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1.
Front Immunol ; 13: 872910, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812404

RESUMO

Metabolic reprogramming is a novel method for the treatment of malignant tumors. The exploration of metabolism procedures between radiosensitive and radioresistant tumors may provide novel perspectives for lung adenocarcinoma (LUAD) patients after radiation therapy. In our study, metabolic reprogramming and immune response changes were found between radioresistant cell line (A549RR) and its parent cells (A549) using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Nucleotide/amino acid, lipid, and glucose metabolic process, including Alanine, aspartate and glutamate metabolism, Tryptophan/Tyrosine metabolism, Butanoate metabolism, Purine/Pyrimidine metabolism, were screened out. Then molecular signatures database and The Cancer Genome Atlas Program (TCGA) lung adenocarcinoma datasets were used to identify metabolism-related genes (MRGs) between radiosensitive and radioresistant lung adenocarcinoma (LUAD) cells. A metabolism-based prognostic model, receiver operating characteristic (ROC) curve and nomogram were constructed using Metabolism Score calculated by 14 metabolism-related genes (MRGs). Three independent public datasets, (GSE72094, GSE3141, GSE8894) and one immunotherapy cohort (IMvigor210) were used as external validation cohorts. Expression of 14 hub genes in cells, normal and LUAD specimens were explored by Human Protein Atlas, TIMER2.0 and RT-qPCR. Patients with low-Metabolism Scores were correlated with longer survival times, higher response rates to immune checkpoint inhibitors (ICIs), different immune cell infiltrations and drug vulnerability. Our study demonstrated a comprehensive landscape between radiosensitive and radioresistant LUAD, and provide novel targets for NSCLC, especially those patients received radiation therapy. Moreover, this metabolism-based prognostic model may help to investigate connections between radiosensitivity, immune response, metabolic reprogramming, and patients' prognosis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Prognóstico
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(2): 162-168, 2022 Feb 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35209981

RESUMO

OBJECTIVES: To study the characteristics of amino acid metabolism in preterm infants in Guangxi, China. METHODS: A retrospective analysis was performed on the medical data of 30 757 neonates who underwent the screening for inherited metabolic diseases and had negative results in Guangxi Neonatal Disease Screening Center from 2018 to 2020. Among these neonates, there were 28 611 normal full-term infants (control group) and 2 146 preterm infants (preterm birth group). According to gestational age, the preterm infants were further divided into four groups: very preterm (n=209), moderately preterm (n=307), and late preterm group (n=1 630). According to birth weight, they were divided into three groups: very low birth weight group (n=161), low birth weight group (n=1 085), and normal birth weight group (n=900). According to blood collection time, they were divided into three groups: 3-7 days group (n=1 664), 8-14 days group (n=314) and 15-28 days group (n=168). Tandem mass spectrometry was performed to measure the levels of 11 amino acids in dried blood spots, which were then compared between groups. RESULTS: After adjustment for confounding factors, there were significant differences in the levels of 11 amino acids among different gestational age groups (P<0.05), and significant differences were observed in the levels of the 11 amino acids between the control group and the various preterm groups (except for citrulline and methionine in the late preterm group). There were significant differences in the levels of 11 amino acids among different birth weight groups (P<0.05). Except for ornithine, there were significant differences in the levels of other amino acids among the different blood collection time groups (P<0.05). CONCLUSIONS: Gestational age, birth weight and blood collection time all affect amino acid metabolism in preterm infants in Guangxi, China. This provides a basis for the laboratory to establish the reference standard and clinical interpretation of blood amino acid levels in preterm infants, and to improve the nutritional metabolism of preterm infants.


