Res ; 20(1): 283, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842883

RESUMO

BACKGROUND: There are limited data available on whether drug-induced hepatotoxicity (DIH) affects the clinical outcomes of tuberculosis (TB) treatment. We explored the effects of DIH on the clinical course and outcomes of pulmonary TB. METHODS: In this retrospective cohort study, we included patients with culture-proven pulmonary TB treated in a tertiary hospital from 2013 to 2016. DIH was defined as proposed by the official American Thoracic Society statement. We compared the clinical outcomes of DIH and non-DIH patients. RESULTS: Between January 1, 2013 and December 31, 2016, a total of 168 TB patients were included, and 20 (11.9%) were diagnosed with DIH. These patients were significantly older, had a higher Charlson Comorbidity Index score, exhibited more chronic liver disease, included more chronic alcoholics, and had a lower body mass index than non-DIH patients. We found no significant differences between DIH and non-DIH patients in the 2-month sputum culture conversion rate, the time to sputum culture conversion, treatment outcomes, or total treatment duration. However, the ratio of treatment interruption time to total treatment duration and the proportion of hepatotonic users were significantly higher among DIH patients. CONCLUSION: DIH development during TB treatment does not significantly affect the clinical outcomes of pulmonary TB. However, treatment interruption caused by DIH may increase the risks of future relapse and acquired resistance. Further study is needed.


Assuntos
Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Antituberculosos/administração & dosagem , Carga Bacteriana , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Esquema de Medicação , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/crescimento & desenvolvimento , Recidiva , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Escarro/microbiologia , Fatores de Tempo , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia
2.
Soft Matter ; 12(3): 674-7, 2016 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-26539746

RESUMO

Herein, we investigated the wetting behavior of hexagonally close-packed polystyrene bead arrays with different bead diameters and surface flatness. The contact angle was found to be influenced by the surface roughness as well as the contact area of the polystyrene bead array with a water droplet.

3.
J Korean Med Sci ; 31(12): 2002-2009, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27822942

RESUMO

This study aimed at exploring the psychometric characteristics of the Korean Version of the Depression and Somatic Symptoms Scale (DSSS) in a clinical sample, and investigating the impact of somatic symptoms on the severity of depression. Participants were 203 consecutive outpatients with current major depressive disorders (MDD) or lifetime diagnosis of MDD. The DSSS was compared with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the 17-items Hamilton Depression Rating Scale (HAMD). The DSSS showed a two-factor structure that accounted for 56.8% of the variance, as well as excellent internal consistency (Cronbach's alpha = 0.95), concurrent validity (r = 0.44-0.82), and temporal stability (intraclass correlation coefficient = 0.79). The DSSS had a high ability to identify patients in non-remission (area under receiver operating characteristic [ROC] curve = 0.887). Maximal discrimination between remission and non-full remission was obtained at a cut-off score of 22 (sensitivity = 82.1%, specificity = 81.4%). The number of somatic symptoms (the range of somatic symptoms) and the scores on the somatic subscale (SS, the severity of somatic symptoms) in non-remission patients were greater than those in remission patients. The number of somatic symptoms (slope = 0.148) and the SS score (slope = 0.472) were confirmed as excellent predictors of the depression severity as indicated by the MADRS scores. The findings indicate that the DSSS is a useful tool for simultaneously, rapidly, and accurately measuring depression and somatic symptoms in clinical practice settings and in consultation fields.


Assuntos
Transtorno Depressivo Maior/patologia , Adulto , Área Sob a Curva , Transtorno Depressivo Maior/diagnóstico , Feminino , Humanos , Masculino , Sintomas Inexplicáveis , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , Curva ROC , República da Coreia , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Inquéritos e Questionários , Traduções
4.
Langmuir ; 31(1): 249-53, 2015 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-25494033

RESUMO

Liquid phase deposition (LPD) is a useful method for the production of oxide film with low reaction temperature and production cost. With the report that the LPD of oxide films is conformally processed with uniform thickness and composition, there has been significant attention given to investigating its kinetic controls and growth mechanism on the flat surface. In this work, we explored the LPD of silicon dioxide on the hexagonally close-packed silica beads array as a nanostructured surface. The deposition and etching reactions of SiO2 occurred locally and simultaneously on silica beads, and were distinguished from the amount of fumed silica added in LPD solution. From locally competitive reactions, we obtained the anisotropic morphology of close-packed silica beads, and proposed a mechanism for the local LPD of SiO2 driven by nanostructured surfaces. This work contributes highly to improve metal oxide-based engineering, and also provide greater insight into the topography-driven LPD.

