ADM Group Research Articles

Effects of propofol and sevoflurane on adriamycin chemotherapy-induced myocardial damage in rats

Objective To investigate the effects of propofol and sevoflurane on adriamycin chemotherapy-induced myocardial damage in rats. Methods Twenty-four healthy male Wistar rats, aged 3 months, weighing 212–270 g, were randomly divided into 4 groups (n = 6 each) using a random number table: control group (group C), adriamycin group (group ADM), adriamycin-propofol group (group ADM-Pro), and adriamycin-sevoflurane group (group ADM-Sevo). The equal volume of normal saline was injected intraperitoneally in group C. In group ADM, adriamycin 2.5 mg/kg was injected intraperitoneally once every other day for 6 times (11 days in total). In group ADM-Pro, adriamycin 2.5 mg/kg was injected intraperitoneally once every other day for 6 times, and at 3 days after the last administration of adriamycin, propofol anesthesia was performed as follows: the total amount of propofol injected intraperitoneally was 200 mg/kg, the initial dose was 100 mg/kg, and 1 h later the remaining amount was added, and the duration of anesthesia was about 2 h. In group ADM-Sevo, adriamycin 2.5 mg/kg was injected intraperitoneally once every other day for 6 times, and at 3 days after the last administration of adriamycin, sevoflurane anesthesia was performed as follows: 1.5%–3.0% sevoflurane was inhaled for 2 h. After the end of anesthesia, blood samples were collected for determination of serum cardiac troponin (cTnI) concentrations.Myocardial specimens were collected for detection of caspase-3 expression by immuno-histochemistry. Results Compared with group C, the serum cTnI concentration was significantly increased, and the caspase-3 expression was up-regulated in ADM, ADM-Pro and ADM-Sevo groups (P 0.05). Conclusion Propofol and sevoflurane both can mitigate adriamycin chemotherapy-induced myocardial damage in rats, without significant difference in the efficacy. Key words: Doxorubicin; Propofol; Anesthetics, inhalation; Drug toxicity

Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism.

The pulmonary vasodilation induced by adrenomedullin may be beneficial in the acute pulmonary embolism (APE) setting. This study examined effects of adrenomedullin in sheep with microsphere-induced APE. Twenty four anesthetized, mechanically ventilated sheep were randomly assigned into 3 groups (n=8 per group): animals not subjected to any intervention (Sham), animals with APE induced by microspheres (500 mg, intravenously) treated 30 min later by intravenous physiological saline (Emb group) or intravenous adrenomedullin (50 ng/kg/min) during 30 min (Emb+Adm group). Plasma concentrations of cyclic adenosine (cAMP) and guanosine monophosphate (cGMP) were determined by enzyme immunoassay. Variables did not change over time in sham animals. In both embolized groups, microsphere injection significantly (P<0.05) increased pulmonary vascular resistance index (PVRI) and mean pulmonary artery pressure (MPAP) from baseline by 181% and 111-142%, respectively (% change in mean values). Adrenomedullin significantly decreased PVRI (18%-25%) and significantly increased cardiac index (22%-25%) from values recorded 30 min after APE (E30), without modifying MPAP. Adrenomedullin decreased mean arterial pressure (18%-24%) and systemic vascular resistance index (32%-40%). Embolization significantly increased arterial-to-end tidal CO2 gradient, alveolar-to-arterial O2 gradient, and pulmonary shunt fraction from baseline, but these variables were unaffected by adrenomedullin. While adrenomedullin significantly increased plasma cAMP, cGMP levels were unaltered. Adrenomedullin induces systemic and pulmonary vasodilation, possibly via a cAMP mediated mechanism, without modifying the gas exchange impairment associated with APE. The pulmonary anti-hypertensive effect of adrenomedullin may be offset by increases in cardiac index.

Itraconazole Combined with Daunorubicin Synergistically Inhibit Proliferation and Enhance Apoptosis on KG-1a Cell Line through the Suppression of Hedgehog Pathway

Background:Itraconazole is widely used as antifungal drug. It was recently found to be a potent antagonist of the Hedgehog (Hh) signaling pathway. Due to its inhibition of Hedgehog singling, it may prove beneficial in the treatment of hematological malignancies when combined with chemotherapy.Objective To explore the effect of single itraconazole and in combination with daunorubicin on the growth, apoptosis and expression of shh and Gli1 of acute myeloid leukemia cell line KG1α.Methods Different concentrations of itraconazole (ITC), daunorubicin (DNR) and IC30 concentration of daunorubicin (0.73 μΜ) in combination with different concentrations of itraconazole (2, 6,15μΜ) were added to acute myeloid leukemia cell line KG1α. Cell proliferation activity were detected with CCK8 method after cultivating for 48h. Cell apoptosis rate, mitochondria injury and cell cycle arrest condition were detected 48 hours after the action with single drug or drug combination with flow cytometry. Clone forming experiment was performed to detect the clone forming ability of KG 1α continuously treated with the drug. 46 kinds of apoptosis related protein were detected by protein array. Expression of shh and Gli1 were detected by Western Blot.Results: The detected KG1α cell proliferation inhibition rate increased with the increase of the concentration of daunorubicin and itraconazole. The combination of DNR 0.73μΜ and ITC 6μΜ showed synergistic effect; The apoptosis rate in two drug combination group was of statistical difference compared with that of ADM 0.73μM group and ITC 6μM group (P<0.01). Mitochondria injury showed that the P2/P3 ratio in single ADM and ITC group was significantly lower than that of the combination group (P<0.05). DNR arrested the cells in G2 phase, while ITC arrested cells in G1 phas; the two drugs combination significantly arrested cells in G2 phase, with statistical difference. Protein array showed significantly decrease of apoptosis inhibit factor Xiap and increase of apoptosis induce factor Smac in the combination group. ITC inhibited cell’s clone forming ability, and down-regulated the expression of shh and Gli1.Conclusion: Itraconazole or in combination with daunorubicin may inhibit KG1α cell proliferation, induce mitochondria injury and apoptosis, which might be caused by the suppression of Hedgehog signal pathway related protein. DisclosuresLiu:It was supported by National Natural Science Foundation of China (81270647, 81300445, 81200388); National High Technology Research and Development Program of China (863 Program) (2011AA020105); National Public Health Grand Research Foundation (201202017);: Research Funding; It was supported by Natural Science Foundation of Guangdong Province (S2012010009299); the project of health collaborative innovation of Guangzhou city (201400000003-4, 201400000003-1);: Research Funding; It was supported by the Technology Plan of Guangdong Province of China (2012B031800403); the project of the Zhujiang Science & Technology Star of Guangzhou city (2013027).: Research Funding.

Clinical evaluation of coronally advanced flap with or without acellular dermal matrix graft on complete defect coverage for the treatment of multiple gingival recessions with thin tissue biotype

The objective of this study was to compare acellular dermal matrix graft (ADM) combination with coronally advanced flap (CAF) on complete defect coverage, aesthetics and patient satisfaction with CAF alone for multiple recessions with gingival thickness (GT) <0.8 mm. Forty-eight Miller Class I multiple recessions ≥3 mm were divided into test (CAF + ADM) and control (CAF) groups. At baseline and 12 months, recession height (RH), keratinized tissue height (KT), GT, mean and complete defect coverage were evaluated. Patient satisfaction, root coverage aesthetic score (RES) and the correlation between GT and defect coverage were also assessed. Baseline RH in CAF + ADM and CAF groups was 3.25 ± 0.34 mm and 3.21 ± 0.26 mm, respectively. Mean and complete defect coverage were 94.84% and 83.33% in test group, 74.99% and 50.00% in control group, respectively. Inter-group differences were found to be statistically significant for RH reduction, attachment gain, KT and GT increase, mean defect coverage and RES in favour of test group (p < 0.05). There was a significant positive correlation between GT and mean defect coverage (p < 0.05). Coronally advanced flap in association with ADM can be proposed as a valid approach for the treatment of multiple recessions with thin tissue biotype.

Commercially available biological mesh does not prevent stricture after esophageal mucosectomy

Endoscopic mucosal resection (EMR) offers a minimally invasive therapy for advanced esophageal dysplasia and early cancers but stricture formation limits its applicability. We aimed at assessing the efficacy of placement of a commercially available biological mesh for preventing stricture formation following esophageal EMR. 25 swine were submitted to circumferential esophageal EMR with 10-cm extent and divided in five groups: one group with EMR only (control); one receiving an uncovered stent (stent-only group); and three groups receiving a stent covered with one of three extracellular matrices, namely small intestine submucosa (SIS group), acellular dermal matrix (ADM group), or urinary bladder matrix (UBM group). Stricture formation was evaluated with weekly esophagograms. The stent-only group had significantly less stricture formation and survival was extended compared with controls (4.8 vs. 2.4 weeks). Compared with stenting only, the addition of a biological mesh did not reduce stricture formation: percent reductions in esophageal diameter for the groups were SIS 86 %, ADM 94 %, and UBM 94 %, compared with 82 % in the stent-only group. Placement of commercially available biological meshes did not alter remodeling sufficiently to prevent stricture formation after esophageal EMR.

Early complications and implant loss in implant-based breast reconstruction with and without acellular dermal matrix (Tecnoss Protexa®): A comparative study

IntroductionAcellular dermal matrix (ADM) may improve outcomes in implant-based breast reconstruction, but recent evidence suggests complication rates may be higher when ADM is used. We retrospectively compared early complications and implant loss in implant-based breast reconstruction (BR) with and without ADM to evaluate the safety of the procedure in our centre. MethodsCase-notes of consecutive women undergoing implant-based BR from May 2011 to November 2012 were retrospectively reviewed. Data were extracted using a standardised pro-forma and the rate of early complications, major complications and implant loss compared between procedure groups. ResultsForty-six implant-based reconstructions were performed for malignancy (n = 31, 67.4%) or prophylaxis (n = 15, 32.6%) in 31 women over the 18-month study period. ADM (Tecnoss Protexa®, Tecnoss S.r.l.) was used in 31 (67.4%) cases. There were no differences in patient age, BMI, co-morbidities, smoking or chemotherapy between groups, but patients receiving ADM were more likely to have received radiotherapy prior to their reconstruction (n = 6, 30% vs. n = 0, 0%, p = 0.043).The overall rate of early complications was 26.1% (n = 12) but there was no significant difference between procedure groups (standard-n = 4, 27.7% vs. ADM-n = 8, 25.8%; p = 0.950). There were 2 (4.3%) major complications none of which were associated with ADM use (standard-n = 2, 13.3% vs. ADM-n = 0, 0.0%; p = 0.038). There were 6 (13.0%) implant losses of which 4 were in the ADM group (standard-n = 2, 13.3% vs. ADM-n = 4, 12.9%; p = 0.968). All of these were associated with pre-reconstruction radiotherapy. ConclusionsADM-assisted implant-based reconstruction with Tecnoss Protexa® is safe and may improve outcomes for women by facilitating a single-stage procedure. Robust prospective evaluation is now needed to definitively evaluate the role of ADM in implant-based BR.

Protective effect of melatonin against Adriamycin-induced cardiotoxicity

The aim of this in vivo study was to explore the protective properties of melatonin against Adriamycin-induced myocardial toxicity. A rat model of breast cancer was established and the rats were randomly divided into the blank group (Blank), the solvent group [Diss; dehydrated alcohol: physiological saline (1:9)], the Adriamycin group (ADM), the melatonin group (MLT) and the melatonin + Adriamycin group (M+A). The concentrations of lipid peroxide (LPO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in myocardial tissues were detected, the changes in myocardial tissues were observed using light microscopy and electron microscopy, and the 1-month survival rates of each group of rats were compared. Breast cancer was established in 116 rats. In the ADM group, the concentration of LPO was higher and the concentrations of SOD and GSH-Px were significantly lower than those in the blank group. In the M+A group, compared with the ADM group, the concentration of LPO was lower (P<0.05) and the concentrations of SOD and GSH-Px were higher (P<0.05). It was observed using light and electron microscopy that the myocardial injuries to the M+A group were significantly alleviated in comparison with those in the ADM group; the 1-month survival rate in the M+A group was higher than that in the ADM group. Melatonin may have a protective role in the myocardium by reducing Adriamycin-induced myocardial oxidative damage.

Corpus callosum shape changes in early Alzheimer’s disease: an MRI study using the OASIS brain database

The corpus callosum (CC) is the largest fiber bundle connecting the left and right cerebral hemispheres. It has been a region examined extensively for indications of various pathologies, including Alzheimer's disease (AD). Almost all previous studies of the CC in AD have been concerned with its size, particularly its mid-sagittal cross-sectional area (CCA). In this study, we show that the CC shape, characterized by its circularity (CIR), may be affected more profoundly than its size in early AD. MRI scans (n = 196) were obtained from the publicly available Open Access Series of Imaging Studies database. The CC cross-sectional region on the mid-sagittal section of the brain was automatically segmented using a novel algorithm. The CCA and CIR were compared in 98 normal controls (NC) subjects, 70 patients with very mild AD (AD-VM), and 28 patients with mild AD (AD-M). Statistical analysis of covariance controlling for age and intracranial capacity showed that both the CIR and the CCA were significantly reduced in the AD-VM group relative to the NC group (CIR: p = 0.004; CCA: p = 0.005). However, only the CIR was significantly different between the AD-M and AD-VM groups (p = 0.006) being smaller in the former. The CCA was not significantly different between the AD-M and AD-VM groups. The results suggest that CC shape may be a more sensitive marker than its size for monitoring the progression of AD. In order to facilitate independent analyses, the CC segmentations and the CCA and CIR data used in this study have been made publicly available (http://www.nitrc.org/projects/art).

Effects of continuous intermedin infusion on blood pressure and hemodynamic function in spontaneously hypertensive rats

ObjectiveTo examine the effects of exogenously administered intermedin (IMD, adrenomedullin-2) on arterial blood pressure, cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats (SHRs) as well as to investigate the associated mechanisms.MethodsThirteen week-old male rats were divided in Wistar Kyoto (WKY) group (n = 12), SHR group (n = 12), IMD group (SHRs infused with IMD 1-47 500 ng/kg per hour, n = 12), and ADM group (SHRs infused with adrenomedullin 500 ng/kg per hour, n = 12).ResultsA two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure, the maximal rates of increase and decrease of left-ventricle pressure development (LV ± dp/dtmax), left ventricular systolic pressure and heart rate in SHRs. Furthermore, IMD also inhibited protein over-expression of cardiovascular IMD receptors, myocardial Receptor Activity-Modifying Proteins (RAMP1 and RAMP2), aortic RAMP1, RAMP2, RAMP3, and calcitonin receptor-like receptor (CRLR); suppressed up-regulation of aortic RAMP1, RAMP2, RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide (ANP) and myocardial brain natriuretic peptide (BNP). Additionally, IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.ConclusionThese findings support the speculation that IMD, as a cardiovascular active peptide, is involved in blood pressure reduction and cardiac function amelioration during hypertension. The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR, and consequential regulation of cAMP levels and other cardiovascular active factors, such as ANP and BNP.

Efficacy of lamivudine and adefovir de novo combination therapy or after mono-therapy in chronic hepatitis B patients

To investigate the efficacy of 104 weeks of lamivudine (LAM) and adefovir (ADV) de novo combination therapy, as compared to optimized combination therapy administered after 48 weeks of treatment with lamivudine or adefovir mono-therapy, in chronic hepatitis B (CHB) patients. A total of 174 patients with CHB were equally divided among three treatment groups: LAM mono-therapy; ADV mono-therapy; and LAM + ADV combination therapy. The patients in the LAM + ADV group were treated with LAM plus ADV for 104 consecutive weeks. The patients in the LAM or the ADV groups were first treated for 48 weeks with LAM or ADV, respectively, after which the patient's virological response was assessed. According to the results, the patient was continued on mono-therapy or switched to combination therapy for the subsequent 56 weeks. Virological and biochemical examinations were carried out at weeks 48 and 104. The rates of undetectable HBV DNA in the LAM mono-therapy, ADV mono-therapy, and LAM-ADV combination therapy groups at week 48 were 68%, 50%, and 84%, and at week 104 were 80%, 72%, and 95%, respectively. For the same groups, the virus breakthrough rates at week 48 were 15%, 0%, and 0%, and at week 104 were 18%, 2%, and 0%, respectively. Statistical analysis showed significant differences for the rate of undetectable HBV DNA between LAM + ADV group and LAM group at week 48 (x2 = 4.473, P= 0.034) and at week 104 (x2 = 5.795, P = 0.016), LAM + ADV group and ADM group at week 48 (x2 = 14.802, P less than 0.001) and week 104 (x2 = 5.547, P = 0.001). The hepatitis B e antigen (HBeAg) seroconversion rates at week 48 were 15% (x2 = 4.543, P = 0.033), 13% (x2 = 4.035, P = 0.045) and 38%, and at week 104 were 21% (x2 = 4.438, P = 0.035), 17% (x2 = 4.223, P = 0.04) and 44%, respectively, among patients positive for HBeAg. Statistical analysis showed that the differences among the three groups for each of these parameters were statistically significant (all, P less than 0.05). When compared with LAM or ADV mono-therapy followed by LAM+ADV at week 48, the LAM plus ADV de novo combination therapy for 104 weeks provided CHB patients with better virological and serological responses and a lower drug resistance rate.

Treatment of Lymphoma in Mice by Intravenous Administration of Vesicular Stomatitis Virus Matrix Protein Gene Encapsulated in Cationic Liposome

Abstract 4712 Background and Objective□FVesicular Stomatitis Virus (VSV) is an enveloped, negativesense RNA virus and prototypic member of the family rhabdoviridae. Some studies have shown that VSV can dissolve tumor cells with oncolytic effect. It has been reported that VSV can infect a variety of tumor cell lines such as glioma, melanoma, hepatocellular carcinoma, breast cancer and prostate cancer, and also demonstrated the antitumor effects on these tumors. Mechanism involving these effects was found that VSV can inhibit host gene expression, to induce cell rounding and to induce apoptosis. However, there is no report of such antitumor effect on lymphoma. Matrix Protein, the most important structural component of VSV, can also induce apoptosis of tumor cells even in absence of other component of VSV. Liposome is a promising non-viral gene vector, which can protect the DNA in vivo escape from degradation of the nuclease, and assist the DNA to penetrate the cell wall, together with the exogenous DNA into the cells. Cationic liposome has displayed high transfection efficiency, low cytotoxicity, no immunogenicity, and it also can improve the drug stability. In the present study, we established EL4 lymphoma model in mice, to explore the antitumor effects in vivo of a recombinant plasmid of pcDNA3.1-Matrix Protein of VSV complexed with cationic liposome in mice with EL4 lymphoma and potential mechanism. Methods□FThe plasmid DNA encoding Matrix Protein of VSV (P-M) has been constructed. Then the recombinant plasmid encapsulated with cationic liposomes, vectors of transfection, was generated. After the lymphoma model was established in sixty C57BL/6 mice by injecting EL4 tumor cells subcutaneouly into the right flank of mice, the mice bearing EL4 lymphoma were divided randomly into five groups including Lip-MP group, Lip-pVAX group, Lip group, ADM group and NS group, which were intravenously injected with liposome-pcDNA3.1 MP complex, liposome-pVAX complex, empty liposome, Adriamycin and normal saline, respectively, every three days in 3 weeks period of time. The side effects, tumor volumes and survival were monitered regularly. After the mice were sacrificed, microvessel density and tumor proliferation index in tumor tissues were determined by CD31, Ki-67 immunohistochemistry staining, meanwhile the tumor apoptosis index was measured by TUNEL method. Results□FSix days after treatments, the tumor volumes in Lip-MP group of C57BL/ 6 mice bearing EL4 lymphoma gradually became much smaller than those in Lip-pVAX, Lip and NS groups (P<0.05). At the 31st day after tumor cell injection, the tumor growth inhibition rates were (70.14±7.56)% in Lip-MP group, (21.67±7.66)% in Lip-pVAX group, (17.43±9.60)% in Lip group, (76.33±3.61)% in ADM group, respectively. The median survival of mice in Lip-MP group, 44 days after inoculation of tumor cells, was significantly longer than those in control groups (P<0.05), the median survival in Lip-pVAX, Lip and NS groups being 39 days, 38.5 days and 34 days, respectively. The MVD values in tumor tissues determined by CD31 staining were 11.38±2.92 in Lip-MP group, 20.13±3.40 in Lip-pVAX group, 27.50±3.16 in Lip group, 14.88±4.02 in ADM group and 33.25±3.11 in NS group, respectively. The MVD values in Lip-MP group were less than those in Lip-pVAX, Lip and NS groups (P<0.05). The proliferation index determined by Ki-67 staining in tumor tissues were (31.07±4.31)% in Lip-MP group, (42.45±4.04)% in Lip-pVAX group, (61.04±8.24)% in Lip group, (29.21±3.05)% in ADM group and (81.19±6.12)% in NS group, respectively. It revealed that Lip-MP complex apparently suppressed the proliferation of EL4 tumor cells in vivo(P<0.05). TUNEL assays showed that apoptosis index of tumor cells were 10.60±1.71 in Lip-MP group, 4.93±1.36 in Lip-pVAX group, 3.35±0.94 in Lip group, 4.51±1.10 in ADM group and 2.27±0.25 in NS group, respectively. The apoptosis index in Lip-MP group was higher than those in other control groups (P<0.05). Conclusions□FLip-MP complex, the plasmid encoding Matrix Protein of Vesicular Stomatitis Virus (VSV-MP) encapsulated in cationic liposome, may significantly inhibit the growth of lymphoma and prolong the survival of mice bearing EL4 lymphoma without any obvious side effects. Furthermore, inducing tumor cell apoptosis, inhibiting tumor angiogenesis, and suppressing tumor cell proliferation by Lip-MP complex may contribute to these antitumor effects in vivo. Disclosures:No relevant conflicts of interest to declare.

E3330 Enhanced Antitumor Effect of Adrinmycin on Human Extranodal Nasal-Type NK/T Cell Lymphoma Xenografted–Nude Mice

Abstract 2723 Abstract:Extranodal Nasal-Type NK/T Cell Lymphoma (EN-NK/T-L) is a distinct clinicopathological entity of non-Hodgkin’s lymphoma, which is characterized by a highly aggressive clinical process and poor prognosis especially when disseminated or recurrent after radiotherapy. Human purinic/apyrimidinic endonuclease/redox factor-1 (hAPE/Ref-1) is a multifunctional protein involved in the repair of DNA damaged by oxidative. Because of its involvement in DNA repair and apoptosis-related signaling mechanisms, APE/Ref-1 is also being discussed as a novel target for tumor-therapeutic approaches. In studies, high level of APE1 expression is associated with an resistance to chemotherapeutic agents and adverse prognosis. And recent studies show that E3330, a small molecule inhibitor of the Ape-1/Ref-1 redox domain, induce inhibition of growth in cancer cell in vitro by specific inhibiting the function of APE/REF-1. E3330 blocks the in vitro growth of pancreatic cancer-associated endothelial cells(J Cell Physiol. 2009 Apr;219(1):209–18.) and of the NK/T-cell lineage in our sdudy already and provides a potential therapeutic strategy in tumor. Thus far, no study has reported the experimental research on E3330 combined with chemotherapy in treating NK/T cell lymphoma. Therefore, we try to establish xenografted-nude mice model of human extranodal nasal type NK/T cell lymphoma and to investigate the effect of E3330 combined with adrinmycin on the human EN-NK/T-L xenografted-nude mice and its mechanism. Methods: EN-NK/T-L Xenografted-nude mice model was established by intraperitoneal injection of NK/T cell lymohoma cells SNK-6. IC50 of E3330 for SNK-6 was calculated according to the result of MTT assay. Xenografted- nude mice were divided into four groups: Control group were given equal volume sodium,po,d1-7□ G E3330 group were given E3330, 6mg/kg, po, d1-7□ GADM group were given ADM, 0.5mg/kg, ip,d1,4,7□ GE3330 + ADM group were given both E3330 and ADM, E3330, 6mg/kg, po, d1-7, ADM 0.5mg/kg, ip, D1,4,7. The tumor weight and the survival rate of tumor–bearing mice were assayed, the apoptosis cells were determined by TdT-mediated Dutp Nick-end-Labeling(Tunel). Immunohistochemistry were used to study the expression of ki-67. Immunofluorescence were used to study the expression of APE/REF-1. Results: Nude mice model of human extranodal nasal type NK/T cell lymphoma was established successfully. The results showed that the expression level of APE/REF-1 was higher in tumor tissues compared with that in normal tissues (Fig 1 A 1B). The transplanted tumor volumes of mice were significantly smaller in E3330 + ADM group than those in other three groups(p<0.05)(Table 1). The expression of ki-67 in E3330 + ADM group was lower than other groups(p<0.05) (Fig 2 A 2B 2C 2D) and the apoptosis cells were increased in the same group (Table 2). Conclusion: Our study showed that E3330 + adrinmycin can significantly inhibit the growth of transplanted tumor of extranodal nasal type NK/T cell lymphoma Xenografted-nude mice. Disclosures:No relevant conflicts of interest to declare.

The effect of sepsis serum on intercellar adhesion molecule-1 of rat intestinal mucosa microvascular endothelial cells and the intervention of Adrenomedullin

：Objective To observe thelevels of intercellar adhesion molecule-1(ICAM-1)of rat intestinal mucosa microvascularendothelial cells in sepsis rat,and to investigate the possible protective effect ofadrenomedullin on the expression of intercellar adhesion molecule-1(ICAM-1)of ratintestinal mucosa microvascular endothelial cells,and to confirm whether adrenomedullincan decrease released inflammatory factors to slow down or inhibit the occurrence anddevelopment of sepsis.Methods The rat intestinal mucosa microvascular endothelial cellswere isolated and cultured in vitro,and it was divided into sham operated(sham operatedserum),sepsis serum(with addition of sepsis serum)and ADM serum(with 0.lng/kgadrenomedullin 6h after sepsis treatment)groups.The soluble ICAM-1(sICAM-1)content inRIMMVECs culture supernatant was measured by ELISA at the 24th hour after serumstimulation.Results The ICAM-1 content in the supernatant of sepsis group [(0.33 ±0.04)ng/L]was obviously higher than that in sham operated [(0.15 ± 0.02)ng/L] and ADM [(0.17 ±0.04)ng/L] group(P ＜ 0.05),but ADM group was nosignificantly different compared with sham operated group(P ＞0.05).Conclusions ADM could decrease theexpression of ICAM-I in RIMMVECs,and the low level of ICAM-1 could suppress its downstreaminflammation factors and inhibit the occurrence and development of sepsis. Key words: Sepsis/BL/ME/DT; Intercellular adhesion molecule-1/ME; Endothelium,vascular/ME; Adrenomedullin/PD

The Effect of Acellular Dermal Matrix Use on Complication Rates in Tissue Expander/Implant Breast Reconstruction

Tissue expander/implant breast reconstructions by 5 surgeons at a single institution from 2005 to 2008 were retrospectively identified and divided into 2 cohorts: use of acellular dermal matrix (ADM, n = 75) versus standard submuscular placement (n = 52). The ADM group had a statistically significant higher rate of infection (28.9% vs. 12.0%, P = 0.022), reoperation (25.0% vs. 8.0%, P = 0.011), expander explantation (19.2% vs. 5.3%, P = 0.020), and overall complications (46.2% vs. 22.7%, P = 0.007). When stratifying by breast size, a higher complication rate was not observed with the use of ADM in breasts less than 600 g, whereas ADM use in breasts larger than 600 g was associated with a statistically significant higher rate of infection when controlling for the occurrence of skin necrosis. The ADM cohort had a significantly higher mean initial tissue expander fill volume (256 mL vs. 74 mL, P < 0.001) and a significantly higher mean initial tissue expander fill ratio (49% vs. 17%, P < 0.001). Further work is needed to define the ideal patient population for ADM use in tissue expander/implant breast reconstruction.

Transcatheter arterial chemoembolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma

To evaluate the efficacy of transcatheter arterial chemoembolization (TACE) using a suspension of a fine-powder formulation of cisplatin (DDPH) for hepatocellular carcinoma (HCC). The study population was comprised of 164 patients who were treated by TACE alone. Of these patients, 76 underwent TACE using a suspension of DDPH in lipiodol (LPD) (DDPH group), and the remaining 88 underwent TACE with an emulsion of doxorubicin (ADM) with LPD (ADM group). We compared the DDPH group with the ADM group in terms of the objective early response rate, progression free survival (PFS) and overall survival (OS). The objective early response rate in the DDPH group was significantly higher than that in the ADM group (54% vs 24%, P < 0.001). The PFS rate in the DDPH group was also significantly higher than that in the ADM group (P < 0.001). Moreover, the OS in the DDPH group was significantly longer than that in the ADM group (P = 0.002). Although the incidence rate of nausea or vomiting in the DDPH group was higher than that in the ADM group, the ADM group showed a higher incidence rate of the adverse events of hepatic arterial damage and leucopenia. No other serious complications were observed in either group. We conclude that TACE using a suspension of DDPH in LPD could be a useful treatment for HCC.

Protection effect of thrombopoietin on adriamycin-induced cardiotoxicity in rats.

Objective To observe the protection effect of thrombopoietin on adriamycin-inducod acute myocardium injury in rats model.Methods 32 Wistar rats were randomized into four groups (n=8):Control group,ADM group,ADM +TPOL group and ADM +TPOH group.All agents were given by intraperitoneal injection.The control group was given normal saline,while the other three groups were given adriamycin at the dosage of 20 mg/kg once.TPO groups were injected TPO at different dosages of 10 μg/kg or 30 μg/kg three times on alternate days.ELISA was used to detect CK-MB and cTnI content of serum in the rats.By HE staining,pathological change was found and grade of tissue morphology was scored.The ultrastructure change of cadiocyte was observed by the electron microscope.Results The energy of CK-MB (14.65±1.91,14.21±1.70) and cTNI (9.66±1.31,10.07±1.20) in TPO groups were obviously lower than that of the ADM group(19.58±3.49,12.50±1.62) (P<0.05),respectively.Pathological score of ADM group was higher than TPO groups (P<0.01).The ultrastructure of myecard tissue in the ADM group was damaged more severely than TPO groups.Above-mentioned indexes were with no significant difference between ADM+TPOL group and ADM+TPOH group.Conclusion TPO can protect the heart which was injured by the ADM. Key words: Thrombopoietin; Adriamycin; Drug toxicity; Rat

Experimental study on thrombopoietin providing protection against adriamycin-induced oxidative damage of myocardial cell in rats

Objective To inwst the antagonistic effect of thrombopoietin on adriamycin induced myocardium injury in rats and explore the mechanism.Methods 32 Wistar rats were randomized into four groups(n=8):Control group,ADM group,ADM+TPOL group and ADM+TPOH group.All agents were given by intraperitoneal injection.The control group was given saline.While the other three groups were given adriamycin at the dosage of20mg/kg.TPO group were injected TPO at the dosages of 10μg/kg or 30μg/kg three times on alternale days.ELISA was used to detect the concentration of CK-MB and cTnI in the serum of rats.The change of cardiocyte ultrastructure was observed by the electron microscope,and pathological change Was observed by immunohistochemistry staining.The expression level of 8- hydroxy-2'-deoxyguanosin(8-OHdG)produced by DNA oxidative damage in myocard tissue were detected.IPP6.0 software was used to detect IOD and calculate the 8-OHdG index.Results The energy of CK-MB and cTNI of TPO group was obviously lower than that in ADM group(P<0.01).The ultragtrueture of cardiocyte in the ADM group Wag damaged more severely than that in TPO group.Pathological Score,IOD and 8-OHdG index of TPO groups were lower than ADM group(P<0.05).These indexes had no significant statistics difference between ADM+TPOL group and ADM+TPOH group.Conclusions TPO can provide heart protection by antagonizing oxidative damage of myocardial cell induced by edriamycin. Key words: Thrombopoietin/PD; Cardiomyopathies; Myocytes,cardiac/DE; Oxidative stress

Assessing the value of disease management: impact of 2 disease management strategies in an underserved asthma population

The goal of disease management (DM) is to improve health outcomes and reduce cost through decreasing health care utilization. Although some studies have shown that DM improves asthma outcomes, these interventions have not been examined in a large randomized controlled trial. To compare the effectiveness of 2 previously successful DM programs with that of traditional care. Nine hundred two individuals with asthma (429 adults; 473 children) were randomly assigned to telephonic DM, augmented DM (ADM; DM plus in-home visits by a respiratory therapist), or traditional care. Data were collected at enrollment and at 6 and 12 months. Primary outcomes were time to first asthma-related event, quality of life (QOL), and rates of asthma-related health care utilization. Secondary outcomes included rate of controller medication initiation, number of oral corticosteroid bursts, asthma symptom scores, and number of school days missed. There were no significant differences between groups in time to first asthma-related event or health care utilization. Adult participants in the ADM group had greater improvement in QOL (P = .04) and a decrease in asthma symptoms (P = .001) compared with other groups. Of children not receiving controller medications at enrollment (13%), those in the intervention groups were more likely to have controller medications initiated than the control group (P = .01). Otherwise, there were no differences in outcomes. Overall, participation in asthma DM did not result in significant differences in utilization or clinical outcomes. The only significant impact was a higher rate of controllermedication initiation in children and improvement in asthma symptoms and QOL in adults who received ADM.

Projects in controlled environments (PRINCE2). Two levels: foundation and practitioner

FURTHER INFORMATION Also see: Office of Government Commerce—www.ogc.gov.uk/methods\_prince\_2.asp ADM Group—www.apmgroup.co.uk Project managers in any industry. Doctors with a project management role, including research. I would not recommend it for doctors who are not involved with projects or management. November 2006. I had been in management for several years, having originally been a senior house officer. At the time, I was a project manager for a national pilot for the junior doctors' Working Time Directive for 2009. I was expected …

Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice

To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice. BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors, and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice. Seventy-five animals were randomized divided into five groups (n = 15). Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg (BF1), 1 mg/kg (BF2) and 0.5 mg/kg (BF3) for d 15-24, respectively. The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15. Ten mice in each group were killed at d 25 and the survival time in each group was calculated. We also observed the morphologic alterations in the myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscopy, measured the apoptotic rate by TUNEL staining method, and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues. The tumor volumes in each group of bufalin were reduced significantly (35.21 +/- 12.51 vs 170.39 +/- 25.29; 49.83 +/- 11.46 vs 170.39 +/- 25.29; 83.99 +/- 24.63 vs 170.39 +/- 25.29, P < 0.01, respectively), and the survival times were prolonged in group BF1-2 (31.8 +/- 4.2 vs 23.4 +/- 2.1 and 29.4 +/- 3.4 vs 23.4 +/- 2.1, P < 0.05, respectively), and necrosis was mainly in severe or moderate degree in group BF1-2. No morphological changes were detected in the myocardium, brain, liver and kidney tissues. Apoptotic characteristics could be seen in group BF1-2. The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0%, 10.0%, 20.0%, 10.0% and 20.0%; 90.0%, 80.0%, 80.0%, 40.0% and 30.0%, respectively. Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR. Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin.