Animals ; Decompression ; Decompression Sickness ; physiopathology ; Electrocardiography ; Electroencephalography ; Electromyography ; Electrophysiology ; Male ; Rabbits

Objective To study the inhibition of berberine on organ anion transporters (OATs) and its bidirectional trans-membrane transport.Method The transgene cell lines of the organ anion transporters including OAT1,OAT2,OAT3,OAT4,OAT7,and URAT1 were constructed and selected by animal cell transgenic method mediated by transporter Lipo 3000.Wild type (WT) cells were used as control group,and activity of OATs was verified by adding their radiolabeled substrates and inhibitors.The inhibition of 100 μmol/L berberine on the transporters was investigated in vitro.The IC50 of berberine on URAT1 was also determined.The bidirectional transport of berberine was studied through the Caco-2 model.Result The results showed that 100 μmol/L berberine inhibited the activity of OAT1,OAT2,OAT3,OAT4,OAT7 and URAT1 to (70.48±4.23)％,(69.13±1.28)％,(72.12±3.28)％,(79.77±6.49)％,(69.51 ±5.99)％ and (38.4 ± 2.67)％ respectively,the IC50 of berberine to URAT 1 was 13.19 μmol/L,the Papp (A-B) of 50 μmol/L and 100 μmol/L berberine were separately 0.28 × 10-6 and 0.40 × 10-6 cm/s,and the effiux rates were separately 3.18 and 3.15.Conclusion Berberine shows a stronger inhibition to URAT1 compared to OAT1,OAT2,OAT3,OAT4 and OAT7.Berberine may be the substrate of some effiux transporters.This study provides theoretical basis for explaining the low bioavailability ofberberine and forecasting the possible drug-drug interaction.

Objective To investigate the uptake of 99Tcm-hydrazinonicotinamide-D-alanine-D-alanine-alanine-proline-arginine-proline-glycine (HYNIC-A(D) A(D) APRPG) in rabbit models of inflammation and VX2 tumor xenografted, so as to evaluate its use as a new tracer for tumor angiogenesis. Methods Ten rabbit models of xenoplanted VX2 tumor and inflammation were randomly divided into two groups which were injected with different injected tracers, 99Tcm-HYNIC-A(D) A (D)APRPG 99Tcm-RGD, followed by serial Gamma images at various time points. The first group underwent 18F-FDG PET ahead of 99Tcm-HYNICA(D)A (D) APRPG SPECT. Analysis of variance and t-test were performed with SPSS 10.0. Results 99TcmHYNIC-A(D) A (D)APRPG scan showed negative uptake at inflammation focus but positive uptake at tumor. Pathological examination confirmed high 99Tcm-HYNIC-A(D)A(D) APRPG accumulation in tumor cells, with the highest tumor/inflammation ratio (3.25 ±0. 171) at 2 h post-injection, which was significantly higher than that of 99Tcm-RGD (2.37 ± 0.076) (F = 15. 63, P<0. 01). The tumor/inflammation ratios of 99Tcm-HYNIC-A(D)A(D)APRPG, 99Tcm-RGD, 18F-FDG were significantly different at 0.5, 1,2,3, 6 h (F = 13. 83～26. 41; t = 23.84, 12.75; all P<0. 01). Conclusion 99Tcm-HYNIC-A (D) A (D)APRPG can be used as a potential tracer for tumor angiogenesis.

Objective To evaluate 99Tcm-Arg-Glu-Ser (99Tcm-RES) as a potential tumor imaging agent. Methods RES was synthesized using solid phase peptide synthesis. The optimal labeling conditions of RES were determined under different reagents and reacting temperatures using SnC12 as reducing agent.The biodistribution of 99Tcm-RES was studied in nude mice bearing human lung cancer A549. Results The radiochemical purity of 99Tcm-RES was up to 85% and the radiochemical purity was 75% ever after 6 h at room temperature. The tumor uptake of 99Tcm-RES was obvious and the radioactivity ratios of tumor/blood,tumor/heart, tumor/liver, tumor/lung, tumor/spleen and tumor/muscle were 5.31, 1.88, 1.57, 3.58,4. 16 and 5.92, respectively at 6 h after 99Tcm-RES injection. Gamma camera imaging showed that tumor uptake of 99Tcm-RES was negative in rabbits with inflammatory mass but positive in those bearing tumor.The radioactivity ratio of tumor/inflammation was 3.12 at 6 h after injection. Conclusion 99Tcm-RES might possibly become a potential tumor imaging agent.

AIMTo determine the feasibility of establishing the heterologous expression model of human- serotonin transporter(hSERT or 5-HTT).

METHODScRNA of SERT was transcribed from cDNA, which was cloned in the pOTV vector. Each oocyte of mature xenopus laevis was injected with transcribed cRNA in vivo and incubated at room temperature for 4-9 days. Recording the current induced by 5-HT with voltage clamp technique tested the function of the expressed 5-HT transporter.

RESULTSThe transporter current could be observed in Ringer's solution containing 5-HT, and the 5-HT induced current were concentration-dependent. Norepinephrine and dopamine could not induce the transporter current while the 5-HT induced current could be specifically inhibited by 5-HTT blocker, desipramine.

CONCLUSIONThe results demonstrate that the heterologous expression product in xenopus laevis oocytes is human 5-HT transporter.