5.
Am J Drug Alcohol Abuse ; 40(1): 75-81, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24266614

RESUMO

BACKGROUND: Ethanol (EtOH) is one of the oldest recreational substances known to man, primarily taken because it induces a sense of well-being (euphoric effects) and relaxation (anxiolytic effects). EtOH use entails various negative consequences. Of particular interest are EtOH-induced psychomotor alterations, because of its immediate manifestation and adverse consequences. Rosa roxburghii (RR), a wild plant of Southwest China, has gained attention on account of its numerous beneficial effects on the immune, nervous, and cardiovascular systems. OBJECTIVE: In the present study we assessed the effects of Rosa roxburghii (RR) on EtOH-induced psychomotor alterations in rats. METHODS: Sprague Dawley rats were orally administered distilled water (control group) or ethanol (4 g/kg BW) (EtOH-group) to induce psychomotor alterations. RR extract (25, 50, and 100 mg/kg, p.o.) was administered 30 min before EtOH treatment (RR-group). EtOH-induced psychomotor alterations were evaluated in the open-field, accelerating rotarod, hanging wire, and cold swimming tests. Behavioral evaluation and hematological analysis (EtOH and acetaldehyde concentration) were done at 1, 2, 4 and 8 hours after EtOH administration. RESULTS: The EtOH group showed psychomotor alterations as compared with the control group. These EtOH-induced psychomotor alterations were directly related to the rise in blood ethanol and acetaldehyde concentrations. Pre-treatment of RR significantly improved EtOH-induced psychomotor alterations on open-field, accelerating rotarod, hanging wire, and cold swimming tests. These improvements in psychomotor performance coincided with the decreased blood ethanol and acetaldehyde levels observed in the RR-treated group. CONCLUSION: These results suggest that RR has ameliorating effects against EtOH-induced psychomotor alterations.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Etanol/antagonistas & inibidores , Etanol/farmacologia , Destreza Motora/efeitos dos fármacos , Resistência Física/efeitos dos fármacos , Rosa , Acetaldeído/sangue , Animais , Relação Dose-Resposta a Droga , Etanol/sangue , Comportamento Exploratório/efeitos dos fármacos , Masculino , Ratos , Teste de Desempenho do Rota-Rod
6.
Angew Chem Int Ed Engl ; 53(24): 6075-9, 2014 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-24596160

RESUMO

Neurite outgrowth is an important preceding step for the development of nerve systems. Given that the in vivo environments of neurons consist of numerous hierarchical micro/nanotopographies, there have been many efforts to investigate the relationship between neuronal behaviors and surface topography. The acceleration of neurite outgrowth was recently reported on surfaces with a periodic nanotopography, but the biological mechanism has not yet been elucidated. In this work, the initial neurite development of hippocampal neurons on assembled silica beads with diameters ranging from 700 to 1800 nm was explored. The acceleration of neurite outgrowth increased with the surface-pitch size and leveled off after a pitch of 1 µm. Biochemical analysis indicated that cytoskeletal actin dynamics were primarily responsible for the recognition of surface topography. This work contributes to the emerging research field of topographical neurochemistry, as well as applied fields including neuroregeneration and neuroprosthetics.


