فهرست مطالب

Pharmaceutical Research - Volume:15 Issue: 4, 2016
  • Volume:15 Issue: 4, 2016
  • تاریخ انتشار: 1395/10/11
  • تعداد عناوین: 39
  • Afshin Zarghi *, Zahra Hajimahdi Pages 595-628
    HIV-1 integrase (IN) enzyme, one of the three main enzymes of HIV-1, catalyzed the insertion of the viral DNA into the genome of host cells. Because of the lack of its homologue in human cells and its essential role in HIV-1 replication, IN inhibition represents an attractive therapeutic target for HIV-1 treatment. Since identification of IN as a promising therapeutic target, a major progress has been made, which has facilitated and led to the approval of three drugs. This review focused on the structural features of the most important IN inhibitors and categorized them structurally in 10 scaffolds. We also briefly discussed the structural and functional properties of HIV-1 IN and binding modes of IN inhibitors. The SAR analysis of the known IN inhibitors provides some useful clues to the possible future discovery of novel IN inhibitors.
    Keywords: HIV, 1, Integrase enzyme, SAR, Molecular diversity, IN Inhibitors
  • Bahram Kazemi *, Amir Zarebkohan, Farhood Najafi, Hamid Reza Moghimi, Mohammad Hemmati, Mohammad Reza Deevband Pages 629-640
    Glioma, as a primary tumor of central nervous system, is the main cause of death in patients with brain cancer. Therefore, development of an efficient strategy for treatment of glioma is worthy. The aim of the current study was to develop a SRL peptide-coated dendrimer as a novel dual gene delivery system for targeting the LRP receptor, an up-regulated gene in both BBB and glioma cells.
    To perform this investigation, our newly developed nanocarrier (PAMAM-PEG-SRL) was used for gene delivery to C6 glioma cell lines. DNA (GFP) was loaded in these functionalized nanoparticles and their cellular uptake/distribution and gene transfection efficacy was evaluated by fluorescence and confocal microscopy. In vitro studies showed that SRL-modified nanoparticles have good transfection efficacy. Results revealed improved gene transfection efficiency of newly-synthesized delivery system. We also found that lactoferrin, as a LRP ligand, reduced the gene transfection efficacy of the delivery system due to its higher affinity compared to SRL peptides (Competitive inhibition). The present results suggest that the synthesized delivery system has the potential to be used as an alternative targeted drug delivery system for brain tumors.
    Keywords: SRL peptide, PAMAM dendrimer, Gene delivery, C6 glioma, Targeted delivery, Brain tumor
  • Farzaneh Sotoudegan, Mohsen Amini, Mehrdad Faizi, Reza Aboofazeli * Pages 641-661
    Nimodipine (NM), as a lipophilic calcium channel blocker indicated for the prevention and treatment of neurological disorders, suffers from an extensive first pass metabolism, resulting in low oral bioavailability. Polymeric micelles, self-assembled from amphiphilic polymers, have a core-shell structure which makes them unique nano-carriers with excellent performance as drug delivery. This investigation was aimed to develop NM-loaded polymeric micelles and evaluate their potential to cross the blood brain barrier (BBB). Micelles from PluronicsP85, F127 and F68 were fabricated for the delivery of NM, using thin film hydration and direct dissolution techniques. Critical micelle concentration of the drug-free micelles was determined by pyrene fluorescence spectroscopy. Dynamic light scattering showed that in most cases, micelles less than 100 nm and low polydispersity indices were successfully developed. Transmission electron microscopy demonstrated spherical shape of micelles. The NM-loaded micelles were also characterized for particle size, morphology, entrapment efficiency, drug loading characteristics, in vitro drug release in phosphate buffer and artificial cerebrospinal fluid (CSF). Stability was assessed from size analysis, clarity of dispersion on standing and EE%, following 3 months storage at room temperature. The in vitro release of NM from polymeric micelles presented the sustained-release profile. Animal studies revealed the existence of fluorescein 5-isothiocyanate-labeled micelles in rat CSF following intraperitoneal administration, proving that the micelles crossed the BBB. Anticonvulsant effect of NM was shown to be significantly greater than that of NM solution. Our results confirm that Pluronic micelles might serve as a potential nanocarrier to improve the activity of NM in brain.
    Keywords: Nimodipine, Blood brain barrier, Polymeric micelles, Pluronics, FITC
  • Alwan Al Qushawi, Ali Rassouli, Fatemeh Atyabi *, Seyed Mostafa Peighambari, Mehdi Esfandyari, Manesh, Gholamreza Shams, Azam Yazdani Pages 663-676
    Tilmicosin (TLM) is an important antibiotic in veterinary medicine with low bioavailability and safety. This study aimed to formulate and evaluate physicochemical properties, storage stability after lyophilization and antibacterial activity of three TLM-loaded lipid nanoparticles (TLM-LNPs) including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid-core nanocapsules (LNCs). Physicochemical parameters such as particle size-mean diameter, polydispersity index, zeta potential, drug encapsulation efficiency (EE), loading capacity, and morphology of the formulations were evaluated and the effects of various cryoprotectants during lyophilization and storage for 8 weeks were also studied. The profiles of TLM release and the antibacterial activities of these TLM-LNPs suspensions (against Escherichia coli and Staphylococcus aureus) were tested in comparison with their corresponding powders. TLM-LNPs suspensions were in nano-scale range with mean diameters of 186.3±1.5, 149.6±3.0 and 85.0±1.0nm, and EE, 69.1, 86.3 and 94.3% for TLM- SLNs, TLM-NLCs and TLM- LNCs, respectively. TLM-LNCs gave the best results with significantly low particle size and high EE (p
    Keywords: Tilmicosin, lipid nanoparticles, Stability, Mannitol, Antibacterial activity
  • Zahra Hesari, Akram Shafiee, Shirin Hooshfar, Naser Mobarra, Seyedalireza Mortazavi * Pages 677-686
    Orally Disintegrating Tablets (ODT) have the advantages of both solid dosage form specially the stability and ease of handling and liquid dosage forms including ease of swallowing and pre-gastric absorption. We focused on taste masking and formulation of ranitidine ODT which disintegrates rapidly in the mouth within 60 seconds using super-disintegrants, special polymers, water soluble and even insoluble excipients, sweeteners and essence. Various formulations were designed and made in four series. The amount of ranitidine in each formulation was 150 mg, and the final weight of tablets was around 500 mg. Prepared formulations were evaluated in terms of several physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Several taste masking techniques were investigated in each series offormulation, in order to cover the bitter taste of ranitidine.These included the addition of sweetener, granulation, solid dispersion with soluble and insoluble agents and complex formation with cellulose derivatives. The best formulation(s) in each group was/were chosen for taste evaluations with the help of 10 volunteers. Finally, formulation F14was selected as the ultimate formulation, based on its better taste and shorter disintegration time (around 5 seconds). Formulation F14contained Na CMC, avicel, Na starch glycolate, xylitol, saccharin, Na benzoate and menthol. The chosen formulation successfully passed the complementary evaluations such as assay of active ingredient and dissolution time. Na CMC was found to be acceptable in terms of decreasing disintegration time and enhanced taste masking potential and can be used in further ODT formulations.
