PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
·
2013
·
IF 2.608
Tao Yang,Bin Kong,Jian-Wen Gu,Yong-Qin Kuang,Lin Cheng,Wen-Tao Yang,Jing-Min Cheng,Yuan Ma,Xiao-Kun Yang
This study was designed to evaluate the anticonvulsant and sedative effects of paederosidic acid isolated from Paederia scandens (Lour.) Merrill. in mice and rats. In the present study, anticonvulsant activities of paederosidic acid were evaluated by maximal electroshock and pentylenetetrazole-induced seizures in male mice. Then, pentobarbital sodium-induced sleeping time and locomotor activity tests in mice were used to evaluate the sedative effects of paederosidic acid. Finally, the mechanism of paederosidic acid was explored by evaluating the contents of Glu and GABA in the brain, and Western blot was used to measure GAD65 expression in the mouse brain. Paederosidic acid (5, 10, 20, and 40 mg/kg, ip) had significant anticonvulsant and sedative effects. Moreover, paederosidic acid increased brain gamma-aminobutyric acid and decreased glutamic acid in the brain, and it up-regulated expressions of GAD 65. In conclusion, our results suggest that paederosidic acid may be a promising future therapeutic agent for treatment of epilepsy .
研究领域:
药理学
·
神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Quancheng Yang,Peng Cao,Yi Lv,Hua Peng,Xuejia Zhai
Pediatric heart failure (HF) is an important clinical disease with high hospitalization rates, morbidity, mortality and medical costs. Sacubitril/valsartan (also known as Entresto), was approved for the treatment of adult HF and is recently used in pediatrics. However, clinical therapy on children is more challenging than adults, and the pharmacokinetics of Entresto in children are still largely unknown and urgently needed. Herein, we aim to develop a simple and sensitive analytic method to monitor Entresto in pediatric patients, which is of great importance for individualized safe medication in children. Specifically, a liquid chromatography tandem mass spectrometry method for simultaneously quantification of valsartan, sacubitril and its bio-active metabolite sacubitrilat in human plasma has been developed and validated in pediatric patients. Plasma samples were pretreated with acetonitrile for protein precipitation. Elution was performed on X Select HSS T3 column (2.1 × 100 mm, 5 µm; Waters) column using an isocratic mobile phase process consisting of 0.1% formic acid aqueous solution and 0.1% formic acid acetonit rile with a total run time of 3.0 min. Valsartan-d3, sacubitrilin-d4 and sacubitrilat-d4 were used as the corresponding deuterium internal standards. According to the Bioanalytical Method Validation Guidance for Industry, the method was validated in the range of 0.5–5000 ng/mL. Intra- and inter-day accuracy of sacubitril,valsartan and sacubitrilat ranged from 93%− 108%, 98%− 109%, 91%− 102%, respectively, with relative standard deviation of precision ranging from 2.0% to 5.1%, 2.4%− 7.5%, 1,3%− 7.4%. The proposed method demonstrated good accuracy, precision and linearity. The matrix factors normalized by internal standard meet the acceptance criteria. The method was fully validated and applied in 39 children. Trough concentration of the three substances to be measured were: valsartan (11.3–938.0 ng/mL), sacubitril (0.5–395.5 ng/mL) and sacubitrilat (522.1–4890.0 ng/mL). Overall, this is the first study to simultaneously determined the plasma valsartan, sacubitril and sacubitrilat concentrations in children, which is believed to facilitate the clinical management of pediatric HF.
