To investigate the influence of the difference enhancers on the transport mechanism of chlorogenic acid (CGA) across Caco-2 cells model, a RP-HPLC method was adopted to detect the concentrations of CGA. At the concentrations of 20 to 80 microg x mL(-1), the difference of absorption rate constants (K(a)) was not statistically significant. At the concentrations of 40 and 20 microg x mL(-1), the ratios of apparent permeability coefficients (P(app)) of the apical to basolateral and the basolateral to apical were 1.14 and 1.18, respectively. With the effect of enhancers K(a) and P(app) increased, the absorption half-life (T1/2) decreased. CGA passed through the Caco-2 cell membrane mainly by passive transport. It showed that monocarboxylic acid transporter (MCT) could be involved in the across membrane transport process of CGA. Borneol had no effect on the cell membrane transport processes. The order of increasing absorption of CGA caused by the enhancers was sodium lauryl sulphate > sodium taurocholate > carbomer.
Absorption ; Acrylic Resins ; pharmacology ; Caco-2 Cells ; Cell Membrane Permeability ; drug effects ; Chlorogenic Acid ; pharmacokinetics ; Humans ; Sodium Dodecyl Sulfate ; pharmacology ; Taurocholic Acid ; pharmacology

Objective To detect the change of cerebral perfusion in pediatric patients with Leigh's syndrome (LS)by using MR perfusion technique.Methods Twelve patients with Leigh's syndrome and thirteen normal children were scanned with the sequence of flow-sensitive alternating inversion recovery exempting separate T_1 measurement (FAIREST).Their relative cerebral blood flow(rCBF)values were obtained in regions of bilateral basilar nuclei and bilateral thalami.Student t-test was used to compare them between the two groups and receiver operating characteristic(ROC)curve analysis was carried out.Results Statistical analysis revealed significant difference between two groups in the regions of bilateral basilar nuclei and right thalamus(t =3.26,P =0.002;t =2.25 ,P =0.018 ;t =2.88 ,P =0.004,respectively).The rCBF values for LS group and control group were 0.432?0.158 and 0.619?0.125 for right basilar nuclear, 0.478?0.186 and 0.621?0.123 for left basilar nuclear,0.630?0.189 and 0.833?0.160 for right thalamus,respectively.The areas under the ROC curves were 0.833 and 0.756 for the rCBF of right and left basilar nuclear,respectively.Conclusion Relative CBF maps may reveal changes of cerebral blood flow in some specific brain regions in patients with Leigh's syndrome.It can provide additional information to the clinicians in the evaluation of the disease.

Objective To investigate the correlation between genetic polymorphisms of glutathione S-transferases (GSTs) and ulcerative colitis (UC) in Hubei Han population. Methods Genetic polymorphisms of GSTM1 and GSTT1 of 270 patients with UC (UC group) who were admitted to the Zhongnan Hospital, People's Hospital of Wuhan University, Tongji Hospital and Union Hospital of Huazhong University of Science and Technology from August 2002 to December 2009 and 623 healthy people ( control group) were detected by restriction fragment length polymorphism-polymerase chain reaction. All UC patients were allocated to distal UC group (n= 229) and extensive UC group (n =41 ) according to the location of the lesions; and all UC patients were also allocated to mild-moderate group (n = 237) and severe group (n = 33 ). The genetic polymorphisms of GSTP1 of these patients and healthy people were detected by polymerase chain reaction. The genotypes of GSTM1, GSTT1 and GSTP1 were also detected. GSTM1 and GSTT1 containing small DNA segments ( 157 bp and 480 bp) were defined as GSTM1 (+) and GSTT1 (+), otherwise, GSTM(-) and GSTT1 (-), respectively. All data were analyzed by chisquare test. Results The frequencies of GSTM1(-), GSTT1(-) and GSTP1 (Val/Val) were 70.7% (191/270),64.8% (175/270) and 48.9% (132/270) in the UC group, and 41.7% (260/623), 47.2% ( 294/623 ) and 34.3% (214/623) in the control group, with a significant difference between the two groups (x2 = 63. 404,22. 320, 25. 384, P ＜0.05 ). The frequencies of GSTT1 (-) and GSTP1 (Val/Val) were 71.6% (164/229) and 57.6% (132/229) in the distal UC group, which were significantly higher than 31.7% (13/41) and 29.3%( 12/41 ) in the extensive UC group ( x2 = 24.528, 9.609, P ＜ 0.05 ). The frequencies of GSTM1 (-) were 65.1%(149/229) in the distal UC group and 56.1% (23/41) in the extensive UC group, with no significant difference between the two groups ( x2 = 1. 210, P ＞ 0.05 ). The frequencies of GSTT1 (-) and GSTP1 ( Val/Val ) were 71.6%(164/229), 31.7% ( 13/41 ) in the distal UC group and 57.6% ( 132/229), 29.3% ( 12/41 ) in the extensive UC group, with a significant difference between the two groups ( x2 = 24. 528, 9. 609, P ＜ 0. 05 ). There was no significant difference in the frequencies of GSTM1 (-), GSTT1 (-), GSTP1 (Val/Val) in the mild-moderate group and the severe group( x2 = 0. 623, 1. 884, 3. 403, P ＞ 0. 05 ). Conclusions Variant genotypes of GSTs are significantly correlated with UC in Hubei Han population. The severity of UC may not be correlated with variant genotypes of GSTs.