    Keywords: Orally Disintegrating Tablets (ODT), Ranitidine HCl, Taste masking, Sodium CMC, Xylitol
  • Amir Amani *, Hosein Kamali, Shayan Abbasi, Mohammad Ali Amini Pages 687-693
    This work aimed to prepare a nanoemulsion preparation containing budesonide and assess its aerodynamic behavior in comparison with suspension of budesonide. In-vitro aerodynamic performance of the corresponding micellar solution (ie. nanoemulsion preparation without oil) was investigated too. Nanoemulsions of almond oil containing budesonide, as a hydrophobic model drug molecule, were prepared and optimized. Then, the effect of variation of surfactant/co-surfactant concentration on the aerodynamic properties of the nebulized aerosol was studied. The results indicated that the most physically stable formulation makes the smallest aerodynamic size. The concentration of co-surfactant was also shown to be critical in determination of aerodynamic size. Furthermore, the optimized sample, with 3% w/w almond oil, 20% w/w Tween 80䪖 80 and 2% w/w ethanol showed a smaller MMAD in comparison with the commercially available suspension and the micellar solution.
    Keywords: nanoemulsion, micelle, budesonide, nebulizer
  • Anil Kumar Bajpai *, Swati Mahobia, Jaya Bajpai Pages 695-711
    The aim of the present work was to prepare and characterize biopolymer nanocarriers and evaluate their suitability in possible oral delivery of insulin. The egg albumin biopolymer was used to prepare nanoparticles which were further characterized by Fourier transformed Infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), zeta potential, Dynamic Light scattering (DLS) and cytotoxicity. From the characterization studies the size of the nanoparticles was found to lie in the range 20-80 nm with surface charge of -23 mV and also offering extremely fair biocompatible. The in-vitro biocompatibility of the prepared nanocarriers was judged by BSA adsorption test and hemolysis assay. The in vitro release kinetics of the insulin loaded nanoparticles was studied in phosphate buffer saline (PBS) solution, and the influence of various factors such as pH, temperature and simulated physiological fluids was studied on the controlled release of insulin.
    Keywords: Egg albumin, insulin, nanocarriers, biopolymers
  • Karim Asadpour, Zeynali *, Elhameh Saeb Pages 713-723
    Three antituberculosis medications are investigated in this work consist of rifampicin, isoniazid and pyrazinamide. The ultra violet (UV) spectra of these compounds are overlapped, thus use of suitable chemometric methods are helpful for simultaneous spectrophotometric determination of them. A generalized version of net analyte signal standard addition method (GNASSAM) was used for determination of three antituberculosis medications as a model system. In generalized net analyte signal standard addition method only one standard solution was prepared for all analytes. This standard solution contains a mixture of all analytes of interest, and the addition of such solution to sample, causes increases in net analyte signal of each analyte which are proportional to the concentrations of analytes in added standards solution. For determination of concentration of each analyte in some synthetic mixtures, the UV spectra of pure analytes and each sample were recorded in the range of 210 nm-550 nm. The standard addition procedure was performed for each sample and the UV spectrum was recorded after each addition and finally the results were analyzed by net analyte signal method. Obtained concentrations show acceptable performance of GNASSAM in these cases.
    Keywords: Simultaneous Determination, Chemometrics, Rifampicin, Isoniazid, Pyrazinamide
  • Slobodan Gad?uri? *, Sanja O. Podunavac, Kuzmanovi?, Milan B. Vrane, Scaron, Marija Petrin, Strahinja Z. Kovacevic Pages 725-734
    The purpose of this work is to promote and facilitate forensic profiling and chemical analysis of illicit drug samples in order to determine their origin, methods of production and transfer through the country. The article is based on the gas chromatography analysis of heroin samples seized from three different locations in Serbia. Chemometric approach with appropriate statistical tools (multiple-linear regression (MLR), hierarchical cluster analysis (HCA) and Wald-Wolfowitz run (WWR) test) were applied on chromatographic data of heroin samples in order to correlate and examine the geographic origin of seized heroin samples. The best MLR models were further validated by leave-one-out technique as well as by the calculation of basic statistical parameters for the established models. To confirm the predictive power of the models, external set of heroin samples was used. High agreement between experimental and predicted values of acetyl thebaol and diacetyl morphine peak ratio, obtained in the validation procedure, indicated the good quality of derived MLR models. WWR test showed which examined heroin samples come from the same population, and HCA was applied in order to overview the similarities among the studied heroine samples.
    Keywords: Illicit drug, Heroin, Forensic profiling, Multiple linear regression, Wald, Wolfowitz run test
  • Fahimeh Jalali *, Zahra Hatami Pages 735-741
    A fast and simple voltammetric method for the determination of methimazole in pharmaceutical products was reported. A glassy carbon electrode was pretreated by anodization at .75 V (vs. SCE) for 5 min, followed by potential cycling in the range of 0.3-1.3 V (20 cycles). The pretreated electrode showed an excellent electrocatalytic effect on the oxidation of methimazole. Compared with untreated electrode, a large decrease (~300 mV) in the oxidation peak of methimazole was observed. The oxidation peak current at the new potential (0.4 V vs. SCE) was linearly dependent on the concentration of methimazole in the range of 7.0 - 130 μM with a detection limit of 3.7 μM (S/N = 3). The method was successfully used in the determination of methimazole in thyramozol tablets. Due to the simple and fast electrode preparation, there is no need for electrode cleaning or storage.
