فهرست مطالب

Pharmaceutical Research - Volume:16 Issue: 1, Winter 2017

Iranian Journal of Pharmaceutical Research
Volume:16 Issue: 1, Winter 2017

  • تاریخ انتشار: 1396/01/06
  • تعداد عناوین: 38
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  • Abdol Majid Cheraghali * Pages 1-7
  • Nima Hamzian, Maryam Hashemi, Mahdi Ghorbani, Mohammad Hossein Bahreyni Toosi, Mohammad Ramezani * Pages 8-21
    The aim of this study was to develop a novel multifunctional nanoparticle, which encapsulates SPION and Gemcitabine in PLGA±PEG to form multifunctional drug delivery system. For this aim, super paramagnetic iron oxide nanoparticles (SPIONs) were synthesized and encapsulated simultaneously with Gemcitabine (Gem) in PLGA±PEG copolymers via W/O/W double emulsification method. Optimum size and encapsulation efficiency for radiosensitization, hyperthermia and diagnostic applications were considered and the preparation parameters were systematically investigated and physicochemical characteristics of optimized nanoparticle were studied. Then SPION-PLGA and PLGA-Gem nanoparticles were prepared with the same optimized parameters and the toxicity of these nanoparticles was compared with Gemcitabine in human breast cancer cell line (MCF-7). The optimum preparation parameters were obtained with Gem/polymer equal to 0.04, SPION/polymer equal to 0.8 and 1% sucrose per 20 mg of polymer. The hydrodynamic diameters of all nanoparticles were under 200 nm. Encapsulation efficiency was adjusted between 13.2% to 16.1% for Gemcitabine and 48.2% to 50.1% for SPION. In-vitro Gemcitabine release kinetics had controlled behavior. Enhancement ratios for PLGA-Gem and SPION-PLGA-Gem at concentration of nanoparticles equal to IC50 of Gemcitabine were 1.53 and 1.89 respectively. The statistical difference was significant (p-value=0.006 for SPION-PLGA-Gem and p-value=0.015 for PLGA-Gem compared with Gemcitabine). In conclusion, we have successfully developed a Gemcitabine loaded super paramagnetic PLGA-Iron Oxide multifunctional drug delivery system. Future work includes in-vitro and in-vivo investigation of radiosensitization and other application of these nanoparticles.
    Keywords: Gemcitabine, multifunctional nanoparticles, SPION-PLGA drug delivery system, optimized preparation parameters, human breast cancer cell line (MCF-7)
  • Mitra Jelvehgari *, Saieede Soltani, Parvin Milani, Mohammad Barzegar Jalali Pages 22-34
    Ketotifen fumarate is a non-bronchodilator anti-asthmatic drug which inhibits the effects of certain endogenous substances known to be inflammatory mediators, and thereby exerts antiallergic activity. The present study describes the formulation of a sustained release nanoparticle (NP) drug delivery system containing ketotifen, using poly (D,L lactide-co-glycolide acid) (PLGA). Biodegradable NPs were prepared using PLGA by a water-in-oil-in-water (w/O/w) double emulsion-solvent evaporation procedure and characterized for drug content , DSC (differential scanning calorimetry, XRD (X-ray diffractionl), FTIR (Fourier transform spectroscopy), particle size, surface morphology using scanning electron microscopy and drug release rate. The effects of different drug-to-polymer ratios on the characteristics of the NPs were investigated. NPs prepared were spherical with a smooth surface. Size of NPs was dependent on the concentration of polymer (10 mg/ml, 754.6 nm). Increasing the external organic phase volume (primary emulsion) resulted in larger particles with higher encapsulation efficiency (55%). The best drug to polymer ratio in the NP was F3 (1:10 ratio) which showed loading efficiency of 55%, and mean particle size of 754.6 nm, respectively. The FTIR, XRPD and DSC results ruled out any chemical interaction between the drug and PLGA. The NPs prepared with low ratio of drug to polymer (1:5) F1 formulation showed faster dissolution rate than those with high drug to polymer ratio (1:10) F3 formulation. In conclusion, by selecting an appropriate level of the investigated parameters, spherical NPs with encapsulation efficiencies higher than 55% and a prolonged drug release over 24h (73.67-90.05%) were obtained.