Assuntos
Actinas/química , Citoesqueleto/química , Neuritos/fisiologia , Animais , Crescimento Neuronal , Ratos , Ratos Sprague-Dawley
7.
Food Sci Biotechnol ; 33(7): 1707-1714, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38623436

RESUMO

Attempts to improve low absorption and rapid metabolic conversion of curcumin were made by developing curcumin-loaded bilayer nanoliposomes coated with chitosan and alginate for intestinal-specific drug delivery. A curcumin-loaded nano-liposome was prepared with optimized formulations with phosphatidylcholine, curcumin, chitosan, and alginate. The particle size of the optimized formulation was approximately 400 nm, and the encapsulation efficiency was more than 99%. In the in vitro release study, curcumin release from the curcumin-loaded nanoliposome with double layers of chitosan/alginate (CNL-CH/AL) was suppressed in the simulated gastric fluid (SGF, pH 1.2) and enhanced in the simulated intestinal fluid (SIF, pH 6.8). In the in vivo pharmacokinetic study in rats, the CNL-CH/AL-treated group showed a prolonged absorption pattern of curcumin and the area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was improved 109-fold compared to the control group treated with a curcumin solution without a nanocarrier.

8.
Behav Pharmacol ; 24(1): 20-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23238086

RESUMO

Previously, we have reported that the N-methyl-D-aspartate (NMDA) receptor antagonist-benzodiazepine veterinary anesthetic combination, zoletil, produced reward and reinforcement, but only in rats repeatedly pretreated with the drug and not in drug-naïve rats. Therefore, we hypothesized that previous drug exposure plays an important role in the abuse of zoletil. In the present study, we examined whether pre-exposure to related substances, NMDA receptor antagonists (tiletamine, ketamine), and benzodiazepines (zolazepam, diazepam) predisposes animals to abuse zoletil. We examined whether animals repeatedly pretreated with tiletamine, ketamine, zolazepam, or diazepam, for 14 days, would show locomotor activation, place preference, and self-administration in response to zoletil. Place preference was observed in groups pretreated with either an NMDA receptor antagonist (ketamine) or a benzodiazepine (diazepam). However, locomotor activation and self-administration were only observed in rats pretreated with NMDA receptor antagonists (tiletamine and ketamine). These results show that pre-exposure to related substances might have induced neurobiological changes that consequently led to the expression of the rewarding and reinforcing effects of zoletil. This provides evidence that zoletil may be used as a substitute drug by abusers of NMDA receptor antagonists or benzodiazepines.


Assuntos
Anestésicos/farmacologia , Proteínas do Tecido Nervoso/antagonistas & inibidores , Neurônios/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Comportamento Espacial/efeitos dos fármacos , Tiletamina/farmacologia , Zolazepam/farmacologia , Anestésicos/administração & dosagem , Anestésicos/efeitos adversos , Anestésicos/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Interações Medicamentosas , Ketamina/efeitos adversos , Ketamina/farmacologia , Locomoção/efeitos dos fármacos , Masculino , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Reforço Psicológico , Recompensa , Autoadministração , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Tiletamina/administração & dosagem , Tiletamina/efeitos adversos , Tiletamina/uso terapêutico , Zolazepam/administração & dosagem , Zolazepam/efeitos adversos , Zolazepam/uso terapêutico
9.
Psychiatry Investig ; 20(2): 144-151, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36891599

RESUMO

OBJECTIVE: Incontrovertible disease markers are absent in delirium. This study investigated the usefulness of quantitative electroencephalography (qEEG) in diagnosing delirium. METHODS: This retrospective case-control study reviewed medical records and qEEG data of 69 age/sex-matched patients (delirium group, n=30; control group, n=39). The first minute of artifact-free EEG data with eyes closed was selected. Nineteen electrodes' sensitivity, specificity, and correlation with delirium rating scale-revised-98 were analyzed. RESULTS: On comparing the means of absolute power by frontal, central, and posterior regions, the delta and theta powers showed significant differences (p<0.001) in all regions, and the magnitude of the absolute power was higher in the delirium group than in the control group; only the posterior region showed a significant (p<0.001) difference in beta power. The spectral power of theta at the frontal region (area under the curve [AUC]=0.84) and theta at the central and posterior regions (AUC=0.83) showed 90% sensitivity and 79% specificity, respectively, in differentiating delirious patients and controls. The beta power of the central region showed a significant negative correlation with delirium severity (R=-0.457, p=0.011). CONCLUSION: Power spectrum analysis of qEEG showed high accuracy in screening delirium among patients. The study suggests qEEG as a potential aid in diagnosing delirium.