    Keywords: Methimazole, Pretreated glassy carbon electrode, Square wave voltammetry, Tablets
  • Afshin Zarghi *, Samaneh Kakhki, Sorayya Shahosseini Pages 743-751
    A new series of anti-cancer agents based on 1,2-diaryl-5,6-dihydropyrrolo[2,1-a]isoquinoline scaffold containing N,N-diethylaminoethoxy, piperidinylethoxy or morpholinylethoxy group at the para position of the C-2 phenyl ring were synthesized and their cytotoxic activities were assessed against several human cancer cell lines including MCF-7 (ER positive breast cancer cell), MDA-MB231 (ER-negative breast cancer cell), T47D (Human ductal breast epithelial tumor cell line), A549 (adenocarcinomic human alveolar basal epithelial cells), and Hela (human cervix adenocarcinoma cells) using MTT assay. Based on results, compounds, 1-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-5,6-dihydro-8,9-dimethoxy-2-phenylpyrrolo[2,1-a]isoquinoline (6a) and 2-(4-(5,6-dihydro-8,9-dimethoxy-2-phenylpyrrolo[2,1-a] isoquinolin-1-yl)phenoxy)-N,N-diethylethanamine (6c) were the most potent cytotoxic compounds and more toxic than the reference compound against T47D cell line, while all the compounds had satisfactory activity against HeLa cell line with mean IC50 values ranging from 1.93 to 33.84 µM.
    Keywords: Synthesis, dihydropyrrolo[2, 1, a]isoquinolines, Cytotoxic activity, MTT, Docking study
  • Saeed Irannejad, Mohsen Amini, Mona Modanlookordi, Mohammad Shokrzadeh, Hamid Irannejad * Pages 753-762
    Carbon nanotubes have unique properties like high stability, high surface to mass ratio and so on which make them suitable for medicinal purpose applications. Treatment of cancer by organoplatinum agents like Cisplatin has become unresponsive in most cases due to low distribution of drug in biological fluids, inability of drug to cross cellular membranes and low stability in biological environments. Recently, carbon nanotubes (CNT) have stimulated much interest to overcome these limitations.ýý Herein, we report the preparation of single-wall carbon nanotube functionalized by diaminedicarboxyplatinum (II) as an analogy of SWCNT-based Carboplatin.
    Functionalization was started by cyclopropanation through Bingel reaction and by use of diethylmalonate to yield cyclopropane-1,1-dicarboxy ethyl ester. Final product was obtained by hydrolysis of ester group and then chelation of platinum (IV) by dicarboxylate groups on the surface of SWCNT. Raman and Fourier transform -Infrared ýspectroscopy (IR), ýThermogravimetric ýanalysis ý(TGA) and energy dispersýive X-ray ýspectroscopy ý(EDAX) truly showed and confirmed the presence of the platinum (II) complex on the side wall of SWCNT. Cytotoxicity evaluation of the functionalized-SWCNTs on HeLa cells showed its higher anticancer ability than Cisplatin as indicated by IC50 value of 13 µg/ml.
    Keywords: singel, wall carbon nanotube (SWCNT)??, novel anti?cancer agent??, ?organoplatinum, Bingel reaction, cytotoxicity
  • Miyase Gozde Gunduz *, Ye?im Kaya, Rahime ?im?eki., Nci ?ahin, Erdemli, Cihat ?afak Pages 763-775
    The present study reports a microwave-assisted method for the synthesis of twelve novel tricyclic 1,4-dihydropyridine derivatives in which dimethyl-substituted cyclohexane and / or tetrahydrothiophene rings are fused to the DHP ring. The structures of the compounds were confirmed by spectral methods and elemental analysis.
    The potassium channel opening effects of the compounds were determined on rat mesenteric arteries and urinary bladders. The obtained results indicated that some compounds produced mesenteric artery-selective relaxant properties and the effects of these compounds were mediated through ATP-sensitive potassium channels. The replacement of the second tetrahydrothiophene ring with dimethyl-substituted cyclohexane ring led to more active compounds.
    Docking studies were carried out to understand the interactions of the compounds with the active site of potassium channel. The unsubstituted nitrogen atom on the 1,4-dihydropyridine ring and one of the sulfonyl oxygens were found to be important for the formation of hydrogen bonds to stabilize the compound in the center of the cavity. The nature and position of phenyl ring substituents were also effective on the activity of the compounds. Finally, a theoretical study was established to predict the ADME of the most active compounds.
    Keywords: 1, 4, dihydropyridine, potassium channel, pinacidil, Docking
  • Karim Akbari Dilmaghani, Fazel Nasuhipur *, Majid Mahammadpour, Jafar Mahammadnejad Pages 777-782
    The glycosylation of 1,3,4-oxadiazole-2-thiones has been performed with peracetylated β-pyranosyl bromide in the presence of potassium carbonate. Deprotection of acetylated thioglycosides was necessary for increasing their antibacterial effects. The structure of nucleosides were confirmed by 1H NMR, 13C NMR and HRMS. The anomeric protons of nucleosides c1–4 were assigned to the doublet, confirming the β-configuration. The synthesized compounds were tested for their antimicrobial activity against Acinetobacter calcoaceticus (Gram-negetive) strain in vitro in comparison with Ampicillin as reference drug which is normally used for treating such infections. The synthetic compounds showed different inhibition zones against tested bacterial strain. Thioglycoside derivatives of 1,3,4-oxadiazole-2-thiones (c set) were more active against Acinetobacter calcoaceticus ATCC 23055 than “parent” 1,3,4-oxadiazole-2-thiones (a set), confirming the relation between glyco-conjugation and increasing of antiproliferative activity of antibiotic agents. The best result belonged to nucleoside bearing 2-furyl moiety in its heterocyclic nucleus (c4). . The existence of m-PhNO2 group as Ar in structures of a set and their corresponding sugar derivatives decreased the antibacterial activity of them in comparison with the rest of synthetic compounds.
