This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.
Animals ; Chlorzoxazone ; metabolism ; Chromatography, Liquid ; Cytochrome P-450 Enzyme System ; metabolism ; Depression ; Dextromethorphan ; metabolism ; Liver ; enzymology ; Midazolam ; metabolism ; Omeprazole ; metabolism ; Rats ; Stress, Physiological ; Tandem Mass Spectrometry ; Theophylline ; metabolism ; Tolbutamide ; metabolism

OBJECTIVE To observe whether human CD4 + T cells could be activated by immuno-globulin D (IgD) via IgD receptor(IgDR)-Lck. METHODS Human CD4+ T cells were purified from peripheral blood mononuclear cells (PBMCs) with microbeads. The viability of T cells were detected by CCK-8. The binding affinity and expression of IgDR on T cells were detected by flow cytometry. The protein expression of IgDR, Lck and P-Lck were analyzed by western blot. RESULTS IgD could concentration-dependent bind to IgDR on CD4+ T cells. The expression of IgDR was increased in response to treatment with IgD in a time- dependent and concentration- dependent manner. Stimulating by IgD resulted in enhanced phosphorylation of Lck compared with that in the medium control sample. The expression of Lck was not changed. As inhibitor of PTK, Herbimycin A or A770041, which combined with IgD could significantly inhibit phosphorylation of Lck(Tyr394). The proliferation promoting effect of IgD was blocked by Herbimycin A or A770041. IgD could stimulate CD4+ T cell activation and proliferation through upreg?ulating activating tyrosine residue of Lck (Tyr394) phosphorylation. CONCLUSION These results demon?strate that IgD exaggerates CD4+T cell activities, which may be through promoting Lck phosphorylation.

To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.
Animals ; Arthritis, Rheumatoid ; drug therapy ; immunology ; Biomarkers ; Female ; Interleukin-17 ; antagonists & inhibitors ; genetics ; Interleukin-6 ; genetics ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Tripterygium ; Triterpenes ; pharmacokinetics ; pharmacology

OBJECTIVETo investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA).

METHODSEquilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions.

RESULTSThe binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16∓2.82)%, (33.42∓4.21)%, and (34.61∓3.42)%, and those of and Rb1 were (50.13∓2.34)%, (51.23∓3.23)%, and (53.11∓3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13∓2.72)%, (21.42∓3.22)%, and (25.45∓3.52)%, and those of Rb1 to (40.13∓3.24)%, (41.25∓4.15)%, and (43.11∓3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA.

CONCLUSIONClopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.

AIMTo search for compounds for the treatment of cardiovascular diseases through prodrug structural modifications of cyclovirobuxine D, a single efficient composition distilled from Box plant in China, which was used to treat angina and myocardial infarction.

METHODSAccording to prodrug design principle, a series of cyclovirobuxine D analogues were prepared, suc as succinate, phosphate and amino acid ester, and their biological activities were tested.

RESULTSSeven new compounds were obtained and confirmed with 1H NMR, MS, and element analysis.

CONCLUSIONIn pharmacology experiment, for treating arrhythmia induced by aconitine, succinate and amino acid ester of cyclovirobuxine D (I and VII) showed better activities than that of cyclovirobuxine D. The normal rhythm of the heart duration of I and VII were ( 11.53 +/- 7.62) min and (12.68 +/- 9.25) min, compared with 0.9% NaCl solution and cyclovirobuxine D, (2.36 +/- 1.68) min and (10.25 +/- 6.59) min (P < 0.01), respectively. Another pharmacology experiment, for treating arrhythmia induced by chloroform, the negative ratio of I and VII were 80% and 82%, compared with 0.9% NaCl solution and cyclovirobuxine D, 43% and 52% (P < 0.05), respectively. The difference between new compounds and cyclovirobuxine D was distinct.

Aconitine ; Animals ; Anti-Arrhythmia Agents ; chemical synthesis ; pharmacology ; Arrhythmias, Cardiac ; chemically induced ; physiopathology ; Buxus ; chemistry ; Chloroform ; Drugs, Chinese Herbal ; chemical synthesis ; pharmacology ; Female ; Heart Rate ; drug effects ; Male ; Mice ; Plants, Medicinal ; chemistry ; Prodrugs ; chemical synthesis ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo prepare polyelectrolyte multilayer film-coated microbubble ultrasound contrast agent (UCA) and evaluate its effects in contrast imaging on normal rabbit's liver parenchyma.

METHODSPerfluorocarbon (PFC) -containing microbubble UCA (ST68-PFC) were prepared by sonication-based on surfactants (Span 60 and Tween 80). Subsequently, the resulting ST68-PFC microbubbles were coated using oppositely charged polylysine (PLL) and alginate (Alg) by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction. The enhancement effects in contrast imaging on normal rabbit's liver parenchyma were assessed.

RESULTSThe obtained microbubble UCA exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film-coated UCA effectively enhanced the imaging of rabbit's liver parenchyma.

CONCLUSIONSThe novel microbubble UCA obtained via layer-by-layer self-assembly, when enabling more functions, has no obvious difference in enhancement effects compared with the premodified microbubbles. The polymers with chemically active groups (such as amino group and carboxyl group) can be used as the outermost layer for the attachment of targeting ligands to microbubbles, which allows the selective targeting of the microbubbles to desired sites.

Alginates ; chemistry ; Animals ; Contrast Media ; administration & dosage ; chemistry ; Fluorocarbons ; chemistry ; Glucuronic Acid ; chemistry ; Hexuronic Acids ; chemistry ; Liver ; diagnostic imaging ; Microbubbles ; Polylysine ; chemistry ; Rabbits ; Ultrasonography

AIMTo search for new compounds for the treatment of cardiovascular diseases by structural modification of cyclovirobuxine D.