研究领域:
药理学
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儿科学
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临床医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Dong Jiang,Huajin Tan,Rujiao Zhang,Kaikang Wang,Yujia Zhang,Xiaochuan Tan,Wensheng Zheng
Background Pediatric pulmonary arterial hypertension (PPAH) is a malignant progressive rare disease characterized by restricted pulmonary artery blood flow and progressively increasing blood pressure, which has shorter survival time of only about 10 months as compared to adults. Previous studies have shown that low-dose vardenafil hydrochloride (Var) could significantly improve the symptoms of PPAH. However, Var is currently available only in tablet form in the market for erectile dysfunction , and no special preparation is available for PPAH. Methods In this study, borneol-mediated vardenafil hydrochloride patch (BO-VarP) with sodium polyacrylate as the skeleton material was prepared by coating method, which was characterized by temperature resistance, formability, adhesive force, skin irritation and in vitro permeation. Blood concentration of optimized BO-VarP was measured by LC-MS/MS using intragastric administration (i.g.) as a control, and pharmacodynamic studies were conducted using a rat model of pulmonary arterial hypertension induced by monocrotaline . Results and discussion Optimized BO-VarP showed good appearance, with optimal temperature resistance and formability, appropriate adhesive force and low skin irritation, and its cumulative permeation flux was 14.9 times higher than patch without penetration enhancer . The blood concentration within therapeutic window of BO-VarP lasted longer than i.g., and BO-VarP could improve symptoms of PPAH by reducing pulmonary arterial pressure and right heart hypertrophy index. Conclusion BO-VarP had good therapeutic effect in PPAH rats and suitable compliance in children, which provided a potential industrial transdermal delivery system for the treatment of PPAH.
研究领域:
药理学
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儿科医学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Pharmacogenomics & Personalized Medicine
·
2021
·
IF 3.912
Xikun Wu,Weichong Dong,Haoran Li,Xiuling Yang,Yiran Jin,Zhiqing Zhang,Ye Jiang
Purpose To perform therapeutic drug monitoring (TDM) of total and free plasma valproic acid (VPA) concentrations in pediatric patients with epilepsy and to analyze related factors.Patients and Methods Pediatric epileptic patients treated in 2015–2019 in our hospital were assessed. Total and free plasma VPA concentrations were obtained by UPLC and LC-MS/MS, respectively. Regression analysis was performed to examine the associations of free plasma VPA with total plasma VPA and plasma protein binding rate. The impacts of individual situation, CYP2C9 genotype, and drug combination on VPA concentration were examined.Results Of the 251 patients, 81 had lower total concentrations than effective therapeutic levels; 86 and 31 patients had infections and central nervous system dysplasia, respectively. VPA’s daily doses and free drug concentrations were significantly lower in the CYP2C9 *3/*3 genotype group versus the CYP2C9 *1/*3 and CYP2C9 *1/*1 groups (P<0.05). Free and total VPA concentrations were linked by Y = 0.0004 X2 + 0.042 X + 0.3035 (r=0.6981); VPA plasma protein binding rate and free VPA concentration were related by Y = 0.0003 X2 - 0.0127 X + 0.9777 (r=0.8136). Both total and free VPA concentrations were significantly decreased in patients simultaneously administered phenobarbital, meropenem and biapenem (P<0.05), with therapeutic failure after meropenem/biapenem co-administration.Conclusion Free VPA amounts have nonlinear relationships with total VPA amounts and plasma protein binding rate in epileptic children. Additionally, CYP2C9 *3/*3 expression affects VPA metabolism. Since phenobarbital affects VPA metabolism, TDM is recommended. Meanwhile, carbapenem-co-administration with VPA should be prohibited.
研究领域:
医学
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药理学
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遗传学
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DOI
高影响因子
Journal of Biomedical Nanotechnology
·
2023
·Vol. 19
·期 11
·1882-1890
·
IF 2.9
Hu Jiansheng,Sun Danli,Feng Qinhui,Wei Liang,Liu Wucai
A sandwich electrochemical immunosensor was developed for sensitive detection of carcinoembryonic antigen (CEA) using hollow nanospheres composite material loaded with gold nanoparticles as the signal tag and gold triangular nanoplate as the substrate material. Samples obtained from
pediatric solid tumor tissue and their blood samples were used to detect CEA using this nanoparticle. The hollow nanospheres constructed in this study, provided abundant reaction sites and high catalytic activity, while the loading of Au NPs enhances conductivity and biocompatibility. The
immunosensor has good analytical ability in detecting CEA in the mass concentration range of 1 pg/mL to 50 ng/mL, with a low detection limit (LOD) of 0.37 pg/mL. This novel method provides a valuable tool for rapid clinical detection of CEA in the context of pediatric solid tumors.
