Rutaecarpine (Rut) is a type of indole quinazoline alkaloid exracted from Ruticarpum. Studies showed that Rut has a wide range of pharmacological effects, such as anti-hypertension, anticancer, anti-inflammation, anti-thrombus formation. Currently, many scholars are committed to developing it into a new antihypertensive and anti-inflammatory drug with all new mechanisms. But studies found that Rut is a highly fat-soluble drug with low water and oil solubility. Its high insolubility is the main obstacle in its oral absorption and application, which greatly reduced its bioavailability. Therefore, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was used as the inclusion material to prepare Rut-HP-beta-CD inclusion complex in this experiment, in order to increase its water solubility and bioavailability. In this experiment, the inclusion complex was prepared by the stirring-freeze-dry method. The preparation process was optimized by the orthogonal test, with the inclusion rate as the index, and molar ratio between host and guest molecules, inclusion temperature, time and stirring speed as the impacting factors. Moreover, the inclusion complex was verified by detecting the apparent solubility, thin layer chromatography, microscopic identification, melting point detection and dissolution study. The results showed that under the conditions of the molar ratio between Rut and HP-beta-CD of 1: 1, temperature at 60 degrees C, inclusion time of 4h and stirring speed at 600 r x min(-1), the inclusion rate of Rut-HP-beta-CD reached 91.04%. Therefore, the preparation process of Rut-HP-beta-CD inclusion under the optimum conditions is simple and feasible, with a highest inclusion rate and reproducibility, and could significantly improve Rut's solubility and bioavailability, and provide a reliable experimental basis for its clinical application.
2-Hydroxypropyl-beta-cyclodextrin ; Alkaloids ; chemistry ; Chemistry, Pharmaceutical ; methods ; Drug Carriers ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Rutaceae ; chemistry ; Solubility ; beta-Cyclodextrins ; chemistry

Acute Disease ; Adult ; Altitude Sickness ; blood ; enzymology ; Glutathione ; blood ; Glutathione Peroxidase ; blood ; Humans ; Lipid Peroxidation ; Male ; Military Personnel ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Oxidoreductases ; metabolism ; Superoxide Dismutase ; blood

OBJECTIVETo evaluate the prognostic effects of neoadjuvant chemotherapy (NAC) in patients with local advanced gastric cancer.

METHODSWe retrospectively analyzed prognosis in 191 patients with advanced gastric cancer, of whom 71 were treated with NAC and 120 received surgery only between February 2007 and July 2013. Postoperative complication rate was recorded. Survival by clinicopathological features, pathological T and N stages, and histopathological tumor regression was retrospectively compared between the two groups.

RESULTSAccording to Response Evaluation Criteria in Solid Tumors, none of the 71 patients in the NAC followed by surgery group showed complete response, 36 showed partial response, 25 had stable disease, and 10 had progressive disease. The chemotherapy response rate was 50.7%; the disease control rate was 85.9%. Grade 3/4 adverse events were seen in less than 20% patients, with acceptable toxicities. No difference was found in the overall postoperative complication rates between the two groups (7 versus 22 cases, P=0.18). Median survival time was significantly different, at 54 months in the NAC combined with surgery group and 25 months in the surgery-only group (P=0.025).

CONCLUSIONIn patients with operable gastric adenocarcinomas, NAC can significantly improve overall survival without increasing surgical complications.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; mortality ; pathology

Metabonomics is a new method to study on the metabolic network and the relationship between body and environment, which conforms to the way of traditional Chinese medicine (TCM) research. In the study process of modernization of traditional Chinese medicine, effectively conjunction with metabonomics method will facilitate the integration of TCM with modern biological science and technology, and promote the modernization of TCM. This paper introduce the application of metabonomics in the research of toxicity mechanism of TCM, compatibility mechanism of TCM formula, pharmacology effect of TCM and processing mechanism of TCM. This paper summarize the problems in the TCM metabonomics research and prospect its bright future.
Animals ; Drug Therapy ; Drugs, Chinese Herbal ; adverse effects ; analysis ; metabolism ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods ; trends ; Metabolomics ; methods ; trends

OBJECTIVETo study the mechanism and significance of peripheral blood mononuclear cell (PBMC) of neonates infected with hepatitis B virus (HBV).

