AIMTo investigate the role of endothelin-1 in the pathogenesis of neurogenetic pulmonary edema.

METHODSThe levels of endothelin-1 in plasma and lung were measured in rats which suffered from diffuse brain injury on Marmarous' model. The changes of endothelin-1 in the lungs were also detected using an immunohistochemical method.

RESULTSAfter heavy diffuse brain injury in rats, the levels of endothelin-1 in plasma and lung began increasing at 1 hour, and peaked at 6 hour. Though a little declining at 24 hour, it maintained a higher level within 48 hours (P < 0.05). Pulmonary pathology showed that after brain injury there were congestion, swelling in pulmonary microvessels with broadened pulmonary interstitial tissue, and leucocyte infiltration was dominated by neutrophils and monocytes from 1 hour on, which peaked at 6 hour. More serious congestion, swelling and protein effusion in pulmonary alveoli were observed at both 24 h and 48 h. Immunohistochemically, endothelin-1 had more significant expression and higher levels of OD in the experimental groups than that in the control's, the most significance of which was at 6 hour.

CONCLUSIONThe inflammatory injury mechanism caused by endothelin-1 may play an important role in neurogenic pulmonary edema.

Animals ; Endothelin-1 ; metabolism ; Lung ; metabolism ; Male ; Pulmonary Alveoli ; metabolism ; Pulmonary Edema ; etiology ; metabolism ; Rats ; Rats, Wistar

AIMTo study preventive and therapeutic effect of zinc sulfate on lung injury during superior mesenteric artery occlusion (SMAO) shock and their mechanism of action.

METHODSModel of rabbit SMAO shock was made. The effect of zinc sulfate on the malondialdehyde (MDA) in erythrocyte membrane and plasma, oxidase (XOD) in plasma, superoxide dismutase (SOD) in erythrocyte and MDA, SOD and pulmonary surfactant (PS) in lung tissues homogenate were observed.

RESULTSThe administration of zinc sulfate decreased MDA and XOD, prevented the reduction of SOD and PS, and alleviated lung injury.

CONCLUSIONIt is suggested that lung is injured during SMAO shock and zinc sulfate possesses preventive and therapeutic effect, through stabilized membrane.

Animals ; Female ; Lung ; metabolism ; Lung Injury ; drug therapy ; etiology ; metabolism ; Male ; Mesenteric Artery, Superior ; pathology ; Mesenteric Vascular Occlusion ; complications ; drug therapy ; metabolism ; Rabbits ; Shock ; complications ; drug therapy ; metabolism ; Zinc Sulfate ; therapeutic use

Aim To investigate the protective effects of supercritical CO2 fluid extract(SFE)of Notoginseng a-gainst glutamate-induced PC12 cells damage and the underlying mechanism. Methods PC12 cells were dealt with glutamate to establish cell models. MTT as-say,LDH method,Hoschst 33342 staining,Fluo-3 /AM fluorescence staining and Western blot were used to observe the changes of cell viability,intracellular Ca2 + concentration and the expression of protein that interacted with C kinase l(PICK1)and glutamate re-ceptors 2 (GluR2),respectively. Results Glutamate was cytotoxic to PC12 cells with an inhibitory concen-tration 50(IC 50 )of 25 mmol·L - 1 . Pretreatment with SFE(25,50,100 mg·L-1)and FSC231(100 μmol ·L-1 )and SFE(100 mg·L-1 )+FSC231(100μmol ·L-1 )remarkablely improved cell viability,reduced LDH leakage,decreased apoptosis rate,debased intra-cellular calcium concentration,decreased the expres-sion of PICK1 ,and increased the expression of GluR2 . Conclusions SFE of Notoginseng shows protective effects against glutamate-induced PC12 cell damage, and its mechanism may be related to the inhibition of PICK1 and the increase of GluR2 protein expression.

Carcinoma, Hepatocellular ; metabolism ; Glypicans ; biosynthesis ; genetics ; Humans ; Liver Neoplasms ; metabolism ; RNA, Messenger ; biosynthesis ; genetics

OBJECTIVETo investigate the efficacy and safety of percutaneous radiofrequency perforation and valvuloplasty in infants with pulmonary atresia with intact ventricular septum (PA/IVS).

METHODSFour infants (body weight 4 - 10 kg) aged 11 months, 9 months, 12 days and 9 months old, respectively, were hospitalized for dyspnea and cyanosis. All patients had a continuous murmur in the left second intercostal space. Doppler echocardiogram showed membranous pulmonary atresia with intact ventricular septum. Right ventriculogram showed a tripartite right ventricle, vasiform infundibulum, and membranous pulmonary valve atresia without ventriculocoronary connections. Descending thoracic aortogram showed good-sized confluent pulmonary arteries being filled from a ductus arteriosus. All the patients were taken up for radiofrequency perforation followed by a balloon dilatation. A 6F Judkins right coronary guiding catheter was positioned in the right ventricular outflow tract and under the atretic pulmonary valve membrane. The radiofrequency perforation catheter along with coaxial injectable catheter was then passed through the right coronary guiding catheter, using it as the guide to the imperforate membrane. The proximal end of the radiofrequency perforation catheter was then connected to radiofrequency generator. After the cusps of pulmonary valve were perforated, the coaxial injectable catheter was moved into the main pulmonary artery. A tiny floppy-tipped coronary guidewire was then passed through the coaxial injectable catheter into the main pulmonary artery and directed through the patent ductus arteriosus into the descending thoracic aorta or directed into pulmonary arteriola. Thereafter, serial balloon dilation catheters were introduced across the pulmonary valve, and dilations were sequentially performed with increasing balloon diameters. The balloon was dilated until the concave of the balloons disappeared. The radiofrequency energy (5 to 8 W) was delivered for 2 to 5 seconds once, but commonly twice, to perforate the valves. After a predilation with a 3 mm x 20 mm to 5 mm x 20 mm balloon at 6 - 14 atm pressure, the valve was subsequently dilated with 10 mm x 30 mm to 14 mm x 30 mm balloon once or twice. The duration of procedures was 120 to 150 min and exposure time was 25.4 to 43.9 min.

RESULTSThe primary procedure was successful in all the infants except one who died early of cardiac perforation with tamponade. After a follow-up period ranging from 2 to 8 months (mean 4.3 m), the remaining 3 survivors achieved complete biventricular circulation. Two of them were awaiting occlusion of the patent ductus arteriosus and 1 needed right ventricular outflow tract reconstruction because of infundibular obstruction.

CONCLUSIONPA/IVS consists of 0.7% to 3.1% of congenital heart defects. 85% of the untreated patients die within half a year. Surgical repair for the infants with PA/IVS is associated with a high mortality. In carefully selected patients with PA/IVS, radiofrequency perforation and balloon dilatation of the pulmonary valve is feasible and may represent a new alternative to surgery due to its low mortality and avoidance of cardiopulmonary bypass.

Balloon Occlusion ; Catheter Ablation ; methods ; Catheterization ; methods ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Pulmonary Atresia ; physiopathology ; therapy ; Pulmonary Valve ; surgery ; Ventricular Septum

OBJECTIVETo detect the expression and variation of p53 gene during tree shrews' hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1).

METHODSTree shrews were divided into four groups: the tree shrews were infected with HBV and fed with AFB1 in group A, only infected with HBV in group B, fed with AFB1 alone in group C, and normal control in group D. All the tree shrews were performed liver biopsy every 15 weeks. The tissues of liver and tumor were detected by immunohistochemistry and molecular biotechnologies.

RESULTS(1) The incidence of hepatocellular carcinoma (HCC) in group A (66.7%) was higher than that in Group B and C (30%). HCC appearance in group A was earlier than that in group C (120.0 weeks +/-16.6 weeks vs 153.3 weeks +/-5.8 weeks, t = 3.336, P<0.01). (2) Mutated p53 protein was not found before the 75th week of the experiment in each group. (3) At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60% and 71.4% in group A, B and C respectively, which were much higher than that (10%) in group D (x2 > or = 5.03, P<0.05). An abnormal band of p53 gene was detected in both group A and C. (4) The mutation points of p53 gene in liver cancer of tree shrew were at codon 275, 78 and 13. The nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 showed 91.7% and 93.4% homology with those of human p53 respectively.

CONCLUSIONSThere is a remarkable synergistic effect between HBV and AFB1 on HCC. Mutated p53 protein is expressed before HCC occurrence, which promotes the development and progress of HCC. HBV and AFB1 may synergistically induce p53 gene mutation.

Aflatoxin B1 ; toxicity ; Animals ; Carcinoma, Hepatocellular ; genetics ; Cocarcinogenesis ; Gene Expression Regulation, Neoplastic ; Genetic Variation ; Hepatitis B ; virology ; Hepatitis B virus ; Liver Neoplasms, Experimental ; genetics ; Point Mutation ; RNA, Neoplasm ; analysis ; Tumor Suppressor Protein p53 ; genetics ; Tupaiidae

OBJECTIVETo investigate the enhancing effect of all-trans retinoic acid (ATRA) on the bystander effect of the herpes simplex virus thymidine kinase(HSV-TK)/ganciclovir (GCV) against androgen unresponsive prostate cancer.

METHODSThe bystander effect of the HSV-TK/GCV system was measured by methyl thiazolyl tetrazolium (MTT) assay on PC-3 cells before and after ATRA treatment. The growth and the histopathology of transplant tumors were observed in 4 groups of nude mice with prostate cancer.

RESULTSATRA augmented significantly the bystander effect of the HSV-TK/GCV system by reducing TK positive PC-3 cells from 50% to 30% (P < 0.05). HSV-TK showed an inhibiting effect, while ATRA with the HSV-TK/GCV system produced significant effect on prostate cancer 1 week earlier than the former (P < 0.05).

CONCLUSIONATRA can argument the in vivo and in vitro bystander effect of the HSV-TK/GCV system in the treatment of androgen unresponsive prostate cancer.

Animals ; Antineoplastic Agents ; pharmacology ; Bystander Effect ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Ganciclovir ; pharmacology ; Genes, Transgenic, Suicide ; genetics ; Genetic Therapy ; methods ; Humans ; Male ; Mice ; Mice, Nude ; Prostatic Neoplasms ; genetics ; pathology ; therapy ; Reverse Transcriptase Polymerase Chain Reaction ; Simplexvirus ; enzymology ; Thymidine Kinase ; genetics ; metabolism ; Tretinoin ; pharmacology ; Xenograft Model Antitumor Assays ; methods

AIMTo study the influence of astragalus and zinc sulfate on the viscosity in erythrocyte membrane during intestinal I/R and their mechanism of action.

METHODSModels of rabbits intestinal I/R injury were made. The effect of astragalus and zinc sulfate on the viscosity and malondialdehyde (MDA) in erythrocyte membrane, superoxide dismutase (SOD) in erythrocyte, oxidase (XO) in plasma and MDA tissues homogenate were observed.

RESULTSThe administration of astragalus and zinc sulfate decreased viscosity and MDA and XO, prevented the reduction of SOD, and alleviated I/R injury.

CONCLUSIONLipid peroxidation injury of the erythrocyte membrane was one of the pathogenesis of I/R injury, and astragalus and the zinc sulfate possessed effects of anti-lipid peroxide, stabilized erythrocyte membrane, increased red blood cell deform ability and raised microcircular perfusion.

Animals ; Astragalus Plant ; Blood Viscosity ; Drugs, Chinese Herbal ; pharmacology ; Erythrocyte Membrane ; drug effects ; Female ; Intestines ; blood supply ; pathology ; Lipid Peroxidation ; Male ; Malondialdehyde ; analysis ; Oxidoreductases ; analysis ; Rabbits ; Reperfusion Injury ; metabolism ; pathology ; Superoxide Dismutase ; analysis ; Zinc Sulfate ; pharmacology

OBJECTIVETo evaluate the mRNA and protein expressions of peroxiredoxin II (PrxII) in hepatocellular carcinoma (HCC) and their significance.

METHODSHCC was induced by aflatoxin B1 (AFB1) in 6 tree shrews (Tupaia belangeri chinensis). The expression levels of PrxII mRNA and protein were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot on HCC tissues and on their surrounding liver tissues (para-HCC). Biopsied liver tissues were taken before the HCC induction (pre-HCC) from the same animals and from a group of blank controlled animals that served as controls. Liver biopsy specimens from 18 cases of human HCC and from 17 healthy human volunteers were studied using the same methods.

RESULTSThe mRNA and protein expressions of PrxII in tree shrew HCC tissues were significantly higher than those in para-HCC and pre-HCC tissues, and also higher than those in the liver tissues from the control animals (all P < 0.05). The expression levels of PrxII mRNA and protein in human HCC tissues were also significantly higher than those in their para-HCC tissues and in the human normal liver tissues (P < 0.05).

CONCLUSIONPrxII might play an important role in hepatocarcinogenesis and might be used as a molecular target for HCC prevention and treatment.

Adult ; Aged ; Animals ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Female ; Humans ; Liver ; metabolism ; pathology ; Liver Neoplasms ; metabolism ; pathology ; Liver Neoplasms, Experimental ; metabolism ; pathology ; Male ; Middle Aged ; Peroxiredoxins ; genetics ; Tupaiidae

OBJECTIVETo explore the protective effects of ischemic preconditioning (IPC) on the lung injury following with limbs ischemia /reperfusion (LI/R).

METHODSThe models of LI/R injury were constructed in rabbits. The blood from right external jugular vein and left common carotid artery, into and out-flowing pulmonary blood (IPB, OPB) respectively. Superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) in IPB and OPB and lung tissues were measured, as well as total nitric oxide synthase (tNOS) and inducible nitric oxide synthase (iNOS) in lung tissues were detected in different groups. The effects of IPC on the lung injury were observed.

RESULTSCompared with sham and before ischemic, the activity of SOD decreased and the content of MDA and NO increased after 4 h ischemia followed by 4 h reperfusion in IPB, OPB and lung tissues. The activity of tNOS and iNOS in lung tissues increased remarkably as well, there was statistical significance (P < 0.05, P < 0.01). SOD increased and MDA, NO, tNOS, iNOS decreased significantly by IPC before ischemia/reperfusion. The correlation analysis indicated that MDA was negatively correlated with SOD and was positively correlated with MDA, NO, iNOS (P < 0.01).

CONCLUSIONOxygen free radicals metabolic confusion of lung occurred in the course of LI/R, IPC could strengthen the resistance of peroxidation in lung and had protective effects on the lung injury following with LI/R.

Animals ; Extremities ; blood supply ; Female ; Ischemic Preconditioning ; methods ; Lipid Peroxidation ; physiology ; Lung Injury ; metabolism ; physiopathology ; prevention & control ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rabbits ; Reperfusion Injury ; physiopathology ; Superoxide Dismutase ; metabolism