Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron

The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of anthracycline antineoplastic antibiotics, which include doxorubicin (adriamycin), daunorubicin or epirubicin. Nevertheless, these compounds remain among the most widely used anticancer drugs. The molecular pathogenesis of anthracycline cardiotoxicity remains highly controversial, although the oxidative stress-based hypothesis involving intramyocardial production of reactive oxygen species (ROS) has gained the widest acceptance. Anthracyclines may promote the formation of ROS through redox cycling of their aglycones as well as their anthracycline-iron complexes. This proposed mechanism has become particularly popular in light of the high cardioprotective efficacy of dexrazoxane (ICRF-187). The mechanism of action of this drug has been attributed to its hydrolytic transformation into the iron-chelating metabolite ADR-925, which may act by displacing iron from anthracycline-iron complexes or by chelating free or loosely bound cellular iron, thus preventing site-specific iron-catalyzed ROS damage. However, during the last decade, calls for the critical reassessment of this “ROS and iron” hypothesis have emerged. Numerous antioxidants, although efficient in cellular or acute animal experiments, have failed to alleviate anthracycline cardiotoxicity in clinically relevant chronic animal models or clinical trials. In addition, studies with chelators that are stronger and more selective for iron than ADR-925 have also yielded negative or, at best, mixed outcomes. Hence, several lines of evidence suggest that mechanisms other than the traditionally emphasized “ROS and iron” hypothesis are involved in anthracycline-induced cardiotoxicity and that these alternative mechanisms may be better bases for designing approaches to achieve efficient and safe cardioprotection.     

Comparison of three dosage regimens of ciprofloxacin in urinary tract infections

Fifty-four patients with complicated UTI were administered ciprofloxacin in doses of 500 mg (30 subjects) and 250 mg (24 subjects) at 12-hour intervals. While a positive effect was noted in 96–100% upon termination of therapy, the effect was still present 3 weeks later in 90% of the high-dose, but only in 71% of the low-dose group. In 23 patients with uncomplicated UTI, a positive effect of the three-day therapy with 100 mg of ciprofloxacin at 12-hour intervals was observed in 91% of subjects. Intolerance to the agent was found in one case only. Development of resistance to ciprofloxacin was not observed.     

The effect of sulphinpyrazone and alpha-tocopherol on platelet activation and function in haemodialysed patients

In 30 patients on chronic haemodialysis treatment the platelet activity and function were studied before and during antiplatelet therapy with alpha-tocopherol and sulphinpyrazone. In both kinds of treatment a significant decrease of ADP-induced and spontaneous aggregation was observed. Sulphinpyrazone exerts an inhibitory effect not only on platelet aggregation but also on platelet factor 3 and provokes a significant prolongation of the bleeding time.     

1H and 13C NMR determination of the hydroxy end-groups in poly(oxypropylene)s

¹H and ¹³C NMR signals of tri(propylene glycol) and of its benzoate and phenyl urethane were assigned by means of 1D and 2D NMR methods such as super-selective long-range INEPT, H-H COSY, H-C COSY and H-H-C RCT spectra. Both ¹H and ¹³C NMR were used as methods for the determination of primary and secondary hydroxy end-groups and of their degree of conversion. ¹³C NMR was found to be a reliable and universal method of end-group determination even for cases where ¹H NMR fails due to the presence of water in the sample or to the nature of the reactant. The results are applied to the analysis of poly(oxypropylene)s with two or three hydroxy end-groups and their derivatives.     

A fluid level in an acute extradural haematoma

We report a fluid level in an acute extradural haematoma developing after placement of a ventriculoperitoneal shunt for hydrocephalus. This fluid level was thought to be due to a mixture of blood and cerebrospinal fluid.     

Current approaches in the treatment of bladder cancer and policy in Marmara University Hospital

Bladder cancer is one of the malignancies encountered frequently in urological practice. Since the three main treatment modalities (surgery, chemotherapy and radiotherapy) may be used alone or together, there are many treatment options. In this paper the current approaches in the treatment of bladder tumours are reviewed and the policy in Marmara University Hospital is described.     

Temporal Lobe Epileptogenesis and Epilepsy in the Developing Brain: Bridging the Gap Between the Laboratory and the Clinic. Progression, But in What Direction?

Summary:  The origins of human mesial temporal lobe epilepsy and hippocampal sclerosis are still not well understood. Hippocampal sclerosis and temporal lobe epileptogenesis involve a series of pathologies including hippocampal neuronal loss and gliosis, axonal reorganization, and maybe hippocampal neoneurogenesis. However, the causality of these events is unclear as well as their relation to the factors that may precipitate epileptogenesis. Significant differences between temporal lobe epileptogenesis in the adult and immature brain may require differential approaches. Hereditary factors also may participate in some cases of hippocampal sclerosis. The key point is to identify the significance of these age-dependent changes and to design preventive treatments. Novel strategies for the prevention and treatment of mesial temporal lobe epilepsy and hippocampal sclerosis may include rational use of neuroprotective agents, hormonotherapy, immunizations, and immunotherapy.     

Abdominal zygomycotic thromboangiitis in a patient with AML and t(1;13;14)

 The case report of a 61 year-old man with AML M2 FAB, t(1; 13; 14) and zygomycotic mesenterial thromboangiitis is presented. Two induction cycles of chemotherapy were administered due to primary drug resistance. They were complicated by pneumonia, colonic pseudo-obstruction and perforation with peritonitis. The patient died on the 40th day of therapy, 4 days after undergoing palliative surgery. Zygomycotic thromboangiitis, which very probably contributed to the intestinal perforation, was confirmed morphologically at necropsy. The novel complex chromosomal translocation t(1; 13; 14) (q31; q32; q24) and the problems connected with the diagnosis of invasive fungal infections are discussed. Received: 26 January 1996 / Accepted: 12 June 1996