METHODSAccording to rational drug design principle, a series of cyclovirobuxine D analogues were prepared, and their bioactivities were tested.

RESULTSTen new compounds were syntheized and confirmed by spectra.

CONCLUSIONEndurance lacking oxygen activity and antiarrhythmia effects of some analogues of cyclovirobuxine D were tested. Some compounds showed better activity than cyclovirobuxine D.

Anaerobic Threshold ; drug effects ; Animals ; Anti-Arrhythmia Agents ; chemical synthesis ; pharmacology ; Buxus ; chemistry ; Chloroform ; Drugs, Chinese Herbal ; chemical synthesis ; isolation & purification ; pharmacology ; Female ; Male ; Mice ; Molecular Structure ; Plants, Medicinal ; chemistry ; Random Allocation ; Ventricular Fibrillation ; chemically induced ; prevention & control

OBJECTIVETo investigate the relationship between 8 endocrine-disrupting chemicals in the serum and insulin resistance in patients with polycystic ovary syndrome (PCOS).

METHODSThis study was conducted among 60 patients with PCOS, including 23 with insulin resistance (PCOS-IR) and 37 without insulin resistance (PCOS-NIR), and 29 non-PCOS women seeking medical attention for infertility or menstrual disorder (control group). The serum levels of 6 phthalic acid esters (PEAs), bisphenol A (BPA) and octylphenol (OP) were measured in all the subjects.

RESULTSThe levels of PAEs, BPA and OP showed no significant differences between PCOS patients and the control group (P>0.05). The serum level of OP was significantly lower in patients PCOS-IR than in those with PCOS-NIR (47.89 ng/ml vs 60.24 ng/ml, P<0.05).

CONCLUSIONPEAs and BPA do not produce obvious effect on the pathogenesis of PCOS or contribute to insulin resistance, but OP may play a role in insulin resistance in PCOS patients.

Adult ; Benzhydryl Compounds ; adverse effects ; blood ; Case-Control Studies ; Endocrine Disruptors ; adverse effects ; blood ; Environmental Pollutants ; adverse effects ; blood ; Female ; Humans ; Insulin Resistance ; Phenols ; adverse effects ; blood ; Phthalic Acids ; adverse effects ; blood ; Polycystic Ovary Syndrome ; blood ; physiopathology ; Young Adult

To establish a LC-MS/MS method to determine caffeic acid, chlorogenic acid in rat plasma and study their pharmacokinetics in rats. Six Sprague-Dawley rats were intravenously injected with 4 mL x kg(-1) of Dengzhanxixin injection, respectively. Their drug plasma concentration was determined by LC-MS/MS, with tinidazole as an internal standard. The pharmacokinetic parameters were calculated by DAS 1.0. The linear concentration ranges of caffeic acid, and chlorogenic acid were 2-128 microg x L(-1) (r = 0.998 1) and 3-384 microg x L(-1) (r = 0.998 7), respectively. The methodological test showed conformance to the requirements. The intraday and inter-day variable coefficients were both less than 10.0%, indicating that both of legitimate precise and accuracy were in conformity with the requirements of biological sample analysis. For caffeic acid, the pharmacokinetic parameter t1/2beta AUC0-t, and CL were (130.91 +/- 38.77) min, (4.89 +/- 0.96) mg x min x L(-1) and (0.12 +/- 0.02) L x min(-1) x kg(-1), respectively. For chlorogenic acid, the pharmacokinetic parameter t1/2beta , AUC0-t, and CL were (49.38 +/- 8.85) min, (9.54 +/- 0.95) mg x min x L(-1) and (0.09 +/- 0.003) L x min(-1) x kg(-1), respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of caffeic acid and chlorogenic acid.
Animals ; Caffeic Acids ; blood ; pharmacokinetics ; Chlorogenic Acid ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods

Objective: To investigate the attitudes of prostate cancer (PCa) patients towards postoperative penile rehabilitation and their influencing factors. METHODS: Seventy-nine PCa patients underwent radical prostatectomy from January through June 2017 and all received a questionnaire investigation before surgery on IIEF-5 and their attitudes towards postoperative penile rehabilitation. We analyzed the reasons for the patients' rejection of postoperative penile rehabilitation. RESULTS: Totally 56 (71%) of the patients accepted and the other 23 (29%) refused postoperative penile rehabilitation. The factors influencing their attitudes towards penile rehabilitation mainly included age (P = 0.023), income (P = 0.040), tumor stage (P = 0.044), and preoperative sexual activity (P = 0.004). The patients who accepted penile rehabilitation had significantly higher IIEF-5 scores than those who refused it (14.75 ± 0.88 vs 8.48 ± 1.16, P = 0.000 2). During the follow-up period, only 29 (36.7%) of the patients bought the vacuum erection device but not the other 50 (63.3%). The tumor stage (P = 0.004), income (P < 0.01) and preoperative androgen-deprivation therapy (P = 0.039) significantly influenced the patients' decision on the purchase of the device. Relevant admission education achieved a 45% decrease in the number of the patients unwilling to accept penile rehabilitation for worrying about its negative effect on cancer treatment, a 25% decrease in those rejecting penile rehabilitation because of age, and a 20% decrease in those refusing it due to the tumor stage. The cost of treatment was an important reason for the patients' rejection of postoperative penile rehabilitation. CONCLUSIONS The tumor stage and income are the main factors influencing PCa patients' decision on postoperative penile rehabilitation. Relevant admission education and reduced cost of rehabilitation are important for popularization of postoperative penile rehabilitation in PCa patients.