    Keywords: 1, 3, 4, Oxadiazole, 2, thione, thioglycoside, nucleoside, Acinetobacter calcoaceticus, Antiproliferative activity
  • Barbaros Eroglu, Ozadali Sari Keriman*, Oya Unsal Tan, Sriram Dharmarajan, Perumal Yogeeswari, Ayla Balkan Pages 783-790
    To develop novel antimycobacterial agents, a new series of thiazolidinone-azole hybrids 4a-b, 5a-b and 6-13 were designed and synthesized. Thiazolidin-4-ones (4a-b and 5a-b) were obtained by the reaction of Schiff bases and hydrazones (2a-b and 3a-b) with mercaptoacetic acid. 5-Benzylidene derivatives (6-13) were gained by treatment of 5a-b with appropriate benzaldehydes according to Knoevenagel condensation. To evaluate their structures 1H NMR, IR, mass spectrometry and elemental analysis data were used. The target compounds were screened for their antimycobacterial activity against M. tuberculosis H37Rv strain using the microplate alamar blue assay method. Among them, 6, 10 and 12 (MIC: 14.27-14.74 μM) were found as most active compounds in the series. It was seen that both phenylamino and benzylidene substitutions on thiazolidin-4-one ring caused an improvement in the antimycobacterial activity.
    Keywords: Thiazolidin, 4, one, triazole, Imidazole, antimycobacterial activity
  • Maryam Iman, Asghar Davood *, Mahboubeh Lotfinia, Golnoush Dehqani, Soroush Sardari, Parisa Azerang, Mohsen Amini Pages 791-799
    Current researches have showed that N3, N5-diaryl-2, 6-dimethyl -1, 4-dihydropyrine-3, 5- dicarboxamide analogues demonstrate notable anti-tubercular activity. In this study, Hantzsch condensation was used to design and synthesize new analogues of dihydropyridine (DHP). Different diary carboxamides were inserted at positions 3 and 5 of the DHP ring. 4(5)-chloro-2-ethyl-5(4)-imidazolyl moiety was considered at position 4 of the DHP ring. The structures of prepared ligands were characterized using TLC followed by FT-IR, elemental analysis, Mass and proton NMR. Results of anti-tubercular activity have indicated all the prepared ligands 3a-f inhibit the mycobacterium tuberculosis growth and the most potent compounds were 3c (3,4-Cl) and 3b (4-Cl). The in-vitro obtained data are agreement with our computational predictions in terms of partial atomic charge of carbonyl moieties at the positions 3 and 5 of dihydropyridine ring and the logP of the molecules.
    Keywords: Dihydropyridine, Mycobaterium, Tuberculosis, Imidazole
  • Amirhossein Sakhteman *, Bijan Zare Pages 801-807
    An interactive application, Modelface, was presented for Modeller software based on windows platform. The application is able to run all steps of homology modeling including pdb to fasta generation, running clustal, model building and loop refinement. Other modules of modeler including energy calculation, energy minimization and the ability to make single point mutations in the PDB structures are also implemented inside Modelface. The API is a simple batch based application with no memory occupation and is free of charge for academic use. The application is also able to repair missing atom types in the PDB structures making it suitable for many molecular modeling studies such as docking and molecular dynamic simulation. Some successful instances of modeling studies using Modelface are also reported.
    Keywords: Application Programming interface, Homology modeling, batch scripting, single point mutation, missing atom types
  • Azadeh Nasiri, Maryam Amirahmadi, Seyed Zahra Mousavi, Shahram Shoeibi, Farzad Kobarfard*, Alireza Khajeamiri Pages 809-816
    Cucumber is one of the main vegetables in Iranian food basket. A wide range of pesticides are used for crops protection during the cultivation of vegetables such as cucumber due to heavy pest infestation. Analysis of pesticide residues in food and other environmental commodities have become essential requirement for consumers, producers, and food quality control authorities. This study was aimed at determination of pesticides residues in cucumber as a main vegetable in Iranian food basket.
    A reliable, rapid and accurate method based on spiked calibration curves and modified QuEChERS sample preparation was developed for determination of 14 pesticide residues in cucumber by gas chromatography-mass spectrometry (GC/MS). The use of spiked calibration standards for constructing the calibration curve substantially reduced adverse matrix-related effects.
    The recovery of pesticides at 5 concentration levels (n=3) was in the range of 80.6-112.3. The method was proved to be repeatable with RSD lower than 20%. The limits of detection and quantification for all pesticides were
    Keywords: Pesticide, spiked calibration curve, GC, MS, cucumber, multi residue
  • Maryam Nakhjavani, Nastaran Nikounezhad, Azadeh Ashtarinezhad, Farshad H. Shirazi * Pages 817-823
    Cancer treatment is still of the greatest challenges that health care providers and patients are facing. One of the unsolved problems in cancer treatment is cells’ reaction to metabolic stress caused by harsh nutritional conditions around tumor. In order to be able to treat this disease properly, it is important to understand the true nature of the disease. In fact, the cells inside the central part of the tumorlack sufficient access to blood vessels, nutrients, and growth signals. After tumor shrinkage, the cells are exposed to favorable environmental conditions and might regrow and cause tumor recurrence. The main purpose of this study was to investigate the effect of serum starvation, as a type of metabolic stress, on human lung cancer cell line, A549. These cells were treated with 10% (control), 0.5% and 0.25% serum for 1 to 5 days. At 24-hour intervals, the cells were released with 10% serum supplemented media. Starved or released cells were studied for their cycle and morphology. The results showed that the cells were actually arrested at G1 phase and following exposure to optimal conditions, the cells could be back to their cycle again. Furthermore, sub-G1 apoptotic cells population was not increased within the starvation period, while control cells had significant increase in sub-G1 cells. Morphological studies also showed that starved cells could make denser colonies while control cells were entering death phase. These observations provide some evidence for the generation of some effective resistance phenomena in cancer cells against harsh metabolic conditions.
