فهرست مطالب

Pharmaceutical Research - Volume:14 Issue: 3, Summer 2015

Iranian Journal of Pharmaceutical Research
Volume:14 Issue: 3, Summer 2015

  • تاریخ انتشار: 1394/03/25
  • تعداد عناوین: 35
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  • Mohammadreza Khanmohammadi, Hamideh Elmizadeh, Keyvan Ghasemi Pages 665-675
    The polymeric nanoparticles are prepared from biocompatible polymers in size between 10-1000 nm. Chitosan is a biocompatible polymer that - can be utilized as drug delivery systems. In this study, chitosan nanoparticles were synthesized using an optimized spontaneous emulsification method. Determining particle size and morphology are two critical parameters in nanotechnology. The aim of this study is to introduce methodology based on relation between particle size and ِِdiffuse reflectance infrared fourier transform (DRIFT) spectroscopy technique. Partial least squares (PLS) technique was used to estimate the average particle size based on DRIFT spectra. Forty two different chitosan nanoparticle samples with different particle sizes were analyzed using DRIFT spectrometry and the obtained data were processed by PLS. Results obtained from the real samples were compared to those obtained using field emission scanning electron microscope (FE-SEM) as a reference method. It was observed that PLS could correctly predict the average particle size of synthesized sample. Nanoparticles and their morphological state were determined by FE-SEM. Based on morphological characteristics analyzing with proposed method the samples were separated into two groups of "appropriate" and "inappropriate". Chemometrics methods such as principal component analysis, cluster analysis (CA) and linear discriminate analysis (LDA) were used to classify chitosan nanoparticles in terms of morphology. The percent of correctly classified samples using LDA were 100 %and 90% for training and test sets, respectively.
    Keywords: Chitosan nanoparticles, DRIFT spectroscopy, Chemometrics, Particle size
  • Pankaj Kumar, Ashok Laxmanrao Ganure, Bharat Bhusan Subudhi, Shubhanjali Shukla Pages 677-691
    The present investigation deals with the development of controlled release tablets of salbutamol sulphate using graft copolymers (St-g-PMMA and Ast-g-PMMA) of starch and acetylated starch. Drug excipient compatibility was spectroscopically analyzed via FT-IR, which confirmed no interaction between drug and other excipients. Formulations were evaluated for physical characteristics like hardness, friability, weight variations, drug release and drug content analysis which satisfies all the pharmacopoeial requirement of tablet dosage form. Release rate of a model drug from formulated matrix tablets were studied at two different pH namely 1.2 and 6.8, spectrophotometrically. Drug release from the tablets of graft copolymer matrices is profoundly pH-dependent and showed a reduced release rate under acidic conditions as compared to the alkaline conditions. Study of release mechanism by Korsmeyer’s model with n values between 0.61-0.67, proved that release was governed by both diffusion and erosion. In comparison to starch and acetylated starch matrix formulations, pharmacokinetic parameters of graft copolymers matrix formulations showed a significant decrease in Cmax with an increase in tmax, indicating the effect of dosage form would last for longer duration. The gastro intestinal transit behavior of the formulation was determined by gamma scintigraphy, using 99mTc as a marker in healthy rabbits. The amount of radioactive tracer released from the labelled tablets was minimal when the tablets were in the stomach whereas it increased as tablets reached to intestine. Thus, in-vitro and in-vivo drug release studies of starch-acrylate graft copolymers proved their controlled release behavior with preferential delivery into alkaline pH environment.
    Keywords: Salbutamol sulphate, methylmethacrylate, graft copolymers, acetylated starch, Korsmeyer's model
  • Karim Dilmaghani, Fazel Nasuhipur, Mahnaz Hatami Nezhad Pages 693-699
    The condensation reaction of 5-(4-aminophenyl)-4-phenyl-1,2,4-triazole-3-thione with salicylaldehyde, 4-hydroxybenzaldehyde, 5-chlorosalicylaldehyde, 5-bromosalicylaldehyde, 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde and 4-methoxybenzaldehyde in methanol results in series of new Schiff bases. The structure of Schiff bases were confirmed by 1H NMR, 13C NMR, IR and mass spectroscopy. The synthesized compounds were tested for their antimicrobial activity against bacterial (Gram negative and Gram positive) strains in vitro. The synthetic compounds showed different inhibition zones against tested bacterial strains. All compounds showed significant antiproliferative activity against Acinetobacter calcoaceticus ATCC 23055. In detail, Entrococcus faecalis (Gram positive) was resistant to all prepared compounds, whereas, A. calcoaceticus (Gram negative) was sensitive to all compounds especially 5c, 5d and 4. S. aureus (Gram positive, relatively resistant to antimicrobials) showed limited sensitivity to only 5c and 5d, and it was resistant to all other compounds and only 5c exhibited low activity against P. aeruginosa (Gram negative). The best results in the table belonged to 5c that showed high activity against A. calcoaceticus (33 mm) as well as S. aureus (20 mm).
    Keywords: Schiff base, in vitro, Acinetobacter calcoaceticus
  • Gehad Genidy Mohamed, Mahmoud Sabry Rizk, Eman Y.Z. Frag Pages 701-714
    The purpose of this investigation was directed to propose sensitive, accurate and reproducible methods of analysis that can be applied to determine distigmine bromide (DTB), cyclopentolate hydrochloride (CPHC), diaveridine hydrochloride (DVHC) and tetrahydrozoline hydrochloride (THHC) drugs in pure form and pharmaceutical preparations via charge-transfer complex formation with 7,7,8,8-tetracyanoquinodimethane (TCNQ) and tetracyanoethylene (TCNE) reagents. Spectrophotometric method involve the addition a known excess of TCNQ or TCNE reagents to DTB, CPHC, DVHC and THHC drugs in acetonitrile, followed by the measurement of the absorbance of the CT complexes at the selected wavelength. The reaction stoichiometry is found to be 1:1 [drug]: [TCNQ or TCNE]. The absorbance is found to increase linearly with concentration of the drugs under investigation which is corroborated by the correlation coefficients of 0.9954-0.9981. The system obeys Beer’s law for 6-400, 20-500, 1-180 and 60-560 µg mL-1 and 80-600, 10-300, 1-60 and 80-640 µg mL-1 for DTB, CPHC, DVHC and THHC drugs using TCNQ and TCNE reagents, respectively. The apparent molar absorptivity, sandell sensitivity, the limits of detection and quantification are also reported for the spectrophotometric method. Intra- and inter-day precision and accuracy of the method were evaluated as per ICH guidelines. The method was successfully applied to the assay of DTB, CPHC, DVHC and THHC drugs in formulations and the results were compared with those of a reference method by applying Student’s t and F-tests. No interference was observed from common pharmaceutical excipients.
