OBJECTIVEThe main objective of this study is to assess the the effect of simvastatin (sim) on myocardial no-reflow (NR) and explore the possible potential mechanisms.

METHODSAdult male Wistar rats were randomized into sham group (n = 12), I/R (90 min ischemia via coronary ligation/120 min reperfusion, n = 18) and I/R plus sim group (20 mgxkg(-1)xd(-1) sim pretreated via gavage beginning 3 days before I/R, n = 18). After reperfusion, area at risk/area of left ventricular (RA/LVA), area of NR, determined by the area not perfused by thioflavin-S/area at risk (NA/RA) and area of myocardial infarction/area at risk (MIA/RA) were measured. Myocardium homogenate was used to determine the activity of eNOS, iNOS and MPO, and the content of NO and MDA. Myocardial immunohistochemistry was performed to determine the positive index of NF-kappaB p65 in cardiomyocytes and arteriole.

RESULTSThe NR and myocardial infarction areas in I/R plus sim group were significantly smaller than those in I/R group (34.10 +/- 7.05 vs. 52.09 +/- 6.89, 78.80 +/- 7.60 vs. 90.13 +/- 5.72, each P < 0.05) while the ischemia area was similar between the 2 groups (P > 0.05). The myocardial activities of iNOS and MPO, the contents of NO and MDA were significantly lower while eNOS activity was significantly higher in I/R plus sim group than those in I/R group (5.02 +/- 1.64 vs. 9.19 +/- 2.89, 586.21 +/- 126.97 vs. 744.49 +/- 137.53, 257.72 +/- 93.43 vs. 384.10 +/- 40.68, 72.10 +/- 18.56 vs. 111.84 +/- 38.58, 7.08 +/- 1.74 vs. 3.72 +/- 0.98, all P < 0.05). The positive index of NF-kappaB p65 in cardiocytes and arteriole at left ventricular wall near the area of myocardial infarction was significantly lower in I/R plus sim group than that in I/R group (21.59 +/- 10.5 vs. 34.32 +/- 9.55, 27.27 +/- 13.19 vs. 44.91 +/- 15.06, each P < 0.05).

CONCLUSIONSimvastatin could improve myocardial NR after ischemia-reperfusion by attenuating endothelial dysfunction and inhibiting inflammation and neutrophil activation.

Animals ; Disease Models, Animal ; Endothelium, Vascular ; drug effects ; Male ; Myocardial Infarction ; drug therapy ; physiopathology ; Myocardial Reperfusion ; Myocardial Reperfusion Injury ; drug therapy ; Myocardium ; metabolism ; Rats ; Rats, Wistar ; Simvastatin ; pharmacology

OBJECTIVETo investigate the efficacy, safety and the life quality improvement of uroacitides injection in the treatment for patients with advanced malignant tumors.

METHODSA total of 160 patients with advanced stage cancers were enrolled into this multicenter, open and non-randomized phase II clinical trial, including cancers of the lung (33 cases), liver (45 cases), breast (17 cases), esophagus (11 cases), stomach (18 cases), colon (19 cases), pancreas (3 cases) and kidney (4 cases), and glioma (10 cases). Uroacitides was administrated in a dose of 300 ml daily via the superior vena cava catheter for consecutive 4-8 weeks.

RESULTSOf the 160 patients, 21 dropped out and one patient died during the trial. Efficacy could be evaluated in 138 patients and safety in 160. The total objective response rate (ORR, CR + PR)) and tumor control rate (CR + PR + MR + SD) of the 138 evaluable patients were 5.8% and 65.2%, respectively. Clinical benefit response (CBR) rate was 57.2%. Major adverse effects were grade I - II and reversible nausea/vomiting (21.9%) and pain (6.3%).

CONCLUSIONUroacitides injection is effective in the control for various kinds of advanced cancers with mild, reversible and tolerable adverse effects, and can also improve the patient's quality of life. It is worth being studied further.

Breast Neoplasms ; blood ; drug therapy ; pathology ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; pathology ; Catheterization, Central Venous ; Colorectal Neoplasms ; blood ; drug therapy ; pathology ; Humans ; Liver Neoplasms ; blood ; drug therapy ; pathology ; Lung Neoplasms ; blood ; drug therapy ; pathology ; Methyltransferases ; administration & dosage ; adverse effects ; antagonists & inhibitors ; therapeutic use ; Nausea ; chemically induced ; Neoplasm Staging ; Peptides ; administration & dosage ; adverse effects ; therapeutic use ; Phenylacetates ; administration & dosage ; adverse effects ; therapeutic use ; Quality of Life ; Remission Induction ; Salvage Therapy ; Treatment Outcome ; Vomiting ; chemically induced ; alpha-Fetoproteins ; metabolism