    Keywords: A549, Serum, Starvation, Cell Cycle, Metabolic, Stress
  • Mehdi Aliomrani, Mohammad Ali Sahraian, Hamid Shirkhanloo, Mohammad Sharifzadeh, Mohammad Reza Khoshyand, Mohammad Hossein Ghahremani * Pages 825-833
    Since industrial revolution heavy metals such as lead (Pb) and cadmium (Cd) have been extensively dispersed in environment which, unknown biological effects and prolong biological half-life make them as a major hazard to human health. In addition, the sharp increase in Multiple sclerosis incidence rates has been recorded in Iran. The propose of this study was to measuring blood lead and cadmium concentration and their correlation with smoking habit in a group of 69 RRMS patients and 74 age/gender-matched healthy individuals resident in Tehran as most polluted city in Iran. All subjects were interviewed regarding age, medical history, possible chemical exposure, acute or chronic diseases, smoking and dietary habits. Blood Pb and Cd levels were measured by double beam GBC plus932 atomic absorption spectrometer. Our result indicated a significant difference in Cd level (p=0.006) in which, MS patients had higher blood concentration (1.82±0.13μg/L) in comparison with healthy individuals (1.47±0.11μg/L). A comparable blood Cd level to similar recent study (1.78µg/L vs.1.82µg/L) was observed. With respect to Pb there was no significant difference between cases and controls, however the geometric means of blood Pb concentration were considerably higher in males than in females in MS patients (57.1±33.7 μg/L vs. 36.7±21.9 μg/L).Taking into consideration tobacco smoking, an elevated contents of each metal were observed in smoker subjects (p
    Keywords: Multiple sclerosis, Lead, Heavy metal, Cadmium, Oxidative stress, Disability
  • Jalal Pourahmad*, Farzad Kahrizi, Nima Naderi, Ahmad Salimi, Farshid Noorbakhsh, Mehrdad Faizi, Parvaneh Naserzadeh Pages 834-841
    Multiple Sclerosis (MS) is a neurodegenerative and autoimmune disease that it’s molecular etiology and factors involving in its progression remains unknown. In this study for evaluation effect of mercuric on progression of MS we investigated the additive effect of mercuric sulfide on the brain mitochondrial dysfunction in experimental autoimmune encephalomyelitis (EAE) model of MS in C57BL/6 mice. EAE model of MS induced by injecting myelin oligodendrocyte glycoprotein (MOG) to female C57BL/6 mice. Neurobehavioral alterations are observed and recorded in the test animals. Experimental animals are divided into four groups (n=8); control, Hg2, EAE, EAE with Hg2. Mice were sacrificed by cervical dislocation at day 28 and brain mitochondria were isolated and mitochondrial toxicity parameters including mitochondrial swelling, reactive oxygen species (ROS) formation, collapse of mitochondrial membrane potential (MMP) and cytochrome c release were measured. Our results showed that repeated treatment of mercury following induction of EAE in mice significantly increased the neurobehavioral scores, as well as mitochondrial toxicity through ROS formation, mitochondrial swelling, collapse of MMP and cytochrome c release in brain mitochondria. Our findings proved that repeated exposure with mercury accelerates progression of MS through mitochondrial damage related to oxidative stress and finally apoptosis in brain mitochondria in MS.
    Keywords: Mercury, EAE model, Brain mitochondria, Oxidative stress, Apoptosis
  • Hamed Shafaroodi, Farnaz Shahbek, Mehrdad Faizi, Farzad Ebrahimi, Leila Moezi * Pages 843-850
    Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice.
    Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models.
    Acute creatine treatment (10, 20, 40 and 80 mg/kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides that, acute creatine (40 and 80 mg/kg) decreased the incidence of tonic seizures after electroshock.
    In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more.
    Keywords: Creatine, Seizure, Pentylenetetrazole, Electroshock, Mice
  • Abbas Haghparast *, Mahboubeh Jahangirvand, Fatemeh Yazdi, Marzieh Moradi Pages 851-859
    Orexin, mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), plays an important role in pain modulation. Moreover, it is shown that the nucleus accumbens (NAc) is one of the important areas involved in this modulation. Orexin-1 (OX1) and orexin-2 (OX2) receptors are densely distributed in the NAc. The study investigated the involvement of OX1 receptors in the NAc on antinociception induced by intra-LH administration of carbachol in formalin test. Rats were unilaterally implanted by two separate cannulae into the LH and NAc. Different doses of SB334867, as an OX1 receptor antagonist, were microinjected into the NAc (1, 3 and 10 nM/0.5 µl DMSO) prior to intra-LH carbachol injection (250 nM/0.5 µl saline). Formalin test was applied as an animal model of persistent inflammatory pain. The animals received a subcutaneous injection of formalin into the hind paw, 5 min after SB334867 administration. Pain scores were calculated at 5-min blocks for a 60-min test period. Results showed that the administration of SB334867 into the NAc decreased LH chemical stimulation-induced antinociception dose-dependently in early and second phase of formalin test. Our findings showed that OX1 receptors in the NAc may be involved in modulation of inflammatory pain.
    Keywords: Pain, Orexin, 1 receptor, SB334867, Lateral hypothalamus, Nucleus accumbens, Formalin test, Rat
  • Seyed Jalal Hoseinimehr *, Seyed Mohammad Abedi, Fateme Yarmand Pages 861-866
    The aim of this study was to investigate the radioprotective effect of thymol as a natural product against salivary glands dysfunction induced by ionizing radiation in rats. The rats were treated with thymol at dose of 50 mg/Kg before exposure to radiation at dose 15Gy. Salivary gland function was evaluated with radioisotope scintigraphy and then salivary gland to background counts ratio was calculated. Ionizing radiation caused significant salivary glands dysfunction at the 3th and the 70th days with reduction in radioactivity uptake in salivary glands. Ratios of salivary gland to background radioactivities were 2.0±0.05, 1.58±0.62 and 1.99±0.07 at 3th days for control, radiation, and thymol plus radiation groups, respectively. Thymol significantly protected acute and chronic salivary gland dysfunction induced by ionizing radiation in the rats. This finding may have been a promising application of thymol for the protection of salivary glands dysfunction induced by ionizing irradiation in patients exposed to radiation in head and neck cancer therapy
    Keywords: Thymol, radioprotective, salivary gland dysfunction, scintigraphy, Radiotherapy
  • Mohammad Hossein Boskabady *, Milad Hashemzehi, Mohammad Reza Khazdair, Vahid Reza Askari Pages 867-874
    The stimulatory effect of the extract of Portulaca oleracea (P. olerace) on β-adrenoceptor of tracheal smooth muscle was examined. To examine β-adrenoceptor stimulatory effect, concentration response curve to isoprenaline was obtained in pre-contracted tracheal smooth muscle in the presence of three concentrations of aqueous-ethanolic extract, propranolol and saline. Values of EC50 (the effective concentration of isoprenaline, causing 50% of maximum response) and dose ratio -1 (CR-1) were measured. This effect was tested in non-incubated tracheal smooth muscle (group 1) and incubated tissues with chlorpheniramine (group 2). Concentration-response curves to isoprenaline in the presence of two higher concentrations of the extract in group 1 and all three concentrations in group 2 showed leftward shifts compared to isoprenaline curves produced in the presence of saline in both groups. EC50 obtained in the presence of propranolol was significantly higher than that of saline in both groups of experiments (p
    Keywords: Portulaca oleracea, Hydroalcoholic extract, ?, adrenoceptor, Guinea pig, Trachea
  • Mehdi Rahnema *, Parisa Seyedemadi, Mohammad Reza Bigdeli, Shahrebano Oryan, Hassan Rafati Pages 875-883
    The prevention of BBB breakdown and the subsequent vasogenic edema are important parts of the medical management of ischemic stroke. The purpose of this study was to investigate the ischemic tolerance effect of Rosmarinus officinalis leaf hydro-alcoholic extract (RHE).
