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Objective To establish a LC-MS method of cisatracurium assay in human plasma for clinical therapeutic drug monitoring. Method Propafenone Hydrochloride was used as the internal standard. The plasma samples were treated with 2% formic acid aqueous solution and acetonitrile containing the internal standard to precipitate protein. Agilent SB-C18 column was used for gradient elution with the mobile phase of 0.1% formic acid-water and 0.1% formic acid-acetonitrile solution at 35 ℃ and 0.3 ml/min flow rate. The degradation products of cisatracurium m/z 464.6-358.4 and propafenone hydrochloride m/z 342.2-116.2 were identified by ESI positive-ion detection. Results There was a linear rage of cisatracurium in 2-500 ng/ml (r=0.996 5) with a detection limit of 2 ng/ml. The intra-day coefficients of variation (CVs) were less than 16.00%, and the inter-day CVs were less than 6.00%. The mean recoveries were in the range of 97.63%-111.93%. The plasma samples were stable for 4 hours at room temperature, 14 days at -80 ℃ and 24 hours after pretreated. Conclusion This method was simple, accurate, fast and repeatable for the cisatracurium assay in human plasma.
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OBJECTIVE: To study the effects of scutellarin on the proliferation of cardiac fibroblasts (CFs) in neonate rats induced by angiotensin Ⅱ (ANG Ⅱ) and signal pathway of extracellular regulated protein kinase (ERK1/2) and p38 mitogen activated protein kinase (p38 MAPK).METHODS: CFs of neonatal rat were isolated and cultured in vitro, and then divided into blank group (blank culture medium), Ang Ⅱ group (10-7 μmol/L), 50 μmol/L scutellarin group and Ang Ⅱ (10-7 μmol/L)+5, 10, 20, 50 μmol/L scutellarin groups. After cultured for 48 h, CCK-8 assay was used to detect the proliferation ability of cells. Other cells were selected and divided into blank group (blank culture medium), Ang Ⅱ group (10-7 μmol/L) and Ang Ⅱ +5, 10, 20, 50 μmol/L scutellarin groups. After cultured for 48 h, mRNA expression of Col I, Col Ⅲ and α-SMA in cells and hydroxyproline (HYP) content in cell culture fluid were detected; phosphorylation levels of ERK1/2 and p38 MAPK in cells were also detected. RESULTS: 5, 10, 20, 50 μmol/L scutellarin could significantly inhibit the proliferation of CFs induced by Ang Ⅱ (P<0. 05), and decreased mRNA expression of Col I, Col Ⅲ and α-SMA in CFs induced Ang Ⅱ (P<0. 05). 5, 10, 20, 50 μmol/L scutellarin could significantly inhibit the increase of HYP content and the phosphorylation of ERK1/2 and p38 MAPK after induced by Ang Ⅱ (P<0. 05), in dose-dependent manner. CONCLUSIONS: Scutellarin inhibits the proliferation of CFs induced by Ang Ⅱ, the mechanism of which may be associated with reduction of ERK1/2 and p38 MAPK phosphorylation.
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Twenty inadequately controlled diabetic patients treated with insulin therapy received dapagliflozin treatment for 12 weeks. HbA1C, glycemic variations, plasma 8-iso-prostaglandin F2α(8-PGF2α), and hypersensitive C-reactive protein (hs-CRP) levels, the change of the insulin dose, and the safety of treatments were analyzed. The results showed that after 12-week dapagliflozin therapy, HbA1C, fasting plasma glucose, postprandial 2h plasma glucose, inter-quartile range, standard deviation of blood glucose, large amplitude glycemic excursions, postprandial glucose excursion, as well as absolute means of daily difference were significantly decreased ( P<0. 01) . Compared with those before treatment, addition of dapagliflozin notably decreased plasma 8-PGF2αand hs-CPR levels, along with reduced insulin dosage ( P<0. 01 ) and decreased body weight of patients ( P<0. 05 ) . After dapagliflozin treatment, the hypoglycemia of the patients was obviously improved, without report of severe hypoglycemia. These results indicate that dapagliflozin treatement improves glucose metabolism,and reduces insulin dosage and the hypoglycemic events in fragile diabetics with intensive insulin therapy.
