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Low-dimensional perovskites afford improved stability against moisture, heat, and ionic migration. However, the low dimensionality typically results in a wide bandgap and strong electron-phonon coupling, which is undesirable for optoelectronic applications. Herein, semiconducting A-site organic cation engineering by electron-acceptor bipyridine (bpy) cations (2,2'-bpy2+ and 4,4'-bpy2+) is employed to optimize band structure in low-dimensional perovskites. Benefiting from the merits of lower lowest unoccupied molecular orbital (LUMO) energy for 4,4'-bpy2+ cation, the corresponding (4,4'-bpy)PbI4 is endowed with a smaller bandgap (1.44 eV) than the (CH3NH3)PbI3 (1.57 eV) benchmark. Encouragingly, an intramolecular type II band alignment formation between inorganic Pb-I octahedron anions and bpy2+ cations favors photogenerated electron-hole pairs separation. In addition, a shortening distance between inorganic Pb-I octahedral chains in (4,4'-bpy)PbI4 single crystal (SC) can effectively promote carrier transfer. As a result, a self-powered photodetector based on (4,4'-bpy)PbI4 SC exhibits 131 folds higher on/off ratio (3807) than the counterpart of (2,2'-bpy)2Pb3I10 SC (29). The presented result provides an effective strategy for exporting novel organic cation-based low-dimensional perovskite SC for high-performance optoelectronic devices.
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Early inflammatory responses post myocardial infarction (MI) is associated with increased myocardial fibrosis and cardiac remodelling. The NLRP3 inflammasome, a key factor in this response, regulates the expression of interleukins (IL)-1ß and IL-18. Inhibiting the inflammatory process may be beneficial for post-MI recovery. Bufalin effectively inhibits inflammation and fibrosis. The aim of this study was to evaluate the effects of bufalin and MCC950, an NLRP3 inflammasome inhibitor, as potential treatment agents for MI using an experimental mouse model. Male C57BL/6 mice were subjected to left coronary artery ligation to induce MI and subsequently treated with bufalin (0.5 mg/kg), MCC950 (10 mg/kg) or saline thrice a week for 2 weeks. After 4 weeks, cardiac function and myocardial fibrosis were evaluated. Myocardial levels of fibrotic markers and inflammatory factors were analysed using western blotting, enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction and immunofluorescence. In mice with MI, cardiac ultrasonography showed decreased cardiac function and myocardial fibrosis. Bufalin treatment restored left ventricular ejection fraction and fractional shortening and decreased the myocardial infarct size. Moreover, both bufalin and MCC950 preserved cardiac function and relieved myocardial fibrosis, with no significant difference. Hence, the present study findings suggest that bufalin can alleviate fibrosis and improve cardiac function in a mouse model by suppressing NLRP3/IL-1ß signalling post-MI.
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Infarto do Miocárdio , Proteína 3 que Contém Domínio de Pirina da Família NLR , Masculino , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Volume Sistólico , Interleucina-1beta/metabolismo , Função Ventricular Esquerda , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Sulfonamidas/farmacologia , Modelos Animais de Doenças , FibroseRESUMO
WHAT IS KNOWN AND OBJECTIVES: Ciclosporin (CsA), a potent immunosuppressive agent used to prevent graft-versus-host disease in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, is characterized by large inter-individual variability and a narrow therapeutic range. The aim of this study was to develop a population pharmacokinetic model for CsA in Chinese allo-HSCT recipients and to identify covariates influencing CsA pharmacokinetics. METHODS: A total of 758 retrospective drug monitoring data points were collected after intravenous infusion or oral administration of CsA from 59 patients. Population pharmacokinetic analysis was performed using nonlinear mixed effects modelling expressed by differential equations. Monte Carlo simulation was applied to optimize dosage regimens. The final model was validated using bootstrap and normalized prediction distribution errors. RESULTS AND DISCUSSION: The results showed that the daily CsA dose, haematocrit, total bile acid, C-reactive protein (CRP) and co-administration of triazole antifungal agent were identified as significant covariates for clearance (CL) of CsA. The typical value of CL was 19.8 L/h with an inter-individual variability of 13.1%. The volume of distribution was 1340 L. Bioavailability was 67.2% with an inter-individual variability of 8.5%. Dosing simulation based on the developed model indicated that patients with high CRP concentration required a higher daily dose to attain the therapeutic trough concentration. The influence of CRP ultimately on the therapy outcome of CsA is not clear, which needs further study. WHAT IS NEW AND CONCLUSION: CRP concentration was identified as a novel marker associated with CsA pharmacokinetics, which should be considered when determining the appropriate dosage of CsA in allo-HSCT recipients.
