RESUMEN
The two most abundant isoforms of amyloid-ß (Aß) are the 40- (Aß40) and 42-residue (Aß42) peptides. Since they coexist and there is a correlation between toxicity and the ratio of the two isoforms, quantitative characterization of their interactions is crucial for understanding the Aß aggregation mechanism. In this work, we follow the aggregation of individual isoforms in a mixture using single-molecule FRET spectroscopy by labeling Aß42 and Aß40 with the donor and acceptor fluorophores, respectively. We found that there are two phases of aggregation. The first phase consists of coaggregation of Aß42 with a small amount of Aß40, while the second phase results mostly from aggregation of Aß40. We also found that the aggregation of Aß42 is slowed by Aß40 while the aggregation of Aß40 is accelerated by Aß42 in a concentration-dependent manner. The formation of oligomers was monitored by incubating mixtures in a plate reader and performing a single-molecule free-diffusion experiment at several different stages of aggregation. The detailed properties of the oligomers were obtained by maximum likelihood analysis of fluorescence bursts. The FRET efficiency distribution is much broader than that of the Aß42 oligomers, indicating the diversity in isoform composition of the oligomers. Pulsed interleaved excitation experiments estimate that the fraction of Aß40 in the co-oligomers in a 1:1 mixture of Aß42 and Aß40 varies between 0 and 20%. The detected oligomers were mostly co-oligomers especially at the physiological ratio of Aß42 and Aß40 (1:10), suggesting the critical role of Aß40 in oligomer formation and aggregation.
RESUMEN
Background: Patients with chronic obstructive pulmonary disease (COPD) expressing eosinophilia experience slightly fewer episodes of community-acquired pneumonia (CAP) than those without eosinophilia. However, the severity and burden of hospitalized pneumonia patients with COPD concerning eosinophilia have not been assessed. Methods: We evaluated the differences in clinical characteristics between patients with CAP and COPD with or without eosinophilia by a post-hoc analysis of a prospective, multi-center, cohort study data. Results: Of 349 CAP patients with COPD, 45 (12.9%) had eosinophilia (blood eosinophil ≥ 300 cells/µL). Patients with eosinophilia had a lower sputum culture percentile (8.1% vs. 23.4%, P < 0.05), a lower percentile of neutrophils (70.3% vs 80.2%, P<0.05), reduced C-reactive protein levels (30.6 mg/L vs 86.6 mg/L, P<0.05), and a lower pneumonia severity index score (82.5 vs. 90.0, P < 0.05) than those without eosinophilia. The duration of antibiotic treatment (8.0 days vs. 10.0 days, P < 0.05) and hospitalization (7.0 days vs. 9.0 days, P < 0.05) were shorter in eosinophilic patients. The cost of medical care per day (256.4 US$ vs. 291.0 US$, P < 0.05), cost for the medication (276.4 US$ vs. 349.9 US$, P < 0.05), and cost for examination (685.5 US$ vs 958.1 US$, P<0.05) were lower in patients with eosinophilia than those without eosinophilia. Conclusion: Eosinophilia serves as a favorable marker for severity of pneumonia, health-care consumption, and cost of medical care in patients with CAP and COPD.
RESUMEN
BACKGROUND: Handgrip strength (HGS) is acknowledged as a key indicator of overall physical fitness and is associated with various health outcomes. OBJECTIVES: This research investigates the correlation between HGS and quality of life (QoL), focusing on its relation to pulmonary function in the general adult population. METHOD: The study involved 19,402 participants aged 40 and above, spanning from 2014 to 2019, who underwent pulmonary function and HGS tests. Participants were categorized based on lung function, and regression analyses were employed to examine the relationship between HGS and QoL, with adjustments made for lung function. RESULTS: The average age of the cohort was 58.2 years, comprising 44.6% males and 41.2% smokers. Out of the 18,708 participants who completed the European Quality of Life Scale-Five Dimensions (EQ-5D-3L) assessment, higher severity levels in mobility, self-care, usual activities, pain or discomfort, and anxiety or depression were linked to lower HGS in both sexes. Additionally, among the 3,723 participants who completed the Health-related Quality of Life Instrument with 8 Items (HINT-8) assessment, higher severity levels in pain, work, and depression were associated with lower HGS in men. In women, higher severity levels in climbing stairs, pain, vitality, and work correlated with lower HGS. CONCLUSIONS: As problems indicated by EQ-5D worsened, there was a consistent decrease in handgrip strength (HGS) across both genders. The HINT-8 assessment further revealed that increased severity in pain and work-related issues led to reduced HGS in both men and women. This study highlights the relationship between HGS and Quality of Life (QoL), taking lung function into consideration, and underscores the importance of HGS as a potential marker of physical health and fitness.
