Circadian clock and vascular disease.

Cardiovascular functions, including blood pressure and vascular functions, show diurnal oscillation. Circadian variations have been clearly shown in the occurrence of cardiovascular events such as acute myocardial infarction. Circadian rhythm strongly influences human biology and pathology. The identification and characterization of mammalian clock genes revealed that they are expressed almost everywhere throughout the body in a circadian manner. In contrast to the central clock in the suprachiasmatic nucleus (SCN), the clock in each tissue or cell is designated as a peripheral clock. It is now accepted that peripheral clocks have their own roles specific to each peripheral organ by regulating the expression of clock-controlled genes (CCGs), although the oscillation mechanisms of the peripheral clock are similar to that of the SCN. However, little was known about how the peripheral clock in the vasculature contributes to the process of cardiovascular disorders. The biological clock allows each organ or cell to anticipate and prepare for changes in external stimuli. Recent evidence obtained using genetically engineered mice with disrupted circadian rhythm showed a novel function of the internal clock in the pathogenesis of endothelial dysfunction, hypertension and hemostasis. Loss of synchronization between the central and peripheral clock also contributes to the pathogenesis of cardiovascular diseases, as restoration of clock homeostasis could prevent disease progression. Identification of CCGs in each organ, as well as discovery of tools to manipulate the phase of each biological clock, will be of great help in establishing a novel chronotherapeutic approach to the prevention and treatment of cardiovascular disorders

Flow cytometric analysis of circadian changes in platelet activation using anti-GMP-140 monoclonal antibody

The hemostatic activity of blood shows a circadian variation with a higher frequency of acute coronary events in the morning. The thrombotic tendency of blood is influenced by many factors, including platelets. Diurnal changes of in vivo platelet activation were investigated by whole blood flow cytometry in 10 young healthy male volunteers using anti-GMP-140 (anti-alpha-granule membrane protein 140 kD) monoclonal antibody at 3h intervals from 06:00 to 24:00. We also studied circulating platelet aggregates to investigate whether there exists a similarity between the results of these methods. Results of flow cytometric analysis indicate that there is an increase in platelet activation during the period from 06:00 to 09:00. Platelet activation then decreases gradually during the period from noon to midnight. These changes are accompanied by a similar trend in circulating platelet aggregates. This suggests that GMP-140 expression on platelets is synchronized with or followed by platelet aggregate formation in vivo, and increased platelet activation may predispose individuals to thrombosis at this time

Hydroxyurea treatment for chronic myeloid leukemia during pregnancy

The incidence of chronic myeloid leukemia (CML) associated with pregnancy is estimated to be 1/75,000. Several types of treatments have been used for CML during pregnancy. These are cytotoxic drugs, alpha-interferone, splenic irradiation (with shielding of the uterus) and leukapheresis. Hydroxyurea is a cytotoxic drug that inhibits the synthesis of DNA and can be used both in the chronic and accelerated phases of CML (1)

Paraneoplastic cerebellar degeneration in association with Hodgkin's disease: A report of two cases

Two patients with paraneoplastic cerebellar degeneration accompanying Hodgkin's disease were treated with plasma exchange in combination with Hodgkin's disease chemotherapy or radiation therapy, respectively. Significant improvement in Plasma exchange neurologic symptoms was obtained in 1 of them

The effect of anthracycline-based (epirubicin) adjuvant chemotherapy on plasma TAFI and PAI-1 levels in operable breast cancer

An increased incidence of thromboembolic events has been described in women receiving systemic chemotherapy for breast cancer. The effect of anthracycline-based adjuvant chemotherapy regimens on fibrinolytic system markers of plasminogen activator inhibitor-1 (PAI-1) and thrombin activitable fibrinolysis inhibitor (TAFI) was investigated in patients with operable breast cancer. Twenty-four patients with operable breast cancer (median age, 54.5 years; range, 37-72 years) enrolled in our study. Stage I-II and stage IIIA cases received EC (Epirubicin 90 mg/m(2)/d1, I.V. and cyclophosphamide 600 mg/m(2)/dI, I.V.) and FEC (5-fluorouracil 500 mg/m(2)/d1, I.V., epirubicin 100 mg/m(2)/d1, I.V., and cyclophosphamide 500 mg/m2/dI, I.V.) as an adjuvant chemotherapy regimen, respectively. Each group consisted of 12 patients. Blood samples were obtained at baseline and just before the third cycle of EC and fourth cycle of FEC chemotherapy regimens. Plasma TAR antigen and PAI-1 levels did not disclose any statistical difference between basal and postchemotherapy levels within each group and between two groups. Although postchemotherapy D-dimer levels were statistically higher in the FEC group than in the EC group, results in both groups were within normal ranges. More studies concerning the role of fibrinolytic system in breast cancer patients receiving chemotherapy, probably including cases with advanced stage and with different chemotherapy regimens and dose intensities, are needed