    Five groups of animals were designed: sham (underwent surgery without MCAO) and MCAO groups, the MCAO groups were pretreated orally by gavages with RHE (50, 75, and 100 mg/kg/day), daily for 30 days. Two hours after the last dose, serum lipid levels were determined and then the rats were subjected to 60 min of middle cerebral artery occlusion followed by 24 h of reperfusion. Subsequently, brain infarct size, brain edema and Evans Blue dye extravasations were measured and neurological deficits were scored.
    Dietary RHE could significantly reduce cortical and sub-cortical infarct volumes (211.55 ± 24.88 mm3 vs. 40.59 ± 10.04 mm3 vs. 29.96 ± 12.19 mm3vs. 6.58 ± 3.2 mm3), neurologic deficit scores, cerebral edema (82.34 ± 0.42% vs. 79.92 ± 0.49% vs. 79.45 ± 0.26% vs. 79.30 ± 0.19%), blood–brain barrier (BBB) permeability (7.73 ± 0.4 μg/g tissue vs. 4.1 ± 0.23 μg/g tissue vs. 3.58 ± 0.3 μg/g tissue vs. 3.38 ± 0.25 μg/g tissue) in doses of 50, 75 and 100 mg/kg/day as compared with the control group in the transient model of focal cerebral ischemia.
    Although pretreatment with RHE plays an important role in the generation of tolerance against cerebral I/R injury, further studies are needed to clarify the mechanism of the ischemic tolerance.
    Keywords: Rosemary leaf hydro, alcoholic extract, cerebral ischemia reperfusion, infarct volume, brain edema, blood–brain barrier permeability
  • Bo Wei, Zhongduo Yang*, Dan, Feng Shi, Xiaojun Yao, Minggang Wang Pages 885-892
    Seven stilbenes and one catechin were bioactivity-guidedly isolated from the rhizomes of Rheum palmatem. Their structures were identified as piceatannol(1), resveratrol(2), piceid(3), rhapontigenin(4), piceatannol-3'-O-β-D-glucopyranoside(5), rhaponticin(6), catechin(7) and desoxyrhapontigenin(8). Anti-monoamine oxidase (MAO) activities of compounds 1–8 were tested. Compounds 1 and 8 showed significant MAO inhibitory activities with IC50 values 16.4±1.5 μM and 11.5±.1.1, respectively, when the IC50 value of iproniazid as a standard was 6.5 ±0.5 μM. The selectivity of compounds 1-8 against MAO-A and MAO-B were also evaluated. The results showed that compounds 4、6、8 preferred to inhibit MAO-A rather than MAO-B with selectivity values ([IC50 of MAO-B]/ [IC50 of MAO-A]) of 4.74, 10.01 and 9.42, respectively . The preliminary structure–activity relationships (SARs) of these compounds were discussed and the molecular modeling was also performed to explore the binding mode of inhibitors at the active site of MAO-A and MAO-B.
    Keywords: stilbenes, monoamine oxidase inhibitors, Rheum palmatum, molecular modeling
  • Maryam Niyyati *, Samira Dodangeh, Jacob Lorenzo Morales Pages 893-900
    Acanthamoeba keratitis (AK) is a sight-threating infection of the cornea that mostly affects contact lens wearers. Until now, AK treatment remains very difficult due to the existence of a highly resistant cyst stage in the life cycle of Acanthamoeba which is extremely resistant to most of the available anti-amoebic compounds. Moreover, current treatment of AK is usually based in the combination of various therapeutic agents such as polyhexamethylene biguanide or chlorhexidine and propamidine isethionate. However, all the mentioned compounds have also showed toxic side effects on human keratocytes and presented poor cysticidal effect at the concentrations currently used in the established AK treatments.
    Nowadays, the elucidation of novel compounds with antimicrobial and anticancer properties from plant and herbs with medicinal properties have encouraged researchers to evaluate plants as a source of new molecules with anti-trophozoite and cysticidal effects.
    Thus, in recent years, many natural products have been reported to present potent anti-Acanthamoeba properties with good selectivity and minimal toxic effects. Therefore, the chemical drugs currently used for AK treatment, their drawbacks as well as the current research in medicinal plants as a source of potent anti-Acanthamoeba compounds are described in this review.
    Keywords: Medicinal plant, Acanthamoeba infections, Chemical therapy
  • Saeid Goodarzi, Abbas Hadjiakhoondi, Narguess Yassa, Mahnaz Khanavi, Zahra Tofighi * Pages 901-906
    There are many efforts for identification of natural compounds from dietary or medicinal plants. Young roots and aerial parts of A. persicus have been used as food additive or salad vegetable in some parts of Iran. In this study, different fractions of the root extract of A. persicus were subjected for isolation and purification of secondary metabolites. The methanol extract of the roots was fractionated with hexane (HE), chloroform (CL), ethyl acetate (EA) and methanol (ME). Five novel compounds were isolated from HE, CL and EA using different chromatographic techniques and were identified by 1H-NMR, 13C-NMR, 2D-NMR and MS spectroscopic methods. Elucidated compounds with benzodioxole structure were characterized for the first time as 5-((propanoyl methyl)amino)-4,7-dimethoxybenzo[d][1,3]dioxole (1), 5-(3-ethyloxiran-2-yloxy)-4,7-dimethoxybenzo[d][1,3]dioxole (2), 4,7-dimethoxy-5-(propanonyl) benzo[d][1,3]dioxole (3), 4-ethoxybenzo[d][1,3]dioxol-6-carbaldehyde (4), and 4-(O-β-D-glucopyranosyl)-6-(3-propanyloxiran-2-yloxy)benzo[d][1,3]dioxole (5).