Assuntos
Recém-Nascido Prematuro , Nascimento Prematuro , Aminoácidos , China , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Estudos Retrospectivos
3.
Front Genet ; 12: 756506, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868231

RESUMO

Purpose: To investigate the prognostic significance of tumor mutational burden (TMB) combined with specific prognosis-related gene mutations in immunotherapy for recurrent and metastatic head and neck squamous cell carcinoma (r/m HNSCC). Methods: One hundred thirty-two r/m HNSCC patients from the Morris and Allen cohorts had undergone immunotherapy. We constructed the immunotherapy-related gene prognostic index TP-PR combining TMB and PIK3CA, TP53, or ROS1 mutation. And we analyzed the differences in overall survival (OS) and immune cell infiltration between samples in different groups. The association of each signature's single-sample gene set enrichment analysis scores with TP-PR was tested using Spearman's correlation test. Results: The median OS of the patients with high TMB (TMB ≥10 mut/Mb) who received immunotherapy for r/m HNSCC was 2.5 times as long as that of the patients with low TMB (25 vs. 10 months). More importantly, the high TP-PR (TP-PR >0) group had better median OS (25 vs. 8 months) than the low TP-PR (TP-PR ≤0) group. CD8+ T cells and activated memory CD4+ T cells in the tissues of the patients with high TP-PR were higher than those in the patients with low TP-PR. Results showed that TP-PR stratification had a higher area under the curve (AUC) value (0.77, 95% CI 0.86-0.68) compared with TMB stratification (0.56, 95% CI 0.68-0.44). The differential gene expression in the high and low TP-PR groups mainly influenced metabolism-related signaling pathways. Conclusion: TP-PR was an effective predictor of immunotherapy outcome for r/m HNSCC, which might be better than TMB alone. Patients with high TP-PR had a better survival benefit than had the patients with low TP-PR.

4.
Orthop Surg ; 13(6): 1707-1720, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34351056

RESUMO

The direct anterior approach (DAA) are attracting increasing attention from orthopedic arthroplasty surgeons, due to the less blood loss, mild soft tissue invasion, rapid rehabilitation and shorter length of stay. However, the longer learning curve in DAA can give rise to several complications, such as intraoperative femoral fracture, lateral femoral cutaneous nerve injury, wound-healing problem, premature revision and so on. This meta-analysis was performed to compare the rate of postoperative orthopedic complications between the DAA and the lateral approach (LA). All studies involving the comparison of postoperative orthopedic complications after THA between the DAA and LA group were searched in 7 databases prior to October 2020. The odds ratio (OR) with the 95% confidence intervals (CI) for each outcome was calculated by using the RevMan 5.3. The methodological bias of included studies was evaluated and the potential heterogeneity sources were analyzed. Thirteen comparative studies including a total of 24853 hips (9575 hips in the DAA group and 15278 hips in the LA group) were eligible for this meta-analysis. There was no significant difference in the rate of surgical site infection [2.59% vs 2.14% (OR = 0.98; 95% CI: 0.59-1.61, P = 0.93)], heterotopic ossification [12.16% vs 26.47% (OR = 0.46; 95% CI: 0.20-1.07, P = 0.07)] and reoperation [2.70% and 2.11% respectively (OR = 0.93; 95% CI: 0.68-1.26, P = 0.64)] between the DAA and LA groups. Although a lower rate in prosthesis malposition [36.19% vs 54.86% (OR = 0.50; 95% CI: 0.35-0.73, P = 0.0003)], leg length discrepancy [1.87% vs 2.37% (OR = 2.35; 95% CI: 1.30-4.25, P = 0.005)] and Trendelenburg gait [1.68% vs 4.78% (OR = 0.29; 95% CI: 0.13-0.65, P = 0.003)] was observed in the DAA group, a higher rate in dislocation [0.77% vs 0.18% (OR = 3.73; 95% CI: 2.35-5.94, P< 0.00001)], periprosthetic fracture [1.05% vs 0.41% (OR = 2.38; 95% CI: 1.58-3.58, P< 0.0001)], prosthesis loosening [0.61% vs 0.37% (OR = 1.66; 95% CI: 1.05-2.62, P = 0.03)] and nerve injury [0.95% vs 0% (OR = 7.12; 95% CI: 1.66-30.48, P = 0.008)] was found in the DAA group. This meta-analysis demonstrated several evidences indicating that the DAA exhibited the advantages in the accurate prosthesis placement and less damage of surrounding hip musculature. However, a higher rate in dislocation, periprosthetic fracture, prosthesis loosening and nerve injury in the DAA group should be paid more attention, due to the limited exposure and a longer learning curve, compared to the LA.


