ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Asarum heterotropoides F. Maekawa var. mandshuricum F. Maekawa (AR) is a traditional herbal medicine used across Asia, including Korea, China, and Japan. AR exhibits a range of biological activities, such as anti-inflammatory, anti-cancer, cold treatment, and anti-nociceptive effects. Various extraction methods, including decoction, which utilizes traditional knowledge and techniques. The AR decoction extract expected to contain fewer toxicants and have reduced toxicity due to the use of hot water in the extraction process. However, scientific evidence on the toxicity of AR decoction extracts is lacking, necessitating further studies for safe usage. AIM OF THE STUDY: This study aimed to evaluate the genotoxicity and toxicity of single and repeated administration of AR decoction extracts. MATERIALS AND METHODS: The genotoxicity was assessed using a bacterial reverse mutation (Ames test), an in vitro mammalian chromosome aberration test (CA test), and an in vivo micronucleus test (MN test) in Sprague-Dawley (SD) rats. The general toxicity was evaluated through single-dose and 13-week repeated-dose toxicity studies. In the single-dose toxicity study, 40 SD rats were orally administered AR decoction extract at doses of 1000, 2000, and 5000 mg/kg. In the 13-week repeated-dose toxicity study, 140 SD rats received daily oral doses of 0, 250, 500, 1000, 2000, and 5000 mg/kg of AR decoction extract. RESULTS: The genotoxicity tests revealed that AR decoction extract was not genotoxic. The single-dose toxicity study showed no changes in body weight, clinical pathology, or macroscopic findings, with the approximate lethal dose (ALD) exceeding 5000 mg/kg. The 13-week repeated-dose toxicity study demonstrated no treatment-related changes in body weight, general symptoms, hematology, clinical chemistry, or urinalysis. Histopathological findings revealed hyperplasia of squamous cells in the forestomach after AR decoction extract administration, a treatment-related effect that resolved during the recovery period. The no observed adverse effect level (NOAEL) for both male and female rats was estimated to be 2000 mg/kg. CONCLUSIONS: This study establishes the non-toxic dose of AR decoction extract, providing a foundation for further non-clinical and clinical evaluations AR safety.
Subject(s)
Asarum , Plant Extracts , Rats , Male , Female , Animals , Plant Extracts/toxicity , Rats, Sprague-Dawley , Anti-Inflammatory Agents/pharmacology , Body Weight , MammalsABSTRACT
Purpose: The combined administration of bazedoxifene, a tissue-selective estrogen receptor modulator, and cholecalciferol can be a promising therapeutic option for postmenopausal osteoporosis patients. This study aimed to examine the pharmacokinetic interactions between these two drugs and the tolerability of their combined administration in healthy male subjects. Patients and Methods: Thirty male volunteers were randomly assigned to one of the six sequences comprised of three treatments: bazedoxifene 20 mg monotherapy, cholecalciferol 1600 IU monotherapy, and combined bazedoxifene and cholecalciferol therapy. For each treatment, a single dose of the investigational drug(s) was administered orally, and serial blood samples were collected to measure the plasma concentrations of bazedoxifene and cholecalciferol. Pharmacokinetic parameters were calculated using the non-compartmental method. The point estimate and 90% confidence interval (CI) of the geometric mean ratio (GMR) were obtained to compare the exposures of combined therapy and monotherapy. The pharmacokinetic parameters compared were the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast). The safety and tolerability of the combined therapy were assessed in terms of the frequency and severity of adverse events (AEs). Results: For bazedoxifene, the GMR (90% CI) of the combined therapy to monotherapy was 1.044 (0.9263-1.1765) for Cmax and 1.1329 (1.0232-1.2544) for AUClast. For baseline-adjusted cholecalciferol, the GMR (90% CI) of the combined therapy to monotherapy was 0.8543 (0.8005-0.9117) for Cmax and 0.8056 (0.7445-0.8717) for AUClast. The frequency of AEs observed was not significantly different between the combined therapy and monotherapy, and their severity was mild in all cases. Conclusion: A mild degree of pharmacokinetic interaction was observed when bazedoxifene and cholecalciferol were administered concomitantly to healthy male volunteers. This combined therapy was well tolerated at the dose levels used in the present study.