    Keywords: Astrodaucus persicus, root, Apiaceae, phytochemistry, benzodioxole structures
  • Maryam Hamzeh, Mivehroud, Siavoush Dastmalchi, Omid Zarei * Pages 907-913
    Yeasts, especially Saccharomyces cerevisiae, are one of the oldest organisms with broad spectrum of applications, owing to their unique genetics and physiology. Yeast extract, i.e. the product of yeast cells, is extensively used as nutritional resource in bacterial culture media. The aim of this study was to develop a simple, rapid and cost benefit process to produce the yeast extract. In this procedure mechanical methods such as high temperature and pressure were utilized to produce the yeast extract. The growth of the bacteria feed with the produced yeast extract was monitored in order to assess the quality of the product. The results showed that the quality of the produced yeast extract was very promising concluded from the growth pattern of bacterial cells in media prepared from this product and was comparable with that of the three commercial yeast extracts in terms of bacterial growth properties. One of the main advantages of the current method was that no chemicals and enzymes were used, leading to the reduced production cost. The method is very simple and cost effective, and can be performed in a reasonable time making it suitable for being adopted by research laboratories. Furthermore, it can be scaled up to produce large quantities for industrial applications.
    Keywords: Baker's yeast, yeast extract, bacterial growth, Saccharomyces cerevisiae
  • Mohamed Ghareib *, Medhat Abo Tahoon, Mona Saif, Wafaa Abdallh Pages 915-924
    The development of green approaches for the biosynthesis of silver nanoparticles (AgNPs) is of prime significance in the field of nanotechnology research. A fast and eco-friendly protocol for the biosynthesis of extracellular AgNPs using culture supernatant (CS) from the fungus Cunninghamella phaeospora was studied in this work. This CS was proved as a potential new source for the extracellular biosynthesis of AgNPs. The AgNPs were formed at 100oC and pH 9 within four min of contact between CS and 1mM silver nitrate (AgNO3) solution. Nitrate reductase (NR) was confirmed to play a pivotal role in the biosynthesis of AgNPs. The enzyme expressed its highest activity at 80oC and pH 9. At 100oC the enzyme retained 70% of its original activity for one hour. The half-life (T1/2) of the enzyme activity was calculated to be 1.55 h confirming its thermostability. The produced AgNPs were characterized by UV-Vis spectroscopy, high resolution-transmission electron microscope (HR-TEM) and x-ray diffraction (XRD). These NPs showed an absorption peak at 415 nm in UV-Vis spectrum corresponding to the plasmon resonance of AgNPs. Transmission electron micrographs revealed the production of monodispersed spherical NPs with average particle size 14 nm. XRD spectrum of the NPs confirmed the formation of metallic crystalline silver. It was also suggested that the aromatic amino acids play a role in the biosynthesis process.The current research provided an insight on the green biosynthesis of AgNPs including some mechanistic aspects using a new mycogenic source.
    Keywords: Characterization, Cunnighamella phaeospora, Rapid biosynthesis, Silver nanoparticles
  • Fatemeh Ardestani * Pages 925-931
    Mycophenolic acid is a secondary extracellular metabolite of Penicillium strains with numerous pharmaceutical properties such as antibiotic and immunosuppressive uses. The aim of this work is the survey of the effect of phenylglyoxal and n-ethylmaleimide concentration in culture medium on mycophenolic acid production by Penicillium brevi-compactum ATCC16024 was investigated. Batch submerged fermentation was performed in 250 mL shake flasks at 24°C and 200 rpm in a rotary shaker for 300 h using a basic culture medium containing different concentrations of phenylglyoxal and n-ethylmaleimide ranged from 0 to 20 mg. L-1. For the basic medium without any amounts of phenylglyoxal and n-ethylmaleimide (control), maximum MPA production, product yield and productivity of process was in order, 1.5042 g. L-1, 20.3 mg. g-1 consumed glucose and 5.37 mg. L-1h-1. Maximum produced MPA of 2.9032 g. L-1, MPA yield of 39.23 mg. g-1 of consumed glucose, productivity of 10.37 mg. L-1 h-1 and total enhancement of 93.11% was obtained when the culture medium was contained 18 mg. L-1 of phenylglyoxal, represented more than 93% raising in compare to control. Maximum MPA concentration, yield and productivity in order was obtained 3.1123 g. L-1, 42.06 mg. g-1 of consumed glucose and 11.11 mg. L-1 h-1, with using 6 mg. L-1 of n-ethylmaleimide. N-ethylmaleimide was caused to 2.138 folds (106.89%) increase in MPA production by P. brevi-compactum ATCC16024.
    Keywords: Antibiotic, Aerobic fermentation, immunosuppressive, Mycophenolic acid, Penicillium brevi, compactum
  • Shahnaz Bahadori, Arman Ahmadzadeh, Mohammad Reza Shams Ardekani, Mohammad Kamalinejad, Mansour Keshavarz, Jamshid Salamzadeh* Pages 933-940
    Rheumatoid arthritis (RA) patients are vulnerable to cardiovascular morbidity and mortality in which atherosclerosis plays a major role. In this study, the lipid profile and fasting blood sugar (FBS) of RA patients receiving a complementary medicine of olive and fig, as add-on therapy for routine disease-modifying antirheumatic drugs (DMARDs) regimen containing low dose methotrexate (MTX), were studied. A randomized controlled clinical trial was designed. Adult RA patients were randomly allocated in two groups receiving routine DMARDs regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), the atherogenic index of plasma (AIP) defined as log(TG/HDL-C), and the fasting blood sugar (FBS) were determined and recorded. 56 patients (control=27 and intervention=29), with mean±sd age of 50.9±12.3 years completed the study. MTX dose received by intervention and control groups were 24.30±18.39 and 17.61±15.53, respectively (p=0.11). Repeated measures analysis of variance (ANOVA) revealed that differences between lipid profile indicators and FBS in the two study groups were not statistically significant (P>0.05). No additional substantial adverse reaction was seen in the study groups. Our findings are more reassuring for patients and their doctors to trust on the safety of the investigated complementary preparation to be used as add-on therapy to manage rheumatoid arthritis.
