The purpose of this study is to investigate the enantioselectivity of norgestrel (NG) transdermal permeation and the potential influence of linalool and lipids on the enantioselectivity. In vitro skin permeation studies of NG across the excised rat skins were performed with Valia-Chien diffusion cells, and the permeation samples were analyzed by enantioselective HPLC. The possible enantioselective permeation of NG across intact rat back skin and lipids extracted rat back skin and the influence of linalool were evaluated. The skin permeation rate of dl-NG was two times higher than that of l-NG when donor solutions (EtOH/H2O 2 : 8, v/v) containing l-NG or dl-NG. It may be mainly attributed to the solubility discrepancy between enantiomer and racemate. The enantioselective permeation of dl-NG across intact rat skin was observed when the donor solutions containing dl-linalool. The permeation flux of l-NG was 22% higher than that of d-NG. But interestingly, the enantioselective permeation of dl-NG disappeared under the same experimental condition except that the lipid extracted rat skin was used. Attenuated total reflection-fourier transform infrared spectroscopy analysis of stratum corneum showed that the wave number for asymmetric CH2 stretching vibrations of lipids treated with dl-linalool was greater than that of the control. The results indicated that the enantioselective permeation of NG may be contributed by the interaction between dl-linalool and lipids. More than half of lipids were composed of ceramides. The stereospecific interaction maybe existed among chiral enhancer (linalool), lipids (ceramides) and/or chiral drugs (NG).

The purpose of this study is to investigate the enantioselectivity of norgestrel (NG) transdermal permeation and the potential influence of linalool and lipids on the enantioselectivity. In vitro skin permeation studies of NG across the excised rat skins were performed with Valia-Chien diffusion cells, and the permeation samples were analyzed by enantioselective HPLC. The possible enantioselective permeation of NG across intact rat back skin and lipids extracted rat back skin and the influence of linalool were evaluated. The skin permeation rate of dl-NG was two times higher than that of l-NG when donor solutions (EtOH/H2O 2 : 8, v/v) containing l-NG or dl-NG. It may be mainly attributed to the solubility discrepancy between enantiomer and racemate. The enantioselective permeation of dl-NG across intact rat skin was observed when the donor solutions containing dl-linalool. The permeation flux of l-NG was 22% higher than that of d-NG. But interestingly, the enantioselective permeation of dl-NG disappeared under the same experimental condition except that the lipid extracted rat skin was used. Attenuated total reflection-fourier transform infrared spectroscopy analysis of stratum corneum showed that the wave number for asymmetric CH2 stretching vibrations of lipids treated with dl-linalool was greater than that of the control. The results indicated that the enantioselective permeation of NG may be contributed by the interaction between dl-linalool and lipids. More than half of lipids were composed of ceramides. The stereospecific interaction maybe existed among chiral enhancer (linalool), lipids (ceramides) and/or chiral drugs (NG).
Administration, Cutaneous ; Animals ; Lipids ; pharmacology ; Monoterpenes ; pharmacology ; Norgestrel ; pharmacokinetics ; Rats ; Skin Absorption ; drug effects ; Spectroscopy, Fourier Transform Infrared ; Stereoisomerism

