Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 153
Filtrar
1.
Clin Exp Dermatol ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39011939

RESUMEN

BACKGROUND: Psoriasis, an autoimmune skin condition, affects 2%-4% of the global population, with significant prevalence among women of childbearing age. Pregnancy presents challenges in managing psoriasis due to hormonal changes and treatment safety concerns. Understanding treatment patterns in pregnant women is crucial, given limited real-world evidence. OBJECTIVES: Explore the utilization patterns of medications among pregnant women diagnosed with psoriasis within a real-world data, utilizing data sourced from a nationwide database in Taiwan. METHODS: This nationwide study utilized Taiwan's National Health Insurance (NHI) database and Birth Certificate Application. It included registered pregnant women diagnosed with psoriasis from 2005 to 2014. Medication usage was tracked three years before conception to three years after delivery. Medications were categorized based on Anatomical Therapeutic Chemical (ATC) codes, and statistical analyses were conducted using SAS software. RESULTS: A total of 30,267 pregnant women with psoriasis were studied. 11,651 (38.49%) mothers had received at least one prescription during follow-up (exposed group), and >60% had never received medication (unexposed group). Demographics and comorbidities were similar between these two groups. Topical corticosteroids were the most prescribed treatment, followed by phototherapy, with systemic drugs and biologics less common. During the study period, 11,096 women with psoriasis had used topical corticosteroids, 3,376 had used non-steroidal topical agents, 218 had used systemic agents or biologics, and 519 had received treatment with phototherapy. Medication usage declined during pregnancy, reaching its lowest in the third trimester but rebounded postpartum. CONCLUSIONS: Psoriasis medications, systemic, biological, or topical, were largely discontinued during pregnancy, sometimes up to 2 years before and extending postpartum. Research is needed to understand its impact on maternal and child health.

3.
Phytomedicine ; 130: 155760, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38797029

RESUMEN

BACKGROUND: The Xin-yi-san herbal decoction (XYS) is commonly used to treat patients with allergic rhinitis in Taiwan. Theophylline is primarily oxidized with high affinity by human cytochrome P450 (CYP)1A2, and has a narrow therapeutic index. PURPOSE: This study aimed to investigate the inhibition of human CYP1A2-catalyzed theophylline oxidation (THO) by XYS and its adverse effects in patients. METHODS: Human CYPs were studied in recombinant enzyme systems. The influence of concurrent XYS usage in theophylline-treated patients was retrospectively analyzed. RESULTS: Among the major human hepatic and respiratory CYPs, XYS inhibitors preferentially inhibited CYP1A2 activity, which determined the elimination and side effects of theophylline. Among the herbal components of XYS decoction, Angelicae Dahuricae Radix contained potent THO inhibitors. Furanocoumarin imperatorin was abundant in XYS and Angelicae Dahuricae Radix decoctions, and non-competitively inhibited THO activity with Ki values of 77‒84 nM, higher than those (20‒52 nM) of fluvoxamine, which clinically interacted with theophylline. Compared with imperatorin, the intestinal bacterial metabolite xanthotoxol caused weaker THO inhibition. Consistent with the potency of the inhibitory effects, the docking analysis generated Gold fitness values in the order-fluvoxamine > imperatorin > xanthotoxol. During 2017‒2018, 2.6 % of 201,093 theophylline users consumed XYS. After inverse probability weighting, XYS users had a higher occurrence of undesired effects than non-XYS users; in particular, there was an approximately two-fold higher occurrence of headaches (odds ratio (OR), 2.14; 95 % confidence interval (CI), 1.99‒2.30; p < 0.001) and tachycardia (OR, 1.83; 95 % CI, 1.21‒2.77; p < 0.05). The incidence of irregular heartbeats increased (OR, 1.36; 95 % CI, 1.07‒1.72; p < 0.05) only in the theophylline users who took a high cumulative dose (≥ 24 g) of XYS. However, the mortality in theophylline users concurrently taking XYS was lower than that in non-XYS users (OR, 0.24; 95 % CI, 0.14‒0.40; p < 0.001). CONCLUSION: XYS contains human CYP1A2 inhibitors, and undesirable effects were observed in patients receiving both theophylline and XYS. Further human studies are essential to reduce mortality and to adjust the dosage of theophylline in XYS users.


