Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.
Acetaminophen ; administration & dosage ; chemistry ; Administration, Oral ; Drug Delivery Systems ; Electrical Equipment and Supplies ; Electrochemical Techniques ; instrumentation ; methods ; Hydrogen Bonding ; Kinetics ; Lipids ; chemistry ; Microspheres ; Solubility ; Taste ; drug effects ; beta-Cyclodextrins ; chemistry

OBJECTIVETo develop a more reliable and stable method for determining monoclonal antibody (mAb) affinity constant based on competitive antibody/antigen binding.

METHODSThe Kd value was calculated based on the relationship between the binding proportion of the antigen and the original concentration of the mAb that competed for the binding site of the antigen.

RESULTSThe Kd values measured with this improved method under two different conditions were 2.61x10(-12) mol/L and 2.39x10(-12) mol/L, and those with Friguent method in these two conditions were 5.57x10(-10) mol/L and 1.41x10(-10) mol/L, respectively.

CONCLUSIONCompared with Friguent method, the Kd values measured with this improved method are closer to the actual value, and the measurement results under different experiment conditions are more stable.

Antibodies, Monoclonal ; immunology ; Antibody Affinity ; immunology ; Antigen-Antibody Complex ; immunology ; Binding, Competitive ; Enzyme-Linked Immunosorbent Assay ; Humans

Objective To study the effect of the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger with antigout activity on liver microsomal cytochrome P450 in rats.Methods Healthy male SD rats were randomly divided into six groups (3 rats of each group):three groups of the petroleum ether fraction of ethanol extracts of Polyrhachisvi-cina Roger ( test groups, the low dose group, the middle dose group and the high dose group with equivalent to 1, 2, 4 g? kg -1, respectively), two positive control groups and one blank control group.The rats in the low dose, the middle dose and the high dose test groups were adminis-tered daily by gavage at corresponding dose of the petroleum ether frac-tion of ethanol extracts of Polyrhachisvicina Roger for 10 consecutive days.The rats in positive control groups were treated by dexamethasone ( 100 mg? kg-1? d-1 , ip, daily for 4 days ) or phenobarbital ( 80 mg? kg-1? d-1 , ip, daily for 3 days ) .Blank control rats received equivalent volume of sterile normal saline daily by gavage for 10 consecu-tive days.The levels of CYP450 activity, mRNA, protein in rat liver mi-crosome were analyzed by LC/MS/MS or RP-HPLC-FLD, RT-PCR, Western blot, respectively.Results CYP1A2 activity, protein expression and mRNA levels were increased signifi-cantly in a dose-dependent manner with the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger at low, middle and high dose, respectively.Conclusion The petroleum ether fraction of ethanol extracts of Polyrhachis-vicina Roger can induce CYP1A2 in rats, suggesting the potential of drug-drug interactions between the petroleum ether fraction of ethanol extracts of Polyrhachisvicina Roger and the inducers, inhibitors, or substrates of CYP1A2.

Objective To explore the expression of P -glycoprotein ( P-gp) in rat liver during acute inflammation ( AI ) and the possible mechanism involved.Methods Twenty rats were randomly divided into two groups:model group (n=10) and control group (n=10).The rats in model group were treated by a single 5 mg? kg -1 intraperitoneal injec-tion of lipopolysaccharide ( LPS).Control rats received equivalent injec-tion of sterile normal saline.The levels of P-gp, ubiquitinated P-gp and 26 S proteasome activity in both groups were analyzed by Western blot, immunoprecipitation and fluorescence detection, respectively. Results Compared to the control groups, ubiquitination levels of liver P-gp and 26S proteasome activity in model groups were significantly in-creased ( P<0.01 ) , accompanied by an decrease of liver P-gp protein expression level. Conclusion The participation of the ubiquitin -proteasome system in down-regulation of liver P-gp expression levels under AI conditions.

In the context of internationalization of education,the military graduate education concepts and models also come to change,and opportunities and challenges coexist.In this article,the challenges and problems of army medical college graduate education were mentioned and analyzed,and the exploration and attempt of graduate education in the process of international were summarized.

Objective To investigate the clinical outcome of patients receiving stereotacticcannula placement for hypertensive intracerebral hematoma drainage and the relationship between thedrainage cannula and the cerebral angioarchitecture. Methods Sixty-three patients with hypertensiveintracerebral hematoma underwent operations for stereotactic placement of a soft tube for hematomadrainage. CT angiography and CT venography were performed prior to cannula withdrawal after thepatients' condition was stabilized or complete hematoma drainage. The relationship between the drainagecarmula, cerebral angioarchitecture and the entry route of the cannula were observed. ResultsPostoperative CT angiography and CT venography showed that the entry route of the cannula allowedsafe passage of the cannula along the cerebral arteries and veins, and the position of the cannula wasaccurate in all the patients. Satisfactory hematoma drainage and good postoperative recovery wasachieved in all the patients, and no significant injuries to the adjacent cerebral arteries or veins occurredin these cases. Conclusion Stereotactic cannula placement with the minimally invasive technique forhemotoma drainage causes minimal injury and is safe, effective, cost-effective and convenient fortreatment of hypertensive intracerebral hematoma.