Objective To observe the rate-adaptive response of dual sensor pacemakers integrated with activity sensor and minute ventilation sensor.Methods Fifty patients with chronotrepic incompetence were implanted with pacemakers of integrated sensor.The patients with pacemakers implanted were arranged to take upstairs test,downstairs test and tapping test under the monitor of integrated sensor,minute ventilation sensor and activity sensor respectirely.The rate-adaptive responses were tracked down every 15 seconds with remote heart rate monitor.The results were compared with the control group patients with normal sinal chronotropic function(n=15).Results In activity sensor group,pacing rates were significantly higher than the normal control group in downstairs test and tapping test.In minute ventilation sensor group,pacing rates increasement was significantly slower in the beginning of upstairs test.Pacing rates of integrated group were similar to the normal control group in upstairs and downstairs tests.Conclusion The rate-adaptive pacing response of dual sensor integrated with activity sensor and minute ventilation sensor,which is mostly close to the normal chronotropic response,better than that of single sensor.

The 125 strains of the symbiotic and epiphyte microorganisms were isolated from marine organisms (Sea cucumber, Sea urchin, Sea anemone, Sea actinia, Ulra, Sargassum, Undaria). Among them,21 strains of bacteria,8 strains of actinomycetes and 2 strains of fungi have shown to have antagonistic activity on bacterial or fungal growth. In the 21 strains of bacteria, 7 strains belong to Bacillus sp., 11 strains belong to Vibro sp., and 3 strains belong to Pseudomonas sp.. In the 8 strains of actinomycetes, 5 strains belong to Streptomyces sp., 3 strains belong to Micromonospora sp.. 2 strains of fungi belong to Penicillum sp..

Objective To study the prevalence of the mtDNA A1555G gene mutation in Chinese population with nonsyndromic hearing impairment.Methods PCR-RFLP,directional sequencing of PCR products were applied in 325 patients with nonsyndromic hearing impairment and 50 normal controls.Results The mutation rate of the mtDNA A1555G was 14.5% (47/325),28 of 47 cases were homozygosis,19 of 47 cases were heterozygosis.The same mutation was not detected in the control subjects.Conclusion The mutation rate of the mtDNA A1555G is relatively high in the Chinese NSHI patients,the mutation type includes both heterozygosis and homozygosis.

AlM:To evaluate the clinical efficacy of intravitreal injection of ranibizumab combined with macular grid photocoagulation for diabetic macular edema ( DME) .METHODS:Totally 60 eyes ( 60 patients ) with DME were randomly divided into 2 groups: 30 eyes of simple injection group underwent intravitreal injection of ranibizumab, and 30 eyes of combined treatment group underwent intravitreal injection of ranibizumab and macular grid photocoagulation 1wk later. The best corrected visual acuity ( BCVA ) , central macular thickness ( CMT ) measured by optical coherence tomography ( OCT ) and postoperative complications were observed.
RESULTS:ln simple injection group, the BCVA after operation were separately 0. 390 ± 0. 075 (4wk), 0. 367 ± 0. 088 (8wk) and 0. 319 ± 0. 064 (12wk), the CMT after operation were separately 221. 63 ± 112. 34μm (4wk), 337. 73±99. 56μm (8wk) and 432. 92 ± 100. 46μm (12wk), which were much better than pre-operation. But during follow-up, the BCVA presented down trend and the CMT was on the rise slowly. ln combined treatment group, the BCVA after operation were separately 0. 385 ± 0. 036 (4wk), 0.382±0.079 (8wk) and 0.377±0.097 (12wk),the CMT after operation were separately 249. 77 ± 106. 55μm (4wk), 270. 40 ± 92. 88μm (8wk) and 275. 84 ± 97. 34μm (12wk ), which were satisfactory and steady during follow-up, better than simple injection group (P<0. 05).CONCLUSlON:lntravitreal injection of ranibizumab can effectively improve visual acuity and decrease central foveal thickness for patients with DME, combining with macular grid photocoagulation can ensure therapeutic effects steady and permanent.

Objective: This study was designed to evaluate the therapeutic efficacy of bronchial arterial infusion with VDS＋ DDP or MMIC＋ ADM＋ DDP in patients with locally advanced nonsmall cell lung cancer(NSCLC). Methods: From June 1992 to October 1998,102 patients with locally advanced NSCLC were enrolled in this study. Of them,8 cases in Stage Ⅱ , 72 cases in Stage Ⅲ a, 22 cases in Stage Ⅲ b, central type: 75 cases,peripheral type:27 cases;preliminary group 64 cases, secondary group 38cases. The patients were treated one to four times by bronchial arterial infusion of the chemical drugs Results: There were 3 complete responses and 66 partial responses for an overall responses rate of 67.65％ (69/102) including responses rate of 72.00％ (54/75) in central type and 55.56％ (15/27), the 1-year and 2-years survival rate was 67.64％ (69/102)and 36.28％ (37/102) respectively. Conclusions: The therapeutic efficacy of bronchial arterial infusion with chemical drugs was excellent to locally advanced non small cell lung cancer, it′ s toxicity were acceptable. The efficacy on central was much better than for peripheral type

Cholesterol ester transfer protein (CETP) is a key regulator of high density lipoprotein (HDL). Owing to its important role in the reverse of cholesterol transport, CETP has become a hotspot target in modulating lipid drug design. In this paper, structure based pharmacophore (SBP) models for CETP inhibitors were built based on the protein structure 4F2A from Protein Database (PDB). The best pharmacophore contained six hydrophobic features, one hydrogen bond acceptor feature and nine excluded volume features, with the N and CAI value was 3.33 and 2.31 respectively. Then the model was used to search the traditional Chinese medicine database (TCMD) and 629 compounds originated from 315 TCM herbs were obtained. Molecular docking was also used to validate SBP by analyzing the critical amino acid residue and the interaction between potential active compounds and receptor. In this study, several TCM herbs, like Lycii Frutus and Schisandrae chinensis fructus, which contained more optimal SBP based screening results, have been reported hypolipidemic effect, and need to be studied deeply in a more focused research on herbal active constituents. Therefore, this study could provide reliable fundamental data for exploring the action mechanisms of TCM, and be applicable to identify lead candidates, which can be utilized as starting scaffolds for natural CETP inhibitors.
Cholesterol Ester Transfer Proteins ; antagonists & inhibitors ; Drug Evaluation, Preclinical ; methods ; Medicine, Chinese Traditional ; Molecular Docking Simulation

Objective To study the influence of fluoride on the expression of osteoprotegerin(OPG) mRNA and protein in suckling rat osteoblasts. Methods Osteoblasts obtained from calvarial of suckling Wistar rats were cultured in vitro in the media supplemented with NaF at a series of doses[O(control), 1,2 and 4 mg/L groups], and OPG mRNA expression and protein were evaluated by RT-PCR and ELISA methods, respectively. Results OPG mRNA expression in suckling rat osteoblasts cultured in vitro significantly increased after exposure to NaF for 48 h and 72 h(F=333.48,808.34,P<0.05). OPG mRNA expression in suckling rat osteoblasts cultured in vitro after exposure to NaF for 48 h at different doses(0.810±0.003, 0.819±0.031 and 0.870±0.044 for 1,2 and 4 mg/L groups, respectively) compared with that of control (0.800±0.040, all P<0.05). OPG mRNA expression further increased for 72 h exposure to NaF(0.933±0.047,1.031±0.051,1.240±0.062 for 1,2 and 4 mg/L, respectively), significantly higher than that of the control (0.805±0.020,all P<0.05) and corresponding groups at 48 h. NaF doses and time exposure exhibited a significant synergistic effect on OPG mRNA expression(F=2004.16, P<0.05). NaF also enhanced OPG protein expression in suckling rat osteoblasts cultured in vitro. Significant differences were observed only in 4 mg/L group(0.228±0.014,0.277±0.048) and control(0.205±0.012,0.229±0.010) at 48 h and 72 h (P<0.05). In addition, OPG protein expression at 72 h post-exposure was higher than that at 48 h,but there was no synergistic effect between concentration and time(F=1.21,P>0.05). Conclusions The results suggested that NaF could increase OPG mRNA and protein expression in suckling rat osteoblasts with a synergistic effect between the doses and exposure time.