THE ROLE OF ESTROGENS AND ESTROGEN RECEPTORS IN MELANOMA DEVELOPMENT AND PROGRESSION.

Melanoma has a significant mortality and its growing incidence is associated with important social and health care costs. Thus, investigation of the complex mechanisms contributing to emergence and development of melanoma are of real interest both in scientific research and clinical practice. Estrogens play an important role in the emergence and development of certain types of cancer, such as breast cancer, endometrial cancer and ovarian cancer, but their role in development of cutaneous melanoma is still a matter of debate. Various data suggest that increased levels of endogenous estrogens during pregnancy or exposure to exogenous estrogens by use of oral contraceptives (OCs) and hormone replacement therapy (HRT) may have a potential role in melanoma development and progression. Moreover, there were revealed several intracellular pathways which can support the connection between estrogens, estrogen receptors (ER) and melanoma. While ER-ß plays an antiproliferative role, ER-α promotes cell growth and cellular atypia. Thus, inhibition of ER-ß activity in the skin can increase the risk for development of cutaneous melanoma and spread of metastatic cells. However, despite recent advances in this area, the exact role and clinical implications of estrogens and estrogen receptors in melanoma are still not entirely understood and require further investigations.

Investigation of the effects of ischemic preconditioning on the HRV response to transient global ischemia using linear and nonlinear methods.

Ischemic preconditioning (IP) has been used as a strategy to prevent cell death in various organs, including the brain and the heart. Investigation of the effects of ischemic preconditioning mostly employed models with reduced complexity, such as cell cultures, tissue slices or perfused organ preparations. Although such models can provide valuable insight into the protective mechanism of preconditioning, the functional (re)organization of the control mechanisms at the level of the living organism cannot be assessed. The purpose of the present animal model study was to evaluate the effect of global ischemic preconditioning on the heart rate variability (HRV) response to the asphyxia insult. The data consisted of 4 h RR interval measurements recorded in five preconditioned and five non-preconditioned Wistar rats. Using linear (time and frequency domain) and nonlinear (approximate entropy and parameters of Poincare plots) measures, we evaluated the dynamic time course of the HRV response to the asphyxia insult and the effect of preconditioning on the autonomic neurocardiac control. Both the linear and nonlinear parameters indicate a faster recovery of the baseline HRV corresponding to the preconditioned groups, though only the spectral analysis identifies a statistically significant difference between the two groups. For the preconditioned group, at about 90 min after the asphyxic insult, the autonomic neural balance (measured by LF/HF ratio) appears fully recovered. The small variation of the rest of the parameters indicates the necessity of further investigation including the design of a larger study with a higher statistical power. Our results show for the first time that global ischemic preconditioning influences the HRV response to the asphyxia injury. The neuroprotective effect of preconditioning translates into a faster recovery of the basal HRV and the autonomic modulation of the heart.

On-line electrical impedance measurement for monitoring blood viscosity during on-pump heart surgery.

BACKGROUND: The viscosity of blood (eta) as well as its electrical impedance at 20 kHz at high shear rate depends on hematocrit, temperature, concentration of macromolecules and red cell deformability. The aim of our study was to investigate the relation between viscosity and electrical impedance in a heart-lung machine-like set-up, because during on-pump heart surgery considerable viscosity changes occur. METHODS: Blood of 10 healthy volunteers was examined under temperature variation between 18.5 and 37 degrees C at four different levels of hemodilution. Blood viscosity was examined with a golden-standard technique, i.e. a Contraves LS 30 Couette viscometer, and the results were compared with measurements of the electrical resistivity (R) at 20 kHz by a specially designed device in series with the tubing system of a heart-lung machine. All measurements were performed at a shear rate of 87 s(-1). RESULTS: Using stepwise multiparameter regression analysis (SPSS) a highly significant correlation was found (r(2) = 0.882) between viscosity (eta) and resistivity (R). Adding the variables sodium ([Na(+)]) and fibrinogen ([Fibr]) concentration the coefficient of correlation further improved to r(2) = 0.928 and the relation became: eta = -0.6844 + 0.038 R + 0.038 [Na(+)] + 0.514 [Fibr]. All coefficients showed a statistical significance of p < 0. 001. CONCLUSIONS: Electrical impedance measurement is feasible in a heart-lung machine-like set-up and allows accurate continuous on-line estimation of blood viscosity; it may offer an adequate way to record and control viscosity changes during on-pump heart surgery.

Characterization of heart rate variability changes following asphyxia in rats.

OBJECTIVES: A non-invasive method to monitor the functioning of the autonomous nervous system consists in heart rate variability (HRV) analysis. The aim of this study was to investigate the changes on HRV after an asphyxia experiment in rats, using several linear (time and frequency domain) and nonlinear parameters (approximate entropy, SD1 and SD2 indices derived from Poincare plots). METHODS: The experiments involved the study of HRV changes after cardiac arrest (CA) resulting from 5 min of hypoxia and asphyxia, followed by manual resuscitation and return of spontaneous circulation. 5 min stationary periods of RR intervals were selected for further analysis from 5 rats in following distinct situations: 1) baseline, 2) 30 min after CA, 3) 60 min after CA, 4) 90 min after CA, 5) 120 min after CA, 6) 150 min after CA. The ANS contribution has been delineated based on time and frequency domain analysis. RESULTS AND CONCLUSIONS: The results indicate that the recovery process following the asphyxia cardiac arrest reflects the impaired functioning of the autonomic nervous system. Both linear and nonlinear parameters track the different phases of the experiment, with an increased sensitivity displayed by the approximate entropy (ApEn). After 150 min the ApEn RRI parameter recovers to its baseline value. The results forward the ApEn as a more sensitive parameter of the recovery process following the asphyxia.