10.
Korean J Intern Med ; 36(1): 1-10, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32972121

RESUMO

BACKGROUND/AIMS: Although a majority of coronavirus disease 2019 (COVID-19) cases were characterized as mild, data assessing the development of pneumonia in mild COVID-19 patients are limited. We aimed to examine the effect of pneumonia development on the clinical course of mild COVID-19 in hospitalized patients. METHODS: A retrospective cohort study was conducted via medical record review between February 25, 2020 and April 11, 2020 at a single center. The impact of pneumonia development on the time to viral clearance in mild COVID-19 patients was evaluated. Risk factors associated with the development of pneumonia were also identified. RESULTS: Chest radiographs revealed the development of pneumonia in 26.8% of mild COVID-19 patients. The time to pneumonia development was a median of 8.0 days from the onset of symptoms and 3.5 days after hospital admission. A multivariate analysis for predicting pneumonia development identified age ≥ 65 years (odds ratio [OR], 3.15; 95% confidence interval [CI], 1.14 to 8.73), cough (OR, 2.18; 95% CI, 1.29 to 3.68), dyspnea (OR, 3.58; 95% CI, 1.10 to 11.69), and diarrhea (OR, 2.69; 95% CI, 1.51 to 4.78) as significant variables. The time to negative conversion was longer in mild COVID-19 patients who developed pneumonia (23.6 days vs. 18.4 days, p = 0.003). In Kaplan-Meier estimation and multivariate Cox regression analyses, newly developed pneumonia was significantly related with delayed time to negative conversion (log-rank test, p = 0.02; hazard ratio, 2.90; 95% CI, 1.06 to 7.97). CONCLUSION: The development of pneumonia delayed viral clearance in patients with mild COVID-19. Elderly patients or those suffering from diarrhea should be closely monitored, given the increased risk of developing pneumonia.


Assuntos
COVID-19/virologia , Pulmão/virologia , SARS-CoV-2/patogenicidade , Adolescente , Adulto , COVID-19/complicações , COVID-19/diagnóstico , Progressão da Doença , Feminino , Hospitalização , Interações Hospedeiro-Patógeno , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
11.
Korean J Intern Med ; 36(6): 1410-1419, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32972119

RESUMO

BACKGROUND/AIMS: We assessed the diagnostic yield of chest computed tomography (CT) as an initial diagnostic method for patients with a tuberculosis (TB) infection detected by mass screening in a country with an intermediate TB burden. METHODS: A retrospective study was conducted on patients with TB infection detected by mass screening performed between January 2015 and March 2018. The patients were classified according to whether they had a chest X-ray (CXR) or CT scan as an initial diagnostic test to exclude active TB. RESULTS: Of 542 patients with TB infection detected by mass screening, 222 and 320 were initially examined by CXR and CT, respectively; the two modalities showed no significant difference in rate of detection of patients with active TB (0.9% and 2.5%, respectively; p = 0.110). However, chest CT was associated with further invasive tests using bronchoscopy and respiratory specimens, and significantly increased the frequency of hospital visits. CONCLUSION: Chest CT was not supported as an initial diagnostic method to rule out active TB in patients with a TB infection detected by mass screening in a country with an intermediate TB burden.