    Keywords: Ketotifen fumarate, Nanoparticles, PLGA, Release, W-O-W
  • Mehrdad Hashemi, Fereshteh Atabi, Seyed Latif Mousavi Gargari *, Parichehreh Yaghmaei Pages 35-49
    Recently, specific attention has been paid to aptamers, short DNA or RNA, as a tool for cancer diagnosis and therapy. In the present study MCS nanogels were prepared by Myristate: chitosan at 1:9 ratio and were characterized by several techniques. A selected ssDNA aptamer(Apt) capable of detecting LNCaP cells was linked to Myristilated chitosan nanogels (Apt-MCS) by glutaraldehyde and loaded with Doxorubicin (DOX) to be used in targeted drug delivery against the Prostate cancer cells. LNCaP and PC-3 cells were treated with Apt-MCS-DOX complex and the binding efficiency was estimated by flow cytometry. The binding affinity of the selected aptamers was above 70% compared to the initial library. The loading capacity of the nanogel was as high as 97% and up to 40% of DOX were released from MCS within 15 days.Cytotoxicity of nanodrugs on LNCaP cells were determined by MTT assay. Apt-MCS-DOX was specifically binded to LNCaP cells whereas it didn’t show any specificity to PC-3 cells as a negative control. Both MCS-DOX and Apt-MCS-DOX showed a lethal effect on LNCaP cells. Our results can lead to an aptamer based simple and applicable technique for early diagnosis and treatment of cancerous cells.
    Keywords: DOX, MCS, nanogel, aptamer, Targeted drug delivery, Prostate cancer
  • Qiang Li, Li Jian Sun, Xian Feng Gong, Yang Wang, Xue Ling Zhao * Pages 50-62
    Angelica essential oil (AO), a major pharmacologically active component of Angelica sinensis (Oliv.) Diels, possesses hemogenesis, analgesic activities and sedative effect. The application of AO in pharmaceutical systems had been limited because of its low oxidative stability. The AO-loaded gelatin-chitosan microcapsules with prevention from oxidation were developed and optimized using response surface methodology. The effects of formulation variables (pH at complex coacervation, gelatin concentration, and core/wall ratio) on multiple response variables (yield, encapsulation efficiency, antioxidation rate, percent of drug released in 1 h, and time to 85% drug release) were systemically investigated. A desirability function that combined these five response variables was constructed. All response variables investigated were found to be highly dependent on the formulation variables, with strong interactions observed between the formulation variables. It was found that optimum overall desirability of AO microcapsules could be obtained at pH 6.20, gelatin concentration 25.00%, and core/wall ratio 40.40%. The experimental values of the response variables highly agreed with the predicted values. The antioxidation rate of optimum formulation was approximately 8 times higher than that of AO. The in vitro drug release from microcapsules was followed Higuchi model with super case-II transport mechanism.
    Keywords: microcapsules, angelica essential oil, multiresponse optimization, gelatin, sustained release, antioxidation rate
  • Ali Hossein Rezayan *, Negar Firoozi, Somayyeh Kheirjou, Seyed Jamal Tabatabaei Rezaei, Mohammad Reza Nabid Pages 63-73
    In this paper, the focus is on a new kind of biodegradable semi-interpenetrating polymer networks, which derived from ɛ-caprolactone, lactide, 1,4-butane diisocyanate and ethylenediamine and also its potential has been investigated in soft tissue engineering applications. The polymers were characterized by nuclear magnetic resonance (NMR) spectrometry, fourier transform infrared spectroscopy (FT-IR), differential thermal analysis (DTA), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). These experiments show that the polymers with the right composition and the expected molecular weight were achieved. Also, the in vitro degradation of polymer network was examined in phosphate buffer solutions (pH 7.4) at 37 °C. In addition, cell viability and adhesion tests were carried out with fibroblast cells by the MTT assay, which confirmed biocompatibility. Polyurethane materials have superior mechanical properties, so these biodegradable and biocompatible films demonstrate potential for future application as cell scaffolds in soft tissue engineering applications.
    Keywords: polymer network, polyurethane, biodegradable, biocompatible, soft tissue engineering
  • Brahmeshwar Mishra *, Madhusmita Mishra, Sarita Kumari Yadav Pages 74-92
    Inhalation delivery of aerosolized antibacterials is preferred over conventional methods of delivery for targeting lung infection. The present study is concerned with the development and characterization of a novel, spray dried, aerosolized, chitosan polyelectrolyte complex (PEC) based microparticles containing antibacterials for the treatment of lung infections.