Subject(s)
Cholecalciferol , Volunteers , Humans , Male , Cross-Over Studies , Cholecalciferol/adverse effects , Therapeutic Equivalency , Healthy Volunteers , Area Under Curve , Administration, OralABSTRACT
Background: Esomeprazole, a proton pump inhibitor (PPI), is widely used to treat acid-related disorders, but it has short plasma half-life which can cause insufficient gastric acid suppression, such as nocturnal acid breakthrough. A new dual delayed-release (DR) formulation of esomeprazole (Esomezol DR), was developed to extend the duration of gastric acid suppression. Purpose: This study aimed to evaluate the pharmacokinetics (PKs) and pharmacodynamics (PDs) of esomeprazole for the DR formulation compared to a conventional enteric-coated (EC) formulation (Nexium) in healthy male subjects. Methods: Two randomized, open-label, multiple-dose, two-way crossover studies with esomeprazole 20 mg and 40 mg were conducted. Subjects received the DR formulation or the EC formulation once daily for 7 days in each period with a 7-day washout. Serial blood samples were collected up to 24 hours after the 1st dose, and 24-hour intragastric pH was continuously monitored before the 1st dose as baseline and after the 1st and the 7th dose. Results: In 20 mg and 40 mg dose groups, 38 and 44 subjects completed the study, respectively. The DR formulation exhibited the dual-release pattern of esomeprazole, resulting in more sustained plasma concentration-time profiles compared to the EC formulation. The systemic exposure of esomeprazole for the DR formulation was comparable to that for the EC formulation, showing the similar area under the plasma concentration-time curve. The 24-hour gastric acid suppression was also similar between the two formulations, while the inhibition during night-time (22:00-06:00) showed a better tendency in the DR formulation. Conclusion: The sustained exposure of esomeprazole in the DR formulation led to well-maintained and higher acid inhibition compared to the EC formulation, especially during the night-time. These results suggest that the DR formulation can be an alternative formulation to the conventional EC formulation, expecting the potential of relieving nocturnal acid-related symptoms.
Subject(s)
Anti-Ulcer Agents , Esomeprazole , Humans , Male , Anti-Ulcer Agents/pharmacology , Cross-Over Studies , Gastric Acid , Healthy Volunteers , Hydrogen-Ion Concentration , Proton Pump Inhibitors/pharmacologyABSTRACT
We compared the efficacy and safety of third-standard-dose triple and third-standard-dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double-blind, parallel-group trial. After a 4-week placebo run-in period, 245 participants were randomized to the third-dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third-dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was -18.3 ± 13.2, -13.0 ± 13.3, -16.3 ± 12.4, and -13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third-standard-dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third-standard-dose dual combination therapies, without increasing adverse drug reactions in patients with mild-to-moderate hypertension.
Subject(s)
Hypertension , Hypotension , Humans , Antihypertensive Agents/adverse effects , Losartan , Chlorthalidone , Amlodipine , Blood Pressure , Hypotension/chemically induced , Double-Blind Method , Drug Therapy, Combination , Treatment OutcomeABSTRACT
A novel dual delayed-release formulation (DR) of esomeprazole was developed to prolong the effect of esomeprazole inhibiting gastric acid secretion. This study investigated the effect of food on the pharmacokinetics (PK) and pharmacodynamics (PD) of DR esomeprazole. A randomized, open-label, single-dose, 2-period, 2-sequence crossover study was conducted in healthy Korean subjects. Subjects were orally administered a single dose of 40- mg DR esomeprazole in fasted and fed states in each period. PK and PD characteristics evaluated through continuous 24-hour intragastric pH monitoring in fasted and fed states were compared between the 2 conditions. A total of 23 subjects completed the study and were included in the PK analysis. PD analysis was conducted in 21 subjects, excluding 2 subjects, because of inappropriate pH profiles. The systemic exposure of esomeprazole after a single dose of DR esomeprazole in the fed state decreased compared to that in the fasted state. However, the percentage decrease from baseline in integrated gastric acidity and the percentage of time at pH ≥4 were not significantly different between the 2 conditions. In conclusion, although the systemic exposure of esomeprazole decreased when DR esomeprazole was administered in the fed state compared to that in the fasted state, the degree of gastric acid secretion inhibition was not clinically different, regardless of food intake.
