Effects of fisetin on hyperhomocysteinemia- induced experimental endothelial dysfunction and vascular dementia

This study was designed to investigate the effect of fisetin (FST) on hyperhomocysteinemia (HHcy) - induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Eight groups of Wistar rats were randomly divided as control, vehicle control, L-methionine, FST (5, 10 and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.) and donepezil (0.1 mg/kg, p.o.) respectively. L-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of L-methionine developed behavioral deficits, triggered brain lipid peroxidation (LPO) and compromised brain acetylcholinesterase activity (AChE) and reduced the levels of brain superoxide dismutase (SOD) ,brain catalase (CAT),brain reduced glutathione (GSH) and serum nitrite, increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta and multiple necrotic foci in brain cortex. HHcy induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Pengaruh Tes Elevasi Tungkai Secara Pasif terhadap Variasi Pletismograf untuk Penilaian Responsivitas Cairan pada Pasien yang Dilakukan Pembedahan dengan Anestesi Umum

Fluid responsiveness assessments have shown to be an important matter in perioperative fluid optimization. Respiratory variations in pulse oximetry plethysmographic waveform amplitude (∆POP) and passive leg raising have been shown as promising indicators due to the ability to predict fluid responsiveness. The aim of this study was to assess the effect of passive leg raising (PLR) on ∆POP to predict fluid responsiveness in mechanically ventilated patients after induction of general anesthesia. This was a trialon 30 patients referred for surgery under general anesthesia, aged 18–60 years and ASA physical status I or II, during the period of February–March 2015 at the Central Surgical Installation of Dr. Hasan Sadikin General Hospital Bandung. Patients were studied immediately after the induction of general anesthesia. This trial use the paired t test, Wilcoxon test, and ANOVA for statistical analysis. Vital signs and ∆POP were recorded at baseline, before, and after PLR. PLR induced changes in ∆POP with a ∆POP greater than 13% compared to the initial PLR allowed discrimination between responders and nonresponders to 6/30. There was a significant decrease in ∆POP in responders when compared to the nonresponders(p<0.05). ∆POP can be reduced by PLR and fluid responsiveness can be predicted noninvasively in mechanically ventilated patients during general anesthesia

Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled sitespecific delivery of acidic anti-inflammatory active ingredient

The purpose of the investigation was to evaluate the potential of polyamidoamine (PAMAM) dendrimer as nanoscale drug delivery units for controlled release of water insoluble and acidic anti-inflammatory drug. Flurbiprofen (FB) was selected as a model acidic anti-inflammatory drug. The aqueous solutions of 4.0 generation (G) PAMAM dendrimer in different concentrations were prepared and used further for solubilizing FB. Formation of dendrimer complex was characterized by Fourier transform infrared spectroscopy. The effect of pH on the solubility of FB in dendrimer was evaluated. Dendrimer formulations were further evaluated for in vitro release study and hemolytic toxicity. Pharmacokinetic and biodistribution were studied in male albino rats. Efficacy of dendrimer formulation was tested by carrageenan induced paw edema model. It was observed that the loaded drug displayed initial rapid release (more than 40% till 3rd hour) followed by rather slow release. Pharmacodynamic study revealed 75% inhibition at 4th hour that was maintained above 50% till 8th hour. The mean residence time (MRT) and terminal half-life (THF) of the dendritic formulation increased by 2-fold and 3-fold, respectively, compared with free drug. Hence, with dendritic system the drug is retained for longer duration in the biosystem with 5-fold greater distribution. It may be concluded that the drug-loaded dendrimers not only enhanced the solubility but also controlled the delivery of the bioactive with localized action at the site of inflammation