Aldehydes ; chemistry ; pharmacology ; Chromatography, High Pressure Liquid ; DNA Adducts

Animals ; Brain ; metabolism ; physiology ; Circadian Rhythm ; physiology ; Female ; Fluorodeoxyglucose F18 ; pharmacokinetics ; Heart ; physiology ; Male ; Mice ; Mice, Inbred C57BL

Objective To explore the inhibition mechanism and safety of pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives against proliferation of human lung cancer A549 cells, H322 cells, and human umbilical vein endothelial cell (HUVEC). Methods Cells were treated with 40μmol/L of the ppo3a, ppo3b, ppo3i, and 0.1% DMSO (control) for 48 hours, respectively. Apoptosis was determined by Hoechst 33258 staining assay in H322 and A549 cells. Cell cycle distribution was determined by flow cytometry analysis in A549 cell. LC3-II, p53, and heat shock protein (HSP) 70 protein levels were detected by Western blotting in A549 cells treated with ppo3b for 48 hours. The morphology and viability of HUVEC were observed by inverted microscope and sulforhodamine B (SRB) assay. Results Ppo3a, ppo3b, and ppo3i significantly induced apoptosis in H322 and A549 cells. A strong G1-phase arrest was concomitant with the growth inhibitory effect on A549 cells. Ppo3b effectively elevated the p53 protein level, but significantly reduced the HSP70 protein level. There were no significantly inhibitory effect on the morphology and viability of HUVEC when treated with ppo3a, ppo3b, and ppo3i. Conclusions ppo3a, ppo3b, and ppo3i could inhibit H322 proliferation through apoptosis and inhibit A549 through apoptosis and G1-phase arrest. The protein p53 and HSP70 might involve in the inhibition effects. These derivatives might be a clue to find effective and safe drug for lung cancers.

Objective To synthesize 99Tcm- (hydrazinonictinamide- [Lys3] -bombesin) (tricine)(trisodium triphenylphosphine-3,3',3"-trisulfonate) ((HYNIC-[Lys3]-BBS) (tricine) (TPPTS)) and evaluate its biodistribution and binding capability with tumor tissue in Balb/c nude mice bearing human pancreatic cancer xenografts. Methods HYNIC was conjugated to the [Lys3] -BBS at pH = 9.0 with SnCl2 as reducing agent and both tricine and TPPTS as coligands for 99Tcm-labeling. 99Tcm-HYNIC-[Lys3]-BBS)(tricine) (TPPTS) was purified by Sep-Pak C18 cartridge and was analysed by HPLC. The radiochemical purity and radiolabeling yield were measured. The stability of 99Tcm-(HYNIC-[Lys3]-BBS) (tricine)(TPPTS) in serum, biodistribution (% ID/g) in the normal mice and imaging of the Balb/c nude mice bearing human pancreatic cancer xenografts in vivo were studied. Results The radiolabeling yield was (90 ±2)% and the radiochemical purity was over 95%. The radiochemical purity after 4 h in serum was over 85%. The distribution in normal mice showed rapid clearance from blood (the uptake was (0.07 ±0.01) %ID/g at 2 h postinjection). 99Tcm-(HYNIC-[Lys3]-BBS) (tricine) (TPPTS) was excreted mainly via the kidney with little radioactivity accumulation in the liver and gastrointestinal tract (the uptake of liver, stomach, intestine was (0.27 ±0.03), (0.06 ±0.03), (0.04 ±0.00) %ID/g at 2 h postinjection). Marked uptake of radioactivity was found in tumor tissue of the Balb/c nude mice bearing human pancreatic cancer with maximum T/NT ratio of 3.71 ± 0.57 at 2 h postinjection. Conclusions 99Tcm-(HYNIC-[Lys3]-BBS)(tricine) (TPPTS) can be easily prepared with high radiolabeling yield and radiochemical purity. The stability in serum and good biodistribution charateristics make it useful for the diagnosis of human pancreatic cancer with over-expression of the gastric-releasing peptide(GRP) receptor.

Two isomers of nitrochlorobenzene (o-, and p-NCB) were treated by a Pd/Fe catalyst in aqueous solutions through catalytic amination and dechlorination. Nitrochlorobenzenes are rapidly converted to form chloroanilines (CAN) first through an amination process, and then rapidly dechlorinated to become aniline (AN) and Cl(-), without the involvement of any other intermediate reaction products. The amination and dechlorination reaction are believed to take place predominantly on the surface site of the Pd/Fe catalysts. The dechlorination rate of the reductive degradation of the two isomers of nitrochlorobenzene (o-, and p-NCB) in the presence of Pd/Fe as a catalyst was measured experimentally. In all cases, the reaction rate constants were found to increase with the decrease in the Gibbs free energy (correlation with the activation energy) of NCBs formation; the activation energy of each dechlorination reaction was measured to be 95.83 and 77.05 kJ/mol, respectively for o- and p-NCB. The results demonstrated that p-NCBs were reduced more easily than o-NCBs.
Catalysis ; Industrial Waste ; prevention & control ; Iron ; chemistry ; Isomerism ; Kinetics ; Metals ; chemistry ; Nitrobenzenes ; chemistry ; Palladium ; chemistry ; Structure-Activity Relationship ; Waste Disposal, Fluid ; methods ; Water ; chemistry ; Water Purification ; methods

Objective To investigate the effect of matrix metalloproteinases(MMPs) in ventilator-induced lung injury inflammatory reaction of newborn rabbits.Methods Seventy-five newborn rabbits aged 1-5 days were randomly arranged to 3 groups:control group(n=3),other 72 rabbits designed by 2?2?3 factorial were divided into high concentration oxygen(100%)and low concentration oxygen(45%) groups,and each group was subdivided into 2 groups:High peak inspiratory pressure(PIP)group and low PIP group.All rabbits were done by mechanical ventilation and killed to obtain lung tissue at 1,3,6 hours after trailing respectively.The concentration of MMP-9 and MMP-2 in lung tissue bomogenate were detected by ELISA,at the same time the ratio of wet to dry was detected and pathological section was analyzed.Results 1.The concentration of MMP-2 in high concentration oxygen group,high PIP group and low PIP group increased compared with that in normal group,and there were significant differences.2.The mean concentration of MMP-9 was lower in high concentration oxygen group than that in normal control group,and there was significant difference between 2 groups.The mean concentration of MMP-9 in low concentration oxygen group was higher than that in normal group,and there was no significant difference between 2 groups.There was no significant difference in effect to mean concentration of MMP-9 by different PIP.3.There were positive correlation between MMP-2 and MMP-9,MMP-2 and the ratio of wet to dry in lung.Conclusions Within 6 hours in newborn rabbits by mechanical ventilation,ventilation with high concentration oxygen up-regulate MMP-2,but down-regulated MMP-9.The lungs stretch by mechanical ventilation increase MMP-9,but decrease MMP-2.Mechanical ventilation can affect the synthesis of MMPs,and MMPs plays an important role in ventilator-induced lung injury of newborn rabbits.

Objective To study the clinical significance of the serum angiopoietin-2(Ang-2) in the diagnosis,recurrence,invasion and metastasis of gastric cancer.Methods The serum Ang-2 and carcino-embryonic antigen (CEA) levels in 158 patients with gastric cancer (gastric cancer group) and 30 normal controls(control group) were measured by enzyme linked immunosorbent assay(ELISA) technique respectively.The serum Ang-2 and CEA levels were also measured 2 weeks after operation in gastric cancer group and reexamined in the recurred gastric cancer patients in 2 years after operation (recurred and metastasis group).The correlation between the serum Ang-2 level and pathologic c haracterization of gastric cancer was evaluated.Results The serum Ang-2 and CEA levels in gastric cancer group [ (331.8 ±64.3),(42.6 ±37.3)μg/L] and recurred and metastasis group [(318.7 ±72.9),(40.5 ±36.7)μg/L] were significantly higher than those in control group [ (187.4 ± 32.7),(4.2 ± 3.1 )μ g/L] (P ＜ 0.01 ),and the serum Ang-2 level 2 weeks after operation [ (211.6 ± 75.1 ) μ g/L ] was significantly decreased to the control group (P ＞ 0.05 ),while the serum CEA level [ (33.4 ± 30.6) μ g/L ] was still significantly higher than the control group (P ＜ 0.01 ).The sensitivity of the serum Ang-2 for diagnosis of gastric cancer was markedly higher than that of the serum CEA (P ＜ 0.01 ).There was correlation between serum Ang-2 and degree of tumor differentiation,TNM pathological staging,lymphatic metastasis,invasion depth and tumor size (p ＜0.01 ),but there was no correlation between serum Ang-2 and tissue classification and location of gastric cancer (P＞ 0.05).Conclusion The serum Ang-2 level is suggested to be a valuable gastric cancer marker and conduce to the diagnosis of gastric cancer,the monitoring of recurrence after operation and evaluation of prognosis.

0.2 g/L)with normal diets. Conclusions Living donor liver transplantation for hepatic complications of Wilson's disease can cure and correct the underlying metabolic defect. It is a lifesaving therapy in children with fulminant Wilsonian hepatitis and has many unsurpassed advantages.

Objective To assess the diagnostic value of MRCP before LC.Methods 944 cases with chronic calculous cholecystitis underwent MRCP before LC from June 2004 to June 2007 in our department.incidence rate of cholecvstolithiasis together with common bile duct stones and incidence rate of anatomic abnormity of bile duct were collected.Results The incidence rate of cholecvstolithiasis together with common bile duct stones were 8.1%(77/944),and the oecurence ofACBDS were 1.2%(11/944).The incidence rate of anatomic abnormity of bile duct were 3.7%(35/944).ConclusionMRCP can not only offer a excellent diagnostic value of ACBDS and anatomic abnormity of bile duct,but also reduce the occurrence of CBDS remainder and iatrogenic bile duct iniuries.

OBJECTIVETo observe the effects of combination of Lumbrukinase Capsule (LC) and Probucol Tablet (PT) in treating cerebral infarction (CI) patients' unstable atheromatous plaque of the carotid artery.

METHODS150 patients were randomly assigned to the PT group and the LC group, 75 cases in each. Patients in the PT group took 0.5 g PT each time, twice daily. On the basis of PT, patients in the LC group also took 600 thousand U LC, thrice daily. The treatment course was 12 months for all. The serum levels of TC, TG, HDL-C, LDL-C, fibrinogen (FIB), and changes of the carotid atherosclerotic plaque were measured before treatment, 6 and 12 months after treatment. Meanwhile, adverse events were recorded.

RESULTSThe serum levels of TC, TG, and LDL-C were all lower 6 months after treatment than before treatment in the two groups, showing statistical significance (P < 0.05). The serum level of HDL-C was higher 6 months after treatment than before treatment in the two groups, showing no statistical significance (P > 0.05). When compared with before treatment in the same group, the serum level of FIB significantly decreased after treatment. Besides, there was statistical difference between the two groups (P < 0.05). There was no statistical difference in the serum levels of blood lipids or FIB between 12-month treatment and 6-month treatment in the same group (P > 0.05). The plaque effective rate in the LC group was superior to that of the PT group, showing statistical significance (P < 0.01). During the treatment period, the occurrence of cerebrovascular event was lower in the LC group than in the PT group (P < 0.05). Partial patients in the two groups had gastric discomfort.

CONCLUSIONSThe combination of LC and PT could prevent and treat arteriosclerosis, stabilize the plaque, effectively lower the occurrence of ischemic events. Its clinical application did not increase the risk of hemorrhage. It was safe and effective, worthy of spreading. It was necessary to further observe whether combination of LC and PT could increase side effects of the digestive tract.

Adult ; Aged ; Animals ; Biological Products ; therapeutic use ; Carotid Artery Diseases ; drug therapy ; Cerebral Infarction ; drug therapy ; pathology ; Female ; Humans ; Male ; Materia Medica ; therapeutic use ; Middle Aged ; Oligochaeta ; enzymology ; Plaque, Atherosclerotic ; drug therapy ; Probucol ; therapeutic use ; Serine Endopeptidases ; therapeutic use ; Treatment Outcome