Assuntos
Artroplastia de Quadril/métodos , Prótese de Quadril , Complicações Intraoperatórias/etiologia , Complicações Pós-Operatórias/etiologia , Falha de Prótese , Humanos , Complicações Intraoperatórias/cirurgia , Complicações Pós-Operatórias/cirurgia , Reoperação
5.
Front Chem ; 9: 666408, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937203

RESUMO

The over-use of antibiotics has promoted multidrug resistance and decreased the efficacy of antibiotic therapy. Thus, it is still in great need to develop efficient treatment strategies to combat the bacteria infection. The antimicrobial photodynamic therapy (aPDT) and silver nanoparticles have been emerged as effective antibacterial methods. However, the silver therapy may induce serious damages to human cells at high concentrations and, the bare silver nanoparticles may rapidly aggregate, which would reduce the antibacterial efficacy. The encapsulation of sliver by nano-carrier is a promising way to avoid its aggregation and facilitates the co-delivery of drugs for combination therapy, which does not require high concentration of sliver to exert antibacterial efficacy. This work constructed a self-assembled supermolecular nano-carrier consisting of the photosensitizers (PSs), the anti-inflammatory agent and silver. The synthesized supermolecular nano-carrier produced reactive oxygen species (ROS) under the exposure of 620-nm laser. It exhibited satisfying biocompatibility in L02 cells. And, this nano-carrier showed excellent antibacterial efficacy in Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as indicated by bacterial growth and colony formation. Its antibacterial performance is further validated by the bacteria morphology through the scanning electron microscope (SEM), showing severely damaged structures of bacteria. To summary, the supermolecular nano-carrier TCPP-MTX-Ag-NP combining the therapeutic effects of ROS and silver may serve as a novel strategy of treatment for bacterial infection.

6.
Cancer Manag Res ; 11: 4757-4772, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213898

RESUMO

Background: The systematic expression characteristics and functions of collagen genes in gastric cancer (GC) have not been reported. Through public data integration, combined with bioinformatics analysis, we identified a panel of collagen genes overexpressed in GC. The functions of these genes were analyzed and validated in a GC-related cohort. microRNAs that may potentially target such genes were investigated in vitro. Methods: Four GC-related datasets retrieved from the Gene Expression Omnibus (GEO) were used to extract differentially expressed genes (DEGs) in GC. Functional annotation was performed to identify the potential roles of the identified DEGs. The association of candidate genes involved in the prognosis of GC patients (n=876) was determined using data provided by the Kaplan-Meier-plotter database, The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) repository, and a GC-related dataset (GSE15459). The expression characteristics of candidate genes and their associations with clinical parameters were validated in our in-house cohort (n=58). MicroRNAs able to target the identified candidate genes were predicted and confirmed using qRT-PCR, Western blotting, and dual-luciferase reporter assays in vitro. Results: After the integration of four GEO datasets, 76 DEGs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these DEGs were significantly enriched in ECM-related functions and pathways. A group of collagen genes was significantly upregulated in the GC tissues and constituted a protein-protein interaction network as important nodes. Some of these collagen genes were closely associated with poor prognosis in GC patients. Overexpression of COL1A1 and COL4A1 was confirmed in our in-house cohort, and this was related to prognosis and certain clinicopathological parameters. We found that microRNA-29c-3p could directly target COL1A1 and COL4A1 in BGC-823 cells. Conclusions: Collagen genes identified in this study were associated with patient prognosis in GC and may represent diagnostic markers or potential therapeutic targets. Aberrant expression of such candidate genes may be induced by microRNA-29c-3p.

