转录因子Egr-1在失血性休克复苏后肝脏损伤中的作用

目的研究转录因子Egr-1在失血性休克复苏（HS/R）后肝脏损伤中的作用.方法利用Egr-1野生型（WT）和基因封闭型（KO）小鼠复制失血性休克复苏模型.取肝组织,RT-PCR法测定肝组织中TNF-α、IL-6、G-CSF、ICAM-1 mRNA的表达变化.通过检测肝组织中MPO的含量、血清ALT水平和组织学检查,评估肝脏炎症细胞浸润和损伤程度.结果失血性休克2.5 h＋复苏4 h后,Egr-1 KO小鼠肝组织中TNF-α、IL-6、G-CSF、ICAM-1 mRNA的表达水平明显低于Egr-1WT组;Egr-1 KO组失血性休克复苏后肝组织炎性浸润和损伤程度减轻,表现为血清ALT水平低,肝组织中MPO含量低,病理损伤轻.结论本实验结果表明转录因子Egr-1参与了失血性休克复苏后肝脏炎症反应基因表达的调节,在失血性休克复苏后的肝脏损伤中起一定的作用.     

Study of interaction of styrene oxide with angiotensin by mass spectrometry.

The present study describes how mass spectrometry was extensively applied to the characterization and quantification of modified amino acids within the polypeptide chain of Angiotensin I, chosen as model substrate, combining the use of fast atom bombardment mass spectrometry with gas chromatography--mass spectrometry. The reaction products after in vitro incubation of Angiotensin I with styrene oxide, a well known carcinogen, under different conditions, have been characterized: a prominent reactivity of several potential nucleophilic sites of Angiotensin I was shown, including two histidine residues and a tyrosine residue; it is worth noting that it has never been stated that tyrosine is highly reactive with styrene oxide. The results obtained demonstrate the usefulness of mass spectrometry for the structural determination of chemically modified amino acids in peptides and proteins, and the presence of a reliable relationship between reaction conditions and the production of alkylated amino acids. This characterization procedure offers the possibility of identifying reactive sites following exposure to unknown alkylating agents.     

Synthesis,Characterization, and in Vitro Stability of Chitosan-Methotrexate Conjugates

Pharmaceutical Research -     

Effect of dietary fat content on the bioavailability of a sustained release quinidine gluconate tablet

Quinidine gluconate 324 mg sustained release tablets (Quinaglute) was administered as a single dose to 15 healthy male subjects following an overnight fast, immediately following a high fat (HF) breakfast or immediately following a low fat (LF) breakfast. Serum samples were obtained over a 48 h period and analyzed for quinidine content using a high performance liquid chromatographic assay. Under the conditions of the study, both the rate and extent of quinidine bioavailability was significantly affected by food. The extent of bioavailability was statistically significantly greater (p less than 0.05) following both the HF and LF meals as compared to that in the fasted state. Rate of bioavailability was significantly enhanced following the LF meal as compared to that of the other two treatment groups. Although peak concentrations were greater and time to peak concentrations somewhat later following the HF meal versus those under fasting conditions, these differences were not statistically significant. In addition, the characteristics of the serum concentration-time profile (as defined by the number, magnitude, and time of occurrence of the multiple absorption maxima) was unique for each of the three treatment groups. Possible mechanisms underlying these results are explored.     

Systematic pelvic and para-aortic lymphadenectomy in advanced ovarian cancer patients with no residual intraperitoneal disease

A comparative non-randomized study was carried out to evaluate the role of systematic pelvic and para-aortic lymphadenectomy (SL) on patients with no residual intraperitoneal disease (NRID) of advanced ovarian cancer (stage IIIC–IV). A total of 142 optimally cytoreduced patients (macroscopic disease absent on peritoneal surface) were divided into two groups: Group A, consisting of 98 patients (53 previously untreated and 45 pretreated at other Institutions), who underwent SL; Group B, consisting of 44 patients (21 previously untreated and 23 pretreated at other Institutions), who did not undergo SL. Each group had statistically equivalent histology, grading, performance status and variety of cytoreductive operations performed. Group A pretreated patients had a greater number of stage III than Group B ( P  = 0.03). Systematic pelvic and para-aortic lymphadenectomy could be carried out with an acceptable morbidity and no mortality. All 142 patients received post-operative chemotherapy including carboplatin. The number of chemotherapy sessions did not differ between the two groups. Comparison of survival revealed that SL significantly improved the survival of previously untreated patients ( P  = 0.02). The survival was significantly different with nodal status ( P  = 0.006). Cox's proportional hazard analysis showed that only systematic lymphadenectomy was a significant covariate. The survival was not significantly different in Group A vs Group B pretreated patients; however, it was significantly different with respect to nodal status ( P <0.001). Cox's proportional hazard analysis showed that only the initial stage of disease was a significant covariate. The results of the present study shows that aggressive surgical cytoreduction with SL could be therapeutic in previously untreated patients with NRID. Currently, an international prospective randomized study is ongoing to clarify definitively the clinical role of SL.