    Keywords: Spectrophotometry, Charge transfer, CT acceptors, Drug donors
  • Bilal Yilmaz, Ulvihan Ci, Ltas, Selcuk Kaban, Bilge Kaan Akcay, Gulsah Nazik Pages 715-722
    In this study, a simple and reliable square wave voltammetric (SWV) method was developed and validated for determination of diclofenac in pharmaceutical preparations and human serum. The proposed method was based on electrooxidation of diclofenac at platinum electrode in 0.1 M TBAClO4/acetonitrile solution. The well-defined two oxidation peaks were observed at 0.87 and 1.27 V, respectively. Calibration curves that were obtained by using current values measured for second peak were linear over the concentration range of 1.5-17.5 μg mL-1 and 2-20 μg mL-1 in supporting electrolyte and serum, respectively. Precision and accuracy were also checked in all media. Intra- and inter-day precision values for diclofenac were less than 3.64, and accuracy (relative error) was better than 2.49%. Developed method in this study is accurate, precise and can be easily applied to Diclomec, Dicloflam and Voltaren tablets as pharmaceutical preparation. Also, the proposed technique was successfully applied to spiked human serum samples. No electroactive interferences from the endogenous substances were found in human serum.
    Keywords: Diclofenac, Cyclic voltammetry, Square wave voltammetry, Pharmaceutical tablet, Serum
  • Akbar Mobinikhaledi, Behvar Asghari, Mahsa Jabbarpour Pages 723-731
    In an endeavor to find a novel series of antihyperglycemic agents, new benzimidazole and pyrimidine derivatives were successfully synthesized efficiently in high yield with high purity, starting from amino acids in the presence of phosphorus oxychloride (POCl3). The synthesized compounds were identified by 1H-NMR, 13C-NMR, FT-IR spectroscopic techniques and elemental analysis. All products were assayed for their inhibitory effect on yeast and rat intestinal α-glucosidases. The results revealed that compounds with aromatic amino acids moiety showed significant inhibition activity on the tested enzymes. Among the benzimidazole derivatives 4c and 4d exhibited the best activity against both of the tested enzymes. Also, among the pyrimidine derivatives 5c and 5d possessed significant inhibition action on the enzymes. The IC50 values for the most potent benzimidazole yeast and intestinal α-glucosidases inhibitor (4d) were found to be 9.1 and 36.7 µM, respectively. The IC50 values for the inhibition of yeast and intestinal α-glucosidases by the most active pyrimidine compound (5d) were calculated to be 8.3 and 21.8 µM, respectively. Overall, this study proved that benzimidazole and pyrimidine derivatives with aromatic amino acids moieties can represent novel promising α-glucosidase inhibitors.
    Keywords: benzimidazole, pyrimidine, amino acids, α glucosidase inhibition, antihyperglycemic activity
  • Abolghasem Moghimi, Mostafa Vojdani, Ali R. Banan, Ahmad Mollaei, Mojtaba Mahmoodian, Sayyed Mojtaba Moosavi Pages 733-738
    Improvements in the two-step synthesis of 1,1,1,3,3,3-hexafluoro-2- (fluoromehoxy)propane (Sevoflurane) that result in the product cost reduction, safety level enhancement and positive environmental impacts are described. This process consists of chloromethylation reaction of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) followed by a halogen-exchange fluorination. This is the first synthesis of Sevoflurane in Iran which was successfully scaled up. During this work, several improvements have been achieved by optimization of the reaction time, the amount of consumed starting materials and solvents and work up procedure while keeping the yield and purity intact. The reaction time of the first step (24 h) was diminished to 4 h. 19F NMR spectroscopy was used to investigate the rate of the reaction in the first step and to evaluate the influence of different parameters mentioned on the achieved improvements.
    Keywords: Inhalation anesthetic, Sevoflurane, Halogen, exchange fluorination, Hexafluoro, 2, propanol
  • Arezoo Asgari, Farzad Kobarfard, Fariborz Keyhanfar, Shohreh Mohebbi, Maryam Noubarani Pages 739-746
    In previous studies, mebudipine, a dihydropyridine calcium channel blocker, showed a considerable potential to be used in cardiovascular diseases. The aim of the current study was to develop a valid method using reversed-phase high performance liquid chromatography coupled with electrospray ionization mass spectrometry to assay mebudipine in the human plasma. Separation was achieved on a Zorbax Eclipse® C18 analytical column using a mobile phase consisted of methanol/water (90:10, v/v). The flow rate was 0.6 mL/min and carbamazepine was used as an internal standard (IS). This method involved the use of [M +Na]+ ions of mebudipine and IS at m/z 411 and 259, respectively with the selected ion monitoring (SIM) mode. There were no interfering peaks from endogenous components in blank plasma chromatograms. Standard curves were linear (r2>0.99) between 5 to 100 ng/mL. The mean extraction efficiency was about 84% and the limit of quantification for mebudipine was 5 ng/mL in plasma. The coefficient of variation and error at all of the intra-day and inter-day assessments were less than 11%. The results indicated that this method is a fast, accurate, sensitive, selective and reliable method for the determination of mebudipine in the human plasma. The assay method has been successfully used to estimate plasma concentration of mebudipine after the oral administration of 2.5 mg tablet in healthy adults.