Subject(s)
Anti-Ulcer Agents , Esomeprazole , Humans , Anti-Ulcer Agents/pharmacology , Cross-Over Studies , Healthy Volunteers , FoodABSTRACT
BACKGROUND/AIMS: Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. METHODS: Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). RESULTS: Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/µL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/µL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/µL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). CONCLUSION: Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.
Subject(s)
Multiple Myeloma , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/drug therapy , Multiple Myeloma/pathology , Antibodies, Monoclonal/adverse effects , Progression-Free Survival , Lymphocyte Count , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Asarum heterotropoides var. seoulense (Nakai) Kitag is a traditional herbal medicine used in Korea and China. It is effective in aphthous stomatitis, local anesthesia, headache, toothache, gingivitis, and inflammatory diseases. However, information on the toxicity of the root of Asarum heterotropoides var. seoulense (Nakai) Kitag (AR) is limited. Therefore, preclinical toxicity studies on AR are needed to reduce the risk of excessive intake. AIM OF THE STUDY: We aimed to evaluate genotoxicity and the potential toxicity due to repeated administration of AR powder. MATERIALS AND METHODS: In vitro bacterial reverse mutation assay (Ames), in vitro chromosomal aberration assay (CA), and in vivo micronucleus (MN) assay in ICR mice were conducted. As positive results were obtained in Ames and CA assays, alkaline comet assay and pig-a gene mutation test were conducted for confirmation. For evaluating the general toxicity of AR powder, a 13-week subchronic toxicity test was conducted, after determining the dose by performing a single and a 4-week dose range finding (DRF) test. A total of 152 Sprague-Dawley (SD) rats were orally administered AR powder at doses of 0, 150, 350, 500, 1000, and 2000 mg/kg/day in the 13-week subchronic toxicity test. Hematology, clinical chemistry, urinalysis, organ weight, macro-, and microscopic examination were conducted after rat necropsy. RESULTS: AR powder induced genotoxicity evidenced in the Ames test at 187.5, 750, 375, and 1500 µg/plate of TA100, TA98, TA1537, and E. coli WP2uvrA in the presence and absence of S9, respectively; CA test at 790 µg/mL for 6 h in the presence of S-9; 75 µg/mL for 6 h in the absence of S-9, and 70 µg/mL for 22 h in the absence of S-9 in the stomach in the comet assay but not in MN and pig-a assays. In the 13-week subchronic toxicity study, clinical signs including irregular respiration, noisy respiration, salivation, and decreased body weight or food consumption were observed in males and females in the 2000 mg/kg/day group. In hematology tests, clinical chemistry, urinalysis, organ weight, and macroscopic examination, changes were observed in the dose groups of 500 mg/kg/day and above. Microscopic examination revealed hyperplasia of the stomach as a test-related change. Hepatocellular adenoma and changes in liver-related clinical chemistry parameters were observed. The rat No Observed Adverse Effect Level (NOAEL) was 150 mg/kg/day in males and <150 mg/kg/day in females. CONCLUSIONS: AR powder is potentially toxic to the liver and stomach and should be used with caution in humans. A long-term study on carcinogenicity is necessitated because DNA damage or changes in tissue lesions were observed in SD rats.
Subject(s)
Asarum , Mice , Humans , Male , Female , Rats , Animals , Rats, Sprague-Dawley , Mutagenicity Tests/methods , Escherichia coli , Powders , Mice, Inbred ICR , DNA Damage , Chromosome Aberrations/chemically inducedABSTRACT
BACKGROUND: Our bodies are a collection of nutrients. For healthy body production and activities, good nutrients must be balanced and supplied steadily. However, as modern people eat more irregular meals and fast food, they are running out of nutrients needed by the human body. As a result, research was conducted on the effect of eggs with good cost-effectiveness on the human body and hair. PURPOSE: The purpose of this paper is to review the literature investigated to convey knowledge of the positive nutrients of modern people's nutrition and eggs. METHODS: These data were reviewed to identify agreement between each section and the unique guiding area. Regarding the survey criteria, it was finally decided that 31 papers were suitable for evaluating the purpose of research as follows. PRISMA flowcharts allow you to determine the number of records identified, included, and excluded. RESULTS: Eggs are considered the most cost-effective foods that deliver protein, biotin, choline, and vitamin A to the world, and eggs that can be easily consumed are known as nutritional foods because they contain protein, lipids, minerals, and embryonic development growth factors. It is widely consumed as a food that can be eaten by anyone, including the elderly and children. CONCLUSIONS: In this study, eggs can be used as important data for modern people by delivering nutrients to the human body and hair of modern people and understanding positive nutrients.