    Chitosan polyelectrolyte complex microparticles were formulated by spray drying process. Prepared spray dried chitosan PEC microparticles were studied for surface morphology, drug encapsulation efficiency, moisture content, Carr’s index, solid state interaction by XRD, aerosolization behaviour and in vitro drug release. In vitro cytotoxicity studies of microparticles were carried out on H1299 alveolar cell lines. Antibacterial efficacy of microparticles was assessed on the basis of determination of pharmacokinetic parameters in bronchial alveolar lavage (BAL) of rats using PK/PD analysis.
    The PEC microparticles were mostly spherical and exhibited high drug encapsulation efficiency. Release profiles showed an initial burst phase followed by a secondary sustained release phase. Good aerosolization behaviour as dry powder inhaler was demonstrated by microparticles with high values of recovered dose, emitted dose, and fine particle fraction. No overt cytotoxicity of microparticles was detected against H1299 alveolar cell line. More than 8 to 9 folds higher Cmax values were obtained in BAL fluid with microparticles as compared to intravenously administered antibacterial solution.
    The findings of the study suggest that chitosan polyelectrolyte complex based microparticles as dry powder inhaler can be an efficient antibacterial delivery system for sustained and effective management of lung infection.
    Keywords: Levofloxacin, doxycycline, inhaler, aerosol, spray dried
  • Mohsen Atefi, Abdorreza Mohammadi, Kooshan Nayebzadeh* Pages 93-102
    Saffron essential oil has a pleasant aroma and medicinal activities. However, it is sensible into the environmental condition. Therefore, it should be protected against unwanted changes during storage or processing. Encapsulation is introduced as a process by which liable materials are protected from unwanted changes. In the present study, different ratios (0:100, 25:75, 50:50, 75:25, and 100:0) of ß-cyclodextrin (ß-CD) and arabic gum (GA) were used as wall martial for encapsulation saffron essential oil. In order to calculate of loading capacity (LC) and encapsulation efficiency (EE), and release (RE), safranal was determined as indicator of saffron essential oil using GC. According to the results, the highest LC and EE were related to the mixture of ß-CD/GA at a 75:25 ratio. In contrast, the lowest encapsulate hygroscopicity (EH) and RE were observed when only ß-CD was applied as wall material (P≤0.05). Comparing the differential scanning calorimetry (DSC) thermograms of the control and encapsulate of ß-CD/GA (75:25) confirmed encapsulation of saffron essential oil. Scanning electron microscopy (SEM) images with high magnifications showed the rhombic structure that partially coated by GA. The mixture of ß-CD/GA at a 75:25 ratio can be recommended for saffron essential oil encapsulation.
    Keywords: Saffron essential oil, Safranal, Encapsulation, ß-cyclodextrin, Arabic gum
  • Mohammad Reza Fazeli *, Najmeh Mahjoubi, Ahmad Fazeli, Rassoul Dinarvand, Mohammad Reza Khoshayand, Maryam Shekarchi Pages 103-111
    Liquid protein formulations are prone to form aggregates. The effect of nonionic surfactants such as Polysorbate 20 (PS 20) and n-Dodecyl β-D-maltoside (DDM) on the prevention of aggregation and conformational changes of recombinant human IFNβ-1b (rhIFN β_1b) was explored. Polysorbate has been used in formulations of protein pharmaceuticals. There have been concerns about using PS 20 due to its residual peroxide content which may negatively affect protein efficacy. n-Dodecyl β-D-maltoside has been of interest and shown to be highly effective in prevention of aggregation. Fresh bulk of rhIFN β_1b was formulated using DDM or different concentrations of PS 20. Formulations were exposed to light stress condition according to the ICH guideline of Q1b. The overall conformational integrity of individual samples was characterized by a combination of Circular dichroism (CD), Fluorescence spectroscopy and RP_HPLC techniques.
    The CD spectrum depicting the conformational integrity of rhIFN β_1b showed 31.9% and 31.2% decreases in α-helix content of protein samples with 0.2% or 0.02% of PS20 compared to only18.2% of that containing 0.2% DDM. The RP-HPLC analysis also showed that the oxidized impurity in formulation containing DDM is less than those contain PS 20.
    Complementary analysis of the liquid formulations using IFR and UV methods also was in compliance with the data obtained by CD.
    Compared to PS 20, the sample of rhIFN β_1b formulation with DDM was more resistant to the destruction effect of light. Results were in accordance with previous studies and could suggest DDM as a reliable anti-aggregation surfactant in biopharmaceutical formulations.