Asunto(s)
Angelica , Inhibidores del Citocromo P-450 CYP1A2 , Citocromo P-450 CYP1A2 , Medicamentos Herbarios Chinos , Furocumarinas , Teofilina , Teofilina/farmacología , Humanos , Medicamentos Herbarios Chinos/farmacología , Citocromo P-450 CYP1A2/metabolismo , Inhibidores del Citocromo P-450 CYP1A2/farmacología , Angelica/química , Furocumarinas/farmacología , Masculino , Interacciones de Hierba-Droga , Estudios Retrospectivos , Femenino , Taiwán , Persona de Mediana Edad , Adulto , Oxidación-Reducción , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica/inducido químicamente
4.
BMC Psychiatry ; 24(1): 284, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627723

RESUMEN

BACKGROUND: Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell's palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell's palsy. METHODS: This nationwide propensity score-weighting cohort study utilized Taiwan National Health Insurance data. 44,198 patients with DD were identified as the DD cohort and 1,433,650 adult subjects without DD were identified as the comparison cohort. The inverse probability of treatment weighting (IPTW) strategy was used to balance the differences of covariates between two groups. The 5-year incidence of Bell's palsy was evaluated using the Cox proportional-hazard model, presenting results in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The average age of DD patients was 48.3 ± 17.3 years, and 61.86% were female. After propensity score-weighting strategy, no significant demographic differences emerged between the DD and comparison cohort. The Cox proportional hazards model revealed a statistically significant adjusted IPTW-HR of 1.315 (95% CI: 1.168-1.481) for Bell's palsy in DD patients compared to comparison subjects. Further independent factors for Bell's palsy in this model were age (IPTW-HR: 1.012, 95% CI: 1.010-1.013, p < 0.0001), sex (IPTW-HR: 0.909, 95% CI: 0.869-0.952, p < 0.0001), hypertension (IPTW-HR: 1.268, 95% CI: 1.186-1.355, p < 0.0001), hyperlipidemia (IPTW-HR: 1.084, 95% CI: 1.001-1.173, p = 0.047), and diabetes (IPTW-HR: 1.513, 95% CI: 1.398-1.637, p < 0.0001) CONCLUSION: This Study confirmed that individuals with DD face an elevated risk of developing Bell's palsy. These findings hold significant implications for both clinicians and researchers, shedding light on the potential interplay between mental health and the risk of certain physical health outcomes.


Asunto(s)
Parálisis de Bell , Trastorno Depresivo , Adulto , Humanos , Femenino , Masculino , Parálisis de Bell/epidemiología , Parálisis de Bell/etiología , Parálisis de Bell/psicología , Puntaje de Propensión , Estudios de Cohortes , Modelos de Riesgos Proporcionales
5.
Postgrad Med J ; 100(1186): 584-591, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38507113

RESUMEN

BACKGROUND: Despite previous concerns about ocular side effects related to amiodarone, the relationship between amiodarone and cataract remains uncertain. Therefore, this study aimed to assess the potential association between amiodarone use and the subsequent risk of cataract, taking into account potential confounders. METHODS: This population-based, active comparator-controlled cohort study utilized the data from the Taiwan National Health Insurance program and involved adults over 40 years old between 2001 and 2013. We analyzed 12 055 new amiodarone users and contrasted them with a propafenone user cohort. The primary outcome was the incidence of cataract. Inverse-probability treatment-weighting (IPTW) was further used to eliminate the potential confounding effects, and Cox proportional-hazard regression analyses were performed to calculate the risk of cataract. Serial subgroup analyses were also performed. RESULTS: In the main analysis, amiodarone users did not exhibit a significant causal relationship in both full cohort [adjusted hazard ratio (aHR): 0.994, 95% confidence interval (CI): 0.913-1.082] and IPTW cohort (IPTW-aHR 0.977, 95% CI: 0.900-1.060). Furthermore, it is important to highlight a significantly reduced risk of cataract among patients with heart failure (IPTW-aHR 0.708, 95% CI: 0.554-0.905) and during the 2-year follow-up period (IPTW-aHR 0.889, 95% CI: 0.794-0.996), implying potential advantages linked to the use of amiodarone. CONCLUSIONS: The study found no increased risk of cataract with amiodarone, one of the most frequently used antiarrhythmic medications, compared to the use of propafenone. Future research is recommended to explore potential mechanisms and their implications for clinical practice.


