Propionyl-L-carnitine as protector against adriamycin-induced cardiomyopathy.

Propionyl- l -carnitine (PLC) is a naturally occurring compound that has been considered for the treatment of many forms of cardiomyopathies. In this study, the possible mechanisms whereby PLC could protect against adriamycin (ADR)-induced cardiomyopathy were carried out. Administration of ADR (3 mg kg(-1)i.p., every other day over a period of 2 weeks) resulted in a significant two-fold increase in serum levels of creatine phosphokinase, lactate dehydrogenase and glutamic oxaloacetic transaminase, whereas daily administration of PLC (250 mg kg(-1), i.p. for 2 weeks) induced non-significant change. Daily administration of PLC to ADR-treated rats resulted in complete reversal of ADR-induced increase in cardiac enzymes except lactate dehydrogenase which was only reversed by 66%. In cardiac tissue homogenate, ADR caused a significant 53% increase in malonedialdehyde (MDA) and a significant 50% decrease in reduced glutathione (GSH) levels, whereas PLC induced a significant 33% decrease in MDA and a significant 41% increase in GSH levels. Daily administration of PLC to ADR-treated rats completely reversed the increase in MDA and the decrease in GSH induced by ADR to the normal levels. In rat heart mitochondria isolated 24 h after the last dose, ADR induced a significant 48% and 42% decrease in(14)CO(2)released from the oxidation of [1-(14)C]palmitoyl-CoA and [1-(14)C]palmitoylcarnitine, respectively, whereas PLC resulted in a significant 66% and 54% increase in the oxidation of both substrates, respectively. Interestingly, administration of PLC to ADR-treated rats resulted in complete recovery of the ADR-induced decrease in the oxidation of both substrates. In addition, in rat heart mitochondria, the oxidation of [1-(14)C]pyruvate, [1-(14)C]pyruvate and [1-(14)C]octanoate were not affected by ADR and/or PLC treatment. Moreover, ADR caused severe histopathological lesions manifested as toxic myocarditis which is protected by PLC. Worth mentioning is that PLC had no effect on the antitumour activity of ADR in solid Ehrlich carcinoma. Results from this study suggest that: (1) in the heart, PLC therapy completely protects against ADR-induced inhibition of mitochondrial beta -oxidation of long-chain fatty acids; (2) PLC has and/or induces a powerful antioxidant defense mechanism against ADR-induced lipid peroxidation of cardiac membranes; and finally (3) PLC has no effect on the antitumour activity of ADR.

Telomerase activity in bilharzial bladder cancer. Prognostic implications.

Background: Bladder cancer is a common malignancy in Egypt and other developing countries in which infection with Schistosoma haematobium is prevalent. Bladder cancer caused by bilharziasis has different clinical and biological characters than that observed in the western world. In this study, we used the TRAP technique to estimate telomerase activity in bilharzial bladder cancer specimens and we correlated the findings with other clinical and pathological findings. Patients and methods: Bladder cancer specimens were obtained from 57 patients who underwent radical cystectomy and pathological diagnosis was obtained in all patients. Tissue samples were frozen in liquid nitrogen and stored at -80 degrees C. Telomerase activity by PCR-ELISA technique was measured using TRAP technique. Results: Our patient group included 45 males and 12 females with a median age of 49 years. The majority of our patients (35/57) have squamous histology and they have proven bilharzial history shown in the pathology specimens. Stage P3b was encountered in 29/57 patients whereas thirty-five patients have grade II tumors. The majority of our patients (41/57) were negative for pelvic nodes metastases. Telomerase activity was detected in 27/57 patients (47.4%). The mean level of telomerase was 0.85+/-0.77 in positive patients and 0.029+/-0.025 in negative patients. The expression of telomerase and its mean level in patients above age of 60, in males and in those with squamous pathology, higher grade of tumors or positive node was higher than those without but the difference did not reach statistical significance (P>0.05). Alternatively, expression was significantly higher in those with stages (P1-P3a) compared with P3b-P4a disease stages (66.6% vs. 37.1, P=0.03). Conclusion: Telomerase activity is increased in bilharzial bladder cancer although to a lesser degree than that reported for TCC in the western world, which could be explained, by different biological behavior or different assay methods. Further larger studies with more number of patients are still needed to determine its potential value for early detection and possible use as a therapeutic target.

Plasma bcl-2 and nitric oxide: possible prognostic role in patients with metastatic breast cancer.

Interest in translational studies on breast cancer is presently devoted to identifying biological predictors of disease prognosis and response to treatment. In this study, we determined the plasma levels of bcl-2 and nitric oxide in 45 patients with metastatic breast cancer using an ELISA technique and correlated them with clinical and biological factors that may affect the outcome of disease. The results were as follows. The mean level of bcl-2 was 278.44 +/- 383.2 U/L compared with 64.42 +/- 14.4 U/L (p = 0.007) for controls. Levels of bcl-2 were higher in patients less than 50 yr old, premenopausals., GIII tumors, positive nodes, ER positive tumors (p = 0.6, 0.5, 0.9, 0.4, and 0.005, respectively). The site of metastatic disease and the number of metastatic sites did not show statistically significant influences over bcl-2 levels. Furthermore, there was a trend, although not significant, toward improvement of survival in patients with higher levels of bcl-2. The mean level of the nitric oxide (NO) was 297.12 +/- 220.54 microM compared with 13.91 +/- 1.1 microM for controls (p = 0.003). The levels were higher in patients over 50 yr, postmenopausal patients, those with visceral deposits, grade III tumors, positive lymph nodes, and those with disease-free survival of less than 6 mo following primary treatment (p = 0.1, 0.2, 0.1, 0.09, 0.4, and 0.08 respectively). Furthermore, there was no correlation between NO levels and survival (r = 0.002). This study demonstrates a potential role for NO and bcl-2 as prognostic factors in patients with metastatic breast cancer. However, larger studies with more patients together with a comparison of serum levels (ELISA) and tissue levels (MOAb) are still required.