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Ciclosporina , Transplante de Células-Tronco Hematopoéticas , Proteína C-Reativa , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores , Modelos Biológicos , Estudos Retrospectivos , TransplantadosRESUMO
1. We aimed to establish a population pharmacokinetic (PK) model of tacrolimus and identify clinical covariates, especially the genetic polymorphisms of CYP3A5, ABCB1 and POR*28 that affected the PK to prevent fluctuation in the trough concentration of tacrolimus during the early period after renal transplantation. 2. Tacrolimus trough concentration, clinical data and CYP3A5/ABCB1/POR28 genotypes were retrospectively collected from 234 kidney transplant recipients during the first month post-transplantation. The population PK model was built using the non-linear mixed effects modeling software NONMEM. Dosing simulation was performed based on the final model. 3. A one-compartment model with first-order absorption and elimination was used to characterize the PK of tacrolimus. Among the genotypes, only CYP3A5 genotype was confirmed to have clinical significance. The final model describing CL/F (l/h) was as follows: 23.3 × ( HCT / 0.309 ) - 0.445 × [ ( 0.897 , i f POD > 10 ) o r ( 1 , i f POD ≤ 10 ) ] × ( 0.657 , i f CYP 3 A 5 * 3 / * 3 genotype ) . The inter-individual variability in CL/F was 21.9%. Monte Carlo simulation based on the final model was carried out to determine the optimal dosage regimen. 4. CYP3A5 genotype, post-operative day and hematocrit were confirmed as critical PK factors of tacrolimus. The model could be used to accurately predict individual PK parameters of tacrolimus and provide valuable insights into the dosage optimization.
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Citocromo P-450 CYP3A/genética , Imunossupressores/farmacocinética , Tacrolimo/farmacocinética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Humanos , Transplante de Rim , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Cardiovascular disease (CVD) is closely associated with sarcopenia. We aimed to examine the relationship between Life's Essential 8 (LE8) and the incidence of sarcopenia among adults in the United States. In this study, a cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey from 2013 to 2018 and included 5999 adult participants. LE8 score was categorized into low (< 49), moderate (49-79), and high CVH (≥ 79) groups and consisted of health behavior score and health factor score based on American Heart Association definitions. Sarcopenia was defined according to The Foundation for the National Institutes of Health Sarcopenia Project. Multivariate logistic regressions, restricted cubic spline regressions, and subgroup analyses were used to assess the association between LE8 and sarcopenia. LE8 and its subscales score were negatively associated with the incidence of sarcopenia in US adults.
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Doenças Cardiovasculares , Sarcopenia , Estados Unidos/epidemiologia , Adulto , Humanos , Estudos Transversais , Inquéritos Nutricionais , Sarcopenia/epidemiologia , American Heart Association , Fatores de RiscoRESUMO
This study was aimed at determining the population pharmacokinetics of digoxin and identifying factors that explain pharmacokinetic variability in elderly patients. The data of 142 elderly patients and 448 samples were collected after repetitive oral digoxin. Blood samples were drawn at various times after administration. Population pharmacokinetic analysis was performed using nonlinear mixed effects modelling program (NONMEM). A one-compartment model with first-order absorption and elimination was selected as the base model. The influence of demographic characteristics, biochemical and haematological indices as well as other commonly used co-medications were explored. The typical values with interindividual variability for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 8.9 L h(-1) (43.2 %) and 420 L (65.8 %), respectively. The residual variability was 31.6 %. CL/F decreased significantly with renal function, total body weight, calcium channel blockers or spironolactone co-therapy and symptom with congestive heart failure. The median parameter estimates from a nonparametric bootstrap procedure were comparable and within 5 % of the estimates from NONMEM. These results provide important information for clinicians to optimize digoxin regimens in elderly patients.