7.
J Chromatogr Sci ; 53(8): 1265-73, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25657289

RESUMO

A rapid sensitive analytical method was established and validated to investigate levistolide A in rat plasma by liquid chromatography-tandem mass spectrometry operated in the positive ion mode. Levistilide A (LA) and internal standard (IS) andrographolide (AD), mixed with the plasma sample, were separated on a reversed phase Spursil™ C18 5 µm column. The precursor/product transitions (m/z) were 398.5/381.3 for LA and (m/z) 368.0/351.1 for AD. The calibration curve was linear over the range from 5 to 1,250 ng/mL for oral administration and 10-4,000 for intravenous administration with a correlation coefficient (r) ≥0.9993. The lower limit of quantification was 5 ng/mL for LA in plasma. The inter- and intra-day accuracy and precision were less than ±15% of the relative standard deviation. In this study, the developed method is successfully applied to the comparative pharmacokinetic study of LA in rats after oral administration of LA alone, Rhizoma Chuanxiong, and Danggui-Shaoyao-San along with the bioavailability study of LA in rats. Our study shows that low bioavailability (7.5%) is observed after oral administration of LA. Traditional formula compatibility of Danggui-Shaoyao-San could significantly enhance LA bioavailability compared with LA alone and Rhizoma Chuanxiong.


Assuntos
Benzofuranos/sangue , Benzofuranos/farmacocinética , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Benzofuranos/química , Medicamentos de Ervas Chinesas , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
8.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(6): 688-90, 2014 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-25046950

RESUMO

OBJECTIVE: To observe the clinical effect of Shen-reinforcing and menstrual cycle-regulating therapy (SRMCRT) combined with Western medicine (WM) in treating decline in ovarian reserve (DOR). METHODS: Totally 78 patients with DOR were assigned to the traditional Chinese medicine combined WM group (abbreviated as IM group, 40 cases), and the WM group (38 cases) according to random digit table method. Patients in the WM group were treated with hormone replacement therapy, while those in the IM group additionally received SRMCRT. The therapeutic course for all was 3 consecutive months. The therapeutic efficacy was compared between the two groups. The serum levels of follicle stimulating hormone (FSH), FSH/luteinizing hormone (LH), and estradiol (E2), as well as the development of sinus follicles were compared between before and after treatment in the two groups. RESULTS: The therapeutic effective rate was 92.5% in the IM group, higher than that of the WM group (73.68%, P < 0.05). The serum levels of FSH, FSH/LH, and E2 decreased (P < 0.05) and the number of the sinus follicle increased (P < 0.05) in the two groups after treatment. Besides, IM was superior in decreasing serum levels of FSH and FSH/LH, and increasing the number of the sinus follicle (P < 0.05). CONCLUSIONS: SRMCRT was an effective method for treating ROD. IM was superior in decreasing serum levels of FSH and FSH/LH, and increasing the number of the sinus follicle.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Doenças Ovarianas/tratamento farmacológico , Reserva Ovariana , Adulto , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Terapia de Reposição Hormonal , Humanos , Medicina Integrativa , Hormônio Luteinizante/sangue , Folículo Ovariano/efeitos dos fármacos , Adulto Jovem
9.
J Chromatogr Sci ; 52(6): 476-81, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23735239

RESUMO

A sensitive and specific liquid chromatography-tandem mass spectrometric (LC-MS-MS) method was developed for the determination and pharmacokinetics of amygdalin in rats. Rat plasma pretreated by solid-phase extraction was analyzed by LC-MS-MS with negative electrospray ionization in the multiple reaction monitoring mode. Amygdalin and geniposide [the internal standard (IS)] were separated on a C18 column eluted with a mobile phase of methanol and water (85:15; v/v) at a flow rate of 0.25 mL/min in a run time of 3.0 min. The precursor to product ion transitions were monitored at m/z 457.2 → 279.1 for amygdalin and m/z 387.1 → 224.9 for the IS. The calibration curve of amygdalin showed good linearity over a concentration range of 10-2,000 ng/mL. The limit of quantification was 10 ng/mL. Intra-day and inter-day precisions and accuracy (percent relative standard deviation) were both within 10%. The method was fully validated for its selectivity, sensitivity, matrix effect, recovery and stability. This accurate and specific assay produced a useful LC-MS-MS method, which was successfully applied to pharmacokinetic studies after the oral administration of amygdalin to rats.


