DARU Journal of Pharmaceutical Sciences184Effects of arsenic trioxide, all-trans-retinoic acid and dexamethasone on NB4 cell line.3039AMandegaryMMehrabani20151109Experimental and preclinical observations have indicated that combination therapy with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) may strongly enhance their therapeutic effects in the treatment of acute promyelocytic leukemia (APL). Whilst dexamethasone (Dex) is routinely used for the control of APL- differentiation syndrome, its effect on the pharmacodynamics of ATO is not clear. Therefore, in this study, effects of therapeutic concentrations of ATO, ATRA and Dex and their sequential usages on the proliferation, differentiation and apoptosis in t(15;17)-positive NB4 cells was investigated.Cells were treated with therapeutic concentrations of ATO, ATRA and Dex either as single or in combination and cell proliferation was assessed by XTT assay. Expression of CD11b as an indicator of cell differentiation and the percentage of 7-AAD positive cells as a marker of apoptosis were determined by flow cytometry.ATO, but not ATRA and Dex, decreased proliferation of the cells dose-dependently. Pre-treatment of the cells with any of the drugs did not alter the effects of other drugs on the proliferation. Pre-treatments with Dex blocked the apoptotic effect of ATO (1 µM).No improvement or antagonistic effects was observed with the pretreatment/ combination of the ATO and ATRA on the differentiation and apoptosis of the cells. It is possible that concomitant usage of Dex with apoptotic doses of ATO in APL patients counteract therapeutic effects of ATO.https://daru.tums.ac.ir/index.php/daru/article/view/451DARU Journal of Pharmaceutical Sciences184Fentanyl supplement expedites the onset time of sensory and motor blocking in interscalene lidocaine anesthesia.298302RsMoharariJSadeghiMrKhajaviMeDavariMMojtahedzadeh20151109Opioids are usually used in regional anesthesia, with or without local anesthetics to improve the regional block or postoperative pain control. Since no data are available on fentanyl's effect on the onset time of lidocaine interscalene anesthesia, the purpose of this study was to examine its effect on the onset time of sensory and motor blockade during interscalene anesthesia.In a prospective, randomized, double-blind study, ninety patients scheduled for elective shoulder, arm and forearm surgeries under an interscalene brachial plexus block.They were randomly allocated to receive either 30 ml of 1.5% lidocaine with 1.5 ml of isotonic saline (control group, n=39) or 30 ml of 1.5% lidocaine with 1.5 ml (75 µg) of fentanyl (fentanyl group, n=41). Then the onset time of sensory and motor blockades of the shoulder, arm and forearm were evaluated every 60 sec. The onset time of the sensory and motor blockades was defined as the time between the last injection and the total abolition of the pinprick response and complete paralysis. The duration of sensory blocks were considered as the time interval between the administration of the local anesthetic and the first postoperative pain sensation.Ten patients were excluded because of unsuccessful blockade or unbearable pain during the surgery. The onset time of the sensory block was significantly faster in the fentanyl group (186.54±62.71sec) compared with the control group (289.51±81.22, Phttps://daru.tums.ac.ir/index.php/daru/article/view/452DARU Journal of Pharmaceutical Sciences184Simultaneous spectrophotometric determination of paracetamol, phenylephrine and chlropheniramine in pharmaceuticals using chemometric approaches.2927M RKhoshayandHAbdollahiAGhaffariMShariatpanahiHFarzanegan20151109The linear multivariate calibration models such as principal components regression (PCR) and partial least squares regressions (PLS1 and PLS2) due to the mathematical simplicity and physical or chemical interpretability are sufficient and generally preferred method for analysis of multicomponent drugs. In this study, simultaneous determination of paracetamol, phenylephrine and chlorpheniramine in pharmaceuticals using chemometric methods and UV spectrophotometry is reported as a simple alternative technique.Principal components regression (PCR) and partial least squares regressions (PLS1 and PLS2) were used for chemometric analyses of data obtained from the spectra of paracetamol, phenylephrine and chlorpheniramine between wavelengths of 200 to 400 nm at several concentrations within their linear ranges. The analytical performance of these chemometric methods were characterized by relative prediction errors and recoveries (%) and compared with each other.PCR, PLS1 and PLS2 were successfully applied to a tablet formulation, with no interference from excipients as indicated by the recovery. However, the PLS1 shows better results