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Objective: To determine the expression of von Willebrand factor Cand epidermal growth factor domains (VWCE ) gene in human breastcancer tissues, and to assess the effects of VWCE overexpression onproliferation and migration of breast cancer cells in vitro .Methods: The expression levels of VWCE mRNA and protein in 36pairs of human breast cancer tissues and their adjacent normal tissues as well as 5 kinds of breast cancer cell lines were detected by real-time fluorescentquantitative PCR and Western blotting, respectively. The recombinant lentivirus carryingVWCE gene was constructed and infected into breast cancer MCF-7 and SK-BR-3 cells. Afterthe overexpression of VWCE gene was verified by real-time fluorescent quantitative PCR andWestern blotting, the proliferation and migration of breast cancer cells were detected byCCK-8 and Transwell chamber assay, respectively.Results: The high expression rate of VWCE mRNA in breast cancer tissues was significantlylower than that in the corresponding adjacent tissues (22% vs 78%, P < 0.05), and wasrelated with the primary tumor stage (P < 0.05). The mean expression level of VWCE proteinin breast cancer tissues was lower than that in the corresponding adjacent tissues (P < 0.05).The expression levels of VWCE mRNA and protein in 5 kinds of breast cancer cell lines werelower than those in immortalized mammary epithelial cell line (all P < 0.05), respectively.After the breast cancer MCF-7 and SK-BR-3 cells were infected with VWCE overexpressionlentivirus, the expression of VWCE protein was significantly increased (both P < 0.05), whilethe cell proliferation and migration were significantly inhibited (all P < 0.05).Conclusion: VWCE is low expressed in human breast cancer tissues and cells. Overexpressionof VWCE can inhibit the proliferation and migration of breast cancer cells in vitro .
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Objective To investigate the safety and effectiveness of high intensity focused ultrasound (HIFU ) in the treat‐ment of uterine fibroid (<4 cm) .Methods Retrospectively studied 79 single fibroid (<4 cm) patients that treated with HIFU in our hospital from January 2011 to February 2013 .Evaluated the improvement of post‐treatment ,shrinkage of fibroid volume and HIFU‐related adverse reaction .Results All the 79 patients were successfully cured by HIFU treatment .The shrinkage rate of fi‐broid was 79 .0% (four point spacing 57 .9% ,92 .1% ) after 2‐year treatment ;Symptom severity score (SSS) and uterine fibroid symptom and quality of life score (UFS‐QOL) were significantly improved ;and there was no adverse reaction .Conclusion HIFU can be safely used in the treatment of small uterine fibroids (diameter<4 cm ) .
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Sphingosine-1-phosphate receptor 1(S1PR1) is a new member of G protein-coupled receptor family. A great body of data suggest S1PR1 is capable of regulating lots of downstream signaling molecules and cellular processes. It is found that S1P/S1PR1 plays an important role in the development and mainte-nance of pain. However, it is controversial whether activation of S1PR1 would enhance or attenuate pain. Here, recent studies ＜br> and current perspectives are discussed in order to better under-stand the biological and pathological roles of S1PR1 in pain mod-ulation.
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This study was aimed to observe the antipyresis and cholagogue effect of theFructus Gardeniae-Fructus Forsythiaeherb couple in order to explore the possible pharmacodynamic mechanism. Dry yeast suspension was subcutaneously injected into the back of rat to establish the fever model. The freeze-dried powders ofF. Gardeniae,F. Forsythiae, andF. Gardeniae-F. Forsythiaeherb couple were prepared. They were dissolved in the water for intragastric administration. SD rats were randomly divided into the normal group, model group, positive control group and Chinese medicine group. The Chinese medicine group was subdivided into the group ofF. Gardeniae,F. Forsythiae, andF. Gardeniae-F. Forsythiaeherb couple. The concentration of herbal water extract was 10 mL·kg-1 (which equaled to 3 g·kg-1 of a single crude herb). The concentration of positive control was 10 mL·kg-1. Intragastric administration of equal amount of normal saline was given to the blank group and the model group. Except rats in the normal group, rats in other groups were subcutaneously injected with 10 mL·kg-1 of 15% dry yeast suspension on the back of to establish the fever model. Electronic thermometer was used to record the body temperature of rats at 0, 1, 4, 5, 6, 7 and 8 h after the injection, respectively. Meanwhile, bile was collected from 1-1, 1-2, 2-4, 4-6, 6-8, 8-12, 12-24 h, respectively. Observation was given on changes of body temperature and bile amount of rat. The results showed thatF. Gardeniae,F. Forsythiae, andF. Gardeniae- F. Forsythiaeherb couple had certain effect to reduce the body temperature of rats. The temperature-reducing effect of the combination of both herbs was better than a single herb. TheF. Gardeniae -F. Forsythiae herb couple can reduce the body temperature of fever rat (P < 0.05, orP < 0.01). It had a little effect on the body temperature of normal rat. TheF. Gardeniae - F. Forsythiaeherb couple can promote the bile secretion, which was better than the single using of F. Gardeniae (P < 0.05). It was concluded that theF. Gardeniae - F. Forsythiaeherb couple had better temperature-reducing effect than the using of a single herb; however, there was no significant difference. But it had obvious effect on the promotion of bile secretion, which indicated the strengthening of cholagogue effect.