Assuntos
Radiografia Torácica , Tuberculose , Humanos , Programas de Rastreamento , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Tuberculose/diagnóstico por imagem
12.
Chest ; 159(1): 128-137, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32805240

RESUMO

BACKGROUND: The presence and progression of interstitial lung abnormalities (ILAs) is known to be associated with a decline of lung function and increased risk of mortality. RESEARCH QUESTION: We aimed to elucidate the clinical course according to ILAs in patients with COPD. STUDY DESIGN AND METHODS: A retrospective study was conducted between January 2013 and December 2018 of COPD patients who underwent chest CT imaging and longitudinal pulmonary function tests. We evaluated radiologic findings, history of acute exacerbations of COPD, and lung function changes during the longitudinal follow-up. RESULTS: Of 363 patients with COPD, 44 and 103 patients had equivocal and definite ILAs, respectively. Patients with ILAs were significantly older and had lower FEV1 and FVC than patients without ILAs. During the mean follow-up period of 5.2 years, ILAs were associated significantly with the annual incidence of moderate to severe acute exacerbation of COPD (ß ± SD, 0.38 ± 0.12; P = .002) and with the risk of frequent exacerbation (adjusted OR, 2.03; P = .045). Patients with progressive ILAs showed a significantly higher rate of annual decline in FEV1 and FVC than those showing no change in, or improved, ILAs. INTERPRETATION: ILAs were associated significantly with moderate to severe acute exacerbation in patients with COPD, and the progression of ILAs was associated with an accelerated decline in lung function.


Assuntos
Doenças Pulmonares Intersticiais/complicações , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Estudos Retrospectivos , Exacerbação dos Sintomas , Tomografia Computadorizada por Raios X , Capacidade Vital
13.
Ann Palliat Med ; 9(5): 3584-3592, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921096

RESUMO

BACKGROUND: HX110-A and HX110-B are compound extracts based on radix adenophorae and rhizoma dioscoreae, respectively, which have anti-inflammatory activity. There are limited data on whether they may help improve respiratory conditions including lung function. Therefore, in this trial, we will evaluate the effectiveness and safety of the use of HX110-A and HX110-B for the treatment of respiratory health in adults with mild respiratory symptoms. METHODS: This will be an 8-week, randomized, double-blind, parallel group, placebo-controlled trial with three arms. Adults more than 40 years old with persistent respiratory symptoms will be enrolled. Patients with definite respiratory disease or with a history of recent intake of antioxidants or anti-inflammatory agents will be excluded. Study subjects will be assigned at a 1:1:1 ratio into the following three arms: controls, experimental group 1 (HX110-A), and experimental group 2 (HX110-B). Control or experimental foods will be administered for 8 weeks, and follow-up will be up to 12 weeks. The primary outcome will be total antioxidant capacity. Secondary outcomes will be inflammatory indexes, respiratory symptoms, lung function, quality of life, and fatigue level. Safety outcomes will be assessed by monitoring adverse events and vital signs, and through clinical pathology tests. RESULTS: This trial will reveal the effectiveness and safety of HX110-A and/or HX110-B for medical purposes in adults with respiratory symptoms. The results should clarify if active intake of specific foods with these functional compounds may promote respiratory health in adults without definite respiratory disease. TRIAL REGISTRATION: Clinical Research Information Service, KCT0003614. Registered 12 May 2019 (Respectively registered, https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=13364).


Assuntos
Qualidade de Vida , Adulto , Método Duplo-Cego , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Korean J Intern Med ; 35(6): 1411-1423, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31752478

RESUMO

BACKGROUND/AIMS: Only a few epidemiologic studies on the patients with pulmonary disorders admitted to intensive care unit exist. We investigated the characteristics and clinical outcomes of the patients with severe pulmonary disorders. METHODS: The sample cohort database of National Health Insurance Sharing Service from 2006 to 2015 was used. Operational definition of critically ill patients was adults who were either admitted to intensive care unit for at least 3 days or expired within first 2 days in the unit. The pulmonary disorder group comprised of critically ill patients with respiratory disease as the main diagnosis. RESULTS: Among the 997,173 patients, 12,983 (1.3%) in 383 intensive care units were categorized as critically ill. Patients in the pulmonary disorder group tended to have more comorbidities or disabilities. The length of hospital stay and duration of mechanical ventilation were longer in the pulmonary disorder group. Overall mortality and re-admission were higher in the pulmonary disorder group, with adjusted incidence rate ratios of 1.22 (95% confidence interval, 1.18 to 1.27) and 1.26 (95% confidence interval, 1.17 to 1.36), respectively. After adjustment by Cox regression, the pulmonary disorder group was an independent risk factor for in-hospital mortality. CONCLUSION: In critically ill patients with pulmonary disorder, the use of healthcare resources was higher, and their clinical outcomes were significantly worse than the non-pulmonary disorder group.