Asunto(s)
Amiodarona , Antiarrítmicos , Catarata , Humanos , Amiodarona/efectos adversos , Masculino , Femenino , Catarata/inducido químicamente , Catarata/epidemiología , Taiwán/epidemiología , Antiarrítmicos/efectos adversos , Persona de Mediana Edad , Anciano , Incidencia , Adulto , Factores de Riesgo , Modelos de Riesgos Proporcionales , Estudios de Cohortes , Propafenona/efectos adversos
6.
Nat Sci Sleep ; 16: 85-97, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38333420

RESUMEN

Objective: Weekend sleep duration is linked to health issues, including mortality. However, how weekend sleep duration can impact chronic kidney disease (CKD) still needs to be understood. Therefore, we aimed to analyze how weekend sleep duration is associated with kidney function. Methods: This is a cross-sectional study. Data were obtained from the 2017-2018 National Health and Nutrition Examination Survey. We included 5362 study participants and categorized them into nine subgroups by sleep duration (short: ≤6 hours, normal: 6-9 hours, and long: ≥9 hours) on weekdays and weekends and analyzed for the respective association with renal function using stratified multivariable linear regression. Results: Weekend sleep duration for 9 hours or more was associated with decreasing estimated glomerular filtration rate (eGFR) levels by 2.8 to 6.4 mL/min/1.73 m2 among people with long to short weekday sleep duration compared with short weekday and weekend sleep durations (control group) after adjusting for demographic characteristics, body measurement, sleep quality, smoking, and comorbidities. The study population with short weekday sleep duration (sWK) and long weekend sleep duration (lWD) had the most significant decline in eGFR. For the study population with sWK, eGFR level significantly decreased by 1.1 mL/min/1.73 m2 as sleep duration on weekends increased by one hour. Conclusion: The underlying mediators of lWD and CKD could be the dysregulation of human behaviors, metabolism, or biological functions. Longer weekend sleep duration was linked to a decrease in eGFR levels. It warrants further study to clarify the mediators.

7.
Int J Chron Obstruct Pulmon Dis ; 18: 3015-3026, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38143921

RESUMEN

Purpose: Palliative care utilization among hospitalized patients with advanced chronic obstructive pulmonary disease (COPD) in Taiwan remains low despite its costs making it eligible for reimbursement since 2009. Few studies have examined the trends of palliative care utilization. We analyzed the annual rate, associated factors, and timing of the inpatient palliative care utilization by hospitalized patients with COPD. Patients and Methods: We conducted a cross-sectional observational study between 1 January 2007 and 31 December 2018. Population-based claims data were extracted from Taiwan's National Health Insurance Research Database to identify patients aged ≧40 years with COPD five years before the first instance of inpatient palliative care utilization. Results: There were 24,502 patients with COPD receiving inpatient palliative care. Our results indicated that older age, concomitant chronic conditions-especially cancer-and severity of comorbidities were associated with a higher rate of palliative care utilization by hospitalized patients with chronic obstructive pulmonary disease. In our study, the proportion of hospitalized patients with COPD receiving inpatient palliative care and having a Charlson comorbidity index score of 1-2 was lower than that of patients with cancer and a Charlson comorbidity index score ≧3 during the 12-year study-observation period. In addition, approximately 50% of hospitalized patients with COPD received palliative care within 18 months after their initial admission for COPD during the study period. However, individuals with a CCI score of 1-2 exhibited a slower entry into palliative care, with nearly 50% initiating it within the first two years. Conclusion: Inpatient palliative care utilization by hospitalized patients with advanced COPD remains low due to various causes. Our findings highlight that palliative care may be considered by professional care providers as routine care and as a way to manage problematic symptoms during hospitalization.


