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Start date: 2010End date: 2019

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    A Randomized controlled trial of effect of Co-Enzyme Q10 on Plasma Level of Cardiac Troponin-I and Creatinine Kinase- MB in patients with myocardial infarctions who undergo Angiplasty
    (Tabriz University of Medical Science, School of pharmacy, 2015) Houshmand, Fatemeh; Garjani, Alireza; Ghaffari, Samad; Entezari Maleki, Taher; Aslanabadi, Naser
    Introduction: Despite the novel technical and medical improvement in performing of percutaneous coronary intervention (PCI), some myocardial complications occur during this procedure. Thus, periprocedural myocardial injury (PMI) following PCI has received serious attention due to its notable relation to mortality and morbidity. Therefore, cardioprotection during PCI is still a worldwide need. Aim: Concerning the potential clinical benefits of CoQ10, this trial was performed to investigate the CoQ10 pretreatment benefits in reduction of PMI in patients undergoing elective PCI. Methods: A randomized controlled trial of 100 patients undergoing elective PCI was designed. The intervention group (n=50) received 300 mg CoQ10 in a single dose and the standard treatment 12 hours before PCI. But the control group (n=50) had the standard treatment only. To evaluate the myocardial injury during PCI, the levels of CK-MB and troponine-I were measured at baseline, 8 h, and 24 h after PCI, and hs-CRP levels were measured at baseline and 24 h after PCI. Afterwards, all patients were assessed for the major adverse cardiac effects in a 1-month following up period. Results: No significant changes in the CK-MB levels at 8 h (p=0.079) and 24 h (p=0.242) following PCI were found in intervention group when compared with the control group. In the same way, no significant changes in troponine-I at 8 h (p=0.062) and 24 h (p=0.826) after PCI were observed. The results of hs-CRP levels indicated significant changes at 24 h (p=0.031) after PCI. Conclusions: Although the biomarker’s changes were not significant in intervention group, there was a trend toward the potential benefits of CoQ10. On the other hand, the changes of hs-CRP were statistically significant, that can relatively support the potential cardioprotective effects of CoQ10 in the prevention of PMI following PCI.
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    Preparation and antimicrobial activity of Azithromycin–Eudragit RS100 electrospuns
    (Tabriz University of Medical Science, School of pharmacy, 2015) Khorasani, Golrokh; Lotfipour, Farzaneh; Adibkia, Khosro
    Introduction: Azithromycin (AZI), an azalide antibiotic, is used to manage a wide range of bacterial infections .Studies have shown that antibiotics in nanocarriers may lead to increased antibacterial activity and reduced toxicity. Aim: The aim of the present study was to describe the preparation of AZI-Eudragit RS100 nanoparticles in drug:polymer ratio of 1:5 and the solution concentrations of 10% and 20% via electrospinning technique and evaluation of their in vitro antibacterial performance against Escherichia coli (PTCC 1330), Salmonella typhi (PTCC 1609), Staphylococcus aureus (PTCC 1112) and Streptococcus pneumoniae (PTCC 1240) in comparison with drug solution. Methods: Evaluation and comparisaon of the minimum Inhibitory Concentration (MIC) values of the AZI-Eudragit RS100 nanofibers and nanobeads which were prepared previously via electrospinnig method, with the untreated AZI solutions using serial macrodilution technique. Results: Nanofibers in the sizes about 100-300 nm in diameter and micro scale in length and nanobeads in the range of 100-500 nm in diameter were achieved. The minimum inhibitory concentration (MIC) of the above mentioned microorganisms showed a significant enhance in the antimicrobial effect of AZI-Eudragit RS100 nanofibers against S. pneumoniae (40 µg/ml) and S. typhi (32 µg/ml) compare to untreated AZI solutions (>160 and 128 µg/ml) respectively. The MIC values of AZI-Eudragit RS100 nanofibers against E. coli and S. aureus were the same as untreated AZI solutions ( >128 µg/ml). Conclusions: These findings are perhaps related to the more adsorption opportunity of nanofibers with higher surface area to the bacteria cell wall and providing an antibiotic depot on the bacterial surface compared to the untreated drug solution. In conclusion, it was shown that AZI-Eudragit RS100 nanofibers with enhanced or even equal antimicrobial effects against tested bacteria could be considered as a candidate for in vivo evaluations in antibiotic therapy of relevant infections.
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    Study on the effects of aqueous extract of Marrubium vulgare on cardiac hemodynamic and infarct size in ischemic-reperfused isolated rat heart
    (Tabriz University of Medical Science, School of pharmacy, 2015) Tila, Dena; Fathiazad, Fatemeh; Garjani, Alireza
    Introduction: Ischemia occurs after cessation of blood flow to the myocardium. With suddenly restoring of blood (reperfusion), an intense reactive oxygen species (ROS) will be produced in reperfused tissue which damage the tissue and accordingly the cell death. This event is known as Ischemia/Reperfusion (I/R) injury. Marrubium vulgare is a medicinal herb from Lamiaceae family and has long been acknowledged for its unique antioxidant and anti-inflammatory properties in traditional medicine. Aim: The Evaluation of the cardioprotective effects of aqueous extract of M. vulgare on cardiac parameters in ischemic-reperfused isolated rat hearts. Method: The dried aerial parts of the plant were extracted with methanol 70% by maceration at room temperature and the solvent was removed by rotary evaporator. The water-soluble portion of the total hydroalcoholic extract was prepared with liquid-liquid extraction (LLE). The evaluation of M. vulgare aqueous extract's effect on cardiac parameters was carried out after phytochemical assays like DPPH radical scavenging assay, nitric oxide radical scavenging assay, total phenolic and flavonoids content assay and stiasny test. In order to evaluate the effect of the extract on cardiac parameters and I/R injury, the Langendroff method was used. Male Wistar rats were heparinized (1000 IU.kg-1) and anaesthetized with kethamin/xylasin (60mg.kg-1, 10mg.kg-1). Harvested hearts were cannulated immediately to the langendroff apparatus and subjected to 30 min regional ischemia and 2 hrs reperfusion, either by a modified Krebs-Henseleit Buffer Solution (KHBS) or enriched KHBS with extract (10, 20, 40 mcg/ml). Result: The 40 µg/mL of M. vulgare aqueous extract significantly decreased the infarct size compared to control group. All three doses (10, 20 and 40 µg/mL) significantly reduced the total ventricular ectopic beats (VEBs) during 30 min of ischemia and 40 µg/mL considerably decreased the arrhythmias during first 30 min of reperfusion. The concentrations of 10 and 20 µg/mL lowered the lactate level of samples during the first 30 min of reperfusion. Conclusion: The aqueous extract of M. vulgare has a cardioprotective effect against I/R injuries in isolated rat hearts.
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    Application of Graphene Quantom dot on determination of ِDoxorubicin on biological samples
    (Tabriz University of Medical Science, School of pharmacy, 2015) Hashemzadeh, Nastaran; Jouyban, Abolghasem; Shadjou, Nasrin
    Introduction: Nowadays anticancer drugs which used as chemotherapy regimen for patients are become more useful. The development of an accurate and repeatable method for determination of these drugs, will improve our understanding of their role in the treatment process. One of the common methods of determining the trace amount of these drugs is electrochemical methods. According to the importance of these methods in the analysis of drugs, in the present study graphene quantum dots (GQDs) used as active ingredient in the preparation of electrochemical sensors. Application of prepared electrochemical sensor for the detection and quantification of doxorubicin in biological samples were studied. Aim: Developing an electrochemical sensor based on graphene quantum dots and its application for the detection and determination of doxorubicin (DOX) in biological samples. Methods: In this study, GQDs were synthesized by pyrolyzing citric acid in alkaline solution.The UV–Vis spectroscopy, X-ray diffraction (XRD), transition electron microscopy (TEM), Fourier transform infrared (Ft-IR) spectroscopy, Atomic force microscopy (AFM) and cyclic and differential pulse voltammetric techniques were used for characterizing synthesized GQDs. The electrochemical behavior of GQD modified glassy carbon electrode (GQD-GCE) was studied using cyclic voltammetry (CV) technique. The electrochemical behavior of DOX was investigated at the GQD-GCE in phosphate buffer solution (PBS), using differential pulse voltammetry technique (DPV). Results and Conclusion: electrochemical behavior GQD-GCE was studied using CV and DPV. DPV was used to evaluate the analytical performance of DOX in the presence of PBS (pH 4) and good limit of detection was obtained by proposed sensor. The results revealed that GQD promotes the rate of oxidation by increasing the peak current. Finally, the applicability of the proposed method was described to the direct assays of spiked human plasma.
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    The effects of methanolic extract of Marrubium vulgare L. on isoproterenol-induced acute myocardial infarction in rats
    (Tabriz University of Medical Science, School of pharmacy, 2012) Yousefi, Keyvan; Maleki Dizaji, Nasrin; Garjani, Alireza; Fathiazad, Fatemeh
    Background- Marrubium vulgare (Lamiaceae) is a popular medicinal herb that previous studies have demonstrated its anti-inflammatory and antioxidant properties. Aim- The present study was designed to investigate the cardioprotective effect of the methanolic extract of M. vulgare against isoproterenol-induced acute myocardial infarction (MI) in rats. Methods- The aerial parts of the plant were extracted with methanol by maceration and subjected to colorimetry to determine flavonoids and phenolic compounds. High-performance TLC analysis and subsequent TLC scanning were performed to quantify the extract marrubiin content. Free radical scavenging activity was determined using 1,1-diphenyl-2-picryl-hydrazil (DPPH) test. Male wistar rats were assigned to six groups of control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg/12h of the extract given orally concurrent with MI induction. Isoproterenol injection (100 mg/kg/day S.C.) for 2 consecutive days was used to induce acute MI. Results- Preliminary HPTLC analysis of the extract revealed the presence of marrubiin with Rf value of 0.82 as the major compound in the M. vulgare extract. Marrubiin was quantified as 156 mg per gram of M. vulgare extract. The amount of total phenolic and flavonoids contents for M. vulgare were determined as 60.4 mg gallic acid equivalent and 12.05 mg quercetin equivalent per each gram of the extract, respectively. The RC50 (reduction concentration of 50%) values of methanolic extract of M. vulgare and quercetin (as a standard free radical scavenger) were obtained as 8.24 and 3 µg/ml, respectively, from DPPH test. Isoproterenol injection exhibited changes in the electrocardiogram (ECG) pattern including ST-segment elevation and suppressed R-amplitude. All doses of the extract significantly amended the ECG changes (p<0.001). A severe myocardial necrosis, fibrosis and edematous along with a sharp reduction in the arterial blood pressure, left ventricular contractility (LVdP/dtmax), and relaxation (LVdP/dtmin), but a marked increase in the left ventricular end-diastolic pressure (LVEDP) were seen in the isoproterenol group. All parameters were significantly improved by the extract treatment. The extract (10 mg/kg) strongly (p<0.001) increased LVdP/dtmax from 2750±309 (mmH/sec) in the infracted myocardiums to 5391±377. Similarly, treatment with 40 mg/kg of M. vulgare lowered the elevated LVEDP from 19±1.2 mmHg to a normal value of 6.4±1.7 (p<0.001) and the heart to body weight ratio from 4.14±0.05 to 3.48±0.08 (p<0.001). In addition to in vitro antioxidant activity, the extract suppressed markedly (p<0.001) the elevation of malondialdehyde levels both in serum and myocardium by 50-65 %. In the groups treated with 10, 20 and 40 mg/kg of M. vulgare extract serum Creatine Kinease-MB was subsided by 55.4%, 52.2% and 69%, respectively. On the other hand treatment with M. vulgare extract greatly reduced the proinflammatory responses, as evidenced by a marked reduction (p<0.001) in the myocardial myeloperoxidase activity from 4605.2±130.98 mU/g tissue in MI group to 2946.93±303 after oral administration of the extract (40 mg/kg). The levels of TNF-α was also declined from 406.15 ± 27.8 pg/ml in the serums of MI group to 100±12.2 (P < 0.001) in the group treated with 10 mg/kg of extract. In addition, peripheral neutrophil count that was elevated (p < 0.001) from 13±2.6% in normal control to 33.4±4.8% by isoproterenol injection, was significantly lowered by all doses of the extract (p < 0.001). Conclusion- Our results suggest that M.vulgare has strong protective effect on MI and these cardioprotective effects can be related to its antioxidant and anti-inflammatory properties.
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    Evaluation of the effect of administration of troxerutin on morphine dependence in mice
    (Tabriz University of Medical Sciences, Faculty of Pharmacy, 20121) Hosseinzad-Monie, Nasrin; Charkhpour, Mohammad; Parvizpour, Alireza
    Introduction: Chronic morphine use is associated with increased oxidative stress and inflammatory factors. Troxerutin is a natural bioflavonoid and has antioxidant and anti-inflammatory effects. Aim: The effects of troxerutin on morphine dependence in mice Method: Troxerutin was prepared. After examining the composition of the extract, the experiment was performed in six groups of 8 mice, so that one group received eight days of morphine with normal saline as an extract carrier, one group received only normal saline, and one group received troxerutin with normal saline. The other three groups received three different doses of troxerutin along with morphine. The ninth day, withdrawal symptoms were recorded after naloxone injection and blood samples were examined for antioxidant factors. Results: The total withdrawal score in the 50 mg/kg dose of extract group with morphine was significantly lower than morphine-saline group (p<0.001***). The total withdrawal score in the 100 mg/kg dose of extract group with morphine was significantly lower than morphine-saline group (p<0.01**). No significant sedative and locomotion activity reduction was observed in mice after using troxerutin. (all P>0.05). Antioxidant tests did not yield acceptable results due to possible errors in various parts of the process. Conclusion: Troxerutin reduces the symptoms of morphine withdrawal syndrome in a dose-independent manner. The results of antioxidant tests were not acceptable.
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    Identification of H3 Ligands through Hybrid Virtual Screening, Docking, Molecular Dynamics Simulations, and Investigation of Their Biological Effects
    (Tabriz University of medical Science, School of Pharmacy, 2019) Ghamari, Nakisa; Dastmalchi, Siavoush; Hamzeh Mivehroud, Maryam
    Introduction: Since the discovery of the histamine H3 receptor (H3R) in 1983, tremendous advances in the pharmacological aspects of H3 receptor antagonists/inverse agonists have been accomplished in preclinical studies. Histamine H3 receptors (H3R) are responsible for modulating the release of histamine and other neurotransmitters by a negative feedback mechanism mainly in the central nervous system (CNS). These receptors have gained increased attention as therapeutic target for several CNS related neurological diseases. Aims: In the current study, we aimed to identify novel H3R ligands using in silico virtual screening methods. Materials and methods: To this end, a combination of ligand- and structure-based approaches was utilized for screening of ZINC database on the homology model of human H3R. Structural similarity- and pharmacophore-based approaches were employed to generate compound libraries. Various molecular modeling methodologies such as molecular docking and dynamics simulation along with different drug likeness filtering criteria were applied to select anti-H3R ligands as promising candidate molecules based on known parent lead compound. Moreover, the antagonistic activity combined with anti-cholinesterase properties of the two more potent lead compounds were also tested. Furthermore, molecular docking and binding free energy calculations were also conducted for prediction of binding mode and affinity of studied ligands towards H3R and cholinesterase enzymes. Results: In vitro binding assays of selected molecules demonstrated three of them being active within the micromolar and submicromolar Ki range. In addition, biological evaluations revealed inhibitory activity of studied compounds in nanomolar and micromolar values for H3R antagonizing and cholinesterase inhibition, respectively. Disccusion: The results can be used for lead optimization where dual inhibitory activity on H3R and cholinesterase enzymes is needed. Conclusion: Collectively, the current integrated computational and experimental methods used in this work can provide new general insights for systematic hit identification for novel anti-H3R and anti cholineseterase agents from large compound libraries.
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    Synthesis and Physicochemical Characterization of poly (D, L-lactide-co-glycolide) Magnetic Nanocomposites Containing Amoxicillin
    (Tabriz University of Medical Sciences, Faculty of Pharmacy, 2010) Amini, Niloofar; Davaran, Soudabeh; Asgari, Davoud
    Introduction: There has been considerable interest in developing nanoparticles as effective drug delivery carriers. The biodegradable polymeric nanoparticles have shown their advantage over other nanocarriers by their increased stability and the unique ability to create an extended release. The biodegredble polyester called poly (D, L-lactide-co-glycolide) (PLGA) is a suitable biomaterial or polymer for for the preparation of novel drug delivery systems due to its biodegradability and biocompatibility. Owing to their excellent biocompatibility, PLGA is the most frequently used biomaterial and is already commercialized for a verity of drug delivery systems. Polymeric nanoparticles of this polymer are used for the delivery of various drugs (antipsychotics, anesthetics, antibiotics, antiparasites, antitumorals, hormones, proteins, etc). Magnetite (Fe3O4) is the most commonly used magnetic material for PLGA-based targeted drug delivery due to their good chemical stability and biocompatibility.Objectives: In this work amoxicillin-carrying magnetic nanocomposite spheres were synthesized by using magnetite nanoparticles and PLGA for the purpose of magnetic targeted drug delivery. The morphology, size, drug loading efficiency and the release of the amoxicillin from drug-loaded magnetic PLGA nanoparticles were investigated.Methods and materials: Magnetic nanoparticles (~13 nm on average) of magnetite were prepared by a chemical co precipitation of ferric and ferrous chloride salts in the presence of a strong basic solution (ammonium hydroxide). Amoxicillin-loaded magnetic PLGA and PLGA-PEG nanoparticles were prepared by a modified double emulsion method (w/o/w) or by an emulsion-evaporation process (o/w). Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) photomicrographs showed that the composite nanoparticles were almost spherical in shape, with rather monomodal distribution in size.Results: All composite nanoparticle formulations were found to have the mean diameter within the range of 60-110 nm. Magnetite nanoparticles prepared with PLGA showed more efficient entrapment (90%) as compared with PLGA-PEG nanoparticles (48%). In-vitro release of amoxicillin from nanoparticles showed that 78% of drug was released over 24 hours. Conclusion: Magnetic PLGA-based polymeric nanoparticles developed in this study may serve as a potential device for the delivery of antibiotic drug in which the primary target is the stomach or the upper small intestine.
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    Evaluation the effects of intracereboventricular injection of riluzole and minocycline on chronic morphine- induced tolernce to the analgesic effect and apoptosis in CNs of rat
    (Tabriz University of Medical Sciences, Faculty of Pharmacy, 2010) Hassanzadeh, Kambiz; Safar, Farajnia; Roshangar, Leila; Habibi Asl, Bohlool
    Long-term exposure to opiates induces tolerance to the analgesic effect. The neurobiological mechanism of this phenomenon is not completely clear. It has been indicated that neuronal apoptotic process is in association with the development of morphine tolerance. In the present study we tried to investigate the effect of intracerebroventricular (icv) administration of minocycline (a tetracycline derivative) and riluzole (an anti-glutamatergic agent) on morphine-induced tolerance and apoptosis in rat’s central nervous system. Different groups of rats received either morphine (ip) and drugs vehicle (icv) or morphine and different doses of minocycline or riluzole (icv) once per day. Nociception was assessed using a hot plate apparatus. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used to analyze apoptosis. The anti-apoptotic factors, Bcl-2 and HSP70 and the pro-apoptotic element caspase-3 were evaluated by immunoblotting. The results showed that central administration of minocycline and riluzole delayed morphine-induced tolerance. Additionally results indicated that minocycline attenuated the number of apoptotic cells in both the cerebral cortex and lumbar spinal cord. Immunoblotting findings showed that the amounts of anti-apoptotic agents (Bcl-2 and HSP70) were greater in the minocycline treated groups than in the controls in both regions. However, minocycline did not change the level of caspase-3 at the doses used with morphine. Furthermore the results showed that intracerebroventricular administration of riluzole attenuated morphine tolerance and number of TUNEL positive cells in both the cerebral cortex and lumbar spinal cord. The amount of anti-apoptotic agents (Bcl-2 and HSP70) was greater in the treatment groups than controls in both regions. Additionally, riluzole significantly decreased the caspase-3 content of the cerebral cortex. In conclusion, we found that intracerebroventricular administration of minocycline or riluzole attenuated the morphine induced tolerance and apoptosis in the cerebral cortex and lumbar spinal cord of rat.
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    Determination of solubility of phenanthrene in binary and ternary solvent mixtures and application of the Jouyban-Acree model for solubility prediction of chemical/drug compounds in mixed solvents
    (Tabriz University of Medical Sciences, Faculty of Pharmacy, 2010) Abolghassemi Fakhree, Mohammad Amin; Jouyban, Abolghasem
    Solubility of a compound in a solvent is an important thermodynamic property in chemical and pharmaceutical sciences. Its major effects can be seen in chemical and pharmaceutical related properties and processes such as synthesis, extraction, purification, crystallization, analysis, formulation, absorption, distribution, metabolism, elimination, and toxicity. Different methods of solubilization are applied to modify this property such as altering temperature, cosolvency, micelization, and complexation. Cosolvency and temperature altering are most accessible methods to modify solubility amount. Numerical methods have been introduced during recent decades; some of these calculative methods were structured, based on only empiric data correlation, some based on empiric data and theoretical models, and some other are based on theoretical calculations. For example, the linear solvation energy relationship (LSER) quantitative structure property relationships (QSPRs) of Abraham were developed based on solvatochromic properties of solvents and solutes and are used for solubility prediction in mono-solvents. Catalan solvent parameters are another set of solvatochromic properties which have been measured for more than 200 solvents. The Jouyban-Acree model is the most accurate semi-empirical model for solubility prediction in non-aqueous binary or multi-component solvents mixtures. In an attempt, coefficients of the Jouyban-Acree model for non-aqueous binary mixtures have been described using Abraham solvent and solute parameters. Phenanthrene is a polycyclic aromatic hydrocarbon (PAH) which can be used as a substrate for synthesis of medicinal compounds and is a model solute in solubility studies. As a part of QSPR modeling of this work, we are going to define Catalan solute parameters based on solubility amounts of a solvent in more than 8 solvents with known Catalan solvent parameters, using a multiple linear regression approach. The solubility data of phenanthrene in alcohols at different temperatures is measured. Another part of this study includes measurement of experimental solubility data for phenanthrene in different non-aqueous binary and ternary solvent mixtures and checking the predictability of the Jouyban-Acree model combined with Abraham parameters. To do this, four different numerical methods have been described. Using experimental solubility data in mono-solvents, numerical method I and II have been defined employing water-to-solvent and gas-to-solvent Abraham parameters, respectively. Predicted solubility amounts using Abraham parameters in mono-solvents and numerical method III and IV have been defined employing water-to-solvent and gas-to-solvent Abraham parameters, respectively. The mean percentage deviation has been used as an error criterion. The overall mean percentage deviations are 3.4 %, 14.6 %, 11.1 %, and 93.8 % for numerical methods I to IV, respectively. In all parts of experiment, phenanthrene has been recycled and reused. The results of this study suggest that the Jouyban-Acree model can be applied for solubility prediction in non-aqueous binary and ternary solvent mixtures with acceptable prediction error. To make it easy-to-use for chemical and pharmaceutical scientists and researchers, developing computer software might be a useful method.