    Keywords: Mebudipine, Liquid chromatography, mass spectrometry, human plasma
  • Manuchehr Dadgarnejad, Hosein Rastegar, Hooshmand Ilka, Maryam Shekarchi, Nooshin Adib, Mahmood Alebouyeh, Nadia Keypour, Shahram Shoeibi, Farzad Kobarfard, Mohammad Reza Fazeli Pages 747-755
    Human interferons (IFNs) are key cytokines secreted by immune system. They have several effects such as antiviral and anti tumors activity, activating immune cells and healing of multiple sclerosis. The type IFNs present in humans are α, β and Υ. IFN β is a polypeptide, normally produced by fibroblasts and seems to be more species-specific than IFN . Structural properties of I FNs are important for their biologic effects. There are a few analytical techniques for separation, identification and determination of IFNs in its formulations such as mass spectroscopy, RP-HPLC and capillary electrophoresis (CE). In this study we used Micellar Electrokinetic Chromatography (MEKC) as a unique mode of CE because of its capability to separate neutral as well as charged solutes. In MEKC, ionic surfactants are added to the running buffer to form micelles which have a three-dimensional structure with the hydrophobic moieties. The selectivity of MEKC can be controlled by the choice of surfactant and also by the addition of modifiers to the buffer. We used sodium tetraborate (Borax) as buffer without any modifier and sodium dodecyl sulfate (SDS) as surfactant. The validated method was used for determination of the IFN β-1b formulation which are manufactured in Iran. From 9 collected different batches, all of them had acceptable potency as claimed on their label with average 102.25 ± 10.030 %. This is the first time that a MEKC method is introduced for quantification of IFN β-1b in its pharmaceutical dosage forms. The method is reliable safe, rapid and accurate.
    Keywords: Analysis, Capillary Electrophoresis, MEKC, Interferon, ZIFERON®
  • Masoume Shahi, Naser Foroughifar, Akbar Mobinikhaledi Pages 757-736
    There has been special interest in the chemistry of quinolone and pyrimidine derivatives due to their diverse biological activities such as anticonvulsant, anti-malarial agents, antibacterial, antiviral, cytostatic, antithelemintic, antigenotoxic, anti-cancer agents. These compounds are also used as targeting delayed-type hypersensivity and anti-convulsant agents. As a part of our research works in the synthesis of pyrimidine derivatives containing biological activities, a series of novel pyrano[2,3-d]pyrimidine derivatives 2 and tetrahydro quinolone dione derivatives 3 were synthesized via reaction of tetrahydrobenzo[b]pyrano derivatives 1 with different reagents in suitable yields. The characterization of these synthesized compounds was established by IR, 1H NMR and 13C NMR spectroscopic data. Furthermore, all compounds were subsequently evaluated for their in vitro antibacterial activity against three bacteria: Staphylococcus aureus (ATTC-25923), Escherichia Coli (ATTC-25922) and Bacillus anthracic (ATTC-25924).
    Keywords: pyrimidine, Quinolone, antimicrobial activity
  • Hayedeh Bagheri Sadeghi, Homayon Ahmad Panahi, Mahsa Mahabadi, Elham Moniri Pages 765-773
    Mefenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic,anti-infammatory and antipyretic actions. It is used to relieve mild to moderate pains. Solid-phase extraction of mefenamic acid by a polymer grafted to silica gel is reported. Poly allyl glycidyl ether/iminodiacetic acid-co-N, N-dimethylacrylamide was synthesized and grafted to silica gel and was used as an adsorbent for extraction of trace mefenamic acid in pharmaceutical and biological samples. Different factors affecting the extraction method were investigated and optimum conditions were obtained. The optimum pH value for sorption of mefenamic acid was 4.0.The sorption capacity of grafted adsorbent was 7.0 mg/g. The best eluent solvent was found to be trifluoroacetic acid-acetic acid in methanol with a recovery of 99.6%. The equilibrium adsorption data of mefenamic acid by grafted silica gel was analyzed by Langmuir model. The conformation of obtained data to Langmuir isotherm model reveals the homogeneous binding sites of grafted silica gel surface. Kinetic study of the mefenamic acid sorption by grafted silica gel indicates the good accessibility of the active sites in the grafted polymer. The sorption rate of the investigated mefenamic acid on the grafted silica gel was less than 5min.This novel synthesized adsorbent can be successfully applied for the extraction of trace mefenamic acid in human plasma, urine and pharmaceutical samples.
    Keywords: Mefenamic acid, Solid phase extraction, High Performance Liquid Chromatography, Pharmaceutical sample, Biological sample
  • Maryam Iman, Asghar Davood, Ali Khamesipour Pages 775-784
    Malaria is a parasitic disease with limited chemotherapy options. Chemotherapy options are limited; moreover, drug resistant frequently occurs. The speed of drug development should be faster to overcome the emerging drug resistance. In the current study, a series of quinolone derivatives were subjected to quantitative structure activity relationship to identify the ideal physicochemical characteristics of potential anti-malaria activities. Quinolone with desirable properties was built using HyperChem program, and conformational studies were performed through the semi-empirical method followed by the PM3 force field. Multi linear regression (MLR) was used as a chemo metric tool for quantitative structure activity relationship modeling and the developed models were shown to be statistically significant according to the validation parameters. The obtained QSAR model reveals that the descriptors PJI2, Mv, PCR, nBM, and VAR mainly affect the anti-malaria activity and descriptors MSD, MAXDP, and X1sol affect the cytotoxicity of the series of ligands.
    Keywords: Cytotoxicity, Quinolone, QSAR, QSTR, Malaria
  • Nima Razzaghi, Asl, Saghi Sepehri, Ahmad Ebadi, Ramin Miri, Sara Shahabipour Pages 785-802
    Human immunodeficiency virus infection / acquired immunodeficiency syndrome (HIV/AIDS) is a disease pertained to the human immune system. Given its crucial role in viral replication, HIV-1 protease (HIV-1 PR) is a prime therapeutic target in AIDS therapy. In this regard, the dynamic aspects of ligand-enzyme interactions may indicate an important role of conformational variability in HIV-1 PR inhibitor/drug design. In the present contribution, the effect of HIV-1 PR flexibility (multiple crystallographic structures of HIV-1 PR) on binding to the Amprenavir was elucidated via an ensemble docking approach. Molecular docking studies were performed via advanced AutoDock4.2 software. Ensemble docking of Amprenavir into active site of various conformations of HIV-1 PR predicted different interaction modes/energies. Analysis of binding factors in terms of docking false negatives/positives revealed a determinant role of enzyme conformational variation in prediction of optimum induced fit (PDB ID: 1HPV). It was also known that deviation of ligand from its minimum energy conformation would not be sufficiently supportive in prediction of HIV-1 PR targeted docking results. The outcomes of this study demonstrated that conformation of receptor may significantly affect the accuracy of docking/binding results in rational design of anti HIV-1 PR agents. Furthermore; some strategies to re-score the docking results in HIV-1 PR targeted docking studies were proposed.
    Keywords: AIDS, HIV, 1 PR, Conformational variation, Amprenavir, Docking
  • Rezvan Zendehdel, Farshad H. Shirazi Pages 803-810
    Variations in biochemical features are extensive among cells. Identification of marker that is specific for each cell is essential for following the differentiation of stem cell and metastatic growing. Fourier transform infrared spectroscopy (FTIR) as a biochemical analysis more focused on diagnosis of cancerous cells. In this study, commercially obtained cell lines such as Human ovarian carcinoma (A2780), Human lung adenocarcinoma (A549) and Human hepatocarcinoma (Hepg2) cell lines in 20 individual samples for each cell lines were used for FTIR spectral measurements. Data dimension were reduced through principal component analysis (PCA) and then subjected to neural network and linear discrimination analysis to classify FTIR pattern in different cell lines. The results showed dramatic changes of FTIR spectra among different cell types. These appeared to be associated with changes in lipid bands from CH2 symmetric and asymmetric bands, as well as amide I and amid II bands of proteins. The PCA-ANN analysis provided over 90% accuracy for classifying the spectrum of lipid section in different cell lines. This work supports future study to establish the data bank of FTIR feature for different cells and move forward to tissues as more complex systems.
    Keywords: Cell line, Discrimination, Fourier transform infrared, artificial neuronal network, linear discriminate analysis
  • Marjan Shariatpanahi, Fariba Khodagholi, Ghorbangol Ashabi, Azar Aghazadeh Khasraghi, Leila Azimi, Mohammad Abdollahi, Mohammad Hossein Ghahremani, Seyed Nasser Ostad, Farshid Noorbakhsh, Mohammad Sharifzadeh Pages 811-824
    It has been proposed that appearance of amyloid beta (Aβ) in hippocampus is one of the characteristic features of Alzheimer’s disease (AD). The role of Nitric oxide (NO) in neurodegenerative disorders is controversy in different contexts. Here, we examined the effect of NO on spatial memory. For this purpose, we compared the effects of three different concentrations of L-NG-Nitroarginine Methyl Ester (L-NAME) as a nitric oxide synthase (NOS) inhibitor. We used Morris water maze (MWM) for evaluation of behavioral alterations. We also assessed the apoptosis and autophagy markers as two possible interfering pathways with NO signaling by western blot method. We found that in Aβ pretreated rats, intra-hippocampal injection of 1or 2 (μg/side) of L-NAME caused a significant reduction in escape latency and traveled distance comparing to Aβ-treatment group. Our molecular findings revealed that L-NAME could induce autophagy and attenuate apoptosis dose dependently. The protective role of autophagy and the deteriorative role of apoptosis is the hypothesis that can vindicate our findings. Thus using NOS inhibitors at low concentrations can be one of the therapeutic approaches in the future studies.
    Keywords: MWM, L, NAME, Alzheimer's disease, Apoptosis, Autophagy
  • Abbas Rezaiean Mehrabadi, Akram Jamshidzadeh, Marzieh Rashedinia, Hossein Niknahad Pages 825-832
    Pioglitazone (PG) is one of thiazolidinediones used for the treatment of type II diabetes mellitus. Some reports of its hepatotoxicity exist, but the mechanism of its hepatotoxicity is not well known. In the present study, the protective effect of some ATP suppliers are investigated against mitochondrial toxicity of PG in isolated rat mitochondria. Mitochondrial viability was investigated by MTT assay. The effects of PG on superoxide dismutase activity, ATP production, mitochondrial swelling and oxidative stress were also investigated. PG reduced mitochondrial viability with an LC50 of 880±32 µM. It reduced ATP production and superoxide dismutase activity in mitochondria and increased mitochondrial swelling, but no oxidant effect was present as measured by TBARS formation. Fructose, dihydroxyacetone, dithioteritol, and N-acetylcysteine reduced mitochondrial toxicity of PG. Therefore, PG toxicity may be due to its mitochondrial toxicity and energy depletion, and ATP suppliers could be effective in preventing its toxicity.
    Keywords: ATP suppliers, Mitochondria, Pioglitazone, Toxicity
  • Zhi, Pei Zhang, Lin, Na Liu, Lei Shi, Shi, Cao Li, Wen, Juan Zhang, Yan Zhang Pages 833-841
    The protective effects of Rheum tanguticum polysaccharide 1 (RTP1), which is extracted from the Chinese traditional medicine Rheum tanguticum, on radiation-induced intestinal mucosal injury was investigated. Rat intestinal crypt epithelial cells (IEC-6 cells) and Sprague-Dawley rats were each divided into control, irradiated and RTP1-pretreated irradiated groups. After irradiation, cell survival was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and the intracellular reactive oxygen species (ROS) was detected by fluorescent probe method. Apoptosis was observed by acridine orange staining, and cell cycle was analysed by flow cytometry. Histological analysis of the rat intestinal mucosa was conducted by haematoxylin and eosin staining. Irradiation at 8 Gy(Gray) decreased cell survival rate to only 54%, significantly increased intracellular ROS levels and induced apoptosis. RTP1 pretreatment significantly inhibited cell death, reduced the formation of intracellular ROS and partially inhibited apoptosis. Irradiation markedly reduced the height and quantity of rat intestinal villi, but it could be antagonised by RTP1 pretreatment. RTP1 can promote the recovery of intestinal mucosa damage, possibly by inhibiting radiation-induced intestinal epithelial apoptosis and intracellular ROS production.
    Keywords: Polysaccharide, Rheum Tanguticum, Ionizing radiation, Small intestine, Radioprotection
  • Alireza Abed, Valiollah Hajhashemi, Hamid Reza Banafshe, Mohsen Minaiyan, Azam Mesdaghinia Pages 843-850
    Primarily opioidergic and adenosine mechanisms are considered to be involved in the antinociceptive effects of antidepressants. This study was designed to determine the efficacy of acute venlafaxine administration in alleviating symptoms of neuropathic pain and the role of endogenous adenosine and opioid systems in this effect of venlafaxine. We have evaluated the effect of caffeine, a non-selective adenosine A1 and A2 receptor antagonist and naloxone as an antagonist of opioid receptors on the antinociceptive effects of venlafaxine. Chronic constriction injury of the sciatic nerve resulted in thermal hyperalgesia, mechanical and cold allodynia in the rats. Animals were received on the 7th day after surgery, when the model had been fully established, venlafaxine (20 and 40 mg/kg i.p.), or venlafaxine (40 mg/kg) in combination with caffeine (5 mg/kg i.p.) or naloxone (1 mg/kg s.c.). Rats were tested for thermal reaction latencies, mechanical and cold allodynia 45 min after drug injection. Acute venlafaxine (40 mg/kg i.p.) administration consistently decreased the thermal hyperalgesia and this effect was not blocked by concomitant caffeine or naloxone administration. There was no effect by either drug or the drug combination on the tactile and cold allodynia. The results of this study indicate that venlafaxine (40 mg/kg i.p.) is effective in alleviating thermal hyperalgesia and this effect is independent through manipulation of adenosine or opioid system. This observation demonstrates that venlafaxine, which is a mixed inhibitor of norepinephrine and serotonin reuptake, differs from the other antidepressants in the mechanism of its antinociception action.
    Keywords: Venlafaxine, Neuropathic pain, Naloxone, Caffeine, Chronic constriction injury
  • Padideh Ghaeli, Shaghayegh Vejdani, Atefeh Ariamanesh, Azita Hajhossein Talasaz Pages 851-855
    Several studies have reported that the antioxidant properties of melatonin can provide cardiac protection through scavenging of free radicals. This study sought to investigate the efficacy of melatonin on cardiac biomarkers, myocardial-specific protein high sensitive troponin-T (hs-TnT) and creatine kinase-MB (CK-MB), in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). In this randomized clinical trial, a total of 40 patients with STEMI planned to undergo pPCI were randomly assigned to two groups of receiving melatonin plus standard treatment [n=20] and control group, receiving only standard therapy [n=20]. The following parameters including hsTnT and CK-MB were assessed preoperatively (baseline) and at six hours after procedure. Melatonin could significantly reduce the level of CK-MB (118.2 ± 21.09 IU/L in the treated group versus 198.24 ± 20.94 IU/L in the control group; p value = 0.01). However, there was no difference in the mean hs-TnT level between two groups (2491 ± 664 μg/L vs. 2801 ± 620 μg/L; p value = 0.73). Our results revealed that melatonin can be considered as a safe adjunctive medication to the standard regimen after pPCI for the aim of decreasing cardiovascular events. Meanwhile, this was a pilot study with a small number of patients and further studies are needed to confirm the beneficial effect of melatonin in patients with STEMI.
    Keywords: Melatonin, Myocardial infarction, Primary percutaneous coronary intervention, High sensitive Troponin, T, Creatine phosphokinase, MB
  • Manuela Perez, Cebrian, Maria M. Morales Suarez, Varela, Isabel Font, Noguera, Emilio Monte, Boquet, Jose Luis Poveda, Andres, Jose Maria Martin, Moreno, Nuria Rubiol., Oacute, Pez, Elias Ruiz Rojo, Agustin Llopis, Gonzalez Pages 857-864
    Indications for linezolid use are nosocomial or community-acquired pneumonia and skin infections or soft tissue infection caused by gram-positive microorganisms, but new recommendations may emerge. It is important to balance benefits with risks because severe adverse events have been described in patients taking linezolid treatment. Accordingly, we evaluated the suitability of linezolid prescription according to approval of indication by evaluating the presence of drug-related problems (DRP) in a University hospital. DRP were identified in 36 patients (50.0%). In most cases, they were related to known or established indications (15 patients, 20.8%), to safety (5 patients, 6.9%), and to both in others (16 patients, 22.2%). No DRP were recorded, which modified linezolid efficacy. DRP were significantly higher in the patients treated by an approved indication in Spain (63.3%) than in those treated by an unapproved indication in Spain (28.6%). We concluded that new studies about extending linezolid indications may be necessary.
    Keywords: Approval of indications, Drug, Related Problems, Drug safety evaluation, Linezolid prescription, University hospital
  • Golnaz Sarafian, Minoo Afshar, Parvin Mansouri, Jinous Asgarpanah, Kosar Raoufinejada, Mehdi Rajabi Pages 865-876
    Psoriasis is an autoimmune and recurrent chronic inflammatory skin disease. About 1-3% of the world wide populations are affected. The characteristic features are hyperprolifration of keratinocytes leading to redness, thickening and scaling of epidermis followed with itching and appearance of the lesions which in most cases bother the patients medically and psychologically. Psoriasis is symptomatically treated by the range of oral and topical medications, however, major side effects in some cases are associated with them. Based on several studies, Curcuma longa can inhibit several inflammatory enzymes mainly involved in the inflammatory process of Psoriasis. Therefore, we decided to target this well-known herbal agent with fantastic safety profile to be formulated as a novel topical microemulgel. The clinical and therapeutic benefit of this novel topical formulation was evaluated on 34 patients with mild to moderate plaque psoriasis in a randomized, prospective intra-individual, right–left comparative, placebo-controlled, double-blind clinical trial. The Dermatology Life Quality Index (DLQI) Questionnaire and Psoriasis area & severity index (PASI) score as well as photos before and after treatment was used to evaluate the outcome. The results show that the clinical and quality of life features in treated lesions in comparison with untreated lesions have improved (P<0.05). The reported side effects were also recorded and were trivial. Based on our findings, the proposed microemulgel may well be considered as an alternative in some patients and most likely as an add-on therapeutic option for many patients suffering with plaque psoriasis.
    Keywords: Curcuma longa L, Plaque psoriasis, Topical turmeric microemulgel, Dermatology Life Quality Index (DLQI) Questionnaire, Psoriasis Area, Severity Index (PASI) score
  • Reza Golpira, Fariborz Bahram Farsad, Hamideh Najafi, Ziya Totonchi, Shirin Salajegheh, Hooman Bakhshandeh, Farshad Hashemian Pages 877-885
    Fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) reverse oral anticoagulants such as Warfarin. We compared the standard dosage FFP and PCC in terms of efficacy and safety for patients with mechanical heart valves undergoing interventional procedures while receiving Warfarin. Fifty patients were randomized (25 for each group) with mechanical heart valves [international normalized ratio (INR) >2.5]. FFP dosage was administered based on body weight (10-15 ml/kg), while PCC dosage was administered based on both body weight and target INR. INR measurements were obtained in different time after PCC and FFP infusion. The mean ± SD of INR pre treatment was not significantly different between the PCC and FFP groups. However, over a 48-hour period following the administration of PCC and FFP, 76% of the patients in the PCC group and only 20% of the patients in the FFP group reached the INR target. Five (20%) patients in the PCC group received an additional dose of PCC, whereas 17 (68%) patients in the FFP group received a further dose of FFP (P=0.001). There was no significant difference between the two groups in Hb and Hct before and during a 48-hour period after PCC and FFP infusion. As regards safety monitoring and adverse drug reaction screening in the FFP group, the INR was high (INR > 2.5) in 86% of the patients. There was no report of hemorrhage in both groups. PCC reverses anticoagulation both effectively and safely while having the advantage of obviating the need to extra doses.
    Keywords: Prothrombin complex concentrates, Fresh frozen plasma, Warfarin reversal, Anticoagulation, International normalized ratio
  • Kourosh Goudarzipour, Farid Ghazizadeh, Hesameddin Hoseini Tavasol, Behdad Behnam Pages 887-890
    An important complication of chemotherapy is thromboembolic events that can occur during treatment course. In this way, Warfarin can be used as an efficient prophylactic agent to prevent these complications. Although bleeding is a common adverse effect of Warfarin, eosinophilia is a rare side effect of this drug. We have reported a 5-year-old boy with Burkitt lymphoma who underwent chemotherapy. In the course of chemotherapy, because of thrombosis of the left jugular vein, we initiated Warfarin as a prophylactic drug for TEE secondary to chemotherapy. Following Warfarin initiation, eosinophilia appeared and subsequent to cessation of drug, eosinophilia disappeared.This case is presented to point out physicians to consider eosinophilia as a rare adverse-effect of Warfarin and monitor blood cell differentiation regularly during the course of treatment with this drug.
    Keywords: Warfarin, Eosinophilia, Anticoagulant therapy, Burkitt lymphoma, Pediatrics
  • Marzieh Majd, Farshad Hashemian, Seyed Mohammad Hosseini, Maryam Vahdat Shariatpanahi, Ali Sharifi Pages 891-899
    This study was designed to examine the antidepressant effect of celecoxib (200 mg/day) augmentation of sertraline in the treatment of female patients with first episode of major depression over 8 weeks of therapy.Thirty female outpatients diagnosed with first episode of major depression, were recruited for this study. Participants were randomly assigned into two equal groups receiving either sertraline plus celecoxib 100 mg twice daily or sertraline plus placebo twice daily. Patients were assessed by Hamilton Depression and Anxiety Rating Scale at baseline, week 4 and week 8 of treatment. Both treatment groups showed notable improvement in their symptoms from baseline; however, celecoxib group showed greater decrease in Hamilton Depression Scores compared to the placebo group after four weeks of treatment. Response rates were also found to be significantly higher in the celecoxib group compared to the placebo group over 4 weeks. Nevertheless, the mentioned differences between two groups were not significant at the end of week 8. Also, remission rate was remarkably higher in celecoxib group in comparison with placebo at the end point. The results suggested that celecoxib may hasten the onset of therapeutic action of sertraline and increase response and remission rate in depressive disorders.
    Keywords: celecoxib, first episode of major depression, inflammatory cytokines
  • Mohammed Rabbani, Fatemeh Shafiee, Zahra Shayegh, Hamid Mirmohammad Sadeghi, Ziaedin Samsam Shariat, Zahra Etemadifar, Fatemeh Moazen Pages 901-906
    Lipases are diversified enzymes in their properties and substrate specificity, which make them attractive tools for various industrial applications. In this study, an alkaline thermostable lipase producing bacteria were isolated from soil of different regions of Isfahan province (Iran) and its lipase was purified by ammonium sulfate precipitation and ion exchange chromatography. To select a thermoalkalophil lipase producing bacterium, Rhodamine B and Horikoshi media were used and the strain that can grow at 45 °C was selected. The isolated strain was identified using microbial and biochemical tests. One strain showed an orange colored zone on plate and grew on Horikoshi plate. Microbial and biochemical tests showed that the isolated strain was Bacillus subtilis, a Gram positive rod. In PCR, an expected band was obtained with about 371 bp. The activity of the purified lipase was 10.2 folds that of the standard enzyme using ammonium sulfate precipitation and ion exchange chromatography. The molecular weight of lipase determined by SDS-PAGE electrophoresis, was 21 and 35 KDa. Existence of two bands in SDS-PAGE electrophoresis and low amount of obtained purified enzyme highlights the necessity of optimization of purification and concentrating process.
    Keywords: Thermoalkalophile, Lipase, Bacillus subtilis, soil
  • Javad Ranjbari, Valiollah Babaeipour, Hossein Vahidi, Hamidreza Moghimi, Mohammadreza Mofid, Mohammadmehdi Namvaran, Sevda Jafari Pages 907-917
    Human insulin-like growth factor I (hIGF-I) is a kind of growth factor with clinical significance in medicine. The major objective of this study is over- production of recombinant human insulin-like growth factor I(rhIGF-I) through a developed process by recruiting effective factors in order to achieve the most recombinant protein. Up to now E. coli expression system has been widely used as a host to produce rhIGF-1 with high yields. Batch cultures as non-continuous fermentation were carried out to overproduce rhIGF-I in E. coli. The effects of culture medium type, induction temperature and amount of inducer on cell growth and IGF-I production were investigated in shaking flask. Taguchi design of experiments (DOE) method was used as the statistical method. Analysis of experimental data showed that maximum production of rhIGF-I was occurred in 32y culture medium at 28°C and 0.05 Mm IPTG. Under this condition, 0.7 g/L of rhIGF-I was produced as the inclusion bodies. Following optimization of these three factors, we have also optimized the amount of glucose and induction time in 5 liter top bench bioreactor. Full factorial design of experiment method was used for these two factors as the statistical method. 10 g/l and OD600=5 were selected as the optimum point of Glucose amount and induction time, respectively. Finally we have had 1.26 g/l rhIGF-1 production as the final product that is one of the best reported amounts.
    Keywords: rhIGF, I, E. coli, batch fermentation, Taguchi design of experiments, optimization
  • Tahereh Hosseinabadi, Hossein Vahidi, Bahman Nikavar, Farzad Kobarfard Pages 919-924
    Microbial steroid biotransformation have found wide-reaching application for the production of more precious and functionalized compounds due to their high regio-and stereoselectivity. In this study, the possibility of using filamentous fungi Aspergillus brasiliensis cells in the biotransformation of progesterone (I), a C-21 steroid hormone was studied for the first time.The fungal strain was inoculated into the transformation medium which supplemented with progesterone as a substrate. Biotransformation of this steroid for 7 days afforded 3 different hydroxylated metabolites: 11α-hydroxyprogesterone (II); 14α-hydroxyprogesterone (III) and 21-hydroxyprogesterone (IV).The metabolites were separated by thin layer chromatography. Structure determinations of the metabolites were performed by comparing NMR, MS and IR spectra of starting compound with those of metabolites.These results may be of industrial importance because the metabolites can be used as precursor of some steroid drugs.
    Keywords: Aspergillus brasiliensis, microbial transformation, steroid, hydroxylation
  • Mohammad, Reza Delnavazi, Abbas Hadjiakhoondi, Abbas Delazar, Yousef Ajani, Saeed Tavakoli, Narguess Yassa Pages 925-931
    Dorema glabrum Fisch. & C.A. Mey. (Apiaceae) is a monocarpic perennial plant distributed in southern Caucasus. In Azerbaijan Republic folk medicine, the gum-resin of this species is used as a diuretic and anti-diarrheal agent. It is also traditionally used for the treatment of bronchitis and catarrh. In the present study, chemical constituents of the essential oil and extract of D. glabrum aerial parts were investigated and their free radical scavenging potentials were assessed. GC-MS and GC-FID analyses of the plant essential oil resulted in identifying twenty compounds, out of which elemicin (38.6%) and myristicin (14.3%) were main compounds. Seven compounds including daucosterol (1), chlorogenic acid (2), a mixture of cynarin (3) and 3,5-di-O-caffeoylquinic acid (4), isorhamnetin-3-O-β-D-glucopyranoside (5), isoquercetin (6) and astragalin (7) were also isolated from the ethyl acetate and methanol fractions of D. glabrum aerial parts using different chromatographic methods on silica gel (normal and reversed-phase) and sephadex LH20. Structures of the isolated compounds were elucidated using UV and 1H, 13C-NMR spectra in comparison with those reported in respective published data. Antioxidant activities of the crude extract, fractions and isolated compounds were evaluated using DPPH free radical scavenging assay method. Among the fractions, methanol fraction (IC50= 53.3 ± 4.7 μg ml-1) and among the isolated compounds, caffeoylquinic acid derivatives exhibited the highest free radical scavenging activity (IC50= 2.2-2.6 μg ml-1).
    Keywords: Dorema glabrum, Apiaceae, elemicin, flavonoid, caffeoylquinic acid
  • Sudipta Kumar Mohanty, Kumaraswamy M., Sushil Kumar Middha, Lokesh P., Balasubramanaya S., Anuradha M. Pages 933-942
    Leptadenia reticulata was reported to be used for several medicinal purposes. The present study was undertaken to evaluate anti-inflammatory, analgesic and lipid peroxidation inhibition activities of L. reticulata. The anti-inflammatory assay was performed by λ-carrageenan and formalin induced paw edema test. Pro inflammatory mediators (IL2, IL6, TNF-α) in serum of treated and control organism were analyzed by quantitative ELISA. Lipid peroxidation inhibition was measured by thiobarbituric acid reactive substances (TBARS) assay. Analysis of the most active fraction revealed the presence of one phenolic compound (p-coumaric acid), two flavonoids (rutin and quercetin) which also determined quantitatively. The ethyl acetate fraction at 600 mg/kg significantly inhibited λ-carrageenan and formalin induced paw edema by 60.59% and 59.24% respectively. Notable reduction in percentage of writhing (76.25%), induced by acetic acid signifies the potent analgesic activity. Lower level of pro-inflammatory cytokines (IL-2, IL-6, TNF-α) in serum at the 4th hour of λ-Carrageenan injection indicated the inhibition of cyclooxigenase-2 (Cox-2), Nitric oxide (NO) and release of prostaglandin to prevent inflammation. The study also demonstrated the decrease in malonaldehyde (MDA) concentration which revealed the lipid peroxidation inhibition potential of the plant. Our finding provides evidence for potent biological activities in tested model which is supported by its characterized bioactive compounds and ethnomedicinal relevance.
    Keywords: Leptadenia reticulata, anti, inflammatory activity, analgesic activity, lipid peroxidation inhibition, pro, inflammatory cytokines
  • Shabnam Mahernia, Kowsar Bagherzadeh, Faraz Mojab, Massoud Amanlou Pages 943-947
    Urease enzyme has a crucial role in the persistent habitation of Helicobacter pylori (H. pylori) that induces gastrointestinal diseases, in particular gastritis, duodenal, peptic ulcer, and gastric cancer. Plants have long been utilized as the biggest source of substances with medicinal properties from natural origin and therefore result in less toxicity and adverse side effects upon usage. 15 medicinal plant extracts were examined against Jack bean urease activity by Berthelot reaction. Each herb was extracted using 80% aqueous methanol. The more effective extracts were further tested and their IC50 values were determined. Three plant extracts including Ginkgo biloba, Rhus coriaria, and Matricaria inodora were found to be the most effective ones with IC50 values of 36.17, 80.29, and 100.6 μg/ml, respectively.
    Keywords: Urease, H. pylori, Medicinal plants, Inhibitor, Gastric diseases
  • Xinchi Feng, Xin Wang, Youping Liu, Xin Di Pages 949-954
    Linarin is a flavone glycoside in the plants Flos chrysanthemi indici, Buddleja officinalis, Cirsium setosum, Mentha arvensis and Buddleja davidii, and has been reported to possess analgesic, antipyretic, anti-inflammatory and neuroprotective activities. In this paper, linarin was investigated for its AChE inhibitory potential both in vitro and ex vivo. Ellman’s colorimetric method was used for the determination of AChE inhibitory activity in mouse brain. In vitro assays revealed that linarin inhibited AChE activity with an IC50 of 3.801 ± 1.149 μM. Ex vivo study showed that the AChE activity was significantly reduced in both the cortex and hippocampus of mice treated intraperitoneally with various doses of linarin (35, 70 and 140 mg/kg). The inhibition effects produced by high dose of linarin were the same as that obtained after huperzine A treatment (0.5 mg/kg). Molecular docking study revealed that both 4’-methoxyl group and 7-O-sugar moiety of linarin played important roles in ligand-receptor binding and thus they are mainly responsible for AChE inhibitory activity. In view of its potent AChE inhibitory activity, linarin may be a promising therapeutic agent for the treatment of some diseases associated with AChE, such as glaucoma, myasthenia gravis, gastric motility and Alzheimer’s disease.
    Keywords: Linarin, Acetylcholinesterase inhibitor, Molecular docking study, Mice brain
  • Abdul Majid Ayatollahi, Mustafa Ghannadian, Atta, Ur Rahman, M. Ahmed Mesaik, A. Shukralla Khalid, Fateme Adeli Pages 955-960
    Aerial parts of Salvia Mirzayanii was extracted with methanol. Methanol extract was suspended in water and defatted with petroleum ether. The defatted part was then partitioned between ethyl acetate and water. The ethyl acetate partition was chromatographed on a silica gel column to afford several fractions. Lymphocyte proliferation inhibitory assay of the resulted fractions was compared in vitro and the fraction with more immunosuppressive activity was subjected to more purification to yield three methoxylated flavones: 5,7-dihydroxy,6,4'–dimethoxyflavone(1), 5-hydroxy,6,7,3',4'–tetramethoxyflavone(2) and 5,3'-dihydroxy,6,7,4'–trimethoxyflavone (3). Compounds 2 and 3 potently suppressed the proliferation of human blood lymphocytes with IC50 values of 1.3 ± 0.04 μg/mL and 1.3 ± 0.21 μg/mL in comparison with prednisolone as one of the lymphocyte suppressor drugs (IC50=1.45 ± 0.6 μg/mL). In phagocyte chemiluminescence assay, compounds 1 and 3 in peripheral mononuclear cells (PMNCs) exerted suppressive moderate activity against ROS with IC50 of 55.3 ± 0.4 and 36.2 ± 0.7 μg/mL, respectively, while compound 2 showed weak activity with IC50 values more than 100 μg/mL. In conclusion, compounds 2 and 3 have a similar suppressive effect more than compound 1 on PHA-activated lymphocyte proliferation, which might be because of their C-3' oxidation pattern of ring B. It is indicated that the presence of 3'-OH or 3'-OMe in flavone ring B, caused more anti-proliferation activity than 3'-H. Oxidative burst assay showed more activity for compound 1 which is less methoxylated than others. It also showed more activity for compounds 3 than 2, which differ only in 3'-OH instead of 3'-OMe.
    Keywords: Methoxylated flavones, Salvia Mirzayanii, immunosuppressive, oxidative burst, T, cell proliferation
  • Farzaneh Naghibi, Saeedeh Ghafari, Somayeh Esmaeili, Kristina Jenett, Siems Pages 961-968
    Some Dorema species are used in Persian traditional medicine. In the present study the total extract from the roots of Dorema hyrcanum Koso-Pol. was investigated for its in vitro (pLDH assay) and in vivo (Peters’ 4-days suppressive test) antiplasmodial effects and assessed for cytotoxicity against the normal cell line MDBK (MTT test). The IC50 values for a chloroquine- sensitive (3D7) and a chloroquine- resistance (K1) strain of Plasmodium falciparum were 28.64 and 9.79 µg/ml, respectively. The inhibition percentage of the rodent parasite, Plasmodium berghei, on day 4 in mice was 77.9% and IC50 value on Madin–Darby bovine kidney cells (MDBK cells) was 59.84µg/ml. The total extract was subjected to a bioassay-guided fractionation protocol based on the in vivo model which resulted in the isolation of an acetophenon (compound 1), one new sesquiterpenoid, 1(2-hydroxy-4-methoxy)- 3,7,11- trimethyl-3-vinyl-6(E), 10 dodecadiene- 1- dione (compound 2) and two known sesquiterpenoid derivatives (compounds 3, 4). Their structures were elucidated by spectroscopic analysis, including 1D and 2D NMR experiments and ESI-MS. All compounds were evaluated for in vivo antiplasmodial effect and the results revealed that compound 2 showed good suppression activity, inhibiting 68.1 % of the parasite growth.
    Keywords: Traditional medicine, Dorema hyrcanum, Antiplasmodial activity, Cytotoxicity, Sesquiterpenoid
  • Population Variability of Main Secondary Metabolites in Hypericum lydium Boiss. (Hypericaceae)(2015 summer)
    Cuneyt Cirak, Jolita Radusiene, Liudas Ivanauskas, Valdas Jakstas, Necdet ÇamaŞ Pages 969-978
    In the present study, we investigated the variation in the content of naphthodianthrones hypericin and pseudohypericin, phloroglucinol derivatives hyperforin and adhyperforin, the phenolic acids as chlorogenic acid, neochlorogenic acid, 2,4-dihydroxybenzoic acid, and the flavonols, namely, hyperoside, isoquercitrin, quercitrin, quercetin, avicularin, rutin, (+)-catechin and (-)-epicatechin, and biflavonoid amentoflavone among wild H. lydium Boiss. populations from five different growing sites of Turkey for the first time. The aerial parts representing a total of 30 individuals were collected at full flowering and dissected into floral, leaf and stem tissues. After dried at room temperature, the plant materials were assayed for chemical contents by HPLC. The populations varied significantly in the content of chemical compounds. Among different plant parts, flowers were found to be main repository site of hyperforin, adhyperforin, hypericin, pseudohypericin, amentoflavone, quercetin, avicularin, rutin and (+)-catechin accumulations whereas rest of the compounds tested were accumulated primarily in leaves in all growing localities. The stems were the least accumulative organ that did not yield hyperforin, adhyperforin and rutin. The chemical diversity among the populations and plant parts is discussed as being possibly the result of different environmental, morphological and genetic factors.
    Keywords: Chemical diversity, Flavonoids, Hyperforins, Hypericins, Hypericum lydium