Asunto(s)
Fuerza de la Mano , Calidad de Vida , Adulto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pulmón , Ansiedad , DolorRESUMEN
BACKGROUND/AIMS: Chronic obstructive pulmonary disease (COPD) is less prevalent in females than males, but it affects mortality in females. There may be sex differences in the clinical characteristics of COPD. METHODS: We analyzed the Korea National Health and Nutrition Examination Survey dataset from 2007 to 2018. We compared the clinical characteristics and comorbidities in subjects with COPD according to sex. We adjusted the multivariate logistic regression of lung cancer prevalence according to COPD and sex by age and smoking amount. RESULTS: Females with COPD tended to be older than males with COPD (64.1 ± 0.4 yr vs. 62.3 ± 0.2 yr, respectively, p < 0.001). Approximately 89% of males with COPD had a smoking history, while 86% of females with COPD were non-smokers (p < 0.001). Household income was lower (p < 0.001) and asthma and overall malignancy were more prevalent in females with COPD than males with COPD (25.5 vs. 11.6%, respectively, p < 0.001; (6.3 vs. 5.4%, respectively, p < 0.001). However, lung cancer was more common in males with COPD than females with COPD (0.9 vs. 0.1%, respectively, p < 0.001). Lung cancer prevalence increased in males with moderate COPD compared to subjects without COPD (OR, 4.409; 95% CI, 1.741-9.419). CONCLUSION: Females with COPD had a lower smoking rate, household income, and lung cancer prevalence than males with COPD. More active COPD screening is needed for women of low socioeconomic status, even if they do not smoke.
Asunto(s)
Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Femenino , Humanos , Masculino , Encuestas Nutricionales , Caracteres Sexuales , Factores de Riesgo , Factores Sexuales , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Neoplasias Pulmonares/epidemiología , República de Corea/epidemiología , PrevalenciaRESUMEN
Soluble oligomers produced during protein aggregation have been thought to be toxic species causing various diseases. Characterization of these oligomers is difficult because oligomers are a heterogeneous mixture, which is not readily separable, and may appear transiently during aggregation. Single-molecule spectroscopy can provide valuable information by detecting individual oligomers, but there have been various problems in determining the size and concentration of oligomers. In this work, we develop and use a method that analyzes single-molecule fluorescence burst data of freely diffusing molecules in solution based on molecular diffusion theory and maximum likelihood method. We demonstrate that the photon count rate, diffusion time, population, and Förster resonance energy transfer (FRET) efficiency can be accurately determined from simulated data and the experimental data of a known oligomerization system, the tetramerization domain of p53. We used this method to characterize the oligomers of the 42-residue amyloid-ß (Aß42) peptide. Combining peptide incubation in a plate reader and single-molecule free-diffusion experiments allows for the detection of stable oligomers appearing at various stages of aggregation. We find that the average size of these oligomers is 70-mer and their overall population is very low, less than 1â nM, in the early and middle stages of aggregation of 1â µM Aß42 peptide. Based on their average size and long diffusion time, we predict the oligomers have a highly elongated rod-like shape.
