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Cardiovascular diseases and cancer represent respectively the first and second cause of death in industrialized countries. These two conditions may become synergistic when cardiovascular complications of anti-cancer therapy are considered. More than 70 of childhood and 50 of adult cancer patients can be cured, however this important success obtained by the biological and medical research is obfuscated by emerging findings of early and late morbidity due to cardiovascular events. Although anthracyclines are effective drugs against cancer a dose-dependent cardiotoxic effects whose mechanism has not been elucidated resulting in failure of therapeutic interventions limit their use. Unexpectedly, tyrosine/ kinase inhibitors (TKIs) aimed at molecularly interfering with oncogenic pathways, have been implicated in cardiac side effects. Possible explanations of this phenomenon have been ambiguous, further strengthening the need to deepen our understanding on the mechanism of cardiotoxicity. In addition to a detailed description of anthracyclines and TKIs-related cardiovascular effects, the present review highlights recent observations supporting the hypothesis that the cellular target of anthracyclines and TKIs may include myocardial compartments other than parenchymal cells. The demonstration that the adult mammalian heart possesses a cell turnover regulated by primitive cells suggests that this cell population may be implicated in the onset and development of cardiovascular effects of anti-cancer strategies. The possibility of preventing cardiotoxicity by preservation and/or expansion of the resident stem cell pool responsible for cardiac repair may open new therapeutic options to unravel an unsolved clinical issue.

Summary A continuous bone remodelling takes place throughout life at different turnover speed according to age, physiological and pathological conditions. The evaluation of bone turnover may be of value for a prognostic and therapeutical assessment. Calcium bone exchange may be considered a suitable marker of bone turnover; for this reason47Ca or45Ca kinetics may be used; these methods have been employed in the past. Labelled diphosphonates, and in particular99Tecnetium-metilen-diphosphonate (99TcmCP) are simpler and safer, because these substances are strongly and almost completely stored in bone and not absorbed by the soft tissue; for this reason they are used at the present time. The evaluation of blood levels and 24 hrs urinary elimination of99TcmDP is used to measure whole bone diphosphonate retention (WBR). This parameter is positively correlated with other markers of bone turnover such as alkaline phosphatase (AP), osteocalcin (OC), urinary hydroxyproline (HOP). A bicompartimental analysis schedule of99TcmDP distribution has been proposed some years ago and therefore applied by our group, based on the mathematical evaluation of serum concentration at different times and urinary elimination of the label given intravenously. This method provides the possibility to calculate not only WBR but also total body retention (TBR) and a constant (Kbh) which reflects the influx speed of the tracer in the bone. Kbh probably represents a more sensitive index of bone turnover than WBR. It presents a better correlation with AP and OC values and also shows some (statistically less significant) correlations with some indices of bone remodelling obtained by hystomorphometry on bone biopsies. Kbh is fairly stable in rest conditions and is elevated in high bone turnover conditions (Paget, osteomalacia and, at a lower extent, high turnover osteoporosis).

Uncorrected and corrected blood viscosity, plasma viscosity and whole blood filterability were evaluated in 15 rats submitted to an iron-copper (Fe-Cu) free diet and 15 rats fed with the same diet supplemented with the daily requirement of the two minerals. Hemathological parameters (Hb, MCV, PCV, MCH, white, red blood cell and platelet total counts) were also measured. Fe-Cu deficient rats developed severe microcytic anemia within 7–8 weeks of diet. This was associated with a 43% and 31% decrease of blood viscosity and whole blood filterability, respectively. Higher values of corrected blood viscosity and white cell total counts were found in anemic respect to control rats fed with Fe-Cu supplemented diet. Results of plasma viscosity were similar in both groups. Our study shows that severe sideropenic anemia is accompanied by hemorheological alterations leading to a significant reduction of whole blood filterability. It is suggested that, in microcytic anemia, microcirculatory flux is impaired and this phenomenon may play an important role in anemia-induced tissue hypoxia.