Objective To explore the growth and developmental parameters and behavioral characteristics of rhesus monkeys during the first year of birth and to establish the background data.Methods A total of 18 (♂=11,♀=7 ) infant rhesus monkeys born from individually caged mothers and with known genetic background and postnatal days were monitored monthly for body weight, body height, head circumference, chest circumference, forelimb length, hind limb length, crown-rump length, tail length and anal-genital distance from postnatal day ( PND) 1 to 360, while hematology, blood chemistry and lymphocyte subsets were examined on PND 28, 175 and 360, and finger maze test was carried out on PND 208.Results The body weight showed linear growth with no significant difference between genders (P>0.05). Except for the anal-genital distance of male infants was significantly greater than that of female infants ( P<0.01 ) , no significant differences were observed between sexes in other morphological parameters.No significant differences of hematology were seen between genders (P >0.05).Compared with that at PND28, TP and BUN were significantly increased (P<0.01) while ALP decreased with no significant difference (P>0.05) at PND 175 and 360.Compared with that at PND28, CD4 +and CD4 +/CD8 +were significantly decreased ( P<0.01) while CD8+significantly increased ( P<0.01) at PND175 and 360.The number of sessions to solve task 2 in learning test was significantly greater than other tasks with females significantly less than males ( P<0.05) .The females had higher correct rate than males in the 2-day random memory test (P<0.05).Conclusions Body weight and morphological parameters show a linear growth.The PND.The RBC, HGB, LYMPH, TP, BUN, ALP, CD4 +, CD8 +and CD4 +/CD8+in hematology, blood chemistry and lymphocyte subsets show relevant changes to the growth and development of organs and systems in infants, which should be highly concerned in drug evaluation.The finger maze test indicates that female infants have better reversal learning and long-term memory than male infants.Background data and behavioral characteristics of infant rhesus monkeys during the first 12 months of birth are established in this study, which provide useful reference and support the evaluation of developmental and reproductive toxicity of drugs in rhesus monkeys.

Objective To compare the performance of HP-083/4 and rational used instrument on detecting six items.Methods The rational instruments were used as contrast instrument,HP-083/4 was the verified instrument.A total of 100 blood specimens and 100 urine specimens were collected,and the levels of antistreptolysin O(ASO),hypersensitive C reactive protein (hsCRP),D-di-mer(D-D),glycosylated hemoglobin(HbA1c),rheumatoid factor(RF)and urine microalbumin(mAlb)were detected.The regression equation and correlation coefficient(r)of the two methods were calculated,and the Kappa values(κ)were analyzed to evaluate the performance of HP-083/4.Results There was a good linear correlation (r >0.950)for the two methods in detecting the serum ASO,hsCRP,D-D,HbA1c,RF and mAlb,r were 0.991,0.995,0.970,0.957,0.980 and 0.967 respectively.Besides,they had good concordance(κ>0.6),theκ values were 0.830,0.957,0.601,0.720,0.920 and 0.694 respectively.Conclusion HP-083/4 is effec-tive in detecting ASO,hsCRP,D-D,HbA1c,RF and mAlb,which should be suitable for clinical application.

Atrial Fibrillation ; therapy ; Catheter Ablation ; adverse effects ; Female ; Humans ; Pulmonary Veins ; Venous Thrombosis ; etiology

ObjectiveTo investigate the feasibility and importance of the application of simulation ward in medical practice between classes.MethodsTo divide the interns into two groups:the experimental group of 30 and the control group of 30. Both groups apply the simulation ward to practice between classes and both are assessed at the end of the practice.ResultsTo compare the final score of the experimental group and the control group,and significant differences are found in the following aspects:humanistic care,history taking,physical examination,medical record analysis,the theoretical knowledge examinations with the data of P ＜0.05.ConclusionThe application of simulation ward in medical practice between classes can improve the quality of clinical teaching.

Objective: To study the effects of procession with wine on the blood-quickening and stasis-transforming actions of Radix Salviae Miltiorrhizae and Radix et Rhizoma Rhei. Methods: The blood stasis model of rat was established by Adr or cold. The effects of the processed products of Radix Salviae Miltiorrhizae and Radix et Rhizoma Rhei on thrombocyte adhesiveness and aggregaltion, prothrombin time (PT), thrombintime(TT), (PTT) were observed.Results: The raw and mix-fried Radix Salviae Miltiorrhizae with yellow wine and white liquor, the steamed Radix et Rhizoma Rhei with wine could obviously decrease thrombocyte adheziveness and aggregation, prolong PT, TT and PTT. The actions of the mix-fried Radix Salviae Miltiorrhizae with wine and the steamed Radix et Rhizoma Rhei with wine were stronger than that of their raw products (P

Background There is no effective method to regenerate the optic nerve after injury. It has been recently reported that α-crystallin could promote the survive rate and axon regeneration of retinal ganglion cells (RGCs) effectively. However,the molecular mechanism is not clear. Objective This study was to identify the site of RGCs where the exogenous α-crystallin bind to. Methods RGCs was isolated from retinas of two 2-day-old Long Evans rats and primarily cultured. The positive rate of the RGCs was assessed by counting the number of positive cells for fluorescently-labeled thy1. 1 and cy3 under the fluorescence microscope. The biotinylated exogenous α-crystallin was evaluated by direct coloration and the activity of molecular chaperones was measured by insulin test.After identifying the success of biotinylation along with the activity of molecular chaperones,biotinylated α-crystallin was co-incubated with RGCs and the cells then were reacted to fluorescently labeled avidin for the observation of binding site of exogenous α-crystallin under the laser confocal microscope. Results RGCs of 94% were survived through primary culture. The coloration of biotinylated α-crystallin labeled by the direct coloration method was more intensive, and the value of A450 descended as the decrease of biotinylated α-crystallin concentration,indicating that the α-crystallin was biotinylated successfully. The activity of molecular chaperones of biotinylated α-crystallin was significantly strong but no significant change after being biotinylated after co-incubation of RGCs with biotinylated α-crystallin. Laser confocal microscope examination revealed that co-incubated RGCs with biotinylated α-crystallin showed the red fluorescence on membrane and axon of RGCs rather than cytoplasm and nucleus. The absent response was seen in the control group. Conclusion Exogenous α-crystallin can specifically combine with the membrane of RGCs to play the biological function,but its binding mode and mechanism need further study.

Objective To develop a multiplex PCR-based reverse line blot(mPCR/RLB) hybridization assay to detect,simultaneously,seven genes encoding AR-erm(A/TR),erm(B),mef(A/ E),tet(M),tet(O),aphA-3,aad-6 and two AR-related genes,int-Tn and mreA in group B streptococcus.Methods Nine pairs of specific primers and Oligonucleotide probes targeting erm(A/TR), erm(B),mef(A/E),tet(M),tet(O),aphA-3,aad-6 int-Tn and mreA respectively were modified according to former studies or designed in this study.The primers and probes were labeled with biotin and amino,respectively.The nine genes were amplified simultaneously in the same tube.PCR product hybridized with the probes labeled in the BiodyneC nylon membrane to detect the nine genes.To detect the sensitivity and specificity of the method developed,PCR with single pair of primer targeting each gene were tested in 318 isolates tested and the results were compared with the one abtained by RLB.Results The nine resistance-related genes could be successfully detected by mPCR/RLB assay developed in this study.Based on sequencing,21 of 22 isolates with mef had mef(E)and eight of 353 with int-Tn had an atypical sequence.Except for the above 29 genes,all the others corresponded well with the results obtained by single pair primer PCR.Conclusion The mPCR/RLB assay developed in this study is simple,rapid and suitable for surveillance of antibiotic resistance in GBS.

Constructing prokaryotic expression vector pKY-RMBAY by gene recombination and research its optimizing productive conditions.By PCR technology synthesizing the gene of the RMBAY with preference codon of E.coli and the RMBAY gene was inserted into high efficiency expression vector pKYB-MCS.Expressed fusion proteins in E.coli ER2566 were purified with Chitin-Beads column.Fusion proteins binding on Chitin-Beads was cut on N-terminus of intein due to the induction of ?-mercaptoethanol and the target peptide RMBAY was released.The RMBAY was identified by mass spectrum.Experiment results showed RMBAY can be high efficiently expressed in E.coli ER2566,with optimizing productive conditions the yield of the RMBAY may be 6.7mg/L fermentation product and its purity is greater than 98%.The molecular weight of RMBAY is 3.887 kDa by mass spectrum and that accords with its theory value.