Animals ; Carrier Proteins ; genetics ; DNA, Complementary ; genetics ; Female ; Gene Expression ; Models, Animal ; Oocytes ; metabolism ; RNA, Messenger ; genetics ; Serotonin ; metabolism ; Serotonin Plasma Membrane Transport Proteins ; biosynthesis ; genetics ; Xenopus laevis

Objective To study the inhibitory effects ofberberine on human organic cation transporter (OCTs) including OCT1,OCT2,OCT3,OCTN1 and OCTN2.Methods Using animal cell transgenic method mediated by transporter Lipo 3000,the drug transporters over expression cell lines S2-OCT1,S2-OCT2,S2-OCT3,S2-OCTN1 and S2-OCTN2 were obtained by selective medium culture.The OCTs evaluation model was established by detecting the trans-membrane transport of radioactive substrate in vitro.Wild type (WT) cells were used as control group,activity of OCTs was verified by adding its inhibitor.The inhibition of berberine on the transporters was investigated in vitro.The IC50 of inhibitory effect of berberine on various drug transporters was also calculated.Result The transport activity of transporter cell lines was increased by more than 5 times compared to the WT cell line respectively,what's more,their transport activity decreased significantly by their corresponding inhibitor.The ICs0 of berberine to OCT1,OCT2,OCT3,OCTN1 and OCTN2 were respectively 7.63,6.80,2.25,4.66 and 210.34 μmol/L.Conclusion Berberine significant inhibition to OCT1,OCT2,OCT3,OCTN1 and OCTN2.The inhibition on OCT1,OCT2,OCT3,OCTN1 is stronger compared to OCTN2.

Objective To explore the feasibility of rapid and sutureless anastomosis of artificial vascular replacement of abdominal aorta in dog models using magnetic compression anastomosis (MCA) technique. Methods Twelve healthy adult crossbred dogs were evenly divided into the MCA and hand suturing (HS) groups according to the anastomosis method between abdominal aorta and artificial blood vessels. The intraoperative duration of abdominal aorta occlusion, intraoperative condition of anastomotic stoma and postoperative imaging examination of anastomotic stoma were compared between two groups. Results The intraoperative duration of abdominal aorta occlusion in the MCA group was significantly shorter than that in the HS group [(5.2±2.3) min vs. (24.4±4.3) min, P < 0.001]. No anastomotic leakage of blood or anastomotic stenosis occurred in the MCA group during the operation. Intraoperative anastomotic leakage of blood occurred in all of the 6 dogs in the HS group. Among them, 1 dog died of excessive blood loss, and 2 dogs experienced mild anastomotic stenosis due to repeated repair. Postoperative color Doppler ultrasound and angiography showed smooth blood flow at the anastomotic stoma without stenosis or thrombosis in the MCA group. In the HS group, 4 dogs presented with anastomotic stenosis on angiography at postoperative 4 weeks. Conclusions MCA technique may achieve rapid and sutureless anastomosis of artificial vascular replacement of abdominal aorta in dog models, which reduces the incidence of anastomotic complications and accelerates postoperative recovery.

This study aimed to investigate the improvement of tolance and pharmacodynamics of nano-micelle irinotecan formulation compared with irinotecan hydrochloride injection(Campto). The toxic effects of the two formulations on colorectal cancer cells COLO205, HT-29, HCT-8 and SW480 were tested in vitro. COLO205 tumor-bearing mouse model was constructed. The two preparations were given via tail vein injection to investigate the maximum tolerance dose(MTD)of tumor-bearing mice to the two preparations, and then to explore the improvement of anti-tumor efficacy of nano-micelle irinotecan formulation near the MTD. The results showed that there was no significant difference in the inhibitory effect of the two formulations on the four colorectal cancer cells in vitro. The MTD of nano-micelle irinotecan formulation and Campto was 432. 0 and 276. 5 mg/m2 respectively. Both of the two formulations showed significant anti-tumor effect in vivo, and the relative tumor proliferation rate and tumor wet weight inhibition rate of nano-micelle irinotecan formulation at high dose(345. 6 mg/m2)were significantly better than those of Campto at two doses(177. 0 and 221. 2 mg/m2)(P< 0. 05).

Amines ; chemistry ; isolation & purification ; Amino Alcohols ; chemistry ; isolation & purification ; Anti-Bacterial Agents ; Avidin ; chemistry ; isolation & purification ; Crown Ethers ; Cyclodextrins ; chemistry ; Electrophoresis, Capillary ; methods ; Polysaccharides ; Serum Albumin ; Stereoisomerism

PURPOSE: The use of oncoplastic reconstruction for breast-conserving surgery (BCS) extends benefits beyond merely minimizing poor cosmetic results. However, the feasibility and oncological safety of oncoplastic surgery (OPS) are controversial. METHODS: This meta-analysis aimed to compare the short-term and long-term oncological outcomes of BCS alone and BCS plus OPS. Relevant studies published before July 2017 in the Embase, the Cochrane Library, PubMed, and Web of Science databases were screened and collected. The meta-analysis was performed using STATA software (Stata Corp.). RESULTS: A total of 3,789 patients from 11 studies were included, with 2,691 patients in the BCS-alone group and 1,098 patients in the BCS plus OPS group. The demographics were similar between both groups, and no significant difference was observed in pathological T and N stages between the two groups. Re-excision was less common (relative risk [RR], 0.66; p=0.009) and the positive-margin rate was lower, but not significantly (RR, 0.83; p=0.191), in the BCS plus OPS group than in the BCS-alone group. The local and distal recurrence rates were similar in both groups. Both disease-free survival (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.96–1.49; p=0.112) and overall survival (HR, 1.14; 95% CI, 0.76–1.69; p=0.527) did not differ between the two groups. CONCLUSION: A combination of BCS and OPS is preferred over BCS alone for decreasing re-excisions and provides similar long-term survival as BCS alone in patients with breast cancer.
Breast Neoplasms ; Demography ; Disease-Free Survival ; Female ; Humans ; Mammaplasty ; Mastectomy ; Mastectomy, Segmental* ; Recurrence