    Keywords: Nonionic surfactant, Circular dichroism (CD), oxidation, anti-aggregation, rhIFN ?-1b
  • Effat Souri *, Farzaneh Sadat Ahmadi, Maliheh Barazandeh Tehrani, Sedighe Fadaye Vatan, Majid Mohammad Hosseini Pages 112-119
    Buprenorphine is a partial mu agonist and kappa antagonist which is used for the treatment of pain and opioid addiction. A mixture of buprenorphine hydrochloride and naloxone hydrochloride has been approved for the treatment of opioid dependence.
    In this study a third order derivative spectrophotometric method based on zero-crossing technique has been used for the simultaneous determination of buprenorphine hydrochloride and naloxone hydrochloride in tablets. The measurements were carried out at wavelengths of 257.8 (zero-crossing point of naloxone hydrochloride) and 252.2 nm (zero-crossing point of buprenorphice hydrochloride) for buprenorphine hydrochloride and naloxone hydrochloride, respectively in the third order derivative spectra obtained in methanol and 0.1 M NaOH (50:50) as solvent. The method was found to be linear in the range of 20-80 µg/mL for buprenorphine hydrochloride and 5-20 µg/mL for naloxone hydrochloride. The within-day and between-day coefficient of variation and error values were less than 2.5% and 1.8%, respectively. The proposed method was successfully used for simultaneous determination of these drugs in pharmaceutical dosage form without any interference from excipients or need to prior separation before analysis.
    Keywords: Buprenorphine hydrochloride, Naloxone hydrochloride, Simultaneous, Derivative spectrophotometry
  • Maryam Vosough, Shiva Ghafghazi, Taraneh Moini Zanjani, Masoumeh Sabetkasaei Pages 120-131
    In the present study, a comprehensive and systematic strategy was described to evaluate the performance of several three-way calibration methods on a bio-analytical problem. Parallel factor analysis (PARAFAC), alternating trilinear decomposition (ATLD), self-weighted alternating trilinear decomposition (SWATLD), alternating penalty trilinear decomposition (APTLD) and unfolded partial least squares combined with the residual bilinearization procedure (U-PLS/RBL) were applied on high performance liquid chromatography with photodiode-array detection (HPLC-DAD) data to quantify carbamazepine (CBZ) in different serum samples. Using the proposed approach, successfully quantification of CBZ in human plasma, even in the presence of diverse uncalibrated serious interfering components was achieved. Moreover, the accuracy and precision of each algorithm for analyzing CBZ in serum samples were compared using root mean square error of prediction (RMSEP), the recovery values and figures of merits and reproducibility of the analysis. Satisfying recovery values for the analyte of interest were obtained by HPLC-DAD on a Bonus-RP column using an isocratic mode of elution with acetonitrile/K2HPO4 (pH=7.5) buffer solution (45:55) coupled with second-order calibrations. Decreasing the analysis time and less solvent consumption are some of the pluses of this method. The analysis of real samples showed that the modeling of complex chromatographic profiles containing CBZ as the target drug using any of the mentioned algorithms can be potentially benefit drug monitoring in therapeutic research.
    Keywords: Carbamazepine, High-performance liquid chromatography, Multi-way algorithms, Serum
  • Bahar Darsazan, Alireza Shafaati, Seyed Alireza Mortazavi, Afshin Zarghi * Pages 132-139
    A simple and reliable stability-indicating RP-HPLC method was developed and validated for analysis of adefovir dipivoxil (ADV).The chromatographic separation was performed on a C18 column using a mixture of acetonitrile-citrate buffer (10 mM at pH 5.2) 36:64 (%v/v) as mobile phase, at a flow rate of 1.5 ml/min. Detection was carried out at 260 nm and a sharp peak was obtained for ADV at a retention time of 5.8 ± 0.01 min. No interferences were observed from its stress degradation products. The method was validated according to the international guidelines. Linear regression analysis of data for the calibration plot showed a linear relationship between peak area and concentration over the range of 0.5–16 μg/ml; the regression coefficient was 0.9999and the linear regression equation was y=24844x–2941.3. The detection (LOD) and quantification (LOQ) limits were 0.12 and 0.35 μg/ml, respectively. The results proved the method was fast (analysis time less than 7 min), precise, reproducible, and accurate for analysis of ADV over a wide range of concentration. The proposed specific method was used for routine quantification of ADV in pharmaceutical bulk and a tablet dosage form.