RESUMEN
BACKGROUND/AIMS: The overall incidence of pneumococcal pneumonia is declining. However, the change in the pathogenic distribution of community-acquired pneumonia (CAP) in chronic obstructive pulmonary disease (COPD) patients and the serotype specificity of Streptococcus pneumoniae have not been evaluated in the post-era of pneumococcal vaccination in Korea. METHODS: We conducted a prospective, multi-center, cohort study from seven University-affiliated hospitals. The primary objective was the identification of serotype-specific prevalence of pneumococcal pneumonia in COPD patients hospitalized for CAP. For the purpose, we conducted serotype-specific urine antigen detection (SS-UAD) assays for S. pneumoniae. The secondary objectives were other clinical characteristics of pneumonia including vaccination status. RESULTS: The total number of participants was 349. Most of them were male (95.1%) with old ages (75.55 ± 8.59 y). The positive rate for S. pneumoniae was 9.2% with SS-UAD assay and the common serotypes were 22F, 6A, and 6B. In the sputum, Pseudomonas aeruginosa (5.0%) and Haemophilus influenzae (4.0%) were common pathogens. The vaccination rate was 78.8%, 53.0%, and 25.8% for influenza, pneumococcal polysaccharide vaccine 23 (PPV 23), and pneumococcal protein- conjugated vaccine 13 (PCV 13), respectively. Thirteen patients died during hospitalization (mortality rate; 3.7%). There was no difference in the respective rate of influenza vaccination (79.2% vs. 69.2%, p = 0.288) and PCV 13 vaccination (25.6% vs. 30.8%, p = 0.443) between survivors and the deceased. CONCLUSION: Serotypes 22F, 6A, and 6B, which are covered either by PPV 23 or by PCV 13, are still common pneumococcal serotypes in COPD pneumonia in the post-vaccination era in Korea.
Asunto(s)
Gripe Humana , Neumonía Neumocócica , Humanos , Masculino , Femenino , Streptococcus pneumoniae , Serogrupo , Neumonía Neumocócica/diagnóstico , Neumonía Neumocócica/epidemiología , Estudios de Cohortes , Prevalencia , Estudios ProspectivosRESUMEN
In single-molecule free diffusion experiments, molecules spend most of the time outside a laser spot and generate bursts of photons when they diffuse through the focal spot. Only these bursts contain meaningful information and, therefore, are selected using physically reasonable criteria. The analysis of the bursts must take into account the precise way they were chosen. We present new methods that allow one to accurately determine the brightness and diffusivity of individual molecule species from the photon arrival times of selected bursts. We derive analytical expressions for the distribution of inter-photon times (with and without burst selection), the distribution of the number of photons in a burst, and the distribution of photons in a burst with recorded arrival times. The theory accurately treats the bias introduced due to the burst selection criteria. We use a Maximum Likelihood (ML) method to find the molecule's photon count rate and diffusion coefficient from three kinds of data, i.e., the bursts of photons with recorded arrival times (burstML), inter-photon times in bursts (iptML), and the numbers of photon counts in a burst (pcML). The performance of these new methods is tested on simulated photon trajectories and on an experimental system, the fluorophore Atto 488.
RESUMEN
BACKGROUND/AIMS: Hip fracture and acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) could increase mortality in patients with COPD. There are no data on the relationship between AE-COPD and hip fracture, which may significantly affect the prognosis of patients with COPD. Therefore, we conducted this study to determine the effects of AE-COPD on hip fractures in patients with COPD. METHODS: This retrospective, nested, case-control study included 253,471 patients with COPD (≥ 40 years of age) identified from the Korea National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) from 2002 to 2015. Among 176,598 patients with COPD, 1,415 patients with hip fractures were identified. Each case was matched to one control for age (within 10 years), sex, and year of COPD diagnosis. We estimated the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for hip fractures associated with AE-COPD using conditional logistic regression analysis, adjusting for underlying diseases and smoking history. RESULTS: In patients with AE-COPD, the risk of hip fracture was 2.50 times higher, regardless of systemic corticosteroid use and underlying disease (aOR, 2.50; 95% CI, 1.67 to 3.75). The risk of hip fracture increased if there was one episode of AE in the year before hip fractures (aOR, 2.25; 95% CI, 1.66 to 3.05). Moreover, the risk of hip fracture also increased in patients with more than two episodes of AE the year before hip fractures (aOR, 2.57; 95% CI, 1.61 to 4.10). CONCLUSION: AE-COPD increases the risk of hip fracture regardless of underlying diseases, including osteoporosis, and treatment with systemic corticosteroids.
