7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide ; toxicity ; Carcinogens ; toxicity ; Cell Line, Tumor ; DNA Damage ; drug effects ; Dose-Response Relationship, Drug ; HSP70 Heat-Shock Proteins ; biosynthesis ; Humans

Objective: To investigate the effects of oxLDL and HMG-CoA reductase inhibitor simvastatin on PKC activity, and level of cytosol ic free Ca 2+ in cultured human umbilical vein endothelial cells. Methods: Th e activity of PKC was determined by its ability to transfer phosphate from 32P-ATP to lysine-rich histone and level of cytosolic free calcium［Ca2+ ］i was measured by flow cytometric analysis loading with the Ca2+ dye F luo-3/Am. Results: oxLDL increased PKC total activity in a dose-de pendent manner and peaked after 12 min, then decreased slowly and maintained for at least 30 min, while oxLDL induced biphasic ［Ca2+］i responses includ ing the rapid initial transient phase and the sustained phase. Removal of extrac ellular Ca2+ did not inhibit the rapid transient phase, but abolished the sustained phase. When simvastatin was added, the activity of PKC wasmarkedly dec reased with no impairment to the initial peak response, but significantly reduce d the sustained phase. Conclusion: oxLDL can induced dynamic changes of signal transduction of PKC and level of cytosolic free Ca2+ in HUVEC, these 2 events are closely linked. The change of rapid initial transient phase i s the result of mobilization of Ca2+ from intracellular pool and the chang e of sustained phase is from the influx of extracellular Ca2+. The inhibit ion of PKC activity induced by simvastatin may contribute to the changes of ［Ca 2+］i.

BACKGROUNDClinical observations have shown that the complex fractionated atrial electrogram (CFAE) associates with ganglionated plexus activity in the cardiac autonomic nervous system. This study aimed to investigate the impact of CFAE ablation on vagal modulation to atria and vulnerability to develop atrial fibrillation (AF).

METHODSTen adult mongrel dogs were involved. Cervical sympathovagal trunks were decentralized and sympathetic effects were blocked. CFAE was color tagged on the atrial 3-dimensional image and ablated during AF induced by S1S2 programmed stimulation plus sympathovagal trunk stimulation. Atrial effective refractory period (ERP) and vulnerability window (VW) of AF were measured on baseline and at vagal stimulation at 4 atrium sites. Serial tissue sections from ablative and control specimens received hematoxylin and eosin staining for microscopic examination.

RESULTSMost CFAE areas were localized at the right superior pulmonary quadrant, distal coronary sinus (CS(d)) quadrant, and proximal coronary sinus (CS(p)) quadrant (21.74%, separately). Sinus rhythm cycle length (SCL) shortening did not decrease significantly after ablation at the sites, including right atrial appendage, left atrial appendage, CS(d), and CS(p) (P > 0.05). ERP shortening during vagal stimulation significantly decreased after ablation (P < 0.01); the VW to vagal stimulation significantly decreased after ablation (P < 0.05). The architecture of individual ganglia altered after ablation.

CONCLUSIONSCFAE has an autonomic basis in dogs. The decreased SCL and ERP shortening to vagal stimulation after CFAE ablation demonstrate that CFAE ablation attenuates vagal modulation to the atria, thereby suppressing AF mediated by enhanced vagal activity. CFAE ablation could suppress AF mediated by enhanced vagal activity.

Animals ; Atrial Fibrillation ; therapy ; Autonomic Nervous System ; Catheter Ablation ; methods ; Dogs ; Electrophysiologic Techniques, Cardiac ; methods ; Electrophysiology ; Female ; Male

Objective The aim of this study was to investigate the efficiency and safety of ibutilide for cardioversion of persistent atrial fibrillation (AF) during radiofrequency ablation.Methods Eighteen patients (16 males) with persistent atrial fibrillation were enrolled in this study.All patients underwent circumferential pulmonary vein ablation guided by a Carto three-dimensional mapping systen.In addition,linear ablation at the top of the left atrium and the isthmus of mitral valves and complex fractionated atrial electrogram (CAFE) ablation were performed.All patients were still in either atrial fibrillation or atrial flutter after ablation,the patients were treated with l mg intravenous ibutilide injection within 10 minutes after unsuccessful ablation.Intravenous injection was stopped in case of sinus rhythm (SR) restoration or occurrence of severe adverse reactions such as ventricular tachycardia.Cardioversion rate within 30 min and adverse reactions within 4 h were observed.Patients were divided into either conversion group or nonconversion group according to whether AF was converted to sinus rhythm within 30 minutes after injection.Results Eleven patients (61.11％ ) converted to SR after ibutilide injection.There were no significant differences in gender,age,body mass index,left atrium and left ventricular function between conversion group and non-conversion groups.The average conversion time was ( 13.80 + 7.64 ) min,left atrium scar area ratio was significantly larger in non-conversion group ( 12.40 + 11.03 ) ％ than in conversion group (5.12 ±3.83)％,P ＜0.05.Ibutilide significantly prolonged the average wavelength of the AF wave ( 171.8 + 29.5 ) ms vs.(242.0 ± 40.0) ms at baseline,P ＜ 0.01.The QT interval at 30 min after ibutilide injection (0.39 ± 0.21 ) s was significantly longer than before injection (0.51 ± 0.08 ) s,P ＜ 0.05.There was no serious arrhythmias or other adverse reactions post ibutilide injection.Conclusions Ibutilide is highly effective and safe agent for cardioversion in patients underwent unsuccessful ablation.Left atrium scar area ratio is an important determinant for the conversion rate in this cohort.