研究领域:
生物医学工程
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肿瘤学
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纳米技术
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DOI
高影响因子
MATERIALS TECHNOLOGY
·
2024
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IF 2.9
Xin Tian,Taoxiang Shi,Shiyang Fu,Zheda Liu,Yalan You,Keke Chen,Anqi Yao,Chengguang Zhu,Minhui Zeng,Wenfang Tang,Xiaojun Tao,Xiangling He
In this study, we grafted cholesterol with pullulan to synthesize hydrophobic pullulan(CHP). Three CHP polymers (CHP1, CHP2, and CHP3), with different degrees of substitution were designed by changing the feed ratio of cholesterol to pullulan. The 1H-NMR results showed that the hydrophobic substitutability of CHP1, CHP2, and CHP3 were calculated to be 8.26%, 5.67%, and 3.52%, respectively. The sizes of CHP1 NPs, CHP2 NPs, and CHP3 NPs were (118±7.9), (123±4.7) and (158±9.3) nm, respectively. The CHP NPs embedded with VCR and adsorbed Tween 80 (CHPT@VCR NPs). The results of microscale thermal imaging (MST) testing indicated the CHP-1 NPs with the highest degree of cholesterol substitution possessed the highest adsorption capacity for Tween 80. In vitro pharmacological studies were conducted in SJ-GBM2 cells, the results showed that the tumor cells inhibition rate and the cellular uptake rate of CHPT@VCR-1 NPs were the highest compared with CHPT@VCR-2 NPs and CHPT@VCR-3 NPs.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2021
·Vol. 35
·期 8
·e23870
·
IF 2.352
Ying Shen,Xia Luo,Huijun Li,Qing Guan,Liming Cheng
Background Urinary oxalate can provide important clues for the screening and monitoring of children with primary hyperoxaluria (PH), which is a potentially life-threatening condition. However, little effort has been devoted to improve the oxalate assay in recent years. We have proposed a reliable and cost-effective high-performance liquid chromatography (HPLC) method for urinary oxalate determination. Methods Urine specimens were centrifuged after one-step derivatization, and the supernatants were subjected to HPLC analysis. Results The method was validated with consistent linearity from 0.0625 to 2.0 mmol/L with coefficients of variation ≤7.73%, good recovery, low carryover, satisfactory sample stability, and analytical specificity. The lower limit of quantification and the limit of detection were 0.03130 and 0.0156 mmol/L, respectively. Imprecision values were ≤2.92% and ≤16.6% for externally and internally produced controls, respectively. The pediatric reference interval of spot urinary oxalate to creatinine ratios was established together with its application in screening of PH in patients with renal diseases, revealing its successful deployment in our laboratory. Conclusions This reliable HPLC method could serve as a significant tool to determine urinary oxalate levels for screening and monitoring of children with PH in routine clinical laboratories.
研究领域:
医学检验
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临床化学
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儿科医学
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产品关联
DOI
PubMed
高影响因子
BMC NURSING
·
2023
·Vol. 22
·期 1
·162
·
IF 3.2
Huang Di,Zhang Weiwei,Peng Weisi,Fan Yi,He Xin,Xing Ruirui,Yan XuDong,Zhou Sijia,Peng YueMing,Luo WeiXiang
Background ICU-AW (Intensive Care Unit Acquired Weakness) is characterized by significant muscle weakness and can be caused by a variety of factors, including immobility, medication use, and underlying medical conditions.ICU-AW can affect critically ill children who have been hospitalized in the PICU for an extended period of time.The knowledge, attitude and practice level of ICU-AW of PICU medical staff directly affect the treatment of critically ill children with ICU-AW.The aim to this study was to explore the knowledge, attitudes, and practices of Chinese medical staff regarding critically ill children with intensive care unit-acquired weakness (ICU-AW) and related factors. Methods A Knowledge, Attitudes, and Practices (KAP) Questionnaire regarding critically ill children with ICU-AW was distributed to a stratified sample of 530 pediatric intensive care unit (PICU) healthcare workers. The questionnaire consisted of 31 items—with scores of 45, 40, and 40 for each dimension and a total score of 125. Results The mean total score of Chinese PICU healthcare workers for the KAP questionnaire regarding children with ICU-AW was 87.36 ± 14.241 (53–121), with mean total knowledge, attitudes, and practices scores of 30.35 ± 6.317, 30.46 ± 5.632, and 26.54 ± 6.454, respectively. The population distribution indicated that 50.56%, 46.04%, and 3.4% of healthcare workers had poor, average, and good scores, respectively. Multiple linear regression showed that gender, education, and hospital level classification influenced the KAP level of PICU healthcare workers regarding critically ill children with ICU-AW. Conclusions Overall, PICU healthcare workers in China have an average KAP level about ICU-AW, and the gender and education level of PICU healthcare workers, as well as the classification of hospitals where they work, predict the KAP status of healthcare workers regarding children with ICU-AW. Therefore, healthcare leaders should plan and develop specific training programs to improve the KAP level of PICU healthcare workers.