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Cardiotônicos/farmacocinética , Digoxina/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , MasculinoRESUMO
Background: Insulin resistance (IR) is a normal feature of pregnancy and plays a crucial role in the pathophysiology of hypertensive disorder of pregnancy (HDP). The triglyceride-glucose index (TyG index) has been shown as a simple and reliable alternative IR marker. This work aimed to investigate the association between the TyG index and the incidence of HDP and adverse pregnancy outcomes. Methods: From January 2016 to December 2018, 289 women with HDP and 861 women without HDP were recruited at Shanghai Fifth People's Hospital, Fudan University to determine the relationship between the TyG index and the incidence of HDP and adverse pregnancy outcomes. Results: In the case-control study, the incidence of HDP was found to be significantly associated with the TyG index. Moreover, logistic regression indicated that the TyG index is an independent risk factor for HDP development and incidence of low birth weight (LBW) and fetal distress. In the cohort study, the results showed that the TyG index increased, there was a stepwise increase in HDP incidence, SBP, and DBP levels one week before delivery as well as in LBW and fetal distress incidence. The early trimester TyG index was positively associated with pre-pregnancy BMI, systolic blood pressure (SBP), and diastolic blood pressure (DBP) one week before delivery. Spline regression showed that there was a significant linear association between HDP incidence and early trimester TyG index when it was >8.5. Conclusions: This work suggested that the early trimester TyG index was closely associated with the development of HDP and adverse pregnancy outcomes.
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Hipertensão Induzida pela Gravidez , Resistência à Insulina , Gravidez , Humanos , Feminino , Resultado da Gravidez/epidemiologia , Estudos de Coortes , Glucose , Incidência , Triglicerídeos , Estudos de Casos e Controles , Sofrimento Fetal , China/epidemiologia , Hipertensão Induzida pela Gravidez/epidemiologiaRESUMO
As a means of visual function testing and visual related mutants screening, the optokinetic response (OKR) and the optomotor response (OMR) behaviour tests are simple and effective tools for visual functional testing, which have been widely used in studying zebrafish larvae. However, adult zebrafish OKR analysis method is rarely reported. In this study, the methods of inducing adult zebrafish OKR behaviour, as well as tracking the movement of eyes using Pattern Match approaches, are presented. The quantitative measurement of the adult zebrafish OKR behaviour was successfully established. Using these methods, the binocular vision area was found to make a certain contribution to OKR behaviour. Moreover, the monocular vision of adult zebrafish showed a certain degree of directional sensitivity to moving gratings. Such approaches can also be applied to the zebrafish larvae OKR. The abnormal OKR behaviour phenomenon of period1b mutant larvae fish was detected.
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Nistagmo Optocinético/fisiologia , Peixe-Zebra/fisiologia , Animais , Comportamento Animal/fisiologiaRESUMO
Aim: Our study aimed to investigate the association between the novel non-insulin-based metabolic score for insulin resistance (METS-IR) index and pre-hypertension (HTN) or HTN in normoglycemia Japanese participants. Methods: The NAGALA medical examination program at Murakami Memorial Hospital in Gifu, Japan was found in 1994. 15,453 participants enrolled in this program from 2004 to 2015 was included in this retrospective study to explore the association between the METS-IR index and pre-HTN or HTN. Covariates included serum biomarkers and clinicodemographic characteristics. Logistic regression was applied to explore the association between METS-IR level and pre-HTN or HTN. Results: This study includes a total of 15453 participants. The prevalence rates of pre-HTN and HTN were 28.55% (4412/15453) and 6.23% (962/15453), respectively. Adjusted for confounding factors in the multivariable logistic regression analysis models, when METS-IR was used as a categorical variable, high METS-IR was significantly associated with both pre-HTN (adjusted odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.61-2.36) and HTN (adjusted OR = 2.12, 95% CI: 1.44-3.11). When METS-IR was used as a continuous variable, each 1 unit increase in METS-IR was associated with a 7% increase in the prevalence of pre-HTN (adjusted OR = 1.07, 95% CI: 1.06-1.08) and with a 13% increase in the prevalence of HTN (adjusted OR = 1.13, 95% CI: 1.10-1.16). Stratified analyses indicated a positive correlation between METS-IR and pre-HTN or HTN in normoglycemia subjects with different characteristics. Conclusions: METS-IR levels are significantly associated with pre-HTN or HTN in normoglycemia individuals in Gifu, Japan. METS-IR may be used as a monitoring indicator for the development of HTN primary prevention and management strategies in the future, but it still needs more research to confirm.
