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The systemic inflammation associated to the simultaneous activation of blood coagulation and the alterated blood fibrinolysis, leads to microvascular endothelial injury, acute organ dysfunction and possibly death. Activated Protein C, a natural, multifunctional protein, has demonstrated antithrombotic, anti-inflammatory, and profibrinolitic properties and may be an important modulator of the vicious cycle whereby inflammation initiates coagulation and coagulation amplifies inflammation. Protein C couples with its receptor, EPCR (endothelial-cell protein-C receptor), and the ligand-receptor complex then interact with thrombin-thrombomodulin on endothelial surface to produce activated protein C (APC). Once activated, protein C then interact with its cofactor, protein S, to catalyze the inactivation of factors Va and VIIILa, two important accelerators of the clotting cascade, reducing thrombin generation and microvascular thrombosis. In addiction to its anticoagulant activity APC promotes profibrinolytic activity through the inhibition of plasminogen activator inhibitor-1, which is upregulated during inflammation. Inhibition of thrombin generation by APC decreases inflammation by inhibiting platelet activation, neutrophil recruitment, and mast-cell degranulation. APC also shows direct antiinflammatory properties, including blocking of cytokines production by monocytes and blocking cell adhesion. Moreover, APC has antiapoptotic properties that may contribute to its efficacy. In conclusion, APC, besides its physiologic role in the coagulation cascade, plays a key role in the pathophysiology of systemic inflammation justifying its potential therapeutic role in sepsis and systemic inflammatory responses.

Purpose: To provide specialists and general practitioners with a review of the more recent data about anthracycline-induced cardiotoxicity and diagnostic methods utilized to reveal it., Design: Reviewers identified studies concerning anthracycline cardiotoxicity, with special emphasis to those dealing with its pathogenesis and tools utilized for diagnosing it, by searching MEDLINE and reviewing references for retrieved articles., Results: Three different clinical patterns of cardiotoxicity were described: acute, chronic and late. Highly sensitive tests are necessary for evaluating, during the time, the cardiotoxic effects associated with anthracycline-based therapy and to predict the development of cardiac dysfunction. For this reason, endomyocardic biopsy and radionuclide-based angiocardiography are considered the "gold standard". However, the bidimensional echocardiography is the most commonly performed because of its high specificity and sensitivity combined with low costs., Conclusions: The peer review of the most recent scientific literature clearly demonstrate that cardiotoxicity is an important complication of anthracycline-based therapy and that the cumulative dose greater than 550 mg/m2 is the main independent risk factor. For the evaluation of anthracycline-related cardiotoxicity, bidimensional echocardiography remains still the easier and faster method.

Multiple myeloma still remains a fatal disease. However, in the last months new biological and clinical informations have been provided about this disease. In particular, the immunophenotype of myeloma cells seems indicate, in some patients, a clonal involvement of a stem cell in the pathogenesis of mieloma. Moreover, new biological insights concerning the cytokine network, have revealed a probable effect of some cytokines, such as IL6, IL3, IL4. Finally, new insights in the biology of multiple myeloma have been provided by studies of molecular biology and flow cytometry. As for therapy, the best conventional induction treatment still remains to be defined. In the last years, the increased use of alpha Interferon and new therapeutic modalities, such as transplantation procedures in multiple myeloma, open new hopes toward a cure of this disease. Therefore, in the future a better knowledge of the multiple myeloma biology, associated with a wider use of new effective therapeutic approaches will certainly improve the natural course of this disease.

A dramatic improvement in the prognosis of multiple myeloma has been obtained since treatment with alkylating agents was introduced in the sixties. In recent years much effort has been made to ameliorate the obtained results by employing polychemotherapy schedules of treatment. However, no significant improvements with respect to the conventional melphalan-prednisone treatment, in terms of survival duration, have been observed. New therapeutic approaches, such as the use of biological response modifiers and the autologous or allogeneic bone marrow transplantation offer new perspectives for multiple myeloma patients. In this paper we discuss current trends in the therapy of multiple myeloma and of related complications.