Assuntos
Amigdalina/sangue , Amigdalina/farmacocinética , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
10.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(5): 586-9, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-23905371

RESUMO

OBJECTIVE: To observe the clinical efficacy of bushen huoxue recipe (BHR) combined estrogen and progesterone in treating premature ovarian failure (POF), and to explore an effective treatment program of POF by integrative medicine. METHODS: Totally 265 POF patients were randomly assigned to 3 groups, i.e., Group I (86 cases, treated by BHR),Group II (88 cases,treated by conjugated estrogens and medroxyprogesterone acetate), and Group III (91 cases,treated by BHR +conjugated estrogens and medroxyprogesterone acetate). The therapeutic course for each group was 6 months. The main symptoms (including menstrual cycle, hectic fever, night sweat, vaginal dryness, and low libido), laboratory indices [including follicle stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), and inhibin B (INH-B)], B-ultrasound indicators (including endometrial thickness, ovarian volume, and antral follicle count), and adverse reactions were observed in the three groups at the end of treatment and 6 months after treatment. RESULTS: Compared with before treatment, the main symptoms, laboratory indices, and B-ultrasound indicators were statistically improved in the three groups at the end of treatment and 6 months after treatment (P <0.05, P <0.01). Better effects were obtained in Group III in improving symptoms of the menstrual cycle, vaginal dryness, and low libido, lowering levels of FSH and LH, elevating levels of E2and INH-B, and ameliorating the endometrial thickness, the ovarian volume, and the antral follicle count (P <0.05, P <0.01). No obvious adverse reaction occurred in the three groups. CONCLUSION: BHR combined estrogen and progesterone showed better clinical efficacy than use of BHR or estrogen/progesterone alone, indicating it was an effective treatment program for POF.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Integrativa , Insuficiência Ovariana Primária/tratamento farmacológico , Adulto , Estrogênios/uso terapêutico , Feminino , Humanos , Progesterona/uso terapêutico
11.
Zhong Yao Cai ; 35(6): 930-5, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23236829

RESUMO

OBJECTIVE: To study the anti-portal hypertension effect of oleanolic acid (OA) in CCl4-induced cirrhosis rats and its mechanism. METHODS: Rats were induced to portal hypertension by CCl4. After treatment with low dose of OA (30 mg/kg) and high dose of OA (60 mg/kg) by intragastrically for a month, the parameters in serum or liver tissue including ALT, AST, MDA, GSH-Px, NOx, eNOS, cGMP and type I collagen were measured. The MAP, PP and HR were determined by hameodynamic method and the eNOS expression in liver was measured by western blot. The pathological changes of liver tissue were also tested by Masson dye. The normal group and model group were given 0.25% of CMC-Na solution. RESULTS: Compared with the model group, treatment with 30 mg/kg and 60 mg/kg OA significantly decreased the levels of ALT, AST, ALP, gamma-GT and MDA and enhanced the level of GSH-Px in liver (P<0.05). Moreover, the collagen content also notably lowered in CCl4-induced cirrhosis rats, thus decreasing the portal pressure (PP). However, the MAP and HR were not affected by OA treatment. In addition, the expression of eNOS in liver markedly increased after one mouth treatment of OA, hereof enhancing the level of cGMP and NOx in the CCl4-induced portal hypertensive rats (P<0.05). CONCLUSION: OA could inhibit the progress of fibrosis and lower the PP in CCl4-induced portal hypertensive rats and the anti-portal hypertension effect might be related to increasing the expression of eNOS and enhance the NOx level in liver.