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Hipertensão , Resistência à Insulina , Síndrome Metabólica , Pré-Hipertensão , Estudos Transversais , Humanos , Japão/epidemiologia , Síndrome Metabólica/epidemiologia , Pré-Hipertensão/complicações , Pré-Hipertensão/epidemiologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To observe that antiretroviral efficacy, immune reconstitution of four-year highly active antiretroviral therapy (HAART), and evaluate its side effect in Chinese HIV-1-infected patients. METHODS: A total of 258 HIV-1 infected patients, given HAART regimens composed of two nucleoside reverse transcriptase inhibitor (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) for mean 51.5 months, measured HIV RNA viral load (VL) and the counts of CD(4)(+) T cell, CD(8)(+) T cell at the baseline and 6, 12, 24, 36 and 48 months after HAART initiation, respectively, monitoring side effect, blood routine, main biochemical parameters, and other disadvantageous accidents during the 51.5-month treatment. RESULTS: Plasma HIV-1 RNA level was determined by fluorescent quantitative polymerase chain reactions (FQ-PCR) at the baseline and 6, 12, 24, 36 and 48 months after starting HAART, and showed 5.27, 2.97, 2.74, 2.62, 2.67 and 2.75 lg (copies/ml), respectively. The counts of CD(4)(+) T cell from (127 ± 63) cells/µl at the baseline increased to (190 ± 115), (248 ± 93), (269 ± 127), (296 ± 156) and (317 ± 195) cells/µl at 6, 12, 24, 36 and 48 months after starting HAART. A total of 149 treated patients (57.8%)had gastrointestinal side effects, peripheral polyneuropathy, various rashes, central nervous system disorders, fever or baldness. Twenty-two patients changed one of three medicines to another because toxicity. Sixteen changed the regimen to the second line HAART for lactic acidosis or other serious toxicities. CONCLUSIONS: A total of 258 HIV-1 infected Chinese patients treated with two NRTI and one NNRTI as first line HAART regimen during mean 51.5 months, showed a good antiretroviral efficacy and immune reconstitution, but a few side-effects at the parts of patients. It is necessary to treat adverse effect and change HAART regimen for severe toxicity in time.
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Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Carga Viral , Síndrome da Imunodeficiência Adquirida/virologia , Adolescente , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Feminino , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
AIMS: We aimed to examine the association between the Triglyceride-glucose (TyG) index and clinical outcome of percutaneous coronary intervention (PCI) patients with drug-eluting stents (DESs). METHODS: From July 2009 to August 2011, 2533 patients who underwent at least one PCI with DESs were enrolled to determine the relationship between the TyG index and MACCEs with a 29.8-month follow-up. In addition, the Logistic regression proportional hazard model was applied to assess the prognostic value of the TyG index. RESULTS: The MACCEs was associated with, history of heart failure (p = 0.049), third degree AVB (p = 0.008) and stroke (p = 0.033), SBP (p < 0.001), DBP (p = 0.001), number of diseased vessels, location of target lesions, characteristics of lesion, number of treated vessels, number of stents, length of stents (p = 0.003) and stent diameter (p < 0.001). The multivariate Logistic regression analysis revealed that the TyG index was an independent prognostic factor for MACCEs in female patients (OR = 1.68, 95 %CI = 1.12-2.54, p = 0.013) but not in male (OR = 0.95, 95 %CI = 0.74-1.21, p = 0.657). CONCLUSION: The TyG index was independently associated with MACCEs in female patients undergoing PCI with DESs, but not in men.