Subject(s)
Eggs , Nutritional Status , Child , Humans , Aged , Choline , Asia, Eastern , DietABSTRACT
A self-powered, color-filter-free blue photodetector (PD) based on halide perovskites is reported. A high external quantum efficiency (EQE) of 84.9%, which is the highest reported EQE in blue PDs, is achieved by engineering the A-site monovalent cations of wide-bandgap perovskites. The optimized composition of formamidinium (FA)/methylammonium (MA) increases the heat of formation, yielding a uniform and smooth film. The incorporation of Cs+ ions into the FA/MA composition suppresses the trap density and increases charge-carrier mobility, yielding the highest average EQE of 77.4%, responsivity of 0.280 A W-1 , and detectivity of 5.08 × 1012 Jones under blue light. Furthermore, Cs+ improves durability under repetitive operations and ambient atmosphere. The proposed device exhibits peak responsivity of 0.307 A W-1 , which is higher than that of the commercial InGaN-based blue PD (0.289 A W-1 ). This study will promote the development of next-generation image sensors with vertically stacked perovskite PDs.
ABSTRACT
INTRODUCTION: Macrolide-resistant Mycoplasma pneumoniae (MRMP) has become prevalent in children. This study investigated the clinical and laboratory variables of MRMP and macrolide-sensitive M. pneumoniae (MSMP) and identified factors associated with prolonged hospital admission in children. METHODS: A prospective multicenter study was conducted in 1063 children <18 years old in July 2018-June 2020. The 454 had a positive M. pneumoniae polymerase chain reaction assay. RESULTS: Most subjects had MRMP (78.4%), and all mutated strains had the A2063G transition. We defined MRMP* (n = 285) as MRMP pneumonia requiring admission and MSMP* (n = 72) as MSMP pneumonia requiring admission. Patients with MRMP pneumonia were older, more likely to have segmental/lobar pneumonia, and had more febrile days than those with MSMP pneumonia. C-reactive protein (CRP), lactate dehydrogenase (LDH), and percentage neutrophils were more strongly associated with MRMP* than MSMP* groups. Percentage neutrophils, CRP, and alanine aminotransferase significantly changed between admission and follow-up measurements in patients with MRMP* (P < 0.05). The duration of admission positively correlated with the number of febrile days after initiation of antibiotic medication and laboratory variables (white blood cell count, CRP, and aspartate aminotransferase [AST]) (P < 0.05). Random forest analysis indicated that the number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission was over five. CONCLUSIONS: This study indicated that children with M. pneumoniae pneumonia with a higher number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission were more likely to have prolonged admission duration.