研究领域:
重症医学
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儿科学
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康复医学
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临床流行病学
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护理学
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DOI
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2021
·Vol. 35
·期 16
·e9129
·
IF 2.419
Pengxuan Xi,Wanxue Cao,Li Li,Weimin Shi,Fuxin Li,Haitao Xu,Xiaojie Xu,Yu Ke,Jianye Zhang
Rationale Tebipenem pivoxil (TBPM-PI) has been developed as the first oral carbapenem drug in the world to treat otolaryngological and respiratory infections in pediatric patients. Due to its structural properties and external factors, some related impurities, which may cause side effects in patients, might be formed during the synthesis and storage of TBPM-PI. It was vital to rapidly separate and identify the related impurities to guarantee the safe use of TBPM-PI. Methods A method using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) was developed to separate and detect TBPM-PI and related impurities in an oral pharmaceutical formulation. LC/MS and MS/MS spectra of these compounds in the formulation were acquired to confirm their elemental compositions and propose their structures based on LC/MS data and fragmentation pathways of available reference substances. Results LC/MS parameters and MS/MS fragmentation pathways of reference substances of TBPM-PI and related impurities were summarized in detail. Based on this, a total of 23 related impurities were found and characterized in the oral pharmaceutical formulation. Eight of these were verified by comparison with reference substances and the structures of the other 15 were proposed for the first time. In addition, four of these compounds were produced by the reaction of excipients and pre-existing related impurities. Conclusions A UHPLC/QTOF-MS method was established and used for the separation and identification of 23 related impurities in a TBPM-PI oral pharmaceutical formulation. Moreover, it was proved that new related impurities could be produced by the reaction of excipients in the pharmaceutical formulation and related impurities in the corresponding active pharmaceutical ingredient (API).
研究领域:
药学
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分析化学
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质谱分析
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药物研发
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产品关联
DOI
PubMed
高影响因子
Expert Opinion on Drug Delivery
·
2020
·
IF 4.838
Yidi Ma,Rou Guan,Shuying Gao,Wei Song,Yubo Liu,Yang Yang,Hongzhuo Liu
Introduction Everolimus (EVR) has been approved for the treatment of various advanced cancers and its indications are increasingly expanding. Therefore, it is crucial for patients who have difficulty in swallowing, such as pediatric and elderly patients, to obtain a convenient formulation. The oral absorption of EVR is limited due to its low solubility in water, intestinal metabolism by CYP3A4 enzyme, P-gp-mediated efflux, and metabolism in the liver. The aim of this study was to develop a novel sublingual orodispersible film loading everolimus for improving patient compliance and enhancing oral bioavailability of EVR.Research design and methods Sublingual orodispersible films loading EVR were prepared by the solvent casting method and evaluated by in vitro and in vivo studies.Results The properties of films were determined by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectrometry. The addition of acacia gum appeared to be crucial for protecting the drug from oxidation. Pharmacokinetic studies showed that loading into the sublingual orodispersible films significantly increased the oral bioavailability of EVR.Conclusion The EVR-loaded sublingual orodispersible films are a promising, economical, and convenient approach for delivering EVR efficiently in a solid dosage form.