Assuntos
Hipertensão Portal/tratamento farmacológico , Cirrose Hepática Experimental/tratamento farmacológico , Óxido Nítrico Sintase Tipo III/metabolismo , Ácido Oleanólico/uso terapêutico , Fitoterapia , Substâncias Protetoras/uso terapêutico , Animais , Peso Corporal , Tetracloreto de Carbono/efeitos adversos , Modelos Animais de Doenças , Hipertensão Portal/etiologia , Hipertensão Portal/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Testes de Função Hepática , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Ácido Oleanólico/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley
12.
Artigo em Inglês | MEDLINE | ID: mdl-22999477

RESUMO

A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method operated in the negative electrospray ionization (ESI) switching mode has been developed and validated for the simultaneous determination of esculin and its metabolite esculetin in rat plasma. After addition of internal standards scopoletin, the plasma sample was pretreated by solid-phase extraction (SPE), and separated on a reversed phase C(18) column with a mobile phase of 0.01% formic acid in water (solvent A) and methanol (solvent B) using isocratic elution (A:B=20:80, v/v). The detection of target compounds was done in multiple reaction monitoring (MRM) mode. The MRM detection was operated in the negative ESI mode using the transitions of m/z 339.1 ([M-H](-))→176.7 for esculetin, m/z 176.9 ([M-H](-))→133.0 and m/z 191.0 ([M-H](-))→175.9 for scopoletin. The standard curves, which ranged from 25 to 3200 ng/mL for esculin with the lowest limit of quantification (LLOQ) of 0.25 ng/mL and from 1.25 to 160 ng/mL for esculetin with the LLOQ of 1.25 ng/mL, were fitted to a 1/x weighted quadratic regression model. The method also afforded satisfactory results in terms of the sensitivity, specificity, precision (intra- and inter-day, RSD<8.73%), accuracy, recovery as well as the stability of the analyte under various conditions. The method was successfully applied to study the pharmacokinetics of esculin and its metabolite esculetin in rat plasma after oral administration of esculin at a dose of 100mg/kg.


Assuntos
Cromatografia Líquida/métodos , Esculina/sangue , Espectrometria de Massas em Tandem/métodos , Umbeliferonas/sangue , Animais , Estabilidade de Medicamentos , Esculina/química , Esculina/farmacocinética , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodos , Umbeliferonas/química , Umbeliferonas/farmacocinética
13.
J Chromatogr B Analyt Technol Biomed Life Sci ; 887-888: 138-42, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22321407

RESUMO

A simple, rapid and sensitive method for the determination of geniposidic acid (GSA) in rat plasma was developed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Geniposide (GS) was used as the internal standard. Rat plasma pretreated by solid-phase extraction (SPE) was analyzed by LC-MS/MS with negative ion mode electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The analytical column was C8 column and the mobile phase was methanol (A) and water (B). The flow rate was set at 0.8 mL/min with split ratio of 1:3, the total run time was 15 min. The MS/MS ion transitions monitored were m/z 373.3-211.1 for GSA and m/z 387.3-225.3 for GS. The quantification limit was 5 ng/mL within a linear range of 10-4000 ng/mL. The inter-day and intra-day accuracy and precision were within ±10%. The method was fully validated for its sensitivity, selectivity, matrix effect, stability study and recovery. The data indicate that our LC-MS/MS assay is an effective method for the pharmacokinetics study of GSA in rat plasma.


Assuntos
Cromatografia Líquida/métodos , Glucosídeos Iridoides/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Estabilidade de Medicamentos , Glucosídeos Iridoides/farmacocinética , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Extração em Fase Sólida
14.
Biopharm Drug Dispos ; 29(4): 237-44, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18350560