due to its flexibility and mathematical principals.The proposed methods are simple and rapid requiring no separation step, and can be easily used as an alternative in the quality control of drugs.https://daru.tums.ac.ir/index.php/daru/article/view/453DARU Journal of Pharmaceutical Sciences184Mutation of the histidin residue of the DRH motif in vasopressin V2 receptor expression and function.28691HMir Mohammad SadeghiMRabbaniAJafarianHNajafzadehLSafaeian20151109Vasopressin type 2 receptor (V2R), a G protein coupled receptor (GPCR), plays an important role in the regulation of renal antidiuretic function. The highly conserved DRH motif is essential for G protein signaling of V2R; however its role especially regarding the histidin residue is not fully understood..Site directed mutagenesis was performed with replacements of the histidin to isoleucine by using nested polymerase chain reaction. ELISA was performed for receptor expression assay and the adenylyl cyclase activity assay was performed for functional characterization of DRI mutation on V2R signaling.The adenylyl cyclase activity assay in COS-7 cells showed no difference in the amount of cAMP production between the wild type and the mutant V2 receptors. The V2 receptor expression was not changed in the presence of this mutation using ELISA assay. These results suggest that the role of histidin residue is not critical in the V2 receptor function, however further mutagenesis studies are required to define the role of this motif in V2R function.https://daru.tums.ac.ir/index.php/daru/article/view/454DARU Journal of Pharmaceutical Sciences184Cloning and expression of human vascular endothelial growth factor gene and inhibition of its expression by antisense in prokaryotic system.2815MYazdanfarMBandehpourFYarianAKoochakiKParivarBKazemi20151109Angiogenesis is an important process in physiology and disease pathogenesis and is controlled in a healthy body by a number of stimulatory and inhibitory factors. The aim of this study was to determine the effect of antisense transcript on the sense transcript of the endothelial growth factor (EGF) gene in bacterial system as an approach for the gene regulation in tumors.The hepatoma cell line (HepG2) was stimulated by PMA. VEGF mRNA was used for RT-PCR. VEGF cDNA was synthesised and cloned into T-vector pTZ57R, then sense fragment of VEGF subcloned into pACYC Duet-1 expression vector and antisense VEGF subcloned into pCDNA3 expression vector. Recombinant plasmids were transforemed into BL21 bacterial cells. Expression of recombinant plasmid was analysed by western blot technique.The recombinant pCDNA3-VEGF (pYZantiVEGF) was successfully expressed in BL21 cells. Western blot analysis showed that the expression of VEGF decreased significantly in the cells transfected with VEGF antisense RNA compared with the pACYCDUET-1-VEGF (pYZsenseVEGF) transfected and control.The expression of VEGF in BL21 cells was strong. In vitro, antisense of VEGF inhibited VEGF expression significantly in BL21 cells.https://daru.tums.ac.ir/index.php/daru/article/view/455DARU Journal of Pharmaceutical Sciences184Upregulation of the ERG11 gene in Candida krusei by azoles.27680MTavakoliFZainiMKordbachehMSafaraRRaoofianMHeidari20151109Candida species are the agents of local and systemic opportunistic infections and have become a major cause of morbidity and mortality in the last few decades. Azole resistance in Candida krusei (C. krusei) species appears to be the result of gene alterations in relation to the ergosterol biosynthesis pathway, as well as efflux pumps. The main objective of this study was to examine the RNA expression of ERG11 in C. krusei which had been identified to be resistance to azoles.The ERG11 mRNA expression was investigated in four Iranian clinical isolates of C. krusei, which were resistant to fluconazole and itraconazole by a semiquantitative RT-PCR.The mRNA expression levels were observed in all four isolates by this technique. Furthermore, it was found that ERG11 expression levels vary among four representative isolates of C. krusei. Although DNA sequencing revealed no significant genetic alteration in the ERG11 gene, one heterozygous polymorphism was observed in two isolates, but not in others. This polymorphism was found in the third base of codon 313 for Thr (ACT>ACC).Even though such a polymorphism creates a new Ear1 restriction site, no significant effect was found on the resistance of C. krusei to azoles. RESULTS of this investigation are consistent with previous studies and may provide further evidence for the genetic heterogeneity and complexity of the ergosterol biosynthetic pathway or efflux pumps.https://daru.tums.ac.ir/index.php/daru/article/view/456DARU Journal of Pharmaceutical Sciences184Antidiabetic properties of the ethanolic