研究领域:
药学
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药物递送系统
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Lin Lin,Siyuan Li,Que Liu,Xingxing Zhang,Ying Xiong,Shaoyun Zhao,Liyue Cao,Jiaxuan Gong,Yaping Liu,Rong Wu
Objective: This study aimed to investigate the potential relation between the retarded growth of skeletal muscle (SM) and dysbiosis of gut microbiota (GM) in children with asthma, and to explore the potential action mechanisms of traditional pediatric massage (TPM) from the perspective of regulating GM and short-chain fatty acids (SCFAs) production by using an adolescent rat model of asthma.Methods: Male Sprague-Dawley rats aged 3weeks were divided randomly into the 5 groups (n=6~7) of control, ovalbumin (OVA), OVA + TPM, OVA + methylprednisolone sodium succinate (MP) and OVA + SCFAs. Pulmonary function (PF) was detected by whole body plethysmograph, including enhanced pause and minute ventilation. Airway allergic inflammation (AAI) status was assessed by concentrations of OVA-specific immunoglobulin E in plasma, interleukin (IL)-4 and IL-1β in bronchoalveolar lavage fluid via ELISA assay. SM mass was assessed by using cross-sectional areas of diaphragm muscle and gastrocnemius via hematoxylin and eosin staining. GM and SCFAs production were detected by 16S rDNA sequencing and GC-MS, respectively. The protein and gene expressions of free fatty acid receptor 2 in SM were detected by using immunohistochemical staining and qRT-PCR, respectively. qRT-PCR was used to detect other relative gene expressions that were closely related with SM mass. The activity of insulin-like growth factor-1 (IGF-1)/protein kinase B (PKB/AKT) pathway in SM was detected by western blotting test.Results: OVA exposure caused obvious AAI and poor PF in adolescent rats. OVA-exposed adolescent rats had a retarded growth of SM mass and inhibited activity of IGF-1/AKT pathway, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, along with alleviating AAI and improving PF. TPM activated IGF-1/AKT pathway in SM, which was closely related with correcting GM dysbiosis, enhanced SCFAs production and FFAR2 expressions.Conclusion: The retarded growth of SM mass and inhibition of IGF-1/AKT pathway existed in OVA-exposed adolescent rats, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, at least, partially via regulating GM, enhancing SCFAs production and activating FFAR2-IGF-1/AKT pathway.
研究领域:
儿科学
·
免疫学
·
药理学
·
微生物学
·
肌肉骨骼系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Redox Biology
·
2024
·
IF 10.7
Ming-Yan Wang,Meng-Xu Yi,Xing-Yu Mo,Shan-Jie Wei,Yu Qiao,Zheng Zhang,Zhao-Liang Su,Hong-Yan Lu
Bronchopulmonary dysplasia (BPD) is a severe lung disease in preterm infants, the abnormal proliferate and differentiate ability of type II epithelial cells (AEC II) is the key to the pathological basis of BPD. Mechanisms regarding abnormal AEC II in BPD remain unclear. The present work investigated the role and mechanisms of invariant natural killer T (iNKT) cells in lung disorder in BPD using public datasets, clinical samples, a hyperoxia-induced BPD mouse model and AEC II-iNKT cells transwell co-culture system. Firstly, we found that the NKT cells development factor IL-15 increased over time in patients with BPD in public databases, and clinically collected peripheral blood NKT cells in patients with BPD were increased. Subsequently, the percentage of iNKT cells increased in hyperoxia group compared with normoxia group, with the highest at P7, accompanied by increased activation with abnormal lung development. The administration of anti-CD1d neutralizing antibody to inhibit iNKT cells could alleviate the abnormal lung development of hyperoxia group mice, while α-GalCer administration could aggravate lung injury in hyperoxia group mice, and adoptive transfer of iNKT cells could aggravate the abnormal lung development in hyperoxia group mice. In addition, to further verify the role of iNKT cells on AEC II, AEC II-iNKT cells co-culture system was established. The presence of iNKT cells could aggravate the abnormal expression of SP-C and T1α under hyperoxia. Meanwhile, RNA-seq analysis showed that ferroptosis-related genes were highly expressed in AEC II co-cultured with iNKT cells under hyperoxia. We further validated the effect of the presence of iNKT cells under hyperoxia environment on AEC II ferroptosis levels, suggested that iNKT cells promote AEC II ferroptosis under hyperoxia, accompanied by decreased expression of SP-C and T1α. Our study found that the recruitment of iNKT cells in the lung may be an important cause of alveolarization disorder in BPD.
研究领域:
免疫学
·
肺科学
·
儿科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）