RESUMO

Aim. To study the pharmacokinetics of dihydroartemisinin (DHA) in Artekin (compound dihydroartemisinin) tablets in Chinese healthy volunteers. Methods. Eighteen healthy volunteers (9 males, 9 females) received Artekin tablets for oral administration. The plasma samples of DHA were analysed by liquid-liquid extraction and determined by HPLC/ESI/MS. Results. The plasma DHA concentration-time curves of single dose and repeated doses of DHA were fitted to a two-compartment open model. The mean pharmacokinetic parameters of DHA in a single dose were: t(1/2(beta))=1.245 +/- 0.495 h, C(max)=243.6 +/- 56.15 microg/l, AUC(0 --> infinity)=450 +/- 69 h x microg/l, V(d)=5.75 +/- 2.2 l/kg and Cl=3.245 +/- 0.38 l/h/kg, while in repeated doses they were: t(1/2(beta))=1.085 +/- 0.298 h, AUC(0 --> infinity)=444.35 +/- 80.43 h x ng/ml, V(d)=4.62 +/- 1.128 ml/kg, Cl=3.0125 +/- 0.875 ml/h/kg, respectively. Conclusion. The study showed that DHA in Artekin was rapidly absorbed, distributed and eliminated in the healthy subjects. The pharmacokinetic properties of DHA in Artekin were not affected by gender in a single dose. While in repeated doses accumulation of DHA did not appear after repeated doses.


Assuntos
Antimaláricos/farmacocinética , Artemisininas/farmacocinética , Povo Asiático , Administração Oral , Adulto , Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Feminino , Humanos , Masculino , Comprimidos
15.
J Chromatogr B Analyt Technol Biomed Life Sci ; 862(1-2): 189-95, 2008 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-18164671

RESUMO

A sensitive method for the determination of CQP propionic acid in rat plasma was developed and validated after solid-phase extraction. Chromatographic separation was achieved on a reversed-phase Alltima C18 column with the mobile phase of methanol-0.15% (v/v) phosphoric acid solution (pH 2.5) and step gradient elution resulted in a total run time of about 20min. The analytes were detected by using UV detector at 345nm. A good linear relationship was obtained in the concentration range of 50-12,800ng/mL (r=0.9998). The intra-day RSDs and the inter-day RSDs at the concentration of 200, 800, 6400 and 12,800ng/mL were less than 7.0% and 11.0%, respectively. The intra-day accuracy ranged from 96.3 to 106.5% and the inter-day accuracy ranged from 98.6 to 113.4%, respectively. Average extraction recoveries ranged from 83.6 to 94.3% in plasma at the concentrations of 200, 800, 6400 and 12,800ng/mL. This method was successfully applied to the pharmacokinetic studies on rats.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Propionatos/sangue , Animais , Masculino , Propionatos/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrofotometria Ultravioleta
16.
Zhongguo Zhen Jiu ; 26(1): 51-5, 2006 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-16491761

RESUMO

OBJECTIVE: To investigate the central modulating mechanism of acupuncture at Sanyinjiao (SP 6) in treatment of primary dysmenorrhea. METHODS: 18F-FDG positron emission tomograph imaging of whole brain was performed in six patients with primary dysmenorrhea during two stimulation: pseudo acupuncture and real acupuncture at Sanyinjiao (SP 6). The areas of cerebral glycometabolism change were obtained by using statistical parametric mapping (SPM). Meanwhile the pain intensity before and after pseudo-acupuncture and real acupuncture was assessed with 0-10 numerical pain intensity scale. RESULTS: No differences in the values of pain before and after pseudo-acupuncture (P > 0.05). The value of pain after acupuncture was significantly lower than that before acupuncture (P < 0.01). Most of the activated brain areas were shared with the areas activated by pain as described in the literature. The brain areas of increasing glycometabolism were ipsilateral lentiformn nucleus (globus pallidus, putamen), cerebellum and insula, bilateral thalamus, ipsilateral paracentral lobule, bilateral amygdala, contralateral midbrain, bilateral second somatosensory cortex, ipsilateral hippocampus and anterior cingulate, contralateral mammillary body. The brain areas of decreasing glycometabolism were limited in small cerebral cortex. CONCLUSION: Acupuncture at Sanyinjiao (SP 6) can relieve significantly the pain of the patient. Primary dysmenorrhea is cured mainly by activating the area involved in pain. It is indicated that acupuncture can relieve pain and balancing the pain-related central networks. Also neuroendocrine may play a role in the therapy.


Assuntos
Pontos de Acupuntura , Dismenorreia , Acupuntura , Terapia por Acupuntura , Dismenorreia/terapia , Feminino , Glucose/metabolismo , Humanos
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