Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration

INTRODUCTION: Results from our laboratory have demonstrated that intracerebroventricular administration of sildenafil to conscious rats promoted a noticeable increase in both lumbar sympathetic activity and heart rate, with no change in the mean arterial pressure. The intracerebroventricular administration of sildenafil may have produced the hemodynamic effects by activating sympathetic preganglionic neurons in the supraspinal regions and spinal cord. It is well documented that sildenafil increases intracellular cGMP levels by inhibiting phosphodiesterase type 5 and increases cAMP levels by inhibiting other phosphodiesterases. OBJECTIVE: To examine and compare, in conscious rats, the hemodynamic response following the intrathecal administration of sildenafil, 8-bromo-cGMP (an analog of cGMP), forskolin (an activator of adenylate cyclase), or dibutyryl-cAMP (an analog of cAMP) in order to elucidate the possible role of the sympathetic preganglionic neurons in the observed hemodynamic response. RESULTS: The hemodynamic responses observed following intrathecal administration of the studied drugs demonstrated the following: 1) sildenafil increased the mean arterial pressure and heart rate in a dose-dependent manner, 2) increasing doses of 8-bromo-cGMP did not alter the mean arterial pressure and heart rate, 3) forskolin did not affect the mean arterial pressure but did increase the heart rate and 4) dibutyryl-cAMP increased the mean arterial pressure and heart rate, similar to the effect observed following the intrathecal injection of the highest dose of sildenafil. CONCLUSION: Overall, the findings of the current study suggest that the cardiovascular response following the intrathecal administration of sildenafil to conscious rats involves the inhibition of phosphodiesterases other than phosphodiesterase type 5 that increase the cAMP level and the activation of sympathetic preganglionic neurons

INVESTIGATION Physiological and lifestyle factors contributing to risk and severity of peri-orbital dark circles in the Brazilian population*

Abstract: BACKGROUND: Peri-orbital dark circles are a cosmetic concern worldwide, and have been attributed to hyperpigmentation from allergy or atopic dermatitis, blood stasis, structural shadowing effects, and a thin epidermis/dermis under the eye. It is of interest to better understand lifestyle and demographic risk factors and the relative impact of melanin, blood and epidermal/dermal factors on the severity of Peri-orbital dark circles. OBJECTIVE: To compare by non-invasive imaging the impact of biological factors to a visual grading scale for Peri-orbital dark circles, and test the correlation of various demographic factors with Peri-orbital dark circles. METHODS: Subjects completed a lifestyle and health survey, and Peri-orbital dark circles severity was evaluated using standardized photographs. Hyperspectral image analysis was used to assess the contributions of melanin, blood volume, degree of blood oxygen saturation, and dermal scattering. RESULTS: Family history was the most signifi cant risk factor for Peri-orbital dark circles. The average age of onset was 24 years, and earlier onset correlated with higher severity scores. Asthma was signifi cantly associated with Peri-orbital dark circles scores, but self-reported allergy was not. In this study, sleep was not correlated with Peri-orbital dark circles scores. Hyperspectral imaging indicated that melanin was the dominant correlate for Peri-orbital dark circles severity, while oxygen saturation was secondary. The difference between under-eye and cheek measurements for ∆L*and ∆E* were the most signifi cant instrumental parameters correlated with visual assessment of Peri-orbital dark circles severity. CONCLUSION: Although typically associated with lack of sleep, risk of Peri-orbital dark circles is primarily hereditary. The main factors contributing to the appearance of Peri-orbital dark circles are melanin and (deoxygenated) blood

A new indirect measurement method of the electron temperature for the Protosphera's pinch plasma

This article presents a new method for estimating the electron temperature of the Protosphera's screw pinch. The temperature radial profile is obtained by a self-consistent modeling of a 1D MHD equilibrium along with a 0D power balance of the plasma column, given measurements and estimates of the axial pinch plasma current, of the plasma rotational frequency and, at the equatorial plane, of the electron density radial profile, of the edge poloidal magnetic field, of the edge electron temperature and of the neutrals pressure in the vacuum vessel. The plasma is considered in equilibrium with its neutral phase and in constant rotation. A MATLAB code has been developed with the aim of estimating the MHD radial equilibrium profiles, the thermodynamic plasma state and the neutrals profile. The numerical estimates are compared with available experimental data showing a good agreement.Comment: 4 pages, 6 figures, 1 table, research presented to the "6th ICFDT

Variation of the divertor geometry in Alcator C-Mod

To be published in the Proceedings of the 1 6th IAEA Fusion Energy Conference