Citoprotektivni učinci silafibrata, novosintetiziranog silikoniranog derivata klofibrata protiv acetaminofenom izazvane toksičnosti u izoliranim hepatocitima štakora

Acetaminophen (N-acetyl para amino phenol, APAP) is a widely used antipyretic and analgesic drug responsible for various drug-induced liver injuries. This study evaluated APAP-induced toxicity in isolated rat hepatocytes alongside the protective effects of silafibrate and N-acetyl cysteine (NAC). Hepatocytes were isolated from male Sprague-Dawley rats by collagenase enzyme perfusion via the portal vein. This technique is based on liver perfusion with collagenase after removing calcium ions (Ca2+) with a chelator. Cells were treated with different concentrations of APAP, silafibrate, and NAC. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation, and mitochondrial depolarisation were measured as toxicity markers. ROS formation and lipid peroxidation occurred after APAP administration to rat hepatocytes. APAP caused mitochondrial depolarisation in isolated cells. Administration of silafibrate (200 μmol L-1) and/or NAC (200 μmol L-1) reduced the ROS formation, lipid peroxidation, and mitochondrial depolarisation caused by APAP. Cytotoxicity induced by APAP in rat hepatocytes was mediated by oxidative stress. In addition, APAP seemed to target cellular mitochondria during hepatocyte damage. The protective properties of silafibrate and/or NAC against APAP‑induced hepatic injury may have involved the induction of antioxidant enzymes, protection against oxidative stress and inflammatory responses, and alteration in cellular glutathione content.Acetaminofen (N-acetil-para-aminofenol, APAP) često je korišteni antipiretik i analgetik koji može izazvati oštećenja jetara. Na modelu izoliranih hepatocita štakora istražili smo toksične učinke APAP-a i protektivne učinke silafibrata i N-acetilcisteina (NAC). Hepatociti su izolirani iz mužjaka štakora soja Sprague-Dawley perfuzijom jetara i uvođenjem enzima kolagenaze putem portalne vene. Ta se tehnika zasniva na perfuziji jetara kolagenazom nakon uklanjanja kalcijevih iona (Ca2+) kelatorom. Stanice su tretirane različitim koncentracijama APAP-a, silafibrata i NAC-a. Kao markeri toksičnosti mjereni su smrt stanica, stvaranje reaktivnih kisikovih vrsta (ROS), lipidna peroksidacija i depolarizacija mitohondrija. Primjena APAP-a u štakora izazvala je stvaranje ROS-ova i lipidnu peroksidaciju. APAP je uzrokovao depolarizaciju mitohondrija u izoliranim stanicama. Primjena silafibrata (200 μmol L-1) i/ili NAC-a (200 μmol L-1) smanjila je stvaranje ROS-a, lipidnu peroksidaciju i depolarizaciju mitohondrija uzrokovanu APAP-om. Utvrdili smo da je citotoksičnost APAP-a posredovana oksidativnim stresom. Nadalje, čini se da su mitohondriji ciljni stanični organeli za oštećenja hepatocita izazvanih APAP-om. Moguće je da su protektivna svojstva silafibrata i/ili NAC-a protiv APAP‑om induciranog oštećenja jetara uključivala i indukciju antioksidacijskih enzima, zaštitu od oksidativnog stresa i upalnih odgovora te promjenu razine staničnoga glutationa

Semi-active fuzzy control for seismic response reduction of building frames using variable orifice dampers subjected to near-fault earthquakes

In this paper, a fuzzy-rule-based semi-active control of building frames using semi-active variable orifice dampers (VODs) is presented. Additionally, the consequences of well-known characteristics of near-fault ground motions, forward directivity and fling step, on the seismic response control is investigated. The membership functions and fuzzy rules of the fuzzy controller were optimized by genetic algorithm. To illustrate the efficiency of the proposed fuzzy controller strategy in application and effects of near-fault ground motions, numerical simulation for a 10-story building frame equipped with VODs is presented. The VODs are installed in all storeys to prevent damage to the structure from severe earthquakes. The controlled response of the frame was compared with results obtained by controlling the frame by the classical clipped-optimal control method based on linear quadratic regulator theory. Results revealed that the fuzzy logic controller is capable of improving the structural responses and VODs are promising for reducing seismic responses during near-fault earthquakes. </jats:p

Robust controller analysis and synthesis with consideration of various uncertainties for building structures

The H∞ control method is one of the most widely used methods of robust control theory, in which system stability can be guaranteed by using linear matrix inequalities (LMIs) and Lyapunov theory. The presence of variousuncertainties such as parametric uncertainty, time delay, sensors/actuators faults and failure is inevitable in the active control of the building structures. This paper focuses on the uncertain structural control system, in whichthe controller synthesis process is complicated by a set of uncertainties and the generation of large and sparse matrices. Synthesizing a sub-optimal controller for this uncertain structural control system is done according to the new approach and to validate it, a comparison with the controller of critically damped conditions(CD) as an ideal state is performed. In order to compare the two mentioned controllers, two 3- and 8-story shear structures excited by synthetic earthquake are considered to assess the responses. The simultaneous presence of various types of uncertainties is examined and their effects on the results are investigated. The results indicate that the sub-optimal designed H∞ robust controller displays good robustness against time delay; however, parametricuncertainty was evaluated as an unfavorable effect for the allowable time delay. Despite the negative impact of the parametric uncertainties, it was illustrated that the nominal sensors/actuators faults do not affect the allowable time delay