Objective To investigate the effect of eukaryotic translation elongation factor 1A1 (eEF1A1) inhibition by siRNA on the apoptotic susceptibility , the chemosensitivity of colon carcinoma cells.Methods Four siRNA specifically targeting eEF1A1 were designed and synthesized in vitro and were transfected into colon carcinoma HCT -116 cells.Reverse transcription -polymerase chain reaction ( RT -PCR ) and Western blot assay were used to validate gene -silencing efficiency of eEF1A1.The cell apoptosis was assessed by flow cytometry ( FCM ).Cell growth state and 50% inhibition concentration ( IC50 ) of 5-fluorouracil ( 5 -FU ) and cisplatin was determined by MTT assay.Results siRNA specific to eEF1A1 can efficiently decrease the expression of eEF1 A1 in colon carcinoma HCT -116 cells.When eEF1A1 was inhibited , the reproductive activity of colon carcinoma HCT-116 cells was significantly lower than the control groups ( P<0.05).The study also showed that IC 50 of 5-FU and cisplatin on colon carcinoma HCT -116 cells treated by siRNA was decreased ( P<0.05).Conclusion The siRNA targeting eEF1A1 gene can effectively inhibit the expression of eEF1A1 gene, resulting in enhancing the apoptotic susceptibility , the chemosensitivity of 5-FU and cisplatin on colon carcinoma HCT -116 cells.

Objective To analysis the spatial autocorrelation on the small-scale distribution of the genetic variation in the population of Oncomelania hupensis in Puge county, Sichuan province, using simple sequence repeat (SSR) marker. Methods 5 pairs of SSR primer were used to amplify the genomic DNA of Oncomelania hupensis, and the alleles with frequency ranging from 15% to 85% were used to calculate Moran' s I spatial autocorrelation coefficients in 14 distance band based on equal numbers of paired samples. Results A total of 274 alleles were scored by 5 pairs of SSR primer, the average polymorphic information content of the 274 alleles were 0.965 which indicated a high level of genetic diversity. 39 alleles showed different patterns of positive spatial autocorrelation of genetic variation, which was non-random spatial structure. When the distance band increased, the spatial auto-correlativity decreased based on the average Moran' s I value at 14 distance band. The alleles which showed a negative spatial autocorrelation were not found in any distance band. Conclusion The spatial distribution of the genetic variation of SSR showed positive spatial autocorrelation in the population of Oncomelania hupensis, and the spatial auto-correlativity decreased with the increase of distance band.

Objective To investigate the reference interval of neonatal nutrition assessment biochemical factor,including total protein (TP),serum albumin (ALB),serum prealbumin (PA) and serum retinol binding protein (RBP).Methods From December 2016 to August 2017,403 serum specimens were collected from health neonates in Hunan Children's Hospital and the serum concentration of TP,ALB,RBP and PA was detected.The results of each item were grouped according to sex and age,and then the reference interval of each item was established.Results When data was separated by gender of each item,there was no statistical significance between each group of each item (P ＞ 0.05).For the TP,ALB and RBP,separating the data of each item by weeks,there were also no statistical significance between each group (P ＞ 0.05).But there was statistical difference between one week old group and the rest groups in the data of PA (P ＜ 0.05).The normal reference interval of neonatal serum total protein,albumin,retinol binding protein and pre-albumin are as follow:(40.69-65.72) g/L,(28.77-42.3) g/L,(12.13-33.19) mg/L,(42.26-161.52) mg/L (no more than 7 days old) and (59.05-170.23) mg/L (range from 8 to 28 days old).Conclusions We can establish the reference interval of TP,ALB and RBP without differentiating gender and weeks.But for the PA,the reference interval of one-week-old neonate needs to differentiate from other neonates.

OBJECTIVETo investigate enhancement of the bystander effect by tanshinone IIA (Tan) in HSV-tK/GCV system and the correlation with expression of connexin 43 mRNA.

METHODSThe cytotoxic effect in HSV-tK/GCV in cervical carcinoma cell line ME180 (ME) and ME/TK was examined by MTT assays. Cx43 mRNA expression was detected by fluor-quantitative RT-PCR.

RESULTSTan markedly increased sensitivity of ME/TK cells for GCV in HSV-tK/GCV system. In the presence of 2 micro g/ml GCV, compared with the absence of Tan (0 mol/L), an obvious decrease in survival rate was seen at any given mixture of ME and ME/TK cells exposed to 1.3 x 10(-9) mol/L Tan. Statistics showed significant difference (P < 0.05). However, enhancement of bystander mediated cell killing occurred only in the range of Tan concentrations used (1.3 x 10(-8), 1.3 x 10(-9) mol/L). RT-PCR showed that the ratio of relative copy number of Cx43 mRNA increased by 8.83 and 8.47-fold in ME cells exposed to 1.3 x 10(-8) and 1.3 x 10(-9) mol/L Tan, respectively.

CONCLUSIONFor the first time we report that in cervical carcinoma ME180 cell line, Tan possesses a remarkable enhancing role on the bystander effect in the HSV-tK/GCV system. It is associated with up-regulation of Cx43 mRNA expression.

Antineoplastic Agents, Phytogenic ; pharmacology ; Bystander Effect ; Cell Line, Tumor ; Cell Survival ; drug effects ; Connexin 43 ; genetics ; Diterpenes, Abietane ; Female ; Ganciclovir ; pharmacology ; Genetic Therapy ; Humans ; Phenanthrenes ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Simplexvirus ; enzymology ; Thymidine Kinase ; genetics ; Uterine Cervical Neoplasms ; therapy