Asunto(s)
Neoplasias , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudios Transversales , Hospitalización , Neoplasias/complicaciones , Cuidados Paliativos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Estudios Retrospectivos , Taiwán/epidemiología , Adulto
8.
J Pharm Pharmacol ; 75(9): 1225-1236, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37364866

RESUMEN

OBJECTIVES: Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats. METHODS: The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine. KEY FINDINGS: XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3-10 fold. In a dose-dependent manner, XYS and imperatorin (0.1-10 mg/kg) treatments significantly decreased theophylline clearance by 27-33% and 19-56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51-112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27-57%) by XYS was moderate. CONCLUSIONS: XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen.


Asunto(s)
Interacciones de Hierba-Droga , Teofilina , Ratas , Humanos , Animales , Teofilina/farmacocinética , Fluvoxamina/farmacología , Broncodilatadores/farmacocinética
9.
Membranes (Basel) ; 13(4)2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37103828

RESUMEN

A superhydrophobic (SH) surface is typically constructed by combining a low-surface-energy substance and a high-roughness microstructure. Although these surfaces have attracted considerable attention for their potential applications in oil/water separation, self-cleaning, and anti-icing devices, fabricating an environmentally friendly superhydrophobic surface that is durable, highly transparent, and mechanically robust is still challenging. Herein, we report a facile painting method to fabricate a new micro/nanostructure containing ethylenediaminetetraacetic acid/poly(dimethylsiloxane)/fluorinated SiO2 (EDTA/PDMS/F-SiO2) coatings on the surface of a textile with two different sizes of SiO2 particles, which have high transmittance (>90%) and mechanical robustness. The different-sized SiO2 particles were employed to construct the rough micro/nanostructure, fluorinated alkyl silanes were employed as low-surface-energy materials, PDMS was used for its heat-durability and wear resistance, and ETDA was used to strengthen the adhesion between the coating and textile. The obtained surfaces showed excellent water repellency, with a water contact angle (WCA) greater than 175° and a sliding angle (SA) of 4°. Furthermore, the coating retained excellent durability and remarkable superhydrophobicity for oil/water separation, abrasion resistance, ultraviolet (UV) light irradiation stability, chemical stability, self-cleaning, and antifouling under various harsh environments.

10.
Eur Arch Otorhinolaryngol ; 280(2): 695-702, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35790554

RESUMEN

BACKGROUND: It is plausible that immunopathological processes associated with psoriasis might contribute to the occurrence of olfactory or taste dysfunction. However, the actual association was still unknown. PURPOSE: To determine the relationship between olfactory or taste dysfunction and psoriasis. METHODS: Two cross-sectional studies were performed by using National Health and Nutrition Examination Survey (NHANES) data. Participants with psoriasis were defined as cases and those without psoriasis were identified as controls. Taste and smell self-reported questionnaires were used to define smell/taste alterations and identification tests were used to assure the smell/taste dysfunctions. Logistic regression models with inverse probability treatment weighting (IPTW) strategies were conducted to investigated the relationship between psoriasis and olfactory or taste dysfunction. RESULTS: Self-reported questionnaires indicated that psoriasis patients were more likely to have perceived taste alteration (IPTW-aOR = 1.43) and smell alteration (IPTW-aOR = 1.22). Identification tests revealed that psoriasis was associated with taste dysfunction (IPTW-aOR = 1.28) and olfactory dysfunction (IPTW-aOR = 1.22). Relevant findings showed that psoriasis may be significantly associated with taste or olfactory dysfunction regardless of the questionnaire data or identification examination data used. CONCLUSION: Olfactory and taste dysfunction could be considered comorbidities in patients with psoriasis based on our observational study. Therefore, physicians should be cautious of olfaction and taste alterations among patients with psoriasis.


Asunto(s)
Trastornos del Olfato , Psoriasis , Humanos , Estados Unidos/epidemiología , Olfato , Encuestas Nutricionales , Estudios Transversales , Trastornos del Gusto/epidemiología , Trastornos del Gusto/etiología , Trastornos del Olfato/epidemiología , Trastornos del Olfato/etiología , Psoriasis/complicaciones , Psoriasis/epidemiología , Disgeusia , Gusto
11.
Proc Natl Acad Sci U S A ; 120(1): e2206850120, 2023 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-36577066

RESUMEN

Atomically dispersed catalysts have been shown highly active for preferential oxidation of carbon monoxide in the presence of excess hydrogen (PROX). However, their stability has been less than ideal. We show here that the introduction of a structural component to minimize diffusion of the active metal center can greatly improve the stability without compromising the activity. Using an Ir dinuclear heterogeneous catalyst (DHC) as a study platform, we identify two types of oxygen species, interfacial and bridge, that work in concert to enable both activity and stability. The work sheds important light on the synergistic effect between the active metal center and the supporting substrate and may find broad applications for the use of atomically dispersed catalysts.