BACKGROUNDBased on the hypothesis that pulmonary vein isolation could result in the damage of the epicardial fat pads, this study aimed to investigated the impact of right upper pulmonary vein (RUPV) isolation on vagal innervation to atria.

METHODSBilateral cervical sympathovagal trunks were decentralized in 6 dogs. Metoprolol was given to block sympathetic effects. Multipolar catheters were placed into the right atrium (RA) and coronary sinus (CS). RUPV isolation was performed via transseptal procedure. Atrial effective refractory period (ERP), vulnerability window (VW) of atrial fibrillation (AF), and sinus rhythm cycle length (SCL) were measured at RA and distal coronary sinus (CSd) at baseline and vagal stimulation before and after RUPV isolation. Serial sections of underlying tissues before and after ablation were stained with haematoxylin and eosin.

RESULTSSCL decreased significantly during vagal stimulation before RUPV isolation (197 +/- 21 vs 13 +/- 32 beats per minute, P < 0.001), but remained unchanged after RUPV isolation (162 +/- 29 vs 140 +/- 39 beats per minute, P > 0.05). ERP increased significantly before RUPV isolation compared with that during vagal stimulation [(85.00 +/- 24.29) ms vs (21.67 +/- 9.83) ms at RA, P < 0.001; (90.00 +/- 15.49) ms vs (33.33 +/- 25.03) ms at CSd P < 0.005], but ERP at baseline hardly changed after RUPV isolation compared with that during vagal stimulation [(103.33 +/- 22.50) vs (95.00 +/- 16.43) ms at RA, P = 0.09; (98.33 +/- 24.83) vs (75.00 +/- 29.50) ms at CSd, P = 0.009]. The ERP shortening during vagal stimulation after RUPV isolation decreased significantly [(63.33 +/- 22.51) ms vs (8.33 +/- 9.83) ms at RA, P < 0.005; (56.67 +/- 20.66) ms vs (23.33 +/- 13.66) ms at CSd, P < 0.05]. AF was rarely induced at baseline before and after RUPV isolation (VW close to 0), while VW of AF to vagal stimulation significantly decreased after RUPV isolation [(40.00 +/- 10.95) vs 0 ms at RA, P < 0.001; (45.00 +/- 32.09) vs (15.00 +/- 23.45) ms at CS, P < 0.05]. The architecture of individual ganglia was significantly altered after ablation.

CONCLUSIONSThe less ERP shortening to vagal stimulation and altered architecture of individual ganglia after right upper pulmonary vein isolation indicate that isolation may result in damage of the epicardial fat pads, thereby attenuating the vagal innervation to atria. The decreased vulnerability window of atrial fibrillation indicates that vagal denervation may contribute to its suppression.

Animals ; Atrial Fibrillation ; etiology ; physiopathology ; surgery ; Dogs ; Female ; Ganglia ; pathology ; Heart Atria ; innervation ; Male ; Pulmonary Veins ; surgery ; Refractory Period, Electrophysiological ; Vagus Nerve ; physiology

BACKGROUNDAll-trans retinoic acid (ATRA) can influence the tumor cell proliferation cycle, and some chemotherapeutic drugs are cycle specific. In this study, we hypothesize that ATRA can enhance chemotherapeutic drug sensitivity by affecting the cell cycle of tumor cells.

METHODSThe cell cycle of LoVo cells was evaluated using flow cytometry (FCM). Cell viability was analyzed using the MTT assay. The morphologic changes in the treated LoVo cells were measured with acridine orange (AO)/ethidium bromide (EB) staining. Expression of survivin in LoVo cells was analyzed by immunofluorescence assay.

RESULTSAfter LoVo cells were treated with ATRA, the G0/G1 ratio of the tumor cells increased and the cell ratio of S- and G2/M-phase decreased. Viability of the cells decreased significantly after combined treatment with ATRA and 5-fluorouracil (5-FU) or mitomycin c (MMC) and was evaluated by fluorescence microscopy. Expression level of survivin in the tumor cells decreased after ATRA combination treatment.

CONCLUSIONSATRA enhances drug sensitivity of the LoVo cell line to cell cycle-specific agents and inhibits the expression of survivin in LoVo cells. The combination of ATRA and 5-FU or MMC promoted cell apoptosis, and the mechanism involved in apoptosis may be related to inhibition of survivin gene expression.

Cell Line, Tumor ; Colonic Neoplasms ; drug therapy ; metabolism ; Drug Resistance, Neoplasm ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins ; genetics ; Neoplasm Proteins ; genetics ; Tretinoin ; pharmacology

OBJECTIVETo compare Cirsium japonicum characteristics with C. leo and C. leducei, along with the content of buddleoside and pectolinarin, and lay the foundation for the quality control of C. japonicum.

METHODSamples were collected and the relevant drugs were bought. The samples were divided into root, stem, leaf and flower, and the content of buddleoside and pectolinarin was determine by the HPLC. Chromatographic column: Waters XBridge C18 (4.6 mm x 250 mm), mobile phase: methanol-water (45: 55), measurement wavelength: 326 nm, flow rate: 0.8 mL x min(-1), column temperature: 30 degrees C. RESULT AND CONDUSION: Standard curve equation of buddleoside: Y = 74 064X-47 748, R2 = 0.991. Standard curve equation of pectolinarin: Y = 1 711 64X - 180 707, R2 = 0.999. The content of buddleoside: C. japonicum leaf was 1.987 3%, C. leo leaf 1.412 2%, C. leducei leaf 0.149 2%. The content of buddleoside was lower in root and stem. Pectolinarin was not detected in the C. japonicum and C. leo. The pectolinarin content was 0.069 0% in C. leducei leaf.

Chromatography, High Pressure Liquid ; Chromones ; analysis ; chemistry ; Cirsium ; chemistry ; Drugs, Chinese Herbal ; analysis ; chemistry ; Reproducibility of Results ; Solubility ; Species Specificity

OBJECTIVETo study the difference of gene expression profile among colorectal cancer tissue, pericancerous mucosa and normal mucosa, and to screen associated novel genes in colorectal carcinogenesis by DNA microarray.

METHODScDNA chip containing approximate 8000 genes was used to detect differentially expressed genes in colorectal cancer tissues, pericancerous mucosa and normal mucosa, and to screen associated novel genes in colorectal carcinogenesis by DNA microarray.

RESULTSAs compared with normal mucosa, 769 genes differentially expressed in cancerous tissue were identified, which included 363 up-regulated and 406 down-regulated genes. In pericancerous mucosa 3 cm away from cancerous tissues, 155 genes differentially expressed were identified, of whom 52 genes were up-regulated and 103 were down-regulated. In pericancerous mucosa 5 cm away from cancerous tissues, 230 genes differentially expressed were identified, of whom 46 genes were up-regulated and 184 genes were down-regulated. The genes expressed differentially were associated with several functional types. According to the primary results, the differentially expressed genes with prominent functions included tumor-related genes, genes regulating cell proliferation and apoptosis, transcriptional control genes, and construction and degradation of extracellular matrix-associated genes. The cancerous mucosa was obviously different from the normal mucosa(about 20%, 769/3944). The differences between the normal mucosa and pericancerous mucosa were relatively small (3.9%,5.8%).

CONCLUSIONSDifferent tissues have their own biological property. Several genes play roles in the development of colorectal carcinogenesis. Genes in adjacent non-cancerous tissues are also expressed differentially, leading to a malignant change.

Colorectal Neoplasms ; genetics ; pathology ; DNA, Complementary ; genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; methods

OBJECTIVETo investigate whether ulinastatin can alleviate the side effect in patients with gastrointestinal cancer undergoing adjuvant chemotherapy,and to explore the probable mechanism of its protective efficacy.

METHODSForty consecutive patients with gastrointestinal cancer who underwent surgical operations from May 2004 to October 2004 were recruited. The patients were randomly divided into therapeutic group and control group, receiving ulinastatin 150,000 U per day or 250 ml hydrochloric sodium before chemotherapy for 5 continuous days respectively. The prevalence of side effects and the levels IL-6 and TNF-alpha were compared between the two groups.

RESULTSThere were no differences in the clinicopathological characteristics between the two groups. The prevalences of white blood cell decline (41.2% versus 13.1%), pigmentation (23.5% versus 4.3%), baldness (17.6% versus 4.3%) were higher in the control group than those in therapeutic group (all P< 0.05). In therapeutic group, IL-6 level was significantly decreased after ulinastatin treatment, but not in the control group while the levels of TNF-alpha were not changed in the both groups.

CONCLUSIONUlinastatin can reduce the common side effects of chemotherapy, and the mechanism may be associated with the decrease of IL-6.

Aged ; Chemotherapy, Adjuvant ; methods ; Female ; Gastrointestinal Neoplasms ; drug therapy ; Glycoproteins ; therapeutic use ; Humans ; Interleukin-6 ; blood ; Male ; Middle Aged ; Postoperative Period ; Tumor Necrosis Factor-alpha ; blood

Aged ; Atrial Fibrillation ; surgery ; Catheter Ablation ; adverse effects ; Humans ; Male ; Pulmonary Veno-Occlusive Disease ; etiology ; therapy