Subject(s)
Mycoplasma pneumoniae , Pneumonia, Mycoplasma , Child , Humans , Adolescent , Mycoplasma pneumoniae/genetics , Prospective Studies , Drug Resistance, Bacterial , Pneumonia, Mycoplasma/drug therapy , Pneumonia, Mycoplasma/epidemiology , Macrolides/therapeutic use , Macrolides/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , C-Reactive ProteinABSTRACT
BACKGROUND: Respiratory infections among children, particularly community-acquired pneumonia (CAP), is a major disease with a high frequency among outpatient and inpatient visits. The causes of CAP vary depending on individual susceptibility, the epidemiological characteristics of the community, and the season. We performed this study to establish a nationwide surveillance network system and identify the causative agents for CAP and antibiotic resistance in Korean children with CAP. METHODS: The monitoring network was composed of 28 secondary and tertiary medical institutions. Upper and lower respiratory samples were assayed using a culture or polymerase chain reaction (PCR) from August 2018 to May 2020. RESULTS: A total of 1023 cases were registered in patients with CAP, and PCR of atypical pneumonia pathogens revealed 422 cases of M. pneumoniae (41.3%). Respiratory viruses showed a positivity rate of 65.7% by multiplex PCR test, and human rhinovirus was the most common virus, with 312 cases (30.5%). Two hundred sixty four cases (25.8%) were isolated by culture, including 131 cases of S. aureus (12.8%), 92 cases of S. pneumoniae (9%), and 20 cases of H. influenzae (2%). The cultured, isolated bacteria may be colonized pathogen. The proportion of co-detection was 49.2%. The rate of antibiotic resistance showed similar results as previous reports. CONCLUSIONS: This study will identify the pathogens that cause respiratory infections and analyze the current status of antibiotic resistance to provide scientific evidence for management policies of domestic respiratory infections. Additionally, in preparation for new epidemics, including COVID-19, monitoring respiratory infections in children and adolescents has become more important, and research on this topic should be continuously conducted in the future.
Subject(s)
COVID-19 , Community-Acquired Infections , Pneumonia, Mycoplasma , Adolescent , Child , Community-Acquired Infections/microbiology , Humans , Multiplex Polymerase Chain Reaction/methods , Staphylococcus aureusABSTRACT
PURPOSE: The combined administration of tadalafil, a phosphodiesterase-5 inhibitor, and amlodipine, a calcium channel blocker, can be a promising therapeutic option for hypertension patients with erectile dysfunction. This study aimed to examine the pharmacokinetic drug interaction between tadalafil and amlodipine and the tolerability of their combined administration in healthy male subjects. SUBJECTS AND METHODS: Healthy volunteers (N = 24) were randomly assigned to one of the six sequences that consisted of three treatments: tadalafil (5 mg) alone, amlodipine (10 mg) alone, and tadalafil plus amlodipine. The study drugs were administered orally for 9 d, and the collected serial blood samples were analyzed up to 72 h after the last dosing. Pharmacokinetic parameters were calculated using non-compartmental analysis. RESULTS: For tadalafil, geometric mean ratios (GMRs) (90% confidence interval (CI)) of the combined therapy over the monotherapy were 1.57 (1.46-1.68) for AUCτ,ss and 1.34 (1.24-1.45) for Cmax,ss. For amlodipine, the GMRs (90% CI) of AUCτ,ss and Cmax,ss were 0.93 (0.90-0.97) and 0.95 (0.91-0.99), respectively. The severity of all observed adverse events (AEs) related to the study drugs was mild, and the frequency of AEs of the combined administration was not significantly different from the monotherapy. CONCLUSION: A substantial pharmacokinetic drug interaction between tadalafil and amlodipine was observed with respect to the concentration of tadalafil when administered concomitantly. However, the dose range of the combined administration of tadalafil and amlodipine in the present study was well tolerated by the subjects.
Subject(s)
Amlodipine , Administration, Oral , Area Under Curve , Cross-Over Studies , Drug Interactions , Healthy Volunteers , Humans , Male , TadalafilABSTRACT
Hypertension is more effectively treated with coadministration of 2 or more antihypertensive drugs than with high-dose monotherapy. Therefore, calcium channel blockers, angiotensin II receptor blockers, and thiazides are coadministered to treat hypertension. The objective of this study was to compare the pharmacokinetic (PK) profiles of HCP1401, a fixed-dose combination of amlodipine 5 mg, losartan 100 mg, and chlorthalidone 25 mg, with the separate components (loose combination) of amlodipine/losartan 5/100 mg and chlorthalidone 25 mg. A randomized, open-label, single-dose, 2-way crossover study was conducted. Blood samples for amlodipine and chlorthalidone were collected for up to 144 hours after dosing, whereas those for losartan were collected up to 48 hours after dosing. The PK parameters of these drugs were calculated using a noncompartmental method. Sixty subjects completed the study. The geometric mean ratios and 90% confidence intervals of maximum plasma concentration and area under the concentration-time curve to the last measurable point for amlodipine, losartan, and chlorthalidone were within the conventional bioequivalence range of 0.80 to 1.25. There were no clinically significant changes in safety assessments, and the treatments were well tolerated. The PK characteristics and tolerability profiles of a single oral FDC of amlodipine, losartan, and chlorthalidone were equivalent to those of individual tablets in a loose combination.
Subject(s)
Chlorthalidone , Losartan , Amlodipine , Cross-Over Studies , Drug Combinations , HumansABSTRACT
Solvent engineering by Lewis-base solvent and anti-solvent is well known for forming uniform and stable perovskite thin films. The perovskite phase crystallizes from an intermediate Lewis-adduct upon annealing-induced crystallization. Herein, it is explored the effects of trimethyl phosphate (TMP), as a novel aprotic Lewis-base solvent with a low donor number for the perovskite film formation and photovoltaic characteristics of perovskite solar cells (PSCs). As compared to dimethylsulfoxide (DMSO) or dimethylformamide (DMF), the usage of TMP directly crystallizes the perovskite phase, i.e., reduces the intermediate phase to a negligible degree, right after the spin-coating, owing to the high miscibility of TMP with the anti-solvent and weak bonding in the Lewis adduct. Interestingly, the PSCs based on methylammonium lead iodide (MAPbI3 ) derived from TMP/DMF-mixed solvent exhibit a higher average power conversion efficiency of 19.68% (the best: 20.02%) with a smaller hysteresis in the current-voltage curve, compared to the PSCs that are fabricated using DMSO/DMF-mixed (19.14%) or DMF-only (18.55%) solvents. The superior photovoltaic properties are attributed to the lower defect density of the TMP/DMF-derived perovskite film. The results indicate that a high-performance PSC can be achieved by combining a weak Lewis base with a well-established solvent engineering process.
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Hybrid density functional theory calculations are commonly used to investigate the electronic structure of semiconductor materials but have not been ideal for high-throughput calculations due to heavy computation costs. We developed a computational approach to obtain the electronic band gap cost-effectively by employing not only non-self-consistent field calculation methods but also sparse k-point meshes for the Fock exchange potential. The benchmark calculation showed that our method is at least 30 times faster than the conventional hybrid density functional theory calculation to quickly screen materials. The band gaps of 290 materials in 5 different structures including cubic, double, and vacancy-ordered perovskites were obtained. The physical properties of Cs2WCl6 and Cs2NaInBr6, screened for optoelectronic applications, were in good agreement with the experiment.
ABSTRACT
Tenofovir is the representative treatment for human immunodeficiency virus and hepatitis B virus infection. This study was conducted to assess the pharmacokinetics (PKs) and safety characteristics after a single administration of tenofovir disoproxil phosphate compared to tenofovir disoproxil fumarate in healthy male subjects. An open-label, randomized, single administration, two-treatment, two-sequence crossover study was conducted in 37 healthy volunteers. Serial blood samples were collected up to 72 hours. Non-compartmental analysis was used to calculate the PK parameters. The 90% confidence intervals (90% CIs) of the geometric mean ratio (GMR) were calculated for comparing tenofovir disoproxil phosphate to tenofovir disoproxil fumarate. Safety assessments were performed including clinical laboratory tests, adverse events, etc. during the study. The GMR and 90% CIs were 1.0514 (0.9527-1.1603) for Cmax and 1.0375 (0.9516-1.1311) for AUClast, respectively, and both fell within the conventional bioequivalence range of 0.8-1.25. Both tenofovir salt forms were tolerable. This study demonstrated that tenofovir disoproxil phosphate (292 mg) was bioequivalent to tenofovir disoproxil fumarate (300 mg).
