The Inhibitory Effect of Epigallocatechin Gallate on the Viability of T Lymphoblastic Leukemia Cells is Associated with Increase of Caspase-3 Level and Fas Expression

Acute lymphoblastic leukemia is the most prevalent cancer in children. Novel components to help struggle aggressive malignancies and overcome some side effects of conventional treatments could be a promising strategy. Epigallocatechingallate (EGCG), have attracted the attention of scientists for prevention or treatment of some cancers. Jurkat cells were incubated with the different concentrations of EGCG (30–100 µm) for 24, 48, and 72 h and cell viability was investigated using MTS test. Apoptosis and the level of caspase 3 alterations were evaluated using flowcytometry and expression of Fas by Real Time PCR. EGCG decreased viability of cells with an inhibition concentration (IC50) of 82.8 ± 3.1, 68.8 ± 4 and 59.7 ± 4.8 μM in 24,48 and 72 h. 50, 70 and 100 µM concentrations of EGCG induced apoptosis in about 31, 40 and 71% of the cells, respectively. The mean value of caspase 3 positive cells in the presence of 50, 70 and 100 µm concentrations of EGCG was 19.3 ± 2.9, 29.5 ± 3.1 and 61.2 ± 3.4 respectively compared to 7.8 ± 1.1 in control with a significant difference at 100 µm concentration. Treatment with EGCG for 48 h enhanced the expression of Fas reaching to a significant level at 100 µM concentration. EGCG is effective in decrease cell viability, apoptosis induction and enhancement of caspase 3 and Fas expression level in jurkat cells. A comprehensive understanding of molecular events and pharmacokinetics of the component and experiments in animal models are required for dose determination and its interaction with other components of combination chemotherapy.     

Evaluation of apoptosis induced in vitro by cladribine (2-CdA) combined with anthracyclines in lymphocytes from patients with B-cell chronic lymphocytic leukemia

The aim of the study was to evaluate the effect of three anthracyclines [doxorubicin (DOX), mitoxantrone (MIT), and idarubicin (IDA)] on the rate of apoptosis triggered by 2-chlorodeoxyadenosine (2-CdA) in peripheral blood mononuclear cells isolated from 52 untreated patients with B-cell chronic lymphocytic leukemia (B-CLL). The cells were cultured up to 48 h in the presence of drugs alone and in the following combinations: 2-CdA+DOX, 2-CdA+MIT, and 2-CdA+IDA. Apoptosis was assessed after 24 h and 48 h of incubation using annexin V/propidium iodide assay by flow cytometry. The apoptotic index (AI) was defined as a percentage of annexin V-positive B-CLL cells. Additionally, in some patients other hallmarks of apoptosis (activation of caspases, DNA fragmentation) were assessed in parallel for confirmation of apoptotic mode of induced cell death. All of the cytostatics induced apoptosis of B-CLL cells at a rate significantly higher than the index of spontaneous apoptosis occurring during 24 h and 48 h of cell culture. 2-CdA in combination with DOX significantly increased the percentage of annexin V-positive cells, particularly after 48 h of incubation, as compared with DOX used in monotherapy (median AI for 2-CdA+DOX=37.9%, median AI for DOX =13.8%, P=0.0011, and median AI for 2-CdA=22.1%, P=0.013). Combination of 2-CdA with MIT induced a similar effect, also more distinct after 48 h (median AI for 2-CdA+MIT=41.05%, median AI for MIT=16.3%, p=0.0012, and median AI for 2-CdA=22.1%, p=0.017). For both combinations median AI were similar to the sum of median AI for each drug when used alone. IDA in a concentration ten times lower (0.1 micro g/ml) than used before in acute leukemia cells produced high cytotoxic effects, masking the additive effect of combination with 2-CdA. Only at a dose of 25 ng/ml of IDA, significant differences in AI after 24 h and 48 h were detected between samples treated with 2-CdA+IDA (median 27.5% and 65.0%, respectively) and those incubated with IDA alone (median 10.5% and 33.4%; P=0.0004 and 0.0274, respectively). Similarly, there were significant differences between AI of cells treated with 2-CdA+IDA and 2-CdA alone (median 9.5% at 24 h and 23.5% at 48 h; P=0.0013 and 0.0207, respectively). In conclusion; these data indicate an additive cytotoxic effect on B-CLL cells of DOX, MIT, and IDA applied in vitro with 2-CdA; all of them induced apoptosis with similar efficacy. We suggest that further preclinical and clinical studies concerning combined use of 2-CdA with anthracyclines are desirable. High sensitivity of B-CLL cells to IDA suggests the possibility of lowering its dose in patients, especially when combined with 2-CdA.     

5-HT再摄取抑制剂氟西汀诱导HepG2细胞凋亡

目的通过观察5-HT再摄取特异性抑制剂氟西汀对人肝癌细胞系HepG2细胞凋亡的影响,探索氟西汀治疗肝细胞癌的可能性。方法采用不同浓度氟西汀(5μmol、7.5μmol、10μmol、12.5μmol、15μmol)分别处理HepG2细胞24 h、48 h,AnnexinV-FITC/PI流式细胞术和蛋白水解酶3免疫荧光法检测细胞凋亡。结果 10μmol、12.5μmol氟西汀处理24 h早期凋亡率分为(14.41±5.40)%、(19.43±5.91)%,与对照组(4.05±1.90)%相比差异均具有统计学意义(均P0.05),5μmol氟西汀处理48 h早期凋亡率为(20.32±6.23)%,与对照组(12.40±4.18)%相比差异有统计学意义(P0.05),10μmol及12.5μmol氟西汀处理24 h活化caspase 3阳性细胞显著增加。结论氟西汀具有促进HepG2细胞凋亡的作用,为临床上应用氟西汀治疗肝细胞癌患者提供了依据。     

西达苯胺联合传统化疗药物促进急性T淋巴细胞系的凋亡

目的:探讨西达苯胺联合伊达比星或左旋门冬酰胺酶对急性T淋巴细胞白血病细胞系Jurkat、MOLT4、CCRF-CEM增殖及凋亡的影响。方法:CCK8法检测西达苯胺、伊达比星、左旋门冬酰胺酶单药或两药联合对Jurkat、MOLT4、CCRF-CEM细胞的增殖抑制作用,流式细胞术检测细胞凋亡,Westernblot法检测凋亡相关蛋白的表达。结果:西达苯胺、伊达比星、左旋门冬酰胺酶单药作用于细胞,细胞的增殖抑制呈现药物浓度及作用时间依赖性。流式细胞术检测发现,西达苯胺联合伊达比星或左旋门冬酰胺酶作用于细胞相较于任何一种单药诱导细胞凋亡更加明显(均P 0. 05),具有明显的协同效应(CI 0. 7),且联合用药组细胞凋亡蛋白表达水平较单药组显著升高。结论:西达苯胺联合伊达比星或左旋门冬酰胺酶具有协同抑制急性T淋巴细胞白血病细胞系Jurkat、MOLT4、CCRF-CEM增殖,促进细胞凋亡的作用。     

Sevelamer is an Effective Drug in Treating Hyperphosphatemia Due to Tumor Lysis Syndrome in Children: A Developing World Experience

We report here a study on efficacy of sevelamer hydrochloride in treating hyperphosphatemia due to tumor lysis syndrome (TLS) in a developing world setting. Twenty one children with hyperphosphatemia due to TLS were included. All received hyper-hydration, allopurinol and sevelamer. Efficacy was assessed by decrease in serum phosphate level, calcium-phosphate product and TLS score as per Cairo Bishop definition. Four children who underwent dialysis were excluded from analysis. Among the remaining 17 patients with hyperphosphatemia, laboratory TLS was recorded in 15 patients and clinical TLS in five. Sevelamer was given according to weight, most often 400 mg twice to thrice daily. Mean phosphatemia decreased from 8.3 ± 3.0 to 6.7 ± 2.1 mg/dl within 24 h of starting sevelamer (p = 0.02), 6.0 ± 2.1 mg/dl at 48 h, 4.9 ± 1.5 mg/dl at 72 h and 4.39 ± 1.7 mg/dl at 96 h. TLS was corrected in 72 h in 14 patients, 96 h in 1 and 120 h in another patient. Mean calcium-phosphate product decreased from 63.0 ± 14.0 to 49.2 ± 9.7 mg/dl (p = 0.002) at 24 h, 46.1 ± 17.0 mg/dl at 48 h and 39.7 ± 13.5 mg/dl at 72 h. There was no mortality due to hyperphosphatemia. Sevelamer is efficacious in children with malignancy-associated hyperphosphatemia in the developing world.     

Effects of silymarin on the spontaneous proliferation and cell cycle of human peripheral blood leukemia T cells

Silymarin is a polyphenolic flavonoid that has a strong antioxidant activity and exhibits anti-carcinogenic, anti-inflammatory, and cytoprotective effects. Although its hepatoprotective effect has been well documented, the effect of silymarin on T cells is largely unknown. The purpose of this study was to analyze the effects of the silymarin on the proliferation and cell cycle progression of Jurkat cells, a human peripheral blood leukemia T cell line. Cells were incubated with various concentrations of silymarin for 24–72 h and examined for cell growth and proliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and DNA 5-bromo 2′-deoxyuridine (BrdU) colorimetric assays. Cell cycle analysis by flow cytometry was also performed using propidium iodide staining. Results of the study revealed that silymarin increased proliferation of Jurkat cells at 50–400 μM concentrations with 24 h exposure, confirmed by both MTT and BrdU assays. However, Jurkat incubation with silymarin at higher concentrations of 400 μM for 48 h and 200–400 μM for 72 h caused inhibition of DNA synthesis, cell cycle arrest at the G2/M phase and significant cell death. Results of the present study also revealed a similarity of cell growth patterns between Jurkat, U937 and RPMI 8866 cells. In conclusion, this study demonstrated an in vitro growth stimulatory effect of silymarin on leukemia cells with monocyte, T and B cell origin that has not been previously reported for either solid tumors or other leukemia cells, suggesting a possible specific stimulatory effect of silymarin on the key cells of the immune system.     

The capillaroscopic findings in idiopathic pernio: is it a microvascular disease?

Objectives

Pernio is a disorder that affects the unprotected skin regions of individuals who are exposed to nonfreezing, damp cold. We aimed to examine nailfold capillaries by video capillaroscopy and evaluate the vascular involvement in patients with idiopathic pernio.

Methods

Fifty-three patients with idiopathic pernio (male/female ratio 35:18, mean age 25 ± 9 years) and 38 age- and sex-matched healthy volunteers (male/female ratio 30:8, mean age 24 ± 4 years) were included in the study. Forty-seven of the 53 patients and all the healthy volunteers were evaluated by nailfold video capillaroscopy.

Results

In the patient group, the mean capillary diameter and the mean apical capillary diameter were 56 ± 15 and 24 ± 7 μm, respectively. In the control group, the mean capillary diameter and the mean apical capillary diameter were 37 ± 8 and 15 ± 4 μm, respectively (both p < 0.001). Both of these differences were independent of the disease activity, smoking, and the number of pernio episodes. There were no architectural derangements, avascular areas, or hemorrhages.

Conclusions

In the present study, increased nailfold capillary diameter and increased apical capillary diameter were found in patients with pernio regardless of the disease activity. These findings suggest organic damage of the microcirculation.     

选择性环氧合酶-2抑制剂NS-398对人肝癌细胞株HepG2增殖和凋亡的影响

目的探讨选择性环氧合酶-2抑制剂NS-398对人肝癌HepG2细胞株的生长抑制、诱导凋亡及其对bcl-2表达的影响。方法采用MTT法检测细胞增殖，流式细胞术检测细胞周期、凋亡及凋亡相关蛋白bcl-2的表达。结果NS-398抑制HepG2的增殖活性，经20、40、80和160μmol／L的NS-398处理细胞48h后，其抑制率分别为6．72％、16．21％、20．86％和25．34％，呈剂量依赖效应关系；细胞经160bLmol／L的NS-398处理24h、48h和72h后，G。／G1期细胞由76．07±0．75％分别减少至62．27±0．74％、59．17±1．47％和53．03±1．60％（P〈0．05），S期细胞由11．40±0．79％分别增加至13．23±0．81％、16．20±1．95％和16．60±1．25％（P〈0．05），G2／M期细胞无明显变化；凋亡细胞增多，凋亡率分别为8．47％、16．3％和23．9％；细胞经160μmol／L的NS-398处理48h后bcl-2蛋白与对照组比，表达下调（P〈0．01）。结论NS-398对人肝癌细胞株HepG2有抑制增殖、诱导凋亡作用，细胞凋亡的机制可能与细胞凋亡相关基因bcl-2表达下调有关。     

Telomerase inhibition and telomere lossin BEL—7404 humen hepatoma cells treated with doxorubicin

AIM：To study the effects of doxorub icin on telomerase activity and telomere length in hepatocellular carcinoma.METHODS:Telomerase activity was assayed with a non-radioisotopic quantitative telomerase repeat amplification protocal-based method.The effect of doxorubicin(DOX) on the growth of BEL-7404 human hepatoma cells was the growth of BEL-7404human hepatoma cells was determined by microculture tetrazoloum assay.Mean telomere length(terminal restriction fragment)was detected by Southern blot method.The expression of telomerase subunits genes was investigated by RT-PCR,Cell apoptosis and cell cycle distribution were evaluated by flow cytometry.RESULTS:Telomerase activity was inhibited in a dose and time-depandent manner in BEL-7404human hepatoma cells treated with DOXfor24,48or72h in concentrations from 0.156to 2.5μMwhich was crrelated with the inhibition of cell growth.No changes were found in the mRNA expression of three telomerase subunits(hTERT,hTR and TP1)after drug exposure for 72h with indicated concentrations.The cells treated with DOX showed shortened mean telomer length and accumulated at he G2/M phase.However,there was almost no effects on cell apoptosis by DOX.CONCLUSION:The telomerase inhibition an d the telomere shortening by ODXmay contribute to its efficiency in the treatment in hepatocellular carcinoma.     

VDD起搏对缓慢性心律失常心力衰竭的血液动力学影响

为了评估ＶＤＤ起搏对缓慢性心律失常心力衰竭的血液动力学影响，对２１例心功能Ⅲ～Ⅳ级的缓慢性心律失常病人安置ＶＤＤ起搏器，并用Ｓｗａｎ－Ｇａｎｚ导管监测起搏前和起搏后３０ｍｉｎ、２４ｈ、４８ｈ、７２ｈ的心输出量（ＣＯ）、心脏指数（ＣＩ）、右房压（ＲＡＰ）、平均肺动脉压（ＭＰＡＰ）和肺毛细血管楔嵌压（ＰＣＷＰ），并记录各时期的心房率（ＡＲ）和心室率（ＶＲ）。结果：ＶＲ在术后即时及各时期显著升高（Ｐ均＜０．０５），ＣＯ、ＣＩ在起搏后３０ｍｉｎ即显著升高〔分别为４．１８±０．８１Ｌ／ｍｉｎｖｓ２．８１±０．９３Ｌ／ｍｉｎ、２．３６±０．６６Ｌ／（ｍｉｎｍ２）ｖｓ１．１８±０．６３Ｌ／（ｍｉｎｍ２），Ｐ均＜０．０５〕，起搏４８ｈ达高峰；ＲＡＰ、ＭＰＡＰ、ＰＣＷＰ在起搏后３０ｍｉｎ无显著改变（Ｐ＞０．０５），但２４ｈ开始显著性下降（分别为１．２８±０．４１ｋＰａｖｓ１．４１±０．３４ｋＰａ、２．６０±０．５１ｋＰａｖｓ３．４０±０．５６ｋＰａ、３．１０±０．５６ｋＰａｖｓ３．５４±０．６８ｋＰａ，Ｐ均＜０．０５），７２ｈ后进一步降低。结果提示ＶＤＤ起搏治疗能显著改善缓慢性心律失常心力衰竭的血液动力学，可作为治疗缓慢性心?     

The Suppression Effects of Thalidomide on Human Lung Fibroblasts: Cell Proliferation, Vascular Endothelial Growth Factor Release, and Collagen Production

Background

Expression of transforming growth factor (TGF)-β₁ and increases in angiogenesis and deposition of extracellular matrix are the key features of tracheal granulation formation. The aim of this study was to investigate the potential role of thalidomide in preventing granulation tissue formation from the aspect of cellular effects in vitro, including fibroblast proliferation, vascular endothelial growth factor (VEGF) release, and collagen production.

Methods

Human lung fibroblasts were obtained from bronchus and cultured. The effects of thalidomide on cell proliferation, migration, TGF-β₁-induced VEGF, and signal pathway were investigated.

Results

Thalidomide (20 μM) not only inhibited cell proliferation after 24 h [fold increase of cell number, 0.85 ± 0.09 vs. 1.47 ± 0.14 (treatment vs. control group); P < 0.01] and 48 h of incubation (0.85 ± 0.10 vs. 1.97 ± 0.12; P < 0.001), it also inhibited cell migration and slowed wound closure at 24 h (P < 0.001). Thalidomide significantly attenuated TGF-β₁-induced VEGF expression at both the mRNA and protein levels. Incubation of thalidomide with cells stimulated with TGF-β₁ significantly inhibited their production of collagen. Thalidomide inhibited Smad3, STAT3, and subsequent p44/42 kinase phosphorylation.

Conclusion

Thalidomide may inhibit human fibroblast proliferation and it is worthy of further in vivo investigation.     

Molecular Imaging of Apoptosis in Ischemia Reperfusion Injury With Radiolabeled Duramycin Targeting Phosphatidylethanolamine: Effective Target Uptake and Reduced Nontarget Organ Radiation Burden

Objectives

The purpose of this study was to evaluate the feasibility of imaging apoptosis in experimental ischemia-reperfusion model by technetium-99m (^99mTc)-labeled Duramycin, and compare it to an established tracer, ^99mTc-labeled Annexin-V, which has a relative disadvantage of high radiation burden to nontarget organs.

Serum biomarkers and the prognosis of AMI patients

Background

It has been proven that serum lactate dehydrogenase (LDH) and total bilirubin (TB) increase during acute myocardial infarction (AMI). However, how they influence the prognosis of AMI patients is still not completely known.

Methods

A total of 239 patients diagnosed with AMI and admitted to the Fourth Clinical Hospital of Harbin Medical University, between 2007 and 2008, were enrolled in this study. All the patients had not undergone primary percutaneous coronary intervention (PCI) because the time window (24 h) was missed. They all underwent PCI 1 week after the onset of symptoms. Serum high-sensitivity C-reactive protein (hs-CRP), TB, LDH, and other biomarkers were determined between 24 and 48 h of symptom onset. All of the patients were followed up for an average of 3.2±0.4 years for occurrence of major adverse cardiac events (MACE).

Results

Patients with MACE had significantly higher levels of hs-CRP, LDH, cystatin C, uric acid, a higher ratio of LDH and TB (LDH/TB), and a lower level of TB: 8.48±3.84 vs. 2.13±1.32 μmol/l, p<0.01; 1,355.8±654.3 vs. 1,151.7±415.4 U/l, p<0.01; 1.69±0.76 vs. 1.00±0.46 mg/l, p<0.01; 419.6±109.2 vs. 343.2±108.2 μmol/l, p<0.01 and 141.1±46.2 vs. 61.2±26.5, p<0.01; 18.3±6.7 vs. 14.8±6.6 mg/l, p<0.01, respectively. In the multivariate COX analysis, LDH, cystatin C, and LDH/TB were significantly associated with the prognosis of these patients.

Conclusions

Patients under higher oxidative stress tend to have more MACE. LDH, cystatin C, and LDH/TB are strongly related to the prognosis of AMI patients undergoing elective PCI.     

Liposomal daunorubicin,fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia

Therapeutic options for patients with relapsed or refractory acute leukemia are still undefined and often unsatisfactory. We report the outcome of 79 patients with relapsed-refractory acute leukemia treated with fludarabine, cytarabine, and liposomal daunorubicin (FLAD regimen) followed by hematopoietic stem cell transplantation (HSCT), when clinically indicated, between May 2000 and January 2013. Forty-one patients had acute myeloid leukemia (AML), and 38 had acute lymphoblastic leukemia (ALL). Two patients with myeloid blast crises of CML and three with lymphoid blast crises were included in the AML and ALL subgroups, respectively. Median age was 48 years (range 13–77). FLAD was well tolerated with negligible, nonhematological toxicity. Six patients (7.5 %) died before response evaluation. Forty-seven patients achieved hematologic complete response (CR). Complete remission rate was 53 and 65 % among AML and ALL patients, respectively. No CR was recorded among 11 refractory AML patients. Twenty-four patients (30 %) underwent HSCT. Nine patients received stem cells from an HLA identical sibling, and 15 from an alternative donor (3 unrelated matched, 12 haploidentical sibling). Median overall survival in AML and ALL patients receiving FLAD therapy was 9 and 8 months, respectively. A 5-year projected OS for patients receiving the whole program (FLAD + HSCT) was 24 % for AML patients (median survival 43 months), 28 % for ALL patients treated in relapse (median survival 15 months), and 0 % for ALL patients treated for refractory disease. In this paper, we show that FLAD seems to be an effective bridge therapy to HSCT for a part of poor prognosis acute leukemia patients. However, prospective studies are needed to confirm our results.     

辛二酰苯胺异羟肟酸对人肝癌SMMC-7721细胞增殖和凋亡的影响

目的：探讨辛二酰苯胺异羟肟酸（SAHA）对人肝癌细胞株SMMC-7721细胞增殖和凋亡的影响。方法体外培养SMMC-7721细胞,给予不同浓度（2.5、5.0和7.5μmol/L）SAHA处理12~72h,采用噻唑蓝（MTT）比色法检测细胞增殖;加入SAHA（5.0和7.5μmol/L）处理SMMC-7721细胞24h或48h,使用流式细胞仪检测细胞凋亡和细胞周期的变化;采用RT-PCR法检测p53、bcl-2及bax基因mRNA水平;采用分光光度法检测Caspase-3蛋白表达。结果经5.0μmol/L SAHA处理细胞24h和48h时,细胞增殖率较对照下降了25.8%和28.8%,经7.5μmol/L SAHA处理细胞24h和48h时,下降了30.6%和48.6%;经5.0μmol/L或7.5μmol/L SAHA处理细胞24 h后,S期细胞从对照水平（24.33±0.17）%分别显著上升至（32.08±0.160）%和（33.96±0.20）%,（P=0.00）,早期凋亡率均由（0.19±0.04）%显著上升至（1.67±0.59）%和（8.92±0.94）%,（P=0.03）,而在48h后,S期细胞由（24.33±1.18）%分别显著上升至（32.25±0.53）%和（34.61±0.08）%,早期凋亡率由（0.19±0.04）%分别显著上升至（14.49±2.26）%和（26.23±0.55）%,（P=0.00）;SAHA能够上调p53、bax基因mRNA水平,下调bcl-2基因mRNA水平;经5.0μmol/L和7.5μmol/L SAHA处理细胞24h后,Caspase-3蛋白活性由对照水平（0.41±0.07）分别上升至（0.81±0.02）,（P=0.01）和（1.09±0.21）,（P=0.00）,而在处理48 h后,Caspase-3蛋白活性由对照水平分别上升至（1.43±0.23）和（2.01±0.01）,（P均=0.00）。结论 SAHA通过影响p53、bcl-2及bax凋亡相关基因水平及Caspase-3蛋白的活性,对人肝癌细胞株SMMC-7721细胞具有抑制增殖和促进凋亡的作用。     

Sparstolonin B Attenuates Hypoxia-Induced Apoptosis,Necrosis and Inflammation in Cultured Rat Left Ventricular Tissue Slices

Purpose

Ischemia/reperfusion results in tissue damage, a rapid increase in cytokines and chemokines and inflammatory cell infiltration. Herein we investigated the ability of a selective TLR2/4 antagonist, Sparstolonin B (SsnB), to protect rat cultured left ventricular tissue (LV) slices from hypoxic injury by inhibiting the myocardial inflammatory response independent of inflammatory cell infiltration.

Methods and Results

Media Lactate dehydrogenase (LDH) levels were measured to reflect hypoxia-induced cytotoxicity and cell injury with and without SsnB. Incubation with SsnB (15 and 30 μM) significantly reduced by 20 and 40 %, respectively, the amount of LDH released from the hypoxic LV slices. TUNEL staining showed that SsnB significantly attenuated the levels of hypoxia-induced apoptotic cells from 61.5?±?4.0 to 27.0?±?2.1 (15 μM SsnB) and 23.5?±?2.2 (30 μM SsnB) cells/unit area. Similarly, the Periodic Acid-Schiff (PAS) staining of ischemic areas in untreated hypoxic LV slices was increased 17 fold from 0.26?±?0.09 to 4.41?±?0.43 %, while in hypoxic slices incubated with 15 and 30 μM of SsnB, the PAS positive ischemic areas were increased by only 6.4 fold to 1.66?±?0.39 % and 3.8 fold to 1.00?±?0.22 %, respectively. Rt-PCR confirmed that MCP1 and IL-6 expression during hypoxia was elevated by 2 and 4 fold, respectively, while their up-regulation was significantly inhibited (i.e., <0.7 fold increase) by SsnB.

Conclusion

The selective TLR2/4 antagonist, Sparstolonin B, can substantially protect LV myocardium via its ability to inhibit injury resulting from hypoxic myocardial-generated inflammation. Accordingly SsnB has potential as a therapeutic agent for the attenuation of myocardial ischemia-reperfusion injury.     

Troponin Release and Reversible Left Ventricular Dysfunction After Transient Pressure Overload

Background

The authors previously demonstrated that brief ischemia elicits cardiac troponin I (cTnI) release and myocyte apoptosis in the absence of necrosis. It remains uncertain whether other pathophysiological stresses can produce apoptosis and transient cTnI release without ischemia.