Electrochemical Construction of Vertical Single-Walled Carbon Nanotubes Array as Clenbuterol Sensor / 分析化学

Vertical single-walled carbon nanotubes (v-SWCNTs) array was constructed on glassy carbon electrode (GCE) by electrochemical method of electro-cyclic voltammetry (CV method).The synthesized electrode was very stable and was not easy to fall off.Via the amino groups of ethylenediamine (Ethylenediamine,EDA) and the carboxyl group of carboxylated carbon nanotubes,the SWCNTs were ordered to grow steadily on GCE(v-SWCNTs/EDA/GCE).The modified electrode was used to detect hydrochloric acid clenbuterol (CLE).The experimental results showed that the regular link of carbon nanotubes on GCE improved its utilization efficiency.The detection sensitivity of clenbuterol was 16.1 times higher than that of the bare GCE.Due to electron accelerating effect and nanometer effect of SWCNTs,the carboxyl peak current of SWCNTs was increased with the added CLE.The carboxyl peak current of SWCNTs had a good linear relationship with CLE concentration in the range of 10-120 ng/mL.The method was successfully applied to the determination of CLE in real urine samples with good recoveries.Also v-SWCNTs/EDA/GCE could be used as a new highly sensitive electrochemical sensor for CLE detection.

Analysis and Countermeasures of Microbial Contamination in Methadone Hydrochloride Oral Solution / 中国药师

Objective:To analyze the causes of microbial contamination in methadone hydrochloride oral solution used for the ma-intenance treatment of heroin addict in Guangxi and propose the relative countermeasures. Methods:The samples of methadone hydro-chloride oral solution were obtained from 10 maintenance treatment clinics, and then the microbial limit test and identification were per-formed,the content of preservative was detected and the relationship between the preservative content and microbial contamination was studied. Results:The total number of aerobe in the samples of methadone hydrochloride oral solution from the 10 clinics was all over the standard limit value of 100 cfu·ml-1 ,and the main contaminating germ was Burkholderia cepacia. The contents of sorbic acid were 78. 2％-98. 3％,the four batches with the lowest concentration of preservative were detected with higher total number of aerobe. Con-clusion:The microbial contamination in methadone hydrochloride oral solution from the 10 maintenance treatment clinics is severe,and the environment of medicine packaging, content of preservatives, packaging machine and storage conditions are the primary causes for the microbial contamination. To ensure drug quality safety, it is suggested that the environment cleanliness of medicine packaging be improved, suitable content of preservatives be added, packaging machine be clean, the products be stored in shade and the quality be tested regularly.

Determination of borneol in Fufang Danshen intestinal adhesion pellets and study its in vitro dissolution in different dosage form / 中国中药杂志

The borneol was included with β-CD and prepared Fufang Danshen intestinal adhesion pellets. GC method for determination of borneol in Fufang Danshen intestinal adhesion pellets was established to study its in vitro dissolution and make a comparison with the Fufang Danshen tablet, in this way, the rationality of dosage form was evaluated. The first method of dissolution determination was used for determining the in vitro dissolution of borneol in Fufang Danshen intestinal adhesion pellets in artificial intestinal juice, and Fufang Danshen tablet in artificial gastric juice and intestinal juice, respectively. Result shows: the concentration of borneol in Fufang Danshen intestinal adhesion pellets and Fufang Danshen tablet was 0.79% and 0.80%, respectively. Its in vitro dissolution was nearly 70% within 12 h in Fufang Danshen intestinal adhesion pellets, and in Fufang Danshen tablet, the dissolution was about 60% within 20 min and more than 90% within 40 min, and in artificial gastric juice, was less than 20% within 40 min but more than 80% till 150 min. Research suggests that in comparison with Fufang Danshen tablet, in vitro dissolution of borneol in the Fufang Danshen intestinal adhesion pellets showed an obvious sustained release behavior. The borneol in Fufang Danshen intestinal adhesion pellets was included with β-CD and prepared enteric preparations. To some extent, the stimulation on stomach and intestinal mucosa can be reduced and safety can be improved.

Studies on release behavior of sustained release tablets of extracts of Gardenia by antioxidant activity / 中国中药杂志

Using sustained release tablets of gardenia extract as model drug and DPPH radical scavenging capacity as antioxidant index, the feasibility of using pharmacodynamics index was explored to evaluate sustained release tablets. Applying the established quantifiable method of DPPH radical scavenging to the dissolved liquid of model drug, release profiles and biological effects profiles were drawn, and their correlation was discussed. A good correlation was observed by linear regression and f2 actor, suggesting that the indicator could be used to evaluate sustained release tabletsofextracts of gardenia in which iridoids were mainly involved.

In vitro and in vivo adhesion properties evaluation carbomer six kinds bioadhesive material / 中国药学杂志

OBJECTIVE: To comprehensively evaluate bioadhesive properties these materials by testing adhesion properties in vitro and in vivo. METHODS: Mucin from porcine stomach model, homemade adhesion measuring device and intestinal propulsion were used for in vitro and in vivo evaluation adhesive materials. RESULTS: Carbomer 934P and HPMCK100M with high viscosity had optimal adhesion in their class, besides chitosan can be specifically bound by mucin from porcine stomach and it performed better than other materials in vivo adhesion. CONCLUSION: Above researches indicate that the bioadhesive properties had a positive correlation with viscosity in the same type material, and the relative molecular mass the materials, moisture absorption capacity, specific binding mucin and other factors should be considered in different types materials in the comprehensive evaluation.

The long lasting effect of the murine fibroblast growth factor-21 on blood glucose control of diabetic animals / 药学学报

Insulin is the most common medicine used for diabetic patients, unfortunately, its effective time is short, even the long-acting insulin cannot obtain a satisfactory effect. Fibroblast growth factor (FGF)-21 is a recently discovered glucose mediator and expected to be a potential anti-diabetic drug that does not rely on insulin. In this study, db/db mice were used as the type 2 diabetic model to examine whether mFGF-21 has the long-term blood lowering effect on the animal model. The results showed that mFGF-21 could stably maintain the blood glucose at normal level for a long-term in a dose-dependent manner. Administration of mFGF-21 once a day with three doses (0.125, 0.25 and 0.5 mg x kg(-1)) could maintain blood glucose of the model animals at normal level for at least 24 h. Administration of mFGF-21 every two days with the same doses could maintain blood glucose of the model animals at normal level for at least 48 h, although it took longer time for blood glucose to reach to normal level depending on doses used (twenty injections for 0.125 mg x kg(-1) and 0.25 mg x kg(-1) doses, ten injections for 0.5 mg x kg(-1) dose). Surprisingly, the blood glucose of the treated model animals still maintained at normal level for 24 h after the experiment terminated. Glycosylated hemoglobin level of the animals treated with mFGF-21, which represented long-term glucose status, decreased significantly compared to the control group and the insulin group. The results suggest that FGF-21 has potential to become a long-acting and potent anti-diabetic drug.

Therapeutic effect of fibroblast growth factor 21 on NAFLD in MSG-iR mice and its mechanism / 药学学报

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia (P<0.01), reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.

Therapeutic effect of fibroblast growth factor 21 on hypertension induced by insulin resistance / 药学学报

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on hypertension induced by insulin resistance in rats and to provide mechanistic insights into its therapeutic effect. Male Sprague-Dawley (SD) rats were fed with high-fructose (10%) water to develop mild hypertensive models within 4 weeks, then randomized into 4 groups: model control, FGF21 0.25, 0.1 and 0.05 micromol x kg(-1) x d(-1) groups. Five age-matched normal SD rats administrated with saline were used as normal controls. The rats in each group were treated once a day for 4 weeks. Body weight was measured weekly, systolic blood pressure (SBP) was measured noninvasively using a tail-cuff method, insulin sensitivity was assessed using oral glucose tolerance test (OGTT) and HOMA-IR assay. At the end of the treatment, blood samples were collected, and blood glucose, serum cholesterol, serum triglyceride and serum insulin were measured. The results showed that blood pressure of the rats treated with different doses of FGF21 returned to normal levels [(122.2 +/- 3.5) mmHg, P < 0.01] after 4-week treatment, whereas, SBP of untreated (model control) rats maintained a high level [(142.5 +/- 4.5) mmHg] throughout the treatment. The observation of blood pressure in 24 h revealed that SBP of FGF21 treated-rats maintained at (130 +/- 4.5) mmHg vs. (143 +/- 5.5) mmHg for model control (P < 0.01). FGF21 treatment groups improved serum lipids obviously, total cholesterol (TC) and triglyceride (TG) levels decreased significantly to normal levels. The serum NO levels of three different doses FGF21 treatment group were significantly higher than that of the model control group [(7.32 +/- 0.11), (7.24 +/- 0.13), (6.94 +/- 0.08) vs. (6.56 +/- 0.19) micromol x L(-1), P < 0.01], and the degree of improvement showed obvious dose-dependent manner, indicating that FGF21 can significant increase serum NO in fructose-induced hypertension rat model and improve endothelial NO release function. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF21 significantly ameliorates blood pressure in fructose-induced hypertension model by relieving insulin resistance. This finding provides a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of essential hypertension.

Median effective target plasma concentration of propofol inhibiting response to laryngeal mask airway insertion when combined with dexmedetomidine / 中华麻醉学杂志

Objective To determine the median effective target plasma concentration (EC50) of propofol inhibiting the response to laryngeal mask airway (LMA) insertion when combined with dexmedetomidine.Methods ASA Ⅰ or Ⅱ patients of both sexes,aged 20-60 yr,with body mass index 20-25 kg/m2,scheduled for surgeries under general anesthesia,were studied.EC50 of propofol was determined by modified Dixon' s up-and-down sequential experiment.After dexmedetomidine 1.0 μg/kg was infused over 10 min,propofol was infused by targetcontrolled infusion.The initial target plasma concentration of propofol was set at 3.0 μg/ml.LMA was inserted when the target effect-site concentration of propofol and target plasma concentration of propofol reached the balance and BIS value was 50-60.Each time the target concentration increased/decreased by 0.2 μg/ml according to the occurrence of the response to LMA insertion.The response to LMA insertion was defined as the occurrence of coughing,body movement,laryngospasm or systemic voluntary movement.EC50 and 95 ％ confidence interval (CI)of propofol for inhibition of the response to LMA insertion were calculated.Results The EC50 of propofol required for inhibition of the response to LMA insertion was 2.351 (95％ Cl 1.737-2.600) μg/ml when combined with dexmedetomidine 1.0 μg/kg.Conclusion The EC50 of propofol inhibiting the response to LMA insertion is 2.351 μg/ml when combined with dexmedetomidine.

Optimization and characterization of a novel FGF21 mutant / 药学学报

Fibroblast growth factor 21 (FGF21) is a member of FGF family. It has been demonstrated that FGF21 is an independent, safe and effective regulator of blood glucose levels in vivo. In order to improve the activity of FGF21, we exchanged the beta10-beta12 domain of the human FGF21 with that of the mouse FGF21 to construct a novel FGF21 gene (named hmFGF21), and then subcloned hmFGF21 gene into the SUMO expression vector to create pSUMO-hmFGF21 and transformed it into E. coli Rosetta for expression of the fusion protein SUMO-hmFGF21. Both in vitro and in vivo glucose regulation activity of hmFGF21 was evaluated. The SDS-PAGE result showed that compared with wild-type hFGF21, the soluble expression of hmFGF21 increased about 2-fold. HmFGF21 was more potent in stimulation of glucose uptake in HepG2 cells in vitro. The results of anti-diabetic effect on db/db mice demonstrated that hmFGF21 had better efficacy on controlling the blood glucose of the db/db diabetic animals than wild-type hFGF21. These results suggest that the biological properties of FGF21 are significantly improved by optimization.

Zebrafish model for the study on drug ototoxicity of aminoglycoside antibiotics / 药学学报

Aminoglycoside antibiotics, due to their strong antibacterial effects and broad antimicrobial spectra, have been very commonly used in clinical practice in the past half century. However, aminoglycoside antibiotics manifest severe ototoxicity and nephrotoxicity, and are one of top factors in hearing loss. In this study, three members of the aminoglycoside antibiotics family, gentamycin, neomycin and streptomycin, were chosen as the representatives to be investigated for their toxicity to the embryonic development and the larva hair cells in zebrafish, and also to their target genes associated with hearing-related genes. The results showed that: (1) the lethal effect of all three drugs demonstrated a significant dependence on concentration, and the severity order of the lethal effect was streptomycin > neomycin > gentamycin; (2) all the three drugs caused the larva trunk bending in resting state at 5 dpf (day past fertilization), probably due to their ototoxicity in the physical imbalance and postural abnormalities; (3) impairment and reducing of the hair cells were observed in all three cases of drug treatment; (4) four genes, eya1, val, otx2 and dlx6a, which play an important role in the development of hearing organs, showed differential and significant decrease of gene expression in a drug concentration-dependent manner. This study for the first time reports the relevance between the expression of hearing genes and the three ototoxic antibiotics and also proved the feasibility of establishing a simple, accurate, intuitive and fast model with zebrafish for the detection of drug ototoxicity.

Zebrafish model for the study on drug ototoxicity of aminoglycoside antibiotics / 药学学报

Aminoglycoside antibiotics, due to their strong antibacterial effects and broad antimicrobial spectra, have been very commonly used in clinical practice in the past half century. However, aminoglycoside antibiotics manifest severe ototoxicity and nephrotoxicity, and are one of top factors in hearing loss. In this study, three members of the aminoglycoside antibiotics family, gentamycin, neomycin and streptomycin, were chosen as the representatives to be investigated for their toxicity to the embryonic development and the larva hair cells in zebrafish, and also to their target genes associated with hearing-related genes. The results showed that: (1) the lethal effect of all three drugs demonstrated a significant dependence on concentration, and the severity order of the lethal effect was streptomycin > neomycin > gentamycin; (2) all the three drugs caused the larva trunk bending in resting state at 5 dpf (day past fertilization), probably due to their ototoxicity in the physical imbalance and postural abnormalities; (3) impairment and reducing of the hair cells were observed in all three cases of drug treatment; (4) four genes, eya1, val, otx2 and dlx6a, which play an important role in the development of hearing organs, showed differential and significant decrease of gene expression in a drug concentration-dependent manner. This study for the first time reports the relevance between the expression of hearing genes and the three ototoxic antibiotics and also proved the feasibility of establishing a simple, accurate, intuitive and fast model with zebrafish for the detection of drug ototoxicity.