ABSTRACT
Organo-halide perovskite solar cells (PSCs) have emerged as next-generation photovoltaics, owing to their high power-conversion efficiency (PCE), lower production cost, and high flexibility. ABX3-structured methylammonium lead triiodide (CH3NH3PbI3 or MAPbI3) perovskite is a widely studied light-absorbing material in PSCs. Interestingly, a small amount of chlorine incorporation into MAPbI3 increases charge carrier diffusion lengths (from 129 nm to 1069 nm), which enables planar structured PSCs with high PCEs. However, existence of chloride ions in the final perovskite film is still under debate. Contrastingly, few studies reported a negligible amount or absence of chloride ions in the final film, while others reported detection of chloride ions in the final film. Herein, we observed the microstructure and chlorine content of MAPbI3-xClx thin films with increasing temperature via an in-situ nano-Auger spectroscopy and in-situ scanning electron microscopic analysis. The relative precipitation of MAPbI3-xClx films occur at lower temperature and MAPbI3-xClx grains grow faster than those of MAPbI3 grains. Local concentrations of chlorine at intragrain and the vicinity of grain boundary were analyzed to understand the behavior and role of the chloride ions during the microstructural evolution of the MAPbI3-xClx films.
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BACKGROUND: The effect of diet on allergic rhinitis (AR), its severity in children, and whether it modifies AR depending on genetic susceptibility are unknown. We investigated the association between dietary patterns and AR in school children and the influence of diet on AR according to a genetic risk score (GRS). METHODS: Totally, 435 7-year-old school children were recruited from the Panel Study on Korean Children. We used dietary patterns (vegetable, sugar, and meat) and dietary inflammatory index (DII) as dietary parameters. AR and its severity were defined by questionnaires about treatment in the previous 12 months and the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, respectively. A GRS was calculated using 6 single nucleotide polymorphisms for allergic diseases. RESULTS: A vegetable diet containing a lot of anti-inflammatory nutrients and higher vitamin D level in blood were negatively correlated, while DII was positively correlated with triglyceride level and triglyceride/HDL cholesterol. Vegetable diet (aOR, 95% CI = 0.73, 0.58-0.94) and DII (1.13, 1.01-1.28) were associated with AR risk. In particular, a high-vegetable diet resulted in a lower risk of mild and persistent AR (aOR, 95% CI = 0.24, 0.10-0.56) while a high DII represented a higher risk (2.33, 1.06-5.10). The protective effect of vegetable diet on AR appeared only among children with a lower GRS (adjusted P = .018). CONCLUSIONS: A vegetable dietary pattern characterized by high intake of anti-inflammatory nutrients and higher vitamin D level in blood might be associated with a lower risk of mild and persistent AR. This beneficial effect is modified by a genetic factor.
Subject(s)
Rhinitis, Allergic , Vegetables , Child , Diet , Humans , Phenotype , Rhinitis, Allergic/epidemiology , Rhinitis, Allergic/genetics , Rhinitis, Allergic/prevention & control , Risk Factors , SchoolsABSTRACT
OBJECTIVE: Asthma patients often have co-existing symptoms of allergic rhinitis and are often prescribed with both asthma and rhinitis treatments such as montelukast and levocetirizine. The objective of this study was to compare the pharmacokinetic profiles of a montelukast/levocetirizine fixed-dose combination chewable tablet with individual administration of montelukast and levocetirizine in healthy subjects. MATERIALS AND METHODS: A randomized, open-label, single-dose crossover study was conducted in healthy male subjects. One of the following treatments was administered in each period: co-administration of 1 chewable tablet of montelukast 5 mg and 1 tablet of levocetirizine 5 mg or administration of 1 chewable tablet of montelukast/levocetirizine 5/5 mg fixed-dose combination. Serial blood samples were collected up to 48 hours post dose. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from dosing to the last measurable concentration (AUClast), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of Cmax and AUClast were calculated to evaluate pharmacokinetic equivalence. RESULTS: A total of 22 subjects were included in pharmacokinetic analysis. The GLSM ratios and 90% CIs of Cmax and AUClast were 1.0054 (0.9535 - 1.0601) and 1.0628 (1.0013 - 1.1281) for montelukast and 1.0105 (0.9488 - 1.0764) and 1.0396 (0.9935 - 1.0879) for levocetirizine, respectively. CONCLUSION: The pharmacokinetic parameters of montelukast and levocetirizine when administered as separate tablets or as a fixed-dose combination were compared, and the parameters met the pharmacokinetic equivalence criteria. (ClinicalTrials.gov Identifier: NCT03371849).