Asunto(s)
Monóxido de Carbono , Hidrógeno , Monóxido de Carbono/química , Oxidación-Reducción , Catálisis , Hidrógeno/química , Platino (Metal)/química
12.
Front Pharmacol ; 13: 1019303, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36353493

RESUMEN

Background: Antimicrobial resistance is a public health problem that threatens the efficacy of antibiotics. Incorrect knowledge of antibiotics may lead to their inappropriate use, hinder their effectiveness, and cause antibiotic resistance. Population-based educational campaigns have been found to have either mixed or no effect on improving knowledge and appropriate antibiotic practices, suggesting the need for more targeted approaches in tailoring education for specific subpopulations. Women are the primary caregivers of their families and are more willing to contact healthcare providers. They had greater knowledge of antibiotics and better adherence to the completion of the antibiotic regimen. Therefore, they are suitable for prioritization in a campaign program. Objective: This study examined the knowledge and practices of female visitors to health centers in Malang, Indonesia with respect to antibiotic use. Methods: This cross-sectional study was conducted in Malang, Indonesia, in July and August 2018. Data were collected from 677 women. Multivariate logistic regression was performed to identify the potential factors associated with antibiotic knowledge, self-medication, and completion of antibiotic regimens. Results: Overall, 82.7% of respondents were aware that antibiotics are used against bacteria, while 38.4% reported self-medication with antibiotics and 51.7% reported completing antibiotic regimens. Women with higher education, previous antibiotic use experience, and very easy accessibility to primary doctors were more likely to have high antibiotic knowledge than those with primary education, no antibiotic use in the previous year, and easy/other level of accessibility to primary doctors. Subjects residing in urban areas and with less accessibility to primary doctors were more likely to self-medicate with antibiotics. Additionally, the completion of antibiotic regimens was positively associated with access to a primary care doctor and high antibiotic knowledge. Conclusion: IF Policymakers tend to reduce inappropriate antibiotic use among women. Priority advocates are recommended for urban residents who have experiences of antibiotic use in the previous year. It is therefore important to increase their awareness, particularly regarding diseases against which antibiotics are effective, and activities such as unnecessary use of antibiotics in healthy animals, which may affect their overall effectiveness among humans. More communication channels should be included in the overall scheme to improve the public awareness and accessibility of health professionals.

14.
Int J Mol Sci ; 23(18)2022 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-36142451

RESUMEN

Endocrine therapy (ET) of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs) has been used as the gold standard treatment for hormone-receptor-positive (HR+) breast cancer. Despite its clinical benefits, approximately 30% of patients develop ET resistance, which remains a major clinical challenge in patients with HR+ breast cancer. The mechanisms of ET resistance mainly focus on mutations in the ER and related pathways; however, other targets still exist from ligand-independent ER reactivation. Moreover, mutations in the ER that confer resistance to SERMs or AIs seldom appear in SERDs. To date, little research has been conducted to identify a critical target that appears in both SERMs/SERDs and AIs. In this study, we conducted comprehensive transcriptomic and proteomic analyses from two cohorts of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) to identify the critical targets for both SERMs/SERDs and AIs of ET resistance. From a treatment response cohort with treatment response for the initial ET regimen and an endocrine therapy cohort with survival outcomes, we identified candidate gene sets that appeared in both SERMs/SERDs and AIs of ET resistance. The candidate gene sets successfully differentiated progress/resistant groups (PD) from complete response groups (CR) and were significantly correlated with survival outcomes in both cohorts. In summary, this study provides valuable clinical implications for the critical roles played by candidate gene sets in the diagnosis, mechanism, and therapeutic strategy for both SERMs/SERDs and AIs of ET resistance for the future.