    Keywords: Rheumatoid arthritis, Lipid profile, Fasting blood sugar, Olive, Fig
  • Narjes Hendoiee*, Fatemeh Sheikhmoonesi, Mehran Zarghami, Shima Mamashli, Jamshid Yazdani Charati, Romina Hamzehpour, Samineh Fattahi, Rahil Azadbakht, Zahra Kashi, Shahram Ala, Mona Moshayedi, Habibollah Alinia Pages 941-950
    In this study, the aim was to determine whether adding vitamin D to the standard therapeutic regimen of schizophrenic male patients with inadequate vitamin D status could improve some aspects of the symptom burden or not. This study was an open parallel label randomized clinical trial. Eighty patients with chronic stable schizophrenia with residual symptoms and Vitamin D deficiency were recruited randomly and then received either 600000 IU Vitamin D injection once along with their antipsychotic regimen or with their antipsychotic regimen only. Serum vitamin D was measured twice: first at the baseline and again on the fourth month. Positive and Negative Syndrome Scale (PANSS) was assessed at the baseline and on the fourth month. During the study, the vitamin D serum changes in vitamin group and control group were 22.1± 19.9(95%CI =15.9-28.8) and 0.2 ± 1.7(95%CI = 0.2-0.8) (ng/ml) (p
    Keywords: Vitamin D deficiency_PANSS negative subscale score_PANSS positive subscale score Positive_Schizophrenic patients_Antipsychotic drugs
  • Mojtaba Mojtahedzadeh, Legese Chelkeba, Mona Ranjvar, Shahrivar, Atabak Najafi, Arezoo Ahmadi * Pages 951-956
    Abdominal aortic aneurysm (AAA) is widely considered as the disease of elderly white men. Inflammation is one of the most well-known mechanisms involved in the pathogenesis of AAA. Magnesium is one of the most important minerals in the body with established anti-inflammatory effects. In this study, we aimed to investigate the impact of Mg loading following AAA surgery on two inflammation markers, IL-6 and CRP, as well as patients’ outcome.
    This study was conducted as a randomized clinical trial on 18 patients (divided into two groups) after surgical correction of Acute Aortic Aneurysm (AAA). All the patients admitted in ICU ward of Sina Hospital. In intervention group, 10 grams of MgSO4 has been infused through 12 hours. The control group has not received the intervention. IL-6 and CRP were measured and compared at times 0,12, 24 and 36 hours. The patients were monitored for 36 hours.
    After intervention, the differences of heart rate and APACHE II score were not statistically significant between intervention and control groups (P=0.097 and P=0.472, respectively). IL-6 levels decreased consistently in both groups after inclusion in the study. However, IL-6 level was significantly less in intervention group early after the end of MgSO4 infusion comparing with control group (P=0.01). Likewise, the CRP level decreased significantly after inclusion in the study (P=0.005). However, these changes were not significant between intervention and control groups (P=0.297).
    According to the results of this study, continuous infusion of MgSO4 after AAA surgery may provide IL-6 suppression.
    Keywords: Key words: Abdominal aortic aneurysm (AAA), MgSO4, ICU, IL, 6, CRP
  • Congpin Wang * Pages 957-961
    objective To investigate acute kidney injury (AKI) in children with acute lymphoblastic leukemia (ALL) who received high dose methotrexate (MTX) chemotherapy and explore the corresponding treatment. Methods 180 children who received high dose MTX chemotherapy were observed with serum MTX concentration and serum creatinine. Patients with AKI of stage 3 or poor response to conventional treatment were performed on hemodialysis and assessed the treatment outcome. Results 9 patients (5%) have appeared AKI, including 7 cases of AKI of stage 3. However, there were not any significant correlation between age, gender, serum MTX concentration and AKI, respectively. Compared with normal serum MTX concentration, the patients with high serum MTX concentration easily were developed to AKI, the MTX and serum creatinine concentration had been significantly decreased in 9 patients after hemodialysis. Conclusion AKI has appeared in some children with ALL who receive high dose MTX chemotherapy, and this may due to increase of serum MTX concentration. The monitoring of serum MTX concentration and AKI index could help to find out AKI, and even to prevent the occurrence of it. Furthermore, once AKI is present, those patients with AKI stage 3 or poor response to conventional treatment should be performed on hemodialysis treatment.
    Keywords: Acute kidney injury, acute lymphoblastic leukemia, methotrexate chemotherapy, children
  • Marzieh Khezri *, Morteza Delkhosh Reihany, Sonia Oveisi, Navid Mohammadi Pages 963-971
    Melatonin has been suggested as a new natural pain killer in inflammatory pain and during surgical procedures. We designed this randomized double-blind controlled study to evaluate the analgesic efficacy and also optimal preemptive dose of melatonin in patients undergoing cesarean section under spinal anesthesia.One hundred twenty patients scheduled for cesarean section under spinal anesthesia were randomly allocated to one of three groups of 40 each to receive melatonin 3 milligram (mg) (group M3), melatonin 6 mg (group M6) or placebo (group P) sublingually 20 minutes before the spinal anesthesia. The time to first analgesic request, analgesic requirement in the first 24hours after surgery, hemodynamic variables, anxiety scores and the incidence of adverse events were recorded.The duration of anesthesia and analgesia didn’t show significant differences between three groups. Total analgesic request during 24 hours after surgery was different among the three groups (P=0.035).The incidence of headache in group M6was significantly higher than others(P
    Keywords: melatonin, analgesia, spinal anesthesia, cesarean section
  • Gholamhossein Mehralian*, Jafar Babpour Pages 973-982
    In the current competitive market, ‘service quality’ management is the key to survival and success of businesses. There exists a variety of definitions of the term ‘service quality’ in the literature and referring to the existing definitions, a variety of scales have been developed for measuring service quality. Amongst the others, ‘SERVQUAL’ is the popular service quality measurement scales (SQMS) that has served as a basis for subsequent research on service quality and has been used for testing different issue related to service quality and using it in the market. This research is aimed at developing service quality scale at the distributors-retailers interface of the pharmaceutical supply chains (PSC) in Iran. It also discusses developing SQMS in a previously ignored sector namely distributors-retailers interface of PSC. Therefore, in order to measuring the satisfaction level of the pharmacies from the services of a medicine distributor in Iran, authors developed a reliable and valid measurement scale consisting of 5 dimension (Reliability, Tangibility, Assurances, Empathy and Responsiveness) with 20 items that can be used effectively to achieving competitive advantage in the distributor-retailor interface.
    Keywords: Pharmaceutical supply chain, Service quality, SERVQUAL, Pharmacy, Iran