METHODSEighty-four HBsAg-positive and HBeAg-negative mothers and their newborns were recruited in this study. Sixteen hepatitis B virus markers (HBVM)-negative mothers and their neonates were served as control. All these cases had no symptoms of hepatitis, serious pregnancy complications and preexisting disease. Age, gestational age and the method of delivery were matched in two groups (P > 0.05). Five ml blood samples were taken from the peripheral vein of the pregnant women before delivery and from neonates within 24 hours after birth, before inoculation of HBV vaccine (HBVac). Serum and PBMC were isolated from 2 ml and 3 ml samples respectively. The sera, PBMC and the last supernatant of PBMC washing were stored at -80 degrees C. HBVM of neonates were detected by using enzyme linked immunosorbent assay (ELISA). HBV DNA in serum, PBMC and the last supernatant of PBMC washing of mothers and neonates were detected by using a nested-polymerase chain reaction (n-PCR). Two pairs of oligonucleotide primers, the outer primer pair for first PCR and inner primer pair for second PCR, designed according to region S of HBV genome were synthesized at Shanghai Cell Biology Institute of Chinese Academy of Sciences. The neonates who were HBV DNA positive in PBMC but HBsAg and HBV DNA negative in serum were followed up for one year, HBsAb in serum and HBV DNA in PBMC were observed in the neonates.

RESULTS(1) The positive rate of HBV DNA in 84 serum and PBMC of mothers were 53.57% and 40.48%, respectively (chi(2) = 2.891, P > 0.05). All the results were weakly positive. (2) Twenty-four (28.57%) newborns in the study group were infected, including 7 who were only HBV DNA positive in serum, 11 only HBV DNA positive in PBMC and 6 in both, all the results were weakly positive. HBsAg was negative in all the newborns. None of the neonates in control group was infected with HBV. There was significant difference between the two groups (chi(2) = 4.55, P < 0.05). (3) Of all the study cases, 11 (13.10%) neonates were HBV DNA weakly positive in PBMC but HBsAg and HBV DNA negative in serum. Of their mothers, 5 were only HBV DNA positive in serum, 2 only positive in PBMC and 4 positive in both serum and PBMC. Seven of the 11 neonates were followed up for one year and at the end of follow-up, 4 were HBsAb positive and HBV DNA negative in PBMC; 3 were HBsAb negative, and among the 3 cases HBV DNA in 2 was still positive in PBMC, HBsAg and HBV DNA in serum were negative in all the 7 neonates.

CONCLUSION(1) HBV DNA positivity either in serum or in PBMC in mothers can result in infection of PBMC with HBV in their neonates. (2) PBMC infection with HBV can exist for a long time in neonates while HBsAg and HBV DNA are negative in serum, and may result in vaccination failure in neonates.

Case-Control Studies ; DNA, Viral ; blood ; Female ; Hepatitis B ; diagnosis ; immunology ; Hepatitis B Vaccines ; administration & dosage ; Hepatitis B virus ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Leukocytes, Mononuclear ; virology ; Pregnancy

OBJECTIVETo explore the relationship between genetic polymorphisms of glutathione S-transferase (GST) M1, T1 and susceptibility to mountain sickness.

METHODSForty-three soldiers with acute mountain sickness and 80 healthy soldiers matching with sex/age and training under the same condition were divided into case group and control group. A multiple polymerase chain reaction method was used to detect GSTM1 and GSTT1 genes in genomic DNA isolated from peripheral blood cells from both cases and controls.

RESULTSThe frequency of the GSTT1 positive genotype was significantly higher in cases (69.8%) than in controls (42.5%) (P = 0.004, OR = 3.12, 95% CI 1.42 approximately 6.86). The frequency of GSTM1 negative genotype was also higher in cases (72.1%) than in controls (52.5%) (P = 0.03, OR = 2.34, 95% CI 1.05 approximately 5.02). Persons with both GSTM1 and GSTT1 negative genotypes had 5-fold more risk than those with GSTT1 negative and GSTM1 positive genotypes in developing mountain sickness (OR = 5.04, 95% CI: 1.00 approximately 25.3).

CONCLUSIONGenetic polymorphisms of glutathione S-transferase M1, T1 may be the risk factors in the development of mountain sickness.

Acute Disease ; Adult ; Altitude Sickness ; genetics ; Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Risk Factors

OBJECTIVETo appraise the effect of single- and two-layer Percoll density gradient centrifugation in sperm separation.

METHODSTwenty semen specimens underwent single-(50%) and two-layer (90% and 45%) density gradient centrifugation, respectively. The sperm class analyzer (SCA) was used to analyze sperm density, motility and dynamic parameters and round cell density before and after the treatment.

RESULTSAfter separation, the sperm recovery rate of the single-layer method was (65.5 +/- 12.8)%, significantly higher than that of the two-layer method (P < 0.01). The percentages of grade a sperm of the single- and two-layer method were significantly higher than pre-treatment (P < 0.05, P < 0.01), that of the single-layer was significantly lower than that of the two-layer method (P < 0.05), but the percentage of grade c sperm of the former was significantly higher than that of the latter (P < 0.05). Compared with pre-treatment, the percentage of grade a + b sperm of the two-layer method was significantly higher (P < 0.05), while that of the single-layer method showed no significant difference (P > 0.05), and the round cell density of both the methods was significantly lower (P < 0.05, P < 0.01), with no significant differences between the two methods (P > 0.05).

CONCLUSIONThe single-layer method yields a higher rate of sperm recovery and causes little change in the sperm motility, while the two-layer method effects a lower rate and significantly improves sperm motility. Both the methods can efficiently separate sperm from round cells, and each has its own advantages and its application value in in vitro treatment of sperm.

Cell Separation ; methods ; Centrifugation, Density Gradient ; methods ; Humans ; Male ; Povidone ; Silicon Dioxide ; Sperm Count ; methods ; Spermatozoa ; cytology

China ; Cost of Illness ; Demography ; Female ; Humans ; Maternal Mortality ; Poverty Areas

OBJECTIVETo evaluate the efficacy and safety of irinotecan combined with xeloda (CAPIRI regimen) in patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin.

METHODSTotally 38 patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin were enrolled. Patients received xeloda 1 000 mg/m2 orally twice daily on day 1 to 14 and intravenous irinotecan 100 mg/m2 on day 1 and 8 every 3 weeks.

RESULTSThe median age of 38 patients was 58.5 (27-77) years. CAPIRI regimen was used 11.0 (3.0-24.0) months after the diagnosis of metastatic colorectal cancer (CAPIRI regimen as second-line chemotherapy in 33 patients, third-line in 4 patients, and fourth-line in 1 patient). A total of 121 cycles of chemotherapy (median 3.0) were administered. Thirty-four patients were evaluable for response. The overall response rate and disease control rate were 5.9% and 61.8%, respectively. The median time to progression and overall survival were 4.5 months (95% CI, 3.4-5.6 months) and 11.0 months (95% CI, 10.2-11.8 months), respectively. All 38 patients were evaluable for safety. The most common adverse events were leukopenia (73.7%), neutropenia (65.8%), nausea and vomiting (60.5%), and diarrhea (28.9%). The occurrence rates of these grade 3-4 events were 10.5%, 13.2%, 10.5%, and 7.9%, respectively. All adverse events were tolerable.

CONCLUSIONCAPIRI regimen is effective and well-tolerated in Chinese patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; analogs & derivatives ; Capecitabine ; Colorectal Neoplasms ; drug therapy ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Organoplatinum Compounds ; therapeutic use ; Treatment Outcome

OBJECTIVETo study the stereoselective glucuronidation of carvedilol (CARV) by three Chinese liver microsomes.

METHODSThe metabolites of CARV were identified by a hydrolysis reaction with beta-glucuronidase and HPLC-MS/MS. The enzyme kinetics for CARV enantiomers glucuronidation was determined by a reversed phase-high pressure liquid chromatography (RP-HPLC) assay using (S)-propafenone as internal standard after precolumn derivatization with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylisothiocyanate.

RESULTSTwo CARV glucuronides were found in three Chinese liver microsomes incubated with CARV. The non-linear regression analysis showed that the values of K(m) and V(max) for (S)-CARV and (R)-CARV enantiomers were (118+/-44) micromol/L, (2 500+/-833) pmol/(min.mg protein) and (24+/-7) micromol/L, (953+/-399) pmol/(min.mg protein), respectively.

CONCLUSIONThese results suggested that there was a significant (P<0.05) stereoselective glucuronidation of CARV enantiomers in three Chinese liver microsomes, which might partly explain the enantioselective pharmacokinetics of CARV.

Carbazoles ; metabolism ; China ; Glucuronic Acid ; metabolism ; Glucuronides ; metabolism ; Microsomes, Liver ; metabolism ; Propanolamines ; metabolism ; Stereoisomerism