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BACKGROUND:Heat shock proteins have unique biological characteristics, and exploration of such proteins expressed in the myocardium under exercise stress has important value. OBJECTIVE:To investigate the studies about the expression of myocardial heat shock proteins under stress condition, and analyze the expression characteristics of myocardial heat shock proteins under different stress conditions. METHODA computer-based online retrieval was performed to find articles about the production, classification and function of heat shock proteins, as wel as the expression of myocardial heat shock proteins published from January 1991 to January 2014 in PubMed database and Wanfang databases. The key words were“heat shock protein;myocardium;exercise stress”in English and Chinese. Final y 48 relevant articles were summarized. RESULTS AND CONCLUSION:Heat shock proteins have the immune synergy effect. Researches show that, exercise training triggers the expression of myocardial heat shock protein. Acute exercise stress leads to a variety of physiological and biochemical changes, accordingly myocardial heat shock protein wil make the corresponding expression and protect myocardial cells. Low-intensity exercise can increase the expression level of heat shock protein 72, and inhibit cardiomyocyte apoptosis. High-intensity exercise reduces the expression of heat shock protein 72, which can not effectively inhibit cardiomyocyte apoptosis and is not conducive to the myocardial protective effect. The expression of heat shock protein under moderate-intensity exercise remains controversial. Exercise-induced expression of heat shock protein may have protection effect against damage induced by exercise, moderate exercise activities play an important role in enhancing myocardial function and preventing myocardial injury.
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Objective To investigate the effects of 20% lipid emulsion on plasma ropivacaine concentration and myocardial ropivacaine content in rats. Methods Sixty male pathogen-free SD rats weighing 220-270 g were randomly divided into 2 groups (n = 30 each): group A normal saline and group B lipid emulsion.The animals were anesthetized with intraperitoneal 4% pentobarbital 40 mg/kg. The femoral vein was cannulated for drug and fluid administration. ECG (lead Ⅱ) was continuously monitored. 1% ropivacainc 5 mg/kg was injected iv. A bolus of 20% lipid emulsion 5 ml/kg was then injected iv in group B, while in group A equal volume of normal saline was administered instead of 20% lipid emulsion. The animals were sacrificed at 5, 10,20, 40, 60 and 120 min after ropivacaine infusion (5 animals at each time point). Blood samples and myocardial specimens were taken for determination of plasma and myocardial ropivacaine levels by HPLC. Results Plasma ropivacaine concentration at 20 min after ropivacaine administration was significantly higher in group B than in group A. The myocardial ropivacaine concents at 5, 10 min after ropivacaine administration were significantly lower in group B than in group A. Conclusion 20% lipid emulsion infusion can bind ropivacaine and decreasee myocardial ropivacaine content thus reducing the cardiac toxicity of ropivacaine.
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OBJECTIVE:To study the relative bioavailability,pharmacokinetics and bioequivalence of domestic nisoldipine tablets in healthy volunteers.METHODS:A single oral dose of 10 mg test and reference nisoldipine tablets were given to 24 male healthy volunteers in an open randomized 2?2 latin square design.The plasma concentrations of nisoldipine at different time points were determined by LC-MS and the pharmacokinetic parameters of the two kinds of tablets were computed and their bioequiavailability was evaluated.RESULTS:The main pharmacokinetic parameters of the test vs.reference formulations of nisoldipine in 24 healthy volunteers were as follows:Cmax(2.94?2.78)ng?mL-1 vs.(3.22?2.16)ng?mL-1,tmax(1.70?1.00)h vs.(1.40?1.00)h,t1/2(6.81?4.11)h vs.(5.55?2.35)h,AUC0～24(10.60?7.70)ng?h?mL-1 vs.(9.90?6.76)ng?h?mL-1,AUC0～∞(11.30?7.90)ng?h?mL-1 vs.(10.20?7.00)ng?h?mL-1.The relative bioavailability of domestic nisoldipine tablets was(110.3?30.8)%.CONCLUSION:The reference preparation and the test preparation of nisoldipine tablets were proved to be bioequivalent.