The metabolism study of radiolabeled drugs plays an important role in the development of new drugs. It provides information on drug absorption, metabolism, tissue distribution and excretion, and plays an irreplaceable role in the metabolite safety evaluation and mass balance of new drugs. The new guidance draft on clinical trials of radiolabeled drugs recently released by the US FDA puts forward higher standards and has been widely concerned by the industry. In recent years, in the research and development of new drugs in China, ¹⁴C labeled drugs have been used to carry out clinical metabolism studies, which has overcome key technical bottlenecks and accumulated experience. This paper summarizes the above research progress, analyzes the existing problems, and preliminarily looks forward to the future technological development and application.

Archives ; Humans ; Occupational Health

Humans ; Occupational Diseases ; epidemiology ; prevention & control ; Occupational Health Services

Objective To study the state of erythrocyte immune function in neonates with hyperbilirubinemia,and analyze the influence of various clinical status on erythrocyte immune function.Methods Fifty-two neonates with hyperbilirubinemia were enrolled and 104 healthy neonates as the control group.The adherence rate of complement 3b-receptor on the surface of red blood cell(RBC-C3bRR) and the immune complex adherence rate of red blood cell(RBC-ICR) were detected with erythrocyte saccha-romycete rosettet test.Results 1.The level of RBC-C3bRR in neonates with hyperbilirubinemia was lower than that in control group,and the level of RBC-ICR in neonates with hyperbilirubinemia was higher than that of control group(Pa0.05).3.Comparing the neonates with unconjugated bilirubin of different concentrations,there were significant difference in RBC-ICR(Pa0.05).4.There were positive correlation between RBC-ICR and bilirubin,unconjugated bilirubin in the neonates(Pa0.05).Conclusion Erythrocyte immune function in neonates with hyperbilirubinemia is obviously lower than that of control group and it is influenced by the concentratron of bilirubin and the time of phototherapy.

Objective To assess the value of ultrasound examination in transvaginal diagnosis of normal fetal heart with 11-14 weeks of gestation.Methods Totally 158 cases of normal fetal heart with high risk pregnancy and nuchal translucency thickness were examined by two ultrasoud approaches:transvaginal(TVS) and tranabdomina(TAS) in 11-14 weeks of gestation.Results The group of TVS was obviously clearer than TAS by displaying the normal fetal cardiac structural in 12 week of gestation and 13-14 weeks of gestation with significant difference between the two groups (P<0.05),respectively.No significant difference between the two groups in 11 week of gestation was observed.Conclusion The transvaginal echocardiogram is of clinical value in the high risk gravida during the late first and the early second trimester.

Death ; Hematoma, Subdural/etiology* ; Humans ; Syphilis, Congenital/complications*

Adult ; Fracture Fixation, Internal ; Fractures, Ununited ; surgery ; Humans ; Male ; Scaphoid Bone ; injuries ; surgery

To express recombinant carboxypeptidase from Thermus aquaticus (Cpase Taq) in Pichia pastosis, the open reading frame coding thermostable Cpase Taq was optimized based on the preference of P. pastoris codon usage and synthesized in vitro. The novel gene was cloned into P. pastoris expression vector pHBM905A and the sequence coding 6xHis tag was fused with the ORF of Cpase Taq gene. The recombinant plasmid was named pHBM905A-Cpase Taq and transformed into P. pastoris GS 115. Transformants were induced with 1% methanol for 72 h until the enzyme yield reached 0.1 mg/ml. The enzyme was purified and its enzymatic properties were analyzed. The results showed that the specific enzyme activity reached maximum at 75 °C and pH 7.5, which was about 80 U/mg. It was the first report about the secretory expression of Cpase Taq in P. pastoris GS115. Because of its large-scale preparation, this enzyme may be applied in industrial hydrolysis of peptides into amino acids in the future.
Bacterial Proteins ; biosynthesis ; genetics ; Carboxypeptidases ; biosynthesis ; genetics ; Cloning, Molecular ; Codon ; Hydrolysis ; Open Reading Frames ; Pichia ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; Thermus ; enzymology

Objective To investigate whether delayed treatment with exogenous kallikrein on neurogenesis after focal cortical infarction in stroke-prone renovascular hypertensive rats (RHRSP). Methods Seventy-two RHRSP were divided into 3 groups. Twenty-four rats were given human tissue kallikrein ( 1.6 × 10-2 PNAU/kg) and 24 rats were given vehicle through tail venous daily for 2 or 6 days consecutively starting at the 24th hour after distal middle cerebral artery occlusion (MCAO). 24 rats underwent sham-operation. Cell proliferation was examined by using 5'-bromo-2'-deoxyuridine (BrdU, 50 mg/kg). Rats were respectively sacrificed 3, 7, 14 or 28 days after MCAO. Results Treatment with kallikrein significantly increased the number of BrdU+ cells in the ipsilateral subventricular zone (SVZ) (304.0±73. 9 vs 167.0±32.2 vs 56.0±12.2 at 7 d after operation, q =7.165, 12.916 and 5.751 respectively,all P<0.05) and in the peri-infarction region (490.0±82.0 vs 308.0±51.5 vs 49.0± 9.5 at 7 d after operation, q = 7.920, 19.184 and 11.264 respectively, all P < 0.01 ), and increased the number of BrdU+/DCX+ cells (225.0±13.6 vs 98.0±9.6 vs 23.0±5.6 at 7 d after operation, q = 30.731,48.735 and 18.004 respectively,all P < 0.01) in the ipsilateral SVZ compared with the vehicle group or the sham-operated group, which began on the 3 day, peaked in 7--14 days after MCAO, and then gradually decreased. Compared with the vehicle group, exogenous kallikrein markedly increased the number of BrdU+/NeuN+ cells (21.0±3.4 vs 13.0±2.6 at 14 d, P =0.001 ) in the peri-infarction region after MCAO. The kallikrein group showed a better functional improvement than the vehicle group after stroke ( all P < 0.05). Conclusion Our study suggests that administration of exogenous kallikrein at 24 h after cortical infarction enhances the SVZ neuroblasts proliferation, migration, and selective differentiation and improves functional recovery after stroke.

3T3-L1 adipocytes were cultured with various concentrations of high-density lipoprotein ( HDL, 0, 10, 50, and 100 μg/ml ) for 16 h and with lipopolysaccharide ( LPS, 100 ng/ml ) for another 6 h. Interleukin-8 in the medium was determined by ELISA, and PPAR-γ mRNA expression by reverse transacription polymerase chain reaction (RT-PCR). Interleukin-8 levels were increased in LPS-treated cells ( P＜0.05 ), but decreased in HDL-treated cells in the dose-dependent manner. PPARγ mRNA expressions were increased in HDL-treated groups than those treated only with LPS. These results suggested HDL may decrease interleukin-8 secretion via up-regulating PPARγ expression in adipocytes.