extract of Rhus coriaria fruits in rats.2705SMohammadiSMontasser KouhsariAMonavar Feshani20151109Fruits of Rhus coriaria L. (Anacardiaceae) are traditionally used as a table spice in Iran and are highly recommended for diabetic patients. The purpose of this study was to determine the antidiabetic properties of the ethanolic extract of Rhus coriaria fruits and also its mechanisms of action.The effects of ethanolic extract of Rhus coriaria fruits were measured on blood glucose, lipids and antioxidant enzymes by commercial kits. mRNA levels of insulin (INS) and glucose transporter type-4 (GLUT-4) genes were investigated by RT-PCR (Reverse transcription- polymerase chain reaction) technique. Moreover, its effects on intestinal a-glucosidases was measured using an in vitro method.Following a single dose administration of the extract it was found that extract could significantly reduce postprandial blood glucose by 24% (at 5 hrs). In the long term experiment, on the day of 21, postprandial blood glucose (PBG) was found to be significantly lower (by 26%) compared to diabetic control group. The plant extract raised markedly serum high-density lipoprotein (HDL) by 34% and also reduced low-density lipoprotein (HDL) by 32%. Also it had noticeable antioxidant effects by elevating superoxide dismutase (SOD) and catalase(CAT) activities by 46% and 77%, respectively. However it did not show a strong effect on glutathione peroxidase (GPX) activity. The extract inhibited maltase and sucrase activities by 44% and 27%, respectively. However it made no changes in the transcript levels of INS and GLUT-4 genes. It can be concluded that constituents of Rhus coriaria fruits have effective components which can be utilized as useful herb for alleviation of diabetes complications.https://daru.tums.ac.ir/index.php/daru/article/view/457DARU Journal of Pharmaceutical Sciences184Effects of Semelil (ANGIPARS™) on focal cerebral ischemia in male rats.2659MAsadi-ShekaariHEftekhar VaghefiATalakoubHrKhorram Khorshid20151109Cerebral ischemia is one of the main causes of long term disability and death in aged populations. Many herbal drugs and extracts have been used for the treatment of cerebral ischemia induced insults. This study was designed to investigate the protective effect of Semelil (ANGIPARS™), a new herbal drug, on focal cerebral ischemia in male rats.MALE RATS WERE DIVIDED INTO FIVE GROUPS: sham-operated, ischemic animals treated with distilled water as vehicle, ischemic animals treated with 1, 10 and 100 mg/kg of Semilil respectively. Middle cerebral artery occlusion (MCAO) model was used in NMRI rats and neuronal injury analyzed in hippocampal CA1 sector after 48 hrs of Middle Cerebral Artery (MCAO).Results of this study showed that treatment with semelil attenuated ischemic damages and has positive effects on focal cerebral ischemia.https://daru.tums.ac.ir/index.php/daru/article/view/458DARU Journal of Pharmaceutical Sciences184Effects of Angipars on oxidative inflammatory indices in a murine model of periodontitis.2604MMousavi-JaziHAslroostaA RMoayerMBaeeriMAbdollahi20151109There are strong evidences linking overproduction of reactive oxygen species and periodontal diseases. The aim of this study was to evaluate efficacy of Angipars a natural potent anti oxidative agent on markers of the oxidative damages and periodontal inflammation in the rat.Periodontitis was induced by single injection of lipopolysaccharide (LPS) from E. coli (10 µg/µl saline) into rat mandibular gingiva. After 10 days, animals in the test group received Angipars (2.1 mg/kg) by gavage once a day and those of control group received same amount of vehicle. The amount of interleukin (IL)-1β, lipid peroxidation (LPO), and 8-hydroxydeoxyguanosine (8-OHdG) were measured in gingival biopsy samples and the degree of apical migration of junctional epithelium (JE), alveolar bone resorption, and the number of polymorphonuclears (PMN) were evaluated by histological analysis of block samples of the left mandibular first molars.Periodontitis group showed a significant increase in periodontal IL-1β, LPO, 8-OHdG, apical migration of JE, alveolar bone resorption and number of PMNs. Angipars treatment resulted in a significant decrease in gingival IL-1β, LPO, 8-OHdG and the apical migration of JE; however, the reduction of alveolar bone resorption was not significant. The number of PMN increased significantly after treatment with Angipars. While intake of vehicle resulted in a significant decrease in gingival IL-1β and LPO, the reduction of 8-OHdG, apical migration of JE, and alveolar bone resorption were not significant. Interestingly, PMNs were increased in groups received Angipars or the vehicle.From the results of this study, it seems that Angipars is beneficial in periodontitis by reduction of inflammatory and oxidative damage. Unexpected increase of PMN count by Angipars strengthens the hypothesis that chronic inflammatory disorders like periodontitis may need more time to get best advantage of anti oxidative drugs like Angipars. Regarding role of microbes in pathogenesis of periodontitis, further studies should be focused on antimicrobial effects of Angipars.https://daru.tums.ac.ir/index.php/daru/article/view/459DARU Journal of Pharmaceutical Sciences184Effect of pomegranate juice pre-treatment on the transport of carbamazepine across rat intestine.2549DAdukondaluYShravan KumarYVamshi VishnuRShiva KumarYMadhusudan Rao20151109Many drug substances along with a variety of naturally occurring dietary or herbal components interact with the CYP enzyme system. The present study was aimed to investigate the effect of pomegranate juice pre-treatment on the transport of carbamazepine across the rat intestine.The transport of carbamazepine across different parts of rat intestine was studied by everted and non-everted sac methods. The control and pomegranate juice (10 ml Kg(-1) for 7 days) pre-treated rats were sacrificed and isolated the intestine. The sacs of intestine were prepared, treated with carbamazepine solution and then placed in dulbeccos buffer. Samples were collected periodically and the drug content was estimated using HPLC.The results show that there was a significant (phttps://daru.tums.ac.ir/index.php/daru/article/view/460DARU Journal of Pharmaceutical Sciences184Formulation and In Vitro evaluation of pH sensitive oil entrapped polymeric blended gellan gum buoyant beads of clarithromycin.24753GTripathiSSingh20151109A gastroretentive pH sensitive system has been a frontier approach to release the drug in controlled manner in stomach and duodenum. The aim of this study was to develop buoyant beads of gellan based, wherein, the oil was entrapped, blended with hydroxypropyl methyl cellulose or carbopol 934 in order to evaluate its potential for targeted sustained delivery of clarithromycin in the gastric region.Buoyant beads of gellan was developed by inotropic gelation technique using calcium carbonate as gas forming agent and the drug polymer dispersion was emulsified with mineral oil. The oil was entrapped and blended with hydroxypropyl methyl cellulose or carbopol 934. The developed beads were evaluated in terms of diameter,% floating, encapsulation efficiency, In vitro drug release, In vivo gastric residence efficacy and clarithromycine concentration in the mucosa of the experimental animal model.The scanning electron microscope photograph indicated that the prepared beads were spherical in shape and buoyancy, encapsulation efficiency and drug content obtained from all batches were satisfactory. Particle size and percentage buoyancy of the gel beads increased by raising the concentration of calcium carbonate. The formulation exhibited sustained release profile and was best fitted in the Peppas model with nhttps://daru.tums.ac.ir/index.php/daru/article/view/461DARU Journal of Pharmaceutical Sciences184Preparation and in vitro antibacterial evaluation of gatifloxacin mucoadhesive gellan system.23746KKesavanGNathJkPandit20151109The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to precorneal elimination of the drug may be overcome by the use of mucoadhesive in situ gel forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac and have good mucoadhesion with ocular mucus layers. The objective of this study was to formulate ophthalmic mucoadhesive system of gatifloxacin (GTN) and to evaluate its in vitro antibacterial potential against, Staphylococcus aureus and Escherichia coli.: Mucoadhesive systems were prepared using gellan combined with sodium carboxymethylcellulose (NaCMC) or sodium alginate to enhance the gel bioadhesion properties. The prepared formulations were evaluated for their gelation, and rheological behaviors, mucoadhesion force, in vitro drug release, and antibacterial activity.All formulations in non-physiological or physiological conditions showed pseudoplastic behaviors. Increase in the concentration of mucoadhesive agent enhanced the mucoadhesive force significantly. In vitro release of gatifloxacin from the mucoadhesive system in simulated tear fluid (STF, pH of 7.4) was influenced significantly by the properties and concentration of gellan, sodium carboxymethyl cellulose and sodium alginate. Significant reduction in the total bacterial count was observed between drug solution (control) and mucoadhesive batches against both tested organisms.The developed mucoadhesive system is a viable alternative to conventional eye drops of GTN due to its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain the release of the drug.https://daru.tums.ac.ir/index.php/daru/article/view/462