Role of carnitine in cancer chemotherapy-induced multiple organ toxicity

In the last few years, cancer chemotherapy has been successfully employed in the treatment of different types of human tumours. Unfortunately, the optimal clinical usefulness of this important treatment modality is usually limited secondary to the development of life-threatening multiple organ toxicity. Cancer chemotherapy may cause these toxic effects by mechanisms not involved in their anticancer activity that can severely affect the life of patients and represent a direct cause of death. Several experimental and clinical studies have demonstrate that some important anticancer drugs interfere with the absorption, synthesis, and excretion of carnitine in non-tumour tissues, resulting in a secondary carnitine deficiency which is reversed by carnitine treatment without affecting anticancer therapeutic efficacy. Prototypes of anticancer drugs that alter carnitine system are doxorubicin, cisplatin, carboplatin, oxaliplatin, cyclophosphamide and ifosfamide. Furthermore, cachectic cancer patients are especially at risk for carnitine deficiency due to decreased oral intake and/or increased renal losses. Altered serum and urine carnitine levels have been reported in cancer patients with various forms of malignant diseases. Recent studies in our laboratory have demonstrated that carnitine deficiency constitute a risk factor and should be viewed as a mechanism during development of oxazaphosphorines-induced cardiotoxicity in rats. Similarly, inhibition of gene expression of heart fatty acid-binding protein and organic cation/carnitine transporter in doxorubicin cardiomyopathic rat model has been reported. In view of these facts and in view of irreplaceability of these important anticancer drugs, this review aimed to highlight the role of carnitine depletion and supplementation during development of chemotherapy-induced multiple organ toxicity

Cardiovascular diseases among Egyptian patients with rheumatoid arthritis and its relation to traditional risk factors

Rheumatoid arthritis [RA] is associated with increased mortality which is due to accelerated coronary artery and cerebrovascular atherosclerosis and researchers have not been able to clearly identify specific aspects of RA or its treatment that might higher the risk for cardiovascular [CV] disease. Prevalence of CV events in patients with rheumatoid arthritis. Effects of rheumatoid arthritis as a risk factor in developing CV diseases as well as influence of early and proper treatment on such risk. Association between RA as a risk factor and other traditional risk factors on CV diseases. 300 patients with RA and 150 controls matched with age and sex were subjected to full clinical assessment, laboratory investigations especially for rheumatoid factor [RF], erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], electrocardiography [ECG], conventional radiographs of both hands and feet to detect joint erosions and Doppler echocardiography. 13.5% of patients with RA has CV events, 7% for myocardial infarction and 2% for stroke. RA-related risk factors [extra articular disease, joints erosions and presence of RF were associated with CV events, the use of disease modifying antirheumatic drugs [DMARDs] were associated with lower risk for CV events. Our study confirm the role of traditional risk factors and their interplay with RA-retated risk factors in development of CV events. It also supports the beneficial effects of some DMARDs in lowering such risks

Subclinical atherosclerosis in patients with early rheumatoid arthritis

Rheumatoid arthritis [RA] patients have increased mortality and morbidity as a result of cardiovascular [CV] and cerebrovascular diseases. Surprisingly the extent of atherosclerosis [AS] in RA is not known, nor have standard CVD risk factors have been fully evaluated. Study of these changes in early RA and early diagnosis of AS in this population might trigger more aggressive prophylaxis. To demonstrate subclinical atherosclerosis in early RA and possible underlying mechanism. 60 patients with early RA and 40 controls matched for age, sex and traditional risk factors for AS were selected. All patients and controls were subjected to a complete history and full clinical examination, laboratory assessment and carotid ultrasonography. Patients with early RA had average greater cIMT than controls and an increased prevalence of atherosclerotic plaques. Positive association between cIMT and age, joint count, disease activity score [DAS], smoking, serum cholesterol and c-reactive protein [CRP] were observed. Age and CRP were independently associated with atherosclerosis. Patients with early RA developed accelerated atherosclerosis compared with controls. Age and CRP are strong predictors for occurrence of CV disease before onset of symptoms