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Stents Farmacológicos , Intervenção Coronária Percutânea , Doenças Cardiovasculares , Transtornos Cerebrovasculares , Stents Farmacológicos/efeitos adversos , Feminino , Glucose , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , TriglicerídeosRESUMO
Aim: We aimed to examine the relationship between the Triglyceride-glucose (TyG) index and the incidence of type 2 diabetes in people with different phenotypes of obesity. Methods: From May 1, 1994 to December 31, 2016, 15,464 participants were enrolled in the medical examination program at the Murakami Memorial Hospital to determine the relationship between the TyG index and the incidence of type 2 diabetes in people with different phenotypes of obesity after 5.38 years of follow-up. Results: Besides triglycerides, HbA1c%, and FPG, the incidence of type 2 diabetes was found to be significantly associated with the TyG index (p <0.001), age (p <0.001), BMI (p = 0.033), current smoker (p <0.001), and fatty liver (p <0.001). In participants with visceral fat obesity and/or ectopic fat obesity and normal BMI, the TyG index was significantly associated with the incidence of type 2 diabetes after adjusting for confounding factors. In patients with BMI ≥25 mg/m2, although there was a trend of the relationship between the TyG index and the incidence of type 2 diabetes, the relationship was no longer positive. Conclusion: In participants with obesity involving visceral fat obesity and/or fatty liver and normal BMI which is not a measure of body fat distribution, there was a significant association between the TyG index and incidence of T2DM.
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Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Obesidade/sangue , Obesidade/epidemiologia , Triglicerídeos/sangue , Adulto , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos RetrospectivosRESUMO
AIM: To establish a model of retinal neurodegeneration induced by N-Methyl-D-aspartic acid (NMDA) in adult zebrafish. METHODS: We compared the effects of three different NMDA delivery methods on retinal neurodegeneration in adult zebrafish: immersion (I.M.), intravitreal injection (I.V.), and intraperitoneal injection (I.P.), and examined retinal pathology and degeneration by hematoxylin and eosin and TUNEL staining in the treated zebrafish. Effects of the NMDA receptor antagonist MK-801 and the natural product resveratrol on NMDA-induced retinal neurodegeneration were also assessed. RESULTS: The thickened inner retina was seen in histology with 100 µmol/L NMDA by I.M. administration. Significant apoptosis in the retinal ganglion cell layer and retinal thickness reduction occurred in 0.5 mol/L NMDA I.P. administration group.Seizure-like behavioral changes, but no retinal histological alteration occurred in 16 mg/kg NMDA I.P. administration group. Resveratrol and MK-801 prevented NMDA-induced retinal neurodegeneration in the zebrafish. CONCLUSION: Among the three drug administration methods, I.V. injection of NMDA is the most suitable for establishment of an acute retinal damage model in zebrafish. I.M. with NMDA is likely the best for use as a chronic retinal damage model. I.P. treatment with NMDA causes brain damage. Resveratrol and MK801 may be a clinically valuable treatment for retinal neurodegeneration.
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OBJECTIVE: The study was to establish a population pharmacokinetic (PPK) model of piperacillin (PIP) and tazobactam (TAZ) that explain pharmacokinetic variability and to propose optimized dosage regimens in patients with nosocomial infections. METHODS: In total, 310 PIP and 280 TAZ concentration-time points were collected at steady state over multiple dosing intervals from 50 patients who received PIP/TAZ infused within 30 min or over 3 h. Drug analysis was performed by high-performance liquid chromatography (HPLC). Nonlinear mixed effects modeling was employed to develop PPK model and 1000 Monte Carlo simulation was used to predict the probability of target attainment (PTA) with a target time of non-protein-bound concentration above MIC > 50 % of the dosing interval. RESULTS: A model with one-compartment model had the best predictive performance for the PPK model. The population estimates of PIP were 13.8 L/h (31.1 %) for clearance (CL) and 21.7 L (38 %) for volume of distribution (V). The population estimates of TAZ were 9.3 L/h (29.1 %) for CL and 16 L (35.3 %) for V. Influence of creatinine clearance (CLcr) and body weight were identified as important covariates for PIP/TAZ CL and V, respectively. A 30-min infusion of 4 g every 6 h achieved robust (≥90 %) PTAs for MIC ≤ 16 mg/L. As an alternative mode of administration, a 3-h infusion of 4 g every 6 h achieved robust PTAs for Pseudomonas aeruginosa and Klebsiella pneumoniae. CONCLUSIONS: Prolonged infusions achieved better PTAs compared with shorter infusions at similar daily doses. This benefit was most pronounced for MICs between 16 and 40 mg/L.
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Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Ácido Penicilânico/análogos & derivados , Piperacilina/farmacocinética , Peso Corporal/efeitos dos fármacos , Feminino , Humanos , Infusões Intravenosas/métodos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Modelos Biológicos , Método de Monte Carlo , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/farmacocinética , Ácido Penicilânico/uso terapêutico , Piperacilina/administração & dosagem , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , TazobactamRESUMO
PURPOSE: We intended to evaluate the superiority of cisplatin-based chronotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and investigate the relationship between the circadian rhythm and the variability of pharmacokinetics for cisplatin. METHODS: Forty-one patients with advanced NSCLC were divided into two groups with minimization randomization, including routine group (24 cases) and chronotherapy group (17 cases). The clinical effect and toxicity between the two groups were investigated. The population pharmacokinetics of cisplatin was calculated using nonlinear mixed-effects modeling method. RESULTS: There is no significant difference in total response rate between chronotherapy group (52.94%) and routine chemotherapy group (50.00%), p = 0.853. The rate of leucopenia (grade 3 or 4) in chronotherapy group (11.76%) is significantly lower than that in routine chemotherapy (37.50%), p < 0.05. The rate of neutropenia (grade 3 or 4) in chronotherapy group (11.76%) is significantly lower than that in routine chemotherapy group (33.33%), p < 0.05. The proportion of gastrointestinal toxicity (nausea, grade 1 vs 2) in chronotherapy group is significantly lower than that in routine chemotherapy, p < 0.05. When cisplatin was administered at 18:00, the CL was 1.38- and 1.22-fold higher than those administered at 6:00 for total and unbound cisplatin, respectively (p < 0.05). CONCLUSIONS: Cisplatin-based chronotherapy has advantage in relieving side effects of chemotherapy, and circadian could influence the metabolism of cisplatin, and more clinical researches are needed.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacocinética , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cronofarmacoterapia , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
BACKGROUND: The usage of Traditional Chinese Medicine (TCM) during pregnancy is very common for Chinese people. However, there are only a few studies relevant to the usage of TCM during pregnancy-providing very little knowledge on the benefits or harmful effects of these medicines to pregnant women or the fetus. OBJECTIVES: The purpose of this study is to survey the current situation of TCM usage during pregnancy, and to explore the factors that affect the use of TCM. METHODS: Data was collected from pregnant patients who delivered in our hospital, from March 2012 to August 2012. All patients who agreed to join this study were asked to fill-up a questionnaire. RESULTS: 1,010 patients were willing to participate in this study. 11.2% (113, 1,010) of patients used at least one kind of TCM during pregnancy. The average TCM usage is 2.1 species. The most commonly used drugs are Antai pill (39 cases, 34.5%), Xiaochaihu granules (31 cases, 27.4%), and Shengxuening tablets (23 cases, 20.4%). Patients who smoke during pregnancy (OR=1.8, 95% CI: 0.7~5.1), drink during pregnancy (OR=1.6, 95% CI: 0.4~6.1), have been hospitalized during pregnancy (OR=4.8, 95% CI: 2.9~7.9), have pregnancy complications (OR=2.7, 95% CI: 1.5~4.9) and those who are infertile (OR=2.6, 95% CI: 1.4~4.8) have higher chances of using TCM during pregnancy. CONCLUSIONS: Pregnant women commonly use TCM during pregnancy. Pregnant women who smoke, drink, hospitalized during pregnancy, experience pregnancy complications and infertility are more likely to use TCM.
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As retrograde labeling retinal ganglion cells (RGCs) can isolate RGCs somata from dying sites, it has become the gold standard for counting RGCs in RGCs survival and regeneration experiments. Many studies have been performed in mammalian animals to research RGCs survival after optic nerve injury. However, retrograde labeling of RGCs in adult zebrafish has not yet been reported, though some alternative methods can count cell numbers in retinal ganglion cell layers (RGCL). Considering the small size of the adult zebrafish skull and the high risk of death after drilling on the skull, we open the skull with the help of acid-etching and seal the hole with a light curing bond, which could significantly improve the survival rate. After absorbing the dyes for 5 days, almost all the RGCs are labeled. As this method does not need to transect the optic nerve, it is irreplaceable in the research of RGCs survival after optic nerve crush in adult zebrafish. Here, we introduce this method step by step and provide representative results.
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Corantes Fluorescentes/química , Células Ganglionares da Retina/química , Células Ganglionares da Retina/citologia , Coloração e Rotulagem/instrumentação , Coloração e Rotulagem/métodos , Animais , Microscopia de Fluorescência/métodos , Peixe-ZebraRESUMO
PURPOSE: The aim of this study was to describe the nonlinear pharmacokinetics of total and unbound plasma cisplatin under different administered time in patients with non-small-cell lung carcinoma. METHODS: Patients receiving chemotherapy with cisplatin were included in this analysis. Patients were divided into two groups depending on the administrated time of cisplatin: 6:00 (Group A) and 18:00 (Group B). The population pharmacokinetics of cisplatin was calculated using nonlinear mixed-effects modeling (NONMEM) method, and the possible influence of covariates on the population pharmacokinetics of cisplatin was also explored. RESULTS: The pharmacokinetics of total and unbound cisplatin could be described well by a linear two-compartment model. The mean population estimates for total and unbound drug were, respectively, 0.463 (17.0 %) and 25.4 (14.0 %) l h⻹ for clearance (CL), 24.2 (19.9 %) and 20.5 (27.1 %) l for central distribution volume (V1), 10.2 (18.2 %) and 9.82 (28.1) l h⻹ for intercompartmental clearance (Q) and 32.0 (24.1 %) and 6.77 (25.4 %) l for peripheral compartment volume (V2). The CL for total and unbound cisplatin was dependent on body surface area (BSA). When cisplatin was administered at 18:00, the CL was 1.38- and 1.22-fold higher than those administered at 6:00 for total and unbound cisplatin, respectively (P < 0.05). The mean parameter estimates from a nonparametric bootstrap procedure were comparable and within 5 % of the estimates from NONMEM. CONCLUSIONS: The results showed that circadian could influence the metabolism of cisplatin and suggested the conventional dose adjustment of cisplatin based on BSA.
Assuntos
Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ritmo Circadiano , Cisplatino/farmacocinética , Neoplasias Pulmonares/tratamento farmacológico , Modelos Biológicos , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Superfície Corporal , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatologia , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/fisiopatologia , Reprodutibilidade dos Testes , SoftwareRESUMO
Optokinetic response (OKR) is a behavior that an animal vibrates its eyes to follow a rotating grating around it. It has been widely used to assess the visual functions of larval zebrafish. Nevertheless, the standard protocol for larval fish is not yet readily applicable in adult zebrafish. Here, we introduce how to measure the OKR of adult zebrafish with our simple custom-built apparatus using a new protocol which is established in our lab. Both our apparatus and step-by-step procedure of OKR in adult zebrafish are illustrated in this video. In addition, the measurements of the larval OKR, as well as the optomotor response (OMR) test of adult zebrafish, are also demonstrated in this video. This OKR assay of adult zebrafish in our experiment may last for up to 4 hours. Such OKR test applied in adult fish will benefit to visual function investigation more efficiently when the adult fish vision system is manipulated.