    Keywords: Adefovir Dipivoxil, Assay, RP-HPLC, Stability-Indicating, Pharmaceutical dosage form
  • Vahid Farzanehfar, Mehrdad Faizi, Nima Naderi, Farzad Kobarfard * Pages 140-145
    Dibutyl phthalate (DBP) is a phthalic acid ester and is widely used in polymeric products to make them more flexible. DBP is found in almost every plastic material and is believed to be persistent in the environment. Various analytical methods have been used to measure DBP in different matrices. Considering the ubiquitous nature of DBP, the most important challenge in DBP analyses is the contamination of even analytical grade organic solvents with this compound and lack of availability of a true blank matrix to construct the calibration line. Standard addition method or using artificial matrices reduce the precision and accuracy of the results. In this study a surrogate analyte approach that is based on using deuterium labeled analyte (DBP-d4) to construct the calibration line was applied to determine DBP in hexane samples.
    Keywords: phthalic acid esters, dibutyl phthalate, phthalates, surrogate analyte, GC-MS
  • Elham Baher *, Naser Darzi Pages 146-157
    In this work the electrooxidation half-wave potentials of some Benzoxazines were predicted from their structural molecular descriptors by using quantitative structure-property relationship (QSAR) approaches. The dataset consist the half-wave potential of 40 benzoxazine derivatives which were obtained by DC-polarography. Descriptors which were selected by stepwise multiple selection procedure are: HOMO energy, partial positive surface area, maximum valency of carbon atom, relative number of hydrogen atoms and maximum electrophilic reaction index for nitrogen atom. These descriptors were used for development of multiple linear regression (MLR) and artificial neural network (ANN) models. The statistical parameters of MLR model are standard errors of 0.016 and 0.018 for training and test sets, respectively. Also, these values are 0.012 and 0.017 for training and test sets of ANN model, respectively. The predictive power of these models was further examined by leave-eight-out cross validation procedure. The obtained statistical parameters are Q2= 0.920 and SPRESS= 0.020 for MLR model and Q2= 0.949 and SPRESS= 0.015 for ANN model, which reveals the superiority of ANN over MLR model. Moreover, the results of sensitivity analysis on ANN model indicate that the order of importance of descriptors is: Relative number of H atom > HOMO energy > Maximum electrophyl reaction index for N atom > Partial positive surface area (order-3) > maximum valency of C atom.
    Keywords: Benzoxazines, Half wave potential, Artificial neural network, pharmaceutical property, Quantitative structure-property relationship
  • Hamid Reza Ahfad-Hosseini, Hasan Bagheri, Salimeh Amidi * Pages 158-164
    Celecoxib is classified as none traditional nonsteroidal anti-inflammatory drugs (NSAIDs). This compound has conventional properties of NSAIDs such as anti-inflammatory, analgesic, and antipyretic activities beside reduced risk of gastrointestinal side effect of traditional NSAIDs such as ibuprofen. This compound gets a second sale rank of NSAIDs market at 2016 in the world and sales more than 17000 kg in Iran during the past 6 month. So, the simple, rapid and green method for synthesis of this compound is important. In the present study, a novel green method was suggested for the synthesis of celecoxib using the ionic liquid.
    Celecoxib was provided by the reaction of trifluorineacetone, 4-methylbenzoylchloride, and 4-hydrazine benzene sulfonate amide hydrochloride. The tris-(2-hydroxyethyl) ammonium acetate as ionic liquid was prepared by mixing tris-(2-hydroxyethyl) ammonium and acetic acid, and used as an efficient catalyst. The structure of the synthetic products was confirmed by analytical and spectroscopic methods including 1HNMR, 13CNMR, IR, MS and elemental analysis.
    This ionic liquid can play dual roles in the synthesis of celecoxib, as a catalyst to improve electrophilicity of carbonyl group and also as a solvent of reaction. The reaction rate and yield (86%) were improved considerably. Moreover IL showed the same efficiency when used in 4 consecutive reactions.
    Keywords: Celecoxib, Anti-inflammatory agent, Ionic liquid, Trifluorineacetone, 4-methylbenzoylchloride, 4-hydrazine benzene sulfonate amide hydrochloride
  • Alireza Aliabadi *, Ahmad Mohammadi Farani, Sahar Roodabeh, Farahnaz Ahmadi Pages 165-172
    In the recent years, the role of LOX enzymes in the cause of neoplastic diseases such as colorectal, skin, pancreatic and renal cancers has been confirmed. A new series of 1,3,4-thiadiazole derivatives bearing 2-pyridyl moiety was synthesized and their cytotoxicity was assessed using MTT protocol. Enzyme inhibitory activity of prepared compounds was also tested against 15-lipoxygenase-1 as novel target for discovery of anticancer drugs. PC3, HT29 and SKNMC cell lines were utilized and the obtained results were compared to doxorubicin. Overall, nitro containing derivatives exerted higher cytotoxic activity against PC3 cell line and methoxylated derivatives showed an acceptable activity against SKNMC cell line. Methoxylated derivatives were also the most potent enzyme inhibitors especially at position ortho of the phenyl residue.
    Keywords: Pyridine, Thiadiazole, Synthesis, Lipoxygenase, MTT
  • Maryam Farrokhnia, Karim Mahnam * Pages 173-186
    Zoanthamine-type alkaloids display a wide spectrum of biological effects. This study aimed to examine the inhibitory effects of norzoanthamine and its ten homologues of zoanthamine class on human fibroblast collagenase by modeling a three-dimensional structure of the ligands at collagenase using energy minimization, docking, molecular dynamics simulation and MM-PB/GBSA binding free energy calculations. The results showed that zoanthamide, zooxathellamine and enol-iminium form of norzoanthamine, with lower binding free energies than other compounds, are potent inhibitors of collagenase. However, the enol-iminium form of norzoanthamine showed a more inhibitory activity against collagenase than its keto form. This suggests that it can be used for treatment of many diseases such as osteoporosis, autoimmune diseases, and cancer. Zinc-binding residues such as His 118, His 122 and His 128 for hydrogen bonds and Leu 81, Tyr 110, Val 115, Leu 126, Pro 138, Ser 139 for hydrophobic interactions should be considered for designing an inhibitor for collagenase. Our theoretical results and MM/GBSA binding free energy calculations are consistent with experimental studies.
    Keywords: Matrix Metaloproteinase-1, Zoanthamine alkaloid class, Docking, Molecular dynamics simulation, MM-PB-GBSA
  • Bahareh Amin, Samira Hosseini, Hossein Hosseinzadeh * Pages 187-200
    The aim of this study was to evaluate the anti-nociceptive effects of a low, sub-effective dose of amitriptyline, in combination with the different doses of ethanolic and aqueous extracts of Crocus sativus following sciatic nerve chronic constriction injury (CCI) in rats.
    Amitriptyline (3, 10 and 30 mg/kg, i.p.) and the extracts (25, 50 and 100 mg/kg, i.p.), were separately administered at the time of CCI for 7 consecutive days. In combination therapy, the sub-antinociceptive dose of amitriptyline (3 mg/kg) was given with the three different doses of extracts for seven days. Mechanical allodynia, thermal allodynia and thermal hyperalgesia were evaluated by von Frey, acetone and radiant heat tests, respectively, 1 day before and on days 3, 5 and 7 after surgery.
    Co-administration of amitriptyline (3 mg/kg) with aqueous extract (50, 100 mg/kg,) produced more potent cold anti-allodynic (P
    Keywords: Amitriptyline, Saffron, Neuropathic pain, Antinociceptive, Allodynia, Combination therapy
  • Mohammad Sharifzadeh, Akram Ranjbar *, Asie Hossini, Mahnaz Khanavi Pages 201-209
    Diabetes mellitus is associated with distribution of cognitive functioning. Hyperglycemia Diabetes mellitus is associated with distribution of cognitive functioning. Hyperglycemia induced oxidative stress has been proposed as a cause of memory complications of diabetes including cognitive impairment. The aim of this study was to examine total green tea extract (TGTE), a potent free radical scavenger against spatial impairment in Streptozotocin-diabetic rats. Eight weeks after diabetes induction, TGTE was administrated in drinking water 3mg/L. The learning and memory behavior was evaluated with Morris water maze task in male rats. Then for estimation of oxidative stress parameters such as lipid peroxidation (LPO), total antioxidant capacity (FRAP) and total thiol groups in blood were scarified. The total green tea extract showed improved cognitive impairment in diabetic groups but these changes weren’t significant. There was also significant increase FRAP level and total thiol groups in treated green tea groups vs. control. group. This study demonstrated the effectiveness of TGTE on spatial impairment and oxidative stress induced in diabetes mellitus.
    Keywords: Spatial memory, Green tea, Oxidative stress, Diabetes, Learning
  • Cumali Keskin*, Necmettin Aktepe, Yunus Yukselten, Asuman Sunguroglu, Mehmet Boga Pages 210-220
    The present study investigates the antioxidant, anticancer, anticholinesterase, anti-genotoxic activities and phenolic contents of flower, fruit and seed methanol extