A NOVEL ROLE OF SIRT1 IN SILDENAFIL INDUCED CARDIOPROTECTION IN MICE

Phosphodiesterase-5 inhibitor, sildenafil (SIL) protects against myocardial ischemia/reperfusion (I-R) injury. We hypothesized that SIL-induced protection may be mediated through activation of SIRT1, an enzyme which deacetylates proteins involved in cellular stress response. Adult male ICR mice were treated with SIL (0.7mg/kg ip), Resveratrol (RSV) (5mg/kg ip) (positive control), or saline (0.2 ml ip). The hearts were harvested 24 h later and homogenized for SIRT1 activity analysis. Both SIL and RSV increased cardiac SIRT1 activity (P\u3c0.001) as compared to Saline. Adult mouse ventricular cardiomyocytes pre-treated with either SIL or RSV (1µM) in vitro also upregulated SIRT1 activity (P\u3c0.05). SIL also reduced infarct size following 30 min. ischemia and 24 h reperfusion in vivo. Sirtinol (5mg/kg in 10% DMSO, ip), a SIRT1 inhibitor abolished the infarct-limiting effect of SIL and RSV (P\u3c0.001). In conclusion, activation of SIRT1 by SIL plays an essential role in cardioprotection against I-R injury

Granulomatous Hypophysitis Masquerading as Hemorrhagic Pituitary Adenoma

Optic neuropathy from granulomatosis with polyangiitis (GPA), formerly termed Wegener's, is rare. Even more unusal is blindness related to hypophysitis in this vasculitis. We encountered a perplexing case of acute vision loss ulitmately found to be result from GPA

PV Integration into Distribution Networks in Saudi Arabia

One of the most important operational requirements for any electrical power network for both distribution and transmission level is voltage control. Many studies have been carried out to improve or develop new voltage control techniques to facilitate safe connection of distributed generation. In Saudi Arabia, due to environmental, economic and development perspectives a wide integration of photovoltaic (PV) generation is expected in the near future. This development in the networks may cause voltage regulation problems due to the interface with the existing conventional control system. Therefore, this work determines the impact of linking PV directly with the grid to find the level of penetration that can be achieved without any technical changes in the distribution network. Then, the effect of Grid-Connected Photovoltaic (GCPV) systems on the voltage regulation in residential networks has been investigated. This thesis introduces a new voltage control scheme for residential area networks in Saudi Arabia based on Fuzzy Logic concept (FL). The structure of two implementations of FL control to regulate the voltage by setting the on-load tap changing transformer in the primary substation is proposed. Finally, another approach for solving the feeder voltage regulation problem at a local level is presented with the goal of fulfilling the plug-and-play feature desired by manufacturers and regulatory bodies. Also, this technique use the FL concept to set up the operating power factor for the inverter used to connect the PV generator. In order to confirm the validity of the proposed methods, simulations using PVSYST, ETAP and MATLAB/Simulink softwares have been carried out for a realistic distribution network with real data for load and solar radiation. Results showing the performance of each scheme are presented in detail, and demonstrate that each scheme is capable of keeping the voltage levels within statutory limits, both in steady-state and under dynamic condition

PV integration into distribution networks in Saudi Arabia

One of the most important operational requirements for any electrical power network for both distribution and transmission level is voltage control. Many studies have been carried out to improve or develop new voltage control techniques to facilitate safe connection of distributed generation. In Saudi Arabia, due to environmental, economic and development perspectives a wide integration of photovoltaic (PV) generation is expected in the near future. This development in the networks may cause voltage regulation problems due to the interface with the existing conventional control system. Therefore, this work determines the impact of linking PV directly with the grid to find the level of penetration that can be achieved without any technical changes in the distribution network. Then, the effect of Grid-Connected Photovoltaic (GCPV) systems on the voltage regulation in residential networks has been investigated. This thesis introduces a new voltage control scheme for residential area networks in Saudi Arabia based on Fuzzy Logic concept (FL). The structure of two implementations of FL control to regulate the voltage by setting the on-load tap changing transformer in the primary substation is proposed. Finally, another approach for solving the feeder voltage regulation problem at a local level is presented with the goal of fulfilling the plug-and-play feature desired by manufacturers and regulatory bodies. Also, this technique use the FL concept to set up the operating power factor for the inverter used to connect the PV generator. In order to confirm the validity of the proposed methods, simulations using PVSYST, ETAP and MATLAB/Simulink softwares have been carried out for a realistic distribution network with real data for load and solar radiation. Results showing the performance of each scheme are presented in detail, and demonstrate that each scheme is capable of keeping the voltage levels within statutory limits, both in steady-state and under dynamic condition.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Power Factor Control of PV Generators in Local Distribution Networks using Fuzzy Logic Concept

ABSTRACT: One of the most important operational requirements for any electrical power network for both distribution and transmission level is voltage control. Many studies have been carried out to improve or develop new voltage control techniques to facilitate safe connection of distributed generation. In Saudi Arabia, due to environmental, economic and development perspectives a wide integration of photovoltaic (PV) generation in distribution network is expected in the near future. This development in the network may cause voltage regulation problems due to the interaction with the existing conventional control system. In a previous paper [1] a control system has been described using a fuzzy logic control to set the on-line tap changer for the primary substation. In this paper a new control system is proposed for controlling the power factor of individual PV invertors based on observed correlation between net active and reactive power at each connection. A fuzzy logic control has been designed to alter the power factor for the remote invertors from the secondary substation to keep the feeder voltage within the permissible limits. In order to confirm the validity of the proposed method, simulations are carried out for a realistic distribution network with real data for load and solar radiation. Results showing the performance of the new control method are presented and discussed. KEYWORDS: Grid connected PV system, Dnetwotk, Power factor, Fuzzy logic, Control. I.INTRODUCTION This paper presents an approach for solving the feeder voltage regulation problem in a local manner, with the goal of fulfilling the plug-and-play feature desired by manufacturers and regulatory bodies. The plug-and-play feature will enable customers to simply connect their PV systems to the distribution feeder, and through a fuzzy logic control (FLC) the power flow from the PV system through the inverters will be controlled to help maintain the feeder voltage level within limits at minimum cost. The chapter paper by the proposed controller objectives. The proposed controller design is based on FLC and the architecture is then presented. Test results of this system are shown to prove that the proposed controller can successfully regulate the voltage of a distribution feeder with PV systems connected to it. Finally the interaction between two controllers at the same feeder has been investigated and a simulation is carried out under MATLAB /Simulink environment to evaluate the stability of the control algorithm. II. CONTROL OF THE REACTIVE POWER OF PV GENERATION USING FLC Consider a voltage source V S ∟δ connected to a utility grid V G ∟0° through a coupling impedance Z=R+jX, as shown i

Sirtuin 1 (SIRT1) activation mediates sildenafil induced delayed cardioprotection against ischemia-reperfusion injury in mice.

BackgroundIt has been well documented that phosphodiesterase-5 inhibitor, sildenafil (SIL) protects against myocardial ischemia/reperfusion (I-R) injury. SIRT1 is part of the class III Sirtuin family of histone deacetylases that deacetylates proteins involved in cellular stress response including those related to I-R injury.Objective/hypothesisWe tested the hypothesis that SIL-induced cardioprotection may be mediated through activation of SIRT1.MethodsAdult male ICR mice were treated with SIL (0.7 mg/kg, i.p.), Resveratrol (RSV, 5 mg/kg, a putative activator of SIRT1 used as the positive control), or saline (0.2 mL). The hearts were harvested 24 hours later and homogenized for SIRT1 activity analysis.ResultsBoth SIL- and RSV-treated mice had increased cardiac SIRT1 activity (PConclusionOur study shows that activation of SIRT1 following SIL treatment plays an essential role in mediating the SIL-induced cardioprotection against I-R injury. This newly identified SIRT1-activating property of SIL may have enormous therapeutic implications

SIRT1 deacetylase activity in the heart tissues from the mice pretreated (<i>i.p.</i>) with saline (0.2 mL), RSV (5 mg/kg), and SIL (0.7 mg/kg) 24 hours prior to 30 min of regional ischemia and 24 hours of reperfusion.

<p>The SIRT1 inhibitor - sirtinol (5 mg/kg) was administered (<i>i.p.</i>) 30 min prior to the onset of ischemia. The Sham group serves as surgical controls, whereas Saline and DMSO groups serve as the drug solvent/vehicle controls. Data are Mean ± SE (n = 3/group). *<i>P</i><0.0001 vs. Control group. #<i>P</i><0.05 vs. all other groups.</p