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PURPOSE: Intensive chemotherapy with daunorubicin (DNR) is associated with serious side effects in acute myeloid leukemia (AML) patients. In this study the effect of small-molecule BH3-mimetic, ABT-737, on the sensitivity of HL60 and U937 AML cell lines was investigated. METHODS: The cytotoxic effects of DNR and ABT-737, alone or in combination were assessed using MTT assay and combination index analysis. The effects of treatments on the cell proliferation was determined by trypan blue assay. ELISA cell death assay was used for measurement of apoptosis. RESULTS: IC50 values of DNR and ABT-737 were 2.52 and 0.59 µM for HL-60 cells line and 1.31 and 0.80 µM for U937 cell line at 24 h, respectively. Surprisingly, combination treatment significantly lowered the IC50 values in a synergic manner in both cell lines. Moreover, treatment with a mixture of two agents had more growth inhibition effect relative to the monotherapy. RESULTS of apoptosis assay showed that the cytotoxic effects are related to the enhancement of apoptosis. CONCLUSION: Our study suggests that ABT-737 synergistically enhances the cytotoxic effect of DNR in AML cell lines and therefore may be useful to overcome chemoresistance of leukemia patients.
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BACKGROUND: Although percutaneous coronary intervention (PCI) improves outcomes compared to thrombolysis, a substantial number of ST-elevation myocardial infarction (STEMI) patients do not achieve optimal myocardial reperfusion. This study was designed to evaluate factors related to suboptimal myocardial reperfusion after primary PCI in patients with STEMI. METHODS: Totally, 155 patients (124 men; mean age = 56.6 ± 11.03 years, range = 31- 85 years) with STEMI undergoing primary PCI were retrospectively studied. Additionally, the relationships between the occurrence of reperfusion failure and variables such as age, sex, cardiac risk factors, family history, Body Mass Index, time of symptom onset, ejection fraction, previous PCI, coronary artery bypass graft surgery or previous myocardial infarction, and angiographic data were analyzed. RESULTS: Procedural success was 97.1% and complete ST resolution occurred in 43.2%. Age; cardiac risk factors; family history; body mass index; previous MI, coronary artery bypass graft surgery, or PCI; and use of thrombectomy device and GPIIb/IIIa inhibitor were not the determining factors (p value > 0.05). According to our multivariate analysis, time of symptom onset (OR [95% CI]: 045 [0.2 to 0.98]; p value = 0.044) and ejection fraction (OR [95% CI]:0.37 [0.26 to .091]; p value = 0.050) had reverse and male gender had direct significant associations with failed reperfusion (OR [95% CI]: 0.34 [0.11 to 1.08]; p value = 0.068). More degrees of ST resolution occurred when the right coronary artery was the culprit vessel (p value = 0.001). The presence of more than three cardiac risk factors was associated with failed reperfusion (p value = 0.050). CONCLUSION: Considering the initial risk profile of patients with acute STEMI, including time of symptom onset and ejection fraction, as well as the accumulation of cardiac risk factors in a given patient, we could predict failed myocardial reperfusion to design a more aggressive therapeutic strategy.
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BACKGROUND: Histology is the unique method for diagnosis of silent liver diseases; so, we aimed to determine the prevalence of fatty liver and other silent liver diseases among those who passed away for causes other than liver diseases in Tehran. METHODS: Over a two-year period (2002 - 2004) we enrolled autopsies performed at the Forensic Medicine Center in Tehran. Demographic information, history of known acute and chronic liver diseases, and causes of death were determined. Samples from the right and left lobe and one sample from deeper areas of the liver as well as specimens from any grossly visible lesions were obtained in each case. Tissue sections stained by hematoxylin and eosin were evaluated. Reticulin and Masson's trichrome stains were also performed for evaluation of liver architecture and degree of fibrosis when necessary. RESULTS: Satisfactory tissue samples for histologic evaluation were available in 896 cases (777 males) with a mean age of 43.8 years. Normal histology was found in 467 cases (52.1%). Important findings included: steatosis in 283 (31.6%), steatohepatitis in 19 (2.1%), chronic hepatitis in 23 (2.6%), and cirrhosis in 7 (0.8%) cases. Causes of death were: trauma (35%), acute myocardial infarction (30%), opiate overdose (13%), cerebrovascular accidents (4%), infectious diseases (3%), and others (15%). CONCLUSION: Silent diseases of the liver are not uncommon. Steatosis is the most common finding but inflammatory disorders comprise a significant minority.