Résumé
To find novel antihepatitis drugs, a series of nitrate-oleanolic acid (OA) hybrids (10a, 10b, 11a-11e and 12a-12c) were designed and synthesized on the basis of previous studies using OA as lead compound, which is widely found in natural plants and liver-specific metabolism. In the present study, ten novel NO-releasing derivatives of OA were synthesized by connecting nitrate to the OA-3-OH through varying lengths of linkers containing antioxidants which were designed to increase the ability of these target compounds to scavenge free radicals. The structures of these objective compounds were determined by IR, MS, 1H NMR and elemental analysis. Their protective effects on anti-Fas mediated HepG2 cell apoptosis were in vitro evaluated by LDH assay. Compound 12a is the most potent inhibitor. Its effect on anti-Fas mediated HepG2 cell apoptosis and amount of NO-releasing in vitro are similar to those of positive control NCX-1000.
Résumé
This study sought to assess the biocompatibility of P(DA-SA)-Adriamycin, a new controlled-release chemotherapy system, in rabbit brain, and to examine its controlled release effect both in vitro and in vivo and its curative effects in vitro. The reaction of animal brain to the implanted P(DA-SA) or P(DA-SA)-Adriamycin was observed. The controlled-release profiles in phosphate buffer solutions and in rabbit brain were measured by UV spectrometry. Then, through flow cytometer, the rate of apoptosis in cultured glioma cells was tested. The reaction of rabbit brain to P(DA-SA) polymer was moderate and not significantly different from that to Gelfoam. The controlled-release rate of P(DA-SA)-Adriamycin in vitro and in vivo was stable and the duration of controlled-release of P(DA-SA)-Adriamycin spanned three weeks. The rate for apoptosis of glioma cells of P(DA-SA)-Adriamycin group was 69.9%, which was significantly higher than that of the control group. In conclusion, P (DA-SA)-Adriamycin controlled release chemotherapy system that bears curative effect has favorable controlled-release effect and good biocompatibility in rabbit brain. This system has potential value in treatment of malignant brain tumor.
Sujets)
Animaux , Lapins , Antibiotiques antinéoplasiques , Pharmacocinétique , Apoptose , Encéphale , Métabolisme , Acides capriques , Métabolisme , Doxorubicine , Pharmacocinétique , Vecteurs de médicaments , Métabolisme , Implant pharmaceutique , Test de matériaux , Polyesters , Métabolisme , Cellules cancéreuses en cultureRésumé
Eighteen cases of forensic re autopsy and histopathological re examination were analyzed retrospectively. The manner and the impression of original autopsy,times of autopsy,the reason and manner of forensic re autopsy,the interval betwwen the original autopsy and the re autopsy as well as the last conclusions were analyzed.It was found that the forensic re autopsy always occured in cases of medical disputes(3 cases,16 7%) and death related to the police investigation(4 cases,22 2%).Only external examination and incomplete forensic autopsy were done originally in 13 out of 18 cases(72 2%).The conclusions of re autopsy were completely different from that of the original autopsy in 5 cases.Attension must be paid and prevention measures for re autopsy must be adopted were also discussed.