Assuntos
Estado Terminal , Unidades de Terapia Intensiva , Pneumopatias , Adulto , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Pneumopatias/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Pharmacology ; 83(6): 367-78, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19451752

RESUMO

The present study describes the bladder-relaxant properties of LDD175 (4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo [3,2-b]indole-1-carboxylic acid), a novel benzofuroindole compound. LDD175 had no significant effect on the spontaneous and electrically evoked bladder contractions, but produced concentration-dependent relaxation in strips precontracted by 1 micromol/l acetylcholine (pEC(50) = 5.9 +/- 0.2, E(max) = 90.3 +/- 2.6%; 100 micromol/l, n = 6). In high K(+)- (20 and 80 mmol/l) stimulated samples, LDD175 caused a concentration-dependent relaxant activity which was significant in 20 mmol/l K(+) (pEC(50) = 5.6 +/- 0.2, E(max) = 63.1 +/- 4.8%, n = 6), but not in 80 mmol/l K(+) (pEC(50) = 5.1 +/- 0.3, E(max) = 12.7 +/- 2.5%, n = 6). Iberiotoxin (100 nmol/l), a specific BKCa blocker, attenuated the compound's relaxative effect (vehicle = 65.7 +/- 9.2% vs. iberiotoxin 28.0 +/- 3.5%, respectively, n = 3), but not tetraethylammonium chloride (10 mmol/l), a nonselective K(+) channel blocker, barium chloride (10 mmol/l), a conventional K(IR) blocker, and glibenclamide (1 mmol/l), a K(ATP) blocker. LDD175 was evaluated in both endothelium-intact and denuded rat aorta contracted with high K(+). In these preparations, LDD175 did not produce significant inhibition. Administered intravenously to conscious restrained rats, LDD175 (10 mg/kg) did not alter the rat's hemodynamic activity (i.e. blood pressure and heart rate). When tested in the spontaneously hypertensive rats (SHR) for its influence on their voiding behavior, LDD175 (5 and 10 mg/kg) significantly reduced voiding frequency and lengthened void intervals of the animals. These observations: (1) reveal the BKCa channel potentiation of LDD175; (2) support previous claims concerning the bladder (vs. vascular) selectivity of benzofuroindole compounds; (3) demonstrate the efficacy of LDD175 in the animal model of bladder overactivity (SHR). Therefore, the compound may be potentially useful in the treatment of bladder overactivity.


Assuntos
Benzofuranos/farmacologia , Benzofuranos/uso terapêutico , Indóis/farmacologia , Indóis/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária/efeitos dos fármacos , Animais , Aorta Torácica/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Canais de Potássio Cálcio-Ativados/agonistas , Distribuição Aleatória , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Micção/efeitos dos fármacos
16.
Arch Pharm Res ; 32(3): 413-20, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19387586

RESUMO

LDD175 (4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid) is a benzofuroindole compound characterized previously as a potent opener of the large conductance calcium activated (BK(Ca)) channels. Activators of the BK(Ca) channels are potential therapies for smooth muscle hyperactivity disorders. The present study investigates the influence of LDD175 on the mechanical activity of the ileum smooth muscle. LDD175 inhibited spontaneous contractions of the ileum in a concentration-dependent manner (pEC(50)=5.9 +/- 0.1) (E (max)=96 +/- 1.0% at 100 muM, n=3). It also remarkably inhibited contractions due to acetylcholine (ACh) (pEC(50)=5.3 +/- 0.1)(E (max)=97.7 +/- 2.3%, n=6) and electrical field stimulation (EFS) (pEC(50)=5.5 +/- 0.1) (E (max)=83.3 +/- 6.0%, n=6). In strips precontracted by 20 mM KCl, LDD175 significantly reduced the contractions yielding a pEC(50) of 6.1 +/- 0.1 and E (max) of 96.6 +/- 0.9%, (n=6). In 60 mM KCl, a concentration-dependent inhibition was observed with respective pEC(50) and E (max) values of 4.1 +/- 0.1 and 50.8 +/- 5.0% (n=3). BK(Ca) channel blockers iberiotoxin (IbTX) and tetraethylammonium chloride (TEA, 1 mM) attenuated the relaxative effect of LDD175 but not barium chloride (BaCl(2)), and glibenclamide (K(IR) and K(ATP) channel blockers, respectively). These data demonstrate the antispasmodic activity of LDD175 attributable to the potentiation of the BK(Ca) channels.


Assuntos
Benzofuranos/farmacologia , Agonistas dos Canais de Cálcio/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Íleo/efeitos dos fármacos , Indóis/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/agonistas , Músculo Liso/efeitos dos fármacos , Parassimpatolíticos/farmacologia , Animais , Colinérgicos/farmacologia , Relação Dose-Resposta a Droga , Estimulação Elétrica , Cobaias , Íleo/metabolismo , Técnicas In Vitro , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia
17.
J Neurotrauma ; 25(6): 695-707, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18457515

RESUMO

We previously reported that uridine blocked glucose deprivation-induced death of immunostimulated astrocytes by preserving ATP levels. Uridine phosphorylase (UPase), an enzyme catalyzing the reversible phosphorylation of uridine, was involved in this effect. Here, we tried to expand our previous findings by investigating the uridine effect on the brain and neurons using in vivo and in vitro ischemic injury models. Orally administrated uridine (50-200 mg/kg) reduced middle cerebral artery occlusion (1.5 h)/reperfusion (22 h)-induced infarct in mouse brain. Additionally, in the rat brain subjected to the same ischemic condition, UPase mRNA and protein levels were up-regulated. Next, we employed glucose deprivation-induced hypoglycemia in mixed cortical cultures of neurons and astrocytes as an in vitro model. Cells were deprived of glucose and, two hours later, supplemented with 20 mM glucose. Under this condition, a significant ATP loss followed by death was observed in neurons but not in astrocytes, which were blocked by treatment with uridine in a concentration-dependent manner. Inhibition of cellular uptake of uridine by S-(4-nitrobenzyl)-6-thioinosine blocked the uridine effect. Similar to our in vivo data, UPase expression was up-regulated by glucose deprivation in mRNA as well as protein levels. Additionally, 5-(phenylthio)acyclouridine, a specific inhibitor of UPase, prevented the uridine effect. Finally, the uridine effect was shown only in the presence of astrocytes. Taken together, the present study provides the first evidence that uridine protects neurons against ischemic insult-induced neuronal death, possibly through the action of UPase.


Assuntos
Hipóxia-Isquemia Encefálica/enzimologia , Degeneração Neural/enzimologia , Neurônios/enzimologia , Fármacos Neuroprotetores/farmacologia , Uridina Fosforilase/metabolismo , Uridina/farmacologia , Trifosfato de Adenosina/metabolismo , Administração Oral , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Infarto Encefálico/enzimologia , Infarto Encefálico/fisiopatologia , Infarto Encefálico/prevenção & controle , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Córtex Cerebral/fisiopatologia , Técnicas de Cocultura , Citoproteção/efeitos dos fármacos , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Glucose/deficiência , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/fisiopatologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/enzimologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Degeneração Neural/fisiopatologia , Degeneração Neural/prevenção & controle , Neurônios/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Uridina Fosforilase/efeitos dos fármacos , Uridina Fosforilase/genética
18.
Psychiatry Investig ; 15(2): 178-185, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29475225

RESUMO

OBJECTIVE: Residual symptoms of depression are related to more severe and chronic course of functional impairment with higher risk of relapse. The objective of this study was to validate, and determine psychometric properties of the Korean version of Depression Residual Symptom Scale (KDRSS). METHODS: A total of 203 outpatients with recent episode of major depression based on DSM-IV criteria were enrolled in this study. They had been treated with antidepressants and assessed by KDRSS, Hamilton Depression Rating Scale-24 (HDRS-24), and Montgomery-Åsberg Depression Rating Scale (MARDS). The validity and reliability of KDRSS were assessed, including internal consistency reliability, concurrent validity, temporal stability, factorial validity, and discriminative validity. RESULTS: Internal consistency (Cronbach's alpha=0.961), concurrent validity (MADRS: r=0.731, p<0.01, HDRS-24: r=0.663, p<0.01), and temporal stability (r=0.726, p<0.01) of KDRSS were all excellent. KDRSS showed good discriminative validity based on MARDS. KDRSS consisted of one-factor structure accounting for 63.8% of total variance. All subjects except two in full remission group had one or more residual symptoms. In 7 subscales of KDRSS consisting of similar items respectively, 'lack of energy' was the most commonly reported, followed by 'increased emotionalism' in this group. CONCLUSION: KDRSS is a useful and sensitive instrument for measuring residual depressive symptoms. Since some depressive symptoms including 'lack of energy' and 'increased emotionalism' in patients with full remission might be persistent during psychiatric intervention, these symptoms need to be focused on in clinical practice.

19.
Psychiatry Investig ; 15(6): 574-583, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29788697

RESUMO

OBJECTIVE: This study is a prospective observational study on 75 late-adolescent survivors of a large passenger ship accident from immediately after the accident to one year later. METHODS: Assessments of student survivors were conducted on day 2 and at months 1, 6, and 12. The PTSD Checklist (PCL), Patient Health Questionnaire-9 (PHQ-9), State subscale of the State and Trait Anxiety Inventory (STAI-S), Athens Insomnia Scale (AIS), and Brief Resilience Scale (BRS) were administered. RESULTS: When the assessments for day 2 and month 12 were compared, all the scales, except the PCL-avoidance subscale, showed a significant improvement in symptoms among males. However, among females, all the scales, except the PCL-re-experience subscale and the STAI-S, failed to show a significant improvement. All the symptoms for both males and females showed a pattern that decreased to the lowest level at month 1 (camp-based controlled intervention period), then increased at months 6 and 12 (voluntary individual treatment after returning to school). CONCLUSION: The rapid deterioration of psychological symptoms was found during the chronic phase, when students returned to their daily routines and received voluntary individual therapy. There is a need to screen high-risk adolescents and be more attentive to them during this period.

20.
Eur J Pharmacol ; 574(2-3): 112-9, 2007 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-17692312

RESUMO

In previous studies, we identified sedative effects of Scutellaria baicalensis extracts and found that these extracts or their constituents may also have anticonvulsive effects. Wogonin is a natural product isolated from S. baicalensis, which possesses central nervous system effects such as anxiolytic and neuroprotective activities. In this study, we investigated the effects of wogonin on convulsion related behaviors, such as myorelaxation, motor coordination, and anticonvulsant effects of wogonin on chemical induced seizure and electroshock seizure in mice or rats. The effect of wogonin on membrane potential was also observed. Wogonin was intraperitoneally injected into mice or rats 30 min prior to testing. Animals treated with wogonin did not change locomotor activities as well as endurance times on the rota-rod, which indicates that wogonin did not cause a sedative and myorelaxation effect. Wogonin significantly blocked convulsion induced by pentylenetetrazole and electroshock but not convulsion induced by strychnine. Wogonin also significantly reduced the electrogenic response score, but flumazenil treatment reversed this decrease to the level of the control group. The wogonin treatment increased Cl(-)influx into the intracellular area as dose increased. Flumazenil and bicuculline treatment, however, inhibited the Cl(-) influx induced by wogonin. These results indicate that the anticonvulsive effects produced by wogonin were mediated by the GABAergic neuron.


Assuntos
Anticonvulsivantes/farmacologia , Flavanonas/farmacologia , Scutellaria baicalensis/química , Animais , Cloretos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/fisiologia , Ácido gama-Aminobutírico/fisiologia
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