Asunto(s)
Neoplasias de la Mama , Moduladores Selectivos de los Receptores de Estrógeno , Inhibidores de la Aromatasa/farmacología , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Humanos , Ligandos , Proteómica , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Transcriptoma
15.
Biomedicines ; 10(8)2022 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-36009462

RESUMEN

Large bone defects may develop fracture nonunion, leading to disability and psychosocial burdens. Bone grafting with anabolic agents is a good autografting alternative. Simvastatin, as a cholesterol-lowering agent worldwide, is proven to enhance osteogenesis. Considering its dose-dependent adverse effects, we developed a simvastatin derivative, named KMUHC-01, which has bone anabolic capacity and lower cytotoxicity than simvastatin. We hypothesize that KMUHC-01 could help bone formation in bone-defect animal models. We used rat models of critical calvarial and long-bone defects to evaluate the effects of KMUHC-01 and simvastatin on biological changes at the bone defect through histology, immunohistology, and mechanical testing using three-point bending and evaluated the new bone formation microstructure through microcomputed tomography analysis. The newly formed bone microstructure at the calvarial defect site showed a significantly improved trabecular bone volume in the KMUHC-01 1-µM group compared with that in the control and simvastatin groups. The biomechanical study revealed a significantly increased maximal strength in the KMUHC-01 1-µM group compared with that in the control group. KUMHC-01, as a simvastatin derivative, showed a great anabolic effect in promoting bone defect healing. However, further studies will be conducted to prove the bioavailability and bone-forming efficacy of KMUHC-01 via systemic administration.

16.
Eur J Pharm Sci ; 177: 106268, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35901930

RESUMEN

In vitro to in vivo extrapolation (IVIVE), an approach for hepatic clearance (CLH) prediction used worldwide, remains controversial due to systematic underprediction. Among the various probable factors, the original assumption of the hepatic mathematical model (i.e., the well-stirred model, WSM) may become problematic, leading to the underestimation of drug CLH. Having a similar prerequisite that the well-stirred conditions are homogenous with perfectly mixed reactants, but using a different driving concentration, the modified well-stirred model (MWSM) stands apart from the WSM. However, we believe that both models should coexist so that the entire well-stirred scenario can be completely illustrated. Consequently, we collected published data from the literature and employed a logistic regression method to differentiate the optimal timing of use between WSM and MWSM in drug CLH prediction. Generally, variances adopted in the regression, including partition coefficient (logP), fraction unbound (fu), volumes of distribution at steady-state (Vss), and mean residence time (MRT), corresponded to our assumption when protein-facilitated uptake was considered. Furthermore, a new empirical approach was introduced to allow practical use of the MWSM. The results showed that this model could provide a more precise prediction compared to previous empirical approaches. Therefore, these preliminary results not only delineated a more detailed structure and mechanism of MWSM but also highlighted its necessity and potential.


Asunto(s)
Hígado , Modelos Biológicos , Hepatocitos , Cinética , Hígado/metabolismo , Tasa de Depuración Metabólica , Preparaciones Farmacéuticas/metabolismo , Unión Proteica
17.
Aging (Albany NY) ; 14(11): 4624-4633, 2022 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-35657641

RESUMEN

Since the late 2020, the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has been characterized by the emergence of spike protein mutations, and these variants have become dominant worldwide. The gold standard SARS-CoV-2 diagnosis protocol requires two complex processes, namely, RNA extraction and real-time reverse transcriptase polymerase chain reaction (RT-PCR). There is a need for a faster, simpler, and more cost-effective detection strategy that can be utilized worldwide, especially in developing countries. We propose the novel use of direct RT-qPCR, which does not require RNA extraction or a preheating step. For the detection, retrospectively, we used 770 clinical nasopharyngeal swabs, including positive and negative samples. The samples were subjected to RT-qPCR in the N1 and E genes using two different thermocyclers. The limit of detection was 30 copies/reaction for N1 and 60 copies/reaction for E. Analytical sensitivity was assessed for the developed direct RT-qPCR; the sensitivity was 95.69%, negative predictive value was 99.9%, accuracy of 99.35%, and area under the curve was 0.978. This novel direct RT-qPCR diagnosis method without RNA extraction is a reliable and high-throughput alternative method that can significantly save cost, labor, and time during the coronavirus disease 2019 pandemic.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Prueba de COVID-19 , Técnicas de Laboratorio Clínico/métodos , Análisis Costo-Beneficio , Humanos , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estudios Retrospectivos , SARS-CoV-2/genética , Sensibilidad y Especificidad
18.
Artículo en Inglés | MEDLINE | ID: mdl-35627534

