Sanazole has been tested clinically as a hypoxic cell radiosensitizer. The aim of the present study was to investigate whether sanazole enhances apoptosis induced by hyperthermia at 44 degrees C for 20 min in human lymphoma U937 cells. Sanazole alone induced continuous increase in the intracellular superoxide generation in a time-dependent manner and transient increase in the peroxide formation, which further were enhanced at 1 hour after HT treatment. Moreover, when the cells were treated first with 10 mM sanazole for 40 min, exposed to HT at 44 degrees C for 20 min and the cells were further treated with the drug at 37 degrees C for 6 h, a significant enhancement of HT-induced apoptosis was evidenced by DNA fragmentation, morphological changes and phosphatidylserine externalization. Studying the apoptotic pathways involved in this enhancement, we found that loss of the mitochondrial membrane potential, release of cytochrome c from mitochondria to cytosol, and activation of caspase-3 and caspase-8 was enhanced significantly in the U937 cells after the combined treatment. Moreover, this combination enhanced activation of Bid, and down regulation of Hsp70. In addition, an increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)), and externalization of Fas were observed immediately after sanazole and HT treatment. Our data indicate that sanazole can enhance the hyperthermia induced-apoptosis through the Fas-caspase-8- and [Ca(2+)](i)-dependent apoptotic pathways. In addition, the down regulation of Hsp70 contributed to this enhancement.

Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted. We studied the laboratory changes, frequency of VOCs per year, frequency of hospital admisions per year and number of transfusions per year, both before and after HU therapy. The follow-up period was 4 to 120 months. Hb F levels after HU therapy positively correlated with the duration of HU therapy, baseline Hb F levels and baseline total hemoglobin (Hb) (r = 0.4, p = 0.04; r = 0.45, p = 0.001; r = 0.5, p = 0.019, respectively) and inversely correlated with baseline total leucocyte count (r = -0.33, p = 0.034). Hydroxyurea therapy was associated with an increase in the total Hb and mean corpuscular volume (MCV) (p = 0.009, p = 0.000; respectively) and with a decrease in total leucocyte count, platelet count and reticulocyte count (p = 0.00, p = 0.03, p = 0.02, respectively). Moreover, a significant reduction in the frequency of VOCs, transfusion frequency and hospital admissions per year after HU therapy was shown in the studied subjects. Hydroxyurea induced an increase in Hb F level, which was maintained over time and was associated with clinical efficacy and acceptable safety.

Iron overload is a potentially fatal complication in thalassemia patients. Accurate assessment of body iron is of utmost importance for these patients. The available methods for iron stores evaluation have limitations. We assessed biochemically the skin iron concentration (SIC) and determined the relation between the hepatic and skin iron level in thalassemia major patients to develop a simple, sensitive, quantitative measure of the body iron stores. Thirty-one cases with thalassemia major were assessed for iron overload. Liver and skin biopsies were performed for the patients and skin biopsies were taken from the 31 controls. The biopsies were subjected to biochemical assay of iron and histologic sections were examined. The SIC of the studied cases was significantly higher than that of the control group with a mean of 2.705 +/- 1.14 and 0.275 +/- 0.13 mg/g dry skin weight, respectively, p < 0.001. There was significant correlation between the SIC and the liver iron concentration (LIC) (r = 0.43, p = 0.01). The amount of liver iron is equivalent to [(3.5 x SIC) + 12.9]. With the use of this equation, we could reliably estimate an LIC value as high as 21.2 mg/g dry liver weight with a standard error of 4.07. Biochemical assay of the skin iron concentration is a reliable quantitative indicator of the body iron stores in patients with thalassemia major.