Asunto(s)
Fracturas de Cadera , Enfermedad Pulmonar Obstructiva Crónica , Estudios de Casos y Controles , Niño , Fracturas de Cadera/diagnóstico , Fracturas de Cadera/epidemiología , Fracturas de Cadera/etiología , Humanos , Programas Nacionales de Salud , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: This pilot study aimed to investigate the current status of e-cigarettes (ECs) use patterns among patients with chronic airway disease or chronic respiratory symptoms and the effects of ECs use on respiratory and mental health. METHODS: A cross-sectional survey was conducted at the outpatient clinic of eight teaching hospitals in South Korea between November 2019 and December 2019. All adult ECs users (19 years and above) who visited the outpatient clinic as a patient with chronic airway disease or chronic respiratory symptoms were eligible to participate in this study. RESULTS: A total of 51 subjects responded to the survey. Most of the participants were male (92.2%) and the mean age was 41.8 years. Dominant airway diseases were asthma and chronic obstructive pulmonary disease. Most of the subjects had a history of cigarette smoking, and 19 subjects were dual users of current cigarettes and ECs. Most of the subjects started ECs use due to health-related reasons. When comparing exclusive ECs users and dual users, St. George's respiratory questionnaire (SGRQ) scores, the proportion of cases with moderate to severe depressive symptoms, and average Fagerstrom test for nicotine dependence scores for ECs were higher in dual users than exclusive ECs users (mean 4.64 vs. 2.38, p = 0.006), respectively. CONCLUSION: Most of the subjects started ECs use due to health concerns, but dual users have more respiratory symptoms and higher nicotine dependence in this pilot study. One hypothesis that comes from these results is that greater nicotine dependence may influence behaviours, habits, and views about ECs. These preliminary observations need confirmation in a large cohort.
Asunto(s)
Asma , Sistemas Electrónicos de Liberación de Nicotina , Enfermedad Pulmonar Obstructiva Crónica , Vapeo , Adulto , Estudios Transversales , Humanos , Masculino , Proyectos Piloto , Fumar/efectos adversos , Vapeo/efectos adversosRESUMEN
BACKGROUND: This study aimed to investigate the association between e-cigarette (EC) use and development of acute severe pneumonia in the Korean population using a national database. METHODS: We conducted a retrospective analysis using linkage of data between the Korean National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service (NHIS) administrative claims database. The primary endpoint of this study was development of severe pneumonia requiring hospital admission according to EC use during the study period. The secondary endpoints were in-hospital mortality, intensive care unit (ICU) admission, ventilator care, and days of hospital stay. RESULTS: The final analysis included 28,950 individuals, of which 578 (2.0%) were EC users. EC users were younger and more often male than non-EC users. The EC users showed higher level of education and household income and had fewer comorbidities. Severe pneumonia was noted in 37 of 28,372 non-EC users (0.13%), but there were no occurrences of severe pneumonia in EC users. The incidence of pneumonia occurrence was not different between the two groups (P = 1.000). CONCLUSIONS: Since e-cigarette or vaping use-associated lung injury (EVALI) is most likely included in acute severe pneumonia occurring within 3 months of EC use, it is considered that there might be no EVALI patients in Korea during the investigation period. A large-scale, prospective study is necessary to evaluate the association between EC use and acute lung injury.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Neumonía/diagnóstico , Adulto , Bases de Datos Factuales , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Almacenamiento y Recuperación de la Información , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud , Encuestas Nutricionales , Neumonía/epidemiología , Neumonía/etiología , Neumonía/mortalidad , República de Corea/epidemiología , Estudios Retrospectivos , Fumadores/estadística & datos numéricos , Vapeo/efectos adversosRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with frequent hospitalizations, higher mortality, and healthcare costs. Low-income COPD patients have higher rates of emergency department visits and hospitalization due to COPD exacerbation. However, other causes of admissions and their economic burden have not been well-elucidated. METHODS: We analyzed the Korean National Health and Nutrition Examination Survey (KNHANES) dataset for 2007-2015. The diagnosis and staging of COPD were based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. RESULTS: Among the 97,622 participants in KNHANES for 2007-2015, we selected 33,963 participants (4,430 with and 29,533 without COPD) aged ≥40 years, who underwent spirometry, and provided the admission history for the previous year. Participants with COPD had a higher admission rate than those without COPD (12.8% vs. 10.4%, P<0.001). The admission rate increased as the stage of COPD advanced from GOLD 1 to GOLD 4 for total causes (11.5%, 13.6%, 15.1%, and 25.0%, respectively, P<0.001) and respiratory illnesses (0.5%, 1.3%, 4.6%, and 12.5%, respectively, P<0.001). The proportion of the lowest quartile household income increased in the late stages of COPD (GOLD 1-4; 35.2%, 32.1%, 44.9%, and 70.8%, respectively, P<0.01). CONCLUSIONS: The hospitalization rate increased in advanced COPD, while GOLD stages 3 and 4 were associated with deterioration in economic status.
RESUMEN
BACKGROUND: E-cigarettes are steadily gaining popularity in Korea. However, the characteristics of e-cigarette smokers, especially nicotine dependence and stress susceptibility, have not been evaluated in comparison to those of non-smokers or combustible cigarette smokers in Korea. METHODS: In this study, 28,059 participants from the Korea National Health and Nutrition Examination Survey (2013-2017) were classified into the following three groups: non-smokers, smokers (current smokers and ex-smokers of combustible cigarettes only), and e-smokers (current smokers and ex-smokers of e-cigarettes regardless of combustible cigarette use). RESULTS: Among the participants, 16,980 (60.5%), 9,247 (33.0%), and 1,832 (6.4%) subjects were non-smokers, smokers, and e-smokers, respectively. E-smokers were younger, more educated, and had a higher household income than non-smokers or smokers. The number of e-smokers who smoked within 5 minutes of waking up (31.5% vs. 19.8%, p<0.001) and who planned to quit smoking within 6 months (39.1% vs. 35.7%, p<0.05) was greater than that of smokers. E-smokers perceived stress as "very much" (7.0% vs. 4.4%, p<0.001) and "a lot" (29.1% vs. 20.5%, p<0.001) compared to non-smokers. Suicidal ideation (6.5% vs. 4.7%, p<0.001), plans (2.4% vs. 1.3%, p<0.001), and attempts (1.1% vs. 0.5%, p<0.001) were higher in e-smokers than in non-smokers. Depressive episodes in 1 year (14.2% vs. 11.4%, p<0.05) and suicidal plans (2.4% vs. 1.8%, p<0.05) were more frequent among e-smokers than among smokers. CONCLUSION: E-smokers were younger, more educated, and had a higher income, but they were more dependent on nicotine and susceptible to stress than non-smokers and smokers. Smoking cessation counseling should be tailored according to the characteristics of e-smokers.
RESUMEN
Raising the tax on tobacco-related products is the most effective and sustainable intervention for smoking cessation. The 2015 tobacco-tax increase resulted in a decreased smoking rate among Korean adult men. However, participation in the government-sponsored smoking-cessation programs developed after the 2015 tobacco tax increase has declined sharply since 2018. The popularity of electronic cigarettes (e-cigarettes) seems to be an important factor in this decline. Indeed, the market share of e-cigarettes has increased steadily since 2007, when the e-cigarette was introduced in Korea as a vaporizer. The introduction of the tobacco-heating device IQOS in 2017 resulted in the skyrocketing popularity of e-cigarettes, especially among the young generation of Koreans. The U.S. Food and Drug Administration (FDA) authorized marketing of IQOS as a "reduced exposure" tobacco product on July 7, 2020, further complicating smoking-cessation efforts. The agency announced that IQOS produces fewer or lower levels of some toxins than combustible cigarettes. However, FDA authorization does not mean that these products are safe. There is no evidence that reducing the harmful chemical components leads to health benefits. Clinicians need to maintain the position that those who smoke, regardless of tobacco-product type, should be counseled for smoking cessation and prescribed appropriate proven pharmacologic agents.
RESUMEN
We describe theory, experiments, and analyses of three-color Förster resonance energy transfer (FRET) spectroscopy for probing sub-millisecond conformational dynamics of protein folding and binding of disordered proteins. We devise a scheme that uses single continuous-wave laser excitation of the donor instead of alternating excitation of the donor and one of the acceptors. This scheme alleviates photophysical problems of acceptors such as rapid photobleaching, which is crucial for high time resolution experiments with elevated illumination intensity. Our method exploits the molecular species with one of the acceptors absent or photobleached, from which two-color FRET data is collected in the same experiment. We show that three FRET efficiencies and kinetic parameters can be determined without alternating excitation from a global maximum likelihood analysis of two-color and three-color photon trajectories. We implement co-parallelization of CPU-GPU processing, which leads to a significant reduction of the likelihood calculation time for efficient parameter determination.
Asunto(s)
Algoritmos , Transferencia Resonante de Energía de Fluorescencia/métodos , Modelos Teóricos , Conformación Proteica , Pliegue de Proteína , Proteínas/química , Color , Transferencia Resonante de Energía de Fluorescencia/instrumentación , Transferencia Resonante de Energía de Fluorescencia/estadística & datos numéricos , Proteínas Intrínsecamente Desordenadas/química , Proteínas Intrínsecamente Desordenadas/metabolismo , Cinética , Microscopía Confocal , Fotoblanqueo , Fotones , Unión Proteica , Proteínas/metabolismo , Factores de TiempoRESUMEN
BACKGROUND: Lead exposure is a resurgent environmental issue globally. Smoking can be a source of lead exposure, although the majority of lead poisonings originate from workplace exposures. However, no study has been undertaken concerning the blood lead levels based on the chronic obstructive pulmonary disease (COPD), smoking status, and other risk factors of COPD. This cross-sectional study was conducted to investigate the blood lead levels according to COPD and clinical variables associated with COPD. METHODS: Data (total number =53,829) were collected from the Korean National Health and Nutrition Examination Survey (IV in 2008 and 2009, V in 2010-2012, and VI in 2013). Multivariable linear regression analyses were performed to determine variables associated with elevated blood lead levels. RESULTS: Univariate regression analysis showed that male sex, older age, smoking, occupation level, income level, education level, and presence of COPD were related to higher blood lead levels, whereas the other co-morbidities including diabetes, hypertension, cerebral stroke, osteoporosis, asthma, and depression were not related (P<0.05). Multivariable regression analysis demonstrated that older age, male sex, smoking, occupation, and education level were independently associated with higher blood lead levels (P<0.05). CONCLUSIONS: Smoking status, occupation, and education level along with old age and male sex were independently associated with higher blood lead levels; however, COPD was not after adjustment of all confounding factors.
RESUMEN
Transition paths of macromolecular conformational changes such as protein folding are predicted to be heterogeneous. However, experimental characterization of the diversity of transition paths is extremely challenging because it requires measuring more than one distance during individual transitions. In this work, we used fast three-color single-molecule Förster resonance energy transfer spectroscopy to obtain the distribution of binding transition paths of a disordered protein. About half of the transitions follow a path involving strong non-native electrostatic interactions, resulting in a transition time of 300 to 800 microseconds. The remaining half follow more diverse paths characterized by weaker electrostatic interactions and more than 10 times shorter transition path times. The chain flexibility and non-native interactions make diverse binding pathways possible, allowing disordered proteins to bind faster than folded proteins.
Asunto(s)
Transferencia Resonante de Energía de Fluorescencia/métodos , Proteínas Intrínsecamente Desordenadas/química , Pliegue de Proteína , Imagen Individual de Molécula/métodos , Unión Proteica , Conformación Proteica , Electricidad EstáticaRESUMEN
Tenofovir disoproxil (TD) has narrow absorption site mostly in upper intestinal tract where tenofovir rapidly decomposes. The aim of this work was to prepare and evaluate tenofovir disoproxil-loaded enteric microparticles (TDEMs) for the enhanced duodenal delivery. TDEMs were composed of TD, eudragit L-100 (EL) and ethyl cellulose (EC) as release-controlling polymers. For the physicochemical characterization, TDEMs were evaluated in terms of encapsulation efficiency (EE%), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR). The dissolution test was also performed while continuously changing the medium pH. The EE% of TD in TDEMs was good and more than 90%. The EC and EL formed a physically mixed structure and maintained their respective properties in TDEMs as confirmed by SEM image and FT-IR analysis. Combination of EL and EC gave higher enteric properties to TDEMs than the single use of EL or EC. The optimized TDEM (TD/EL/EC = 0.2/1/1, w/w/w ratio) yielded mean dissolution rate less than 10% in 1 h at pH 1.2, but completed dissolution with a dissolution more than 85% within 1 h at pH 6.5. Thus, the suggested TDEM would be promising enteric microparticles for the intensive delivery of TD to the duodenum.
RESUMEN
Deinococcus radiodurans (DR) survives in the presence of hundreds of double-stranded DNA (dsDNA) breaks by efficiently repairing such breaks. RecO, a protein that is essential for the extreme radioresistance of DR, is one of the major recombination mediator proteins in the RecA-loading process in the RecFOR pathway. However, how RecO participates in the RecA-loading process is still unclear. In this work, we investigated the function of drRecO using single-molecule techniques. We found that drRecO competes with the ssDNA-binding protein (drSSB) for binding to the freely exposed ssDNA, and efficiently displaces drSSB from ssDNA without consuming ATP. drRecO replaces drSSB and dissociates it completely from ssDNA even though drSSB binds to ssDNA approximately 300 times more strongly than drRecO does. We suggest that drRecO facilitates the loading of RecA onto drSSB-coated ssDNA by utilizing a small drSSB-free space on ssDNA that is generated by the fast diffusion of drSSB on ssDNA.
Asunto(s)
Proteínas Bacterianas/metabolismo , Roturas del ADN de Cadena Simple , Reparación del ADN/fisiología , Deinococcus/fisiología , Tolerancia a Radiación/fisiología , Recombinasas/metabolismo , Adenosina Trifosfato/metabolismo , Transferencia Resonante de Energía de FluorescenciaRESUMEN
BACKGROUND/AIMS: There is insufficient quality data to recommend the use of herbs for the treatment of acute bronchitis. Small number of randomized trials of plant extracts for this purpose were determined to be low quality and there are concerns for the safety. HL301 is a combined product of seven medicinal plants. In the present study, we tried to evaluate the efficacy and safety of HL301 for the treatment of acute bronchitis with a randomized, double-blind, placebo-controlled, multicenter trial design. METHODS: A total of 166 patients with acute bronchitis were randomized to receive placebo or HL301 (600 mg/day) for 7 days. The primary endpoint was change in bronchitis severity score (BSS) from baseline visit (visit 2) to the end of treatment (visit 3). Other efficacy variables were the change of each component of the BSS (cough, sputum, dyspnea, chest pain, and crackle) with treatment, response rate, improvement rate, satisfaction rate and number of rescue medications taken. RESULTS: Changes in the BSS from visit 2 to visit 3 were higher in the HL301 group than in the placebo group both in the full analysis set (4.57 ± 1.82 vs. 3.15 ± 3.08, p < 0.01) and in the per protocol set (4.62 ± 1.81 vs. 3.30 ± 3.03, p < 0.01). Four BSS components (cough, sputum, dyspnea, and chest pain) improved more with HL301 treatment than with placebo treatment. Participants treated with HL301 showed higher response, improvement, and satisfaction rates and less use of rescue medication than the placebo group. CONCLUSION: HL301 (600 mg/day) was effective and safe for symptomatic treatment of acute bronchitis.