RESUMEN

The modified dose (MD) regimen of pembrolizumab (2 mg/kg or 100 mg every 3 weeks) is an alternative option to reduce the financial burden resulting from the extremely high cost of the standard dose (SD) regimen (200 mg every 3 weeks). However, the clinical effectiveness and prognostic outcomes have not been fully elucidated in real-word clinical practice. Sixty-four consecutive patients in Taiwan receiving pembrolizumab for advanced NSCLC between 2018 and 2020 were recruited in this study. Comparisons of overall survival (OS) and progression-free survival (PFS) were performed using Kaplan−Meier survival curves. Additionally, 12 predictors, including pembrolizumab regimen, dose, neutrophil-to-lymphocyte ratio (NLR), age, sex, histopathology, smoking history, ECOG PS, EGFR mutation, PD-L1 expression, distant metastases and treatment line, were analyzed in multivariable Cox models for predicting OS and PFS. The results showed that the MD group and the SD group had similar OS and PFS, especially in patients beyond first-line treatment or with a pretreatment NLR < 5. The NLR was the only independent factor associated with both OS (adjusted HR = 0.052; p = 0.010) and PFS (adjusted HR = 0.259; p = 0.021). The results of this study assure the clinical effectiveness of MD pembrolizumab and suggest that the pretreatment NLR could highlight patients who may benefit from MD pembrolizumab.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/genética , Pronóstico
19.
Healthcare (Basel) ; 10(5)2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35628047

RESUMEN

Taste and smell dysfunction are suspected to be associated with substance use. However, representative epidemiological studies remain insufficient. This cross-sectional study explored the relationship between drug use (including cannabis or hashish, cocaine, heroin, and methamphetamine) and olfactory/gustatory dysfunction using data from the 2013-2014 National Health and Nutrition Examination Survey. In this study, participants who completed the smell examination with mean age of 59 were classified into four groups: cannabis users (n = 845), participants without cannabis use (n = 794), illicit drug users (n = 450), and participants without illicit drug use (n = 2000). Participants who completed the taste examination with mean age of 58 were also categorised into four groups: cannabis users (n = 810), participants without cannabis use (n = 714), illicit drug users (n = 428), and participants without illicit drug use (n = 1815). Logistic regression models investigated the association between cannabis or illicit drug use and smell or taste dysfunctions among study participants. Odds ratios and 95% confidence intervals were calculated. Finally, we did not find correlations between illicit drug use and dysfunction of taste or smell senses; our findings were consistent in many subgroup analyses. We recommend that further studies explore the mechanism and dose of illicit drug use that could have chemosensory impacts.

20.
Biotechnol J ; 17(8): e2100603, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35467782

RESUMEN

Microalgae, a group of photosynthetic microorganisms rich in diverse and novel bioactive metabolites, have been explored for the production of biofuels, high value-added compounds as food and feeds, and pharmaceutical chemicals as agents with therapeutic benefits. This article reviews the development of omics resources and genetic engineering techniques including gene transformation methodologies, mutagenesis, and genome-editing tools in microalgae biorefinery and wastewater treatment (WWT). The introduction of these enlisted techniques has simplified the understanding of complex metabolic pathways undergoing microalgal cells. The multiomics approach of the integrated omics datasets, big data analysis, and machine learning for the discovery of objective traits and genes responsible for metabolic pathways was reviewed. Recent advances and limitations of multiomics analysis and genetic bioengineering technology to facilitate the improvement of microalgae as the dual role of WWT and biorefinery feedstock production are discussed.


Asunto(s)
Microalgas , Purificación del Agua , Biocombustibles , Biomasa , Edición Génica , Ingeniería Genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA