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The present study examined whether measurement of hemoglobin-acetaldehyde (HbA1-AcH) using an improved methodology may be useful as a biological marker of alcohol abuse. Red blood cell hemolysates of 182 patients consecutively admitted to the drug and alcohol treatment unit of our institution were analyzed for HbA1-AcH concentration using cation exchange HPLC. Mean HbA1-AcH of those who claimed to drink ≥6 drinks/day [mean = 0.055 (% total hemoglobin), SD = 0.051] was significantly higher than the mean of those who drank < 6 drinks/day (mean = 0.026, SD = 0.0174). The greatest sum of sensitivity (67%) and specificity (77%) came with a cut-score of 0.030 area% of total hemoglobin. A cut-score of 0.080 produced a 100% specificity, but lowered the sensitivity to 20%. The Pearson product moment correlation ( r) between HbA1-AcH and reported drinks per day was r= 0.30 ( p < 0.001). There was no significant difference in the association of HbA1-AcH and reported drinking between males and females, and the small difference observed was shown to be entirely associated with differences in hemoglobin levels between the sexes. Cocaine use did not significantly alter the correlation between reported drinking and HbAl-AcH levels. Hemoglobin levels were shown to have a significant correlation with HbA1-AcH independent of drinking. HbA1-AcH was shown to have a better sensitivity and specificity than γ-glutamyltransferase, ALT, AST, or mean corpuscular volume in this population. The results suggest that HbA1-AcH may be a useful marker to help detect alcohol abuse, especially in populations where other markers have been shown to fail. [ABSTRACT FROM AUTHOR]

Drug resistance and associated immune deregulation limit use of current therapies in chronic lymphocytic leukaemia (CLL), thus warranting alternative therapy development. Herein we demonstrate that OSU-DY7, a novel D-tyrosinol derivative targeting p38 mitogen-activated protein kinase (MAPK), mediates cytotoxicity in lymphocytic cell lines representing CLL (MEC-1), acute lymphoblastic leukaemia (697 cells), Burkitt lymphoma (Raji and Ramos) and primary B cells from CLL patients in a dose- and time-dependent manner. The OSU-DY7-induced cytotoxicity is dependent on caspase activation, as evidenced by induction of caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage and rescue of cytotoxicity by Z-VAD-FMK. Interestingly, OSU-DY7-induced cytotoxicity is mediated through activation of p38 MAPK, as evidenced by increased phosphorylation of p38 MAPK and downstream target protein MAPKAPK2. Pretreatment of B-CLL cells with SB202190, a specific p38 MAPK inhibitor, results in decreased MAPKAPK2 protein level with concomitant rescue of the cells from OSU-DY7-mediated cytotoxicity. Furthermore, OSU-DY7-induced cytotoxicity is associated with down regulation of p38 MAPK target BIRC5, that is rescued at protein and mRNA levels by SB202190. This study provides evidence for a role of OSU-DY7 in p38 MAPK activation and BIRC5 down regulation associated with apoptosis in B lymphocytic cells, thus warranting development of this alternative therapy for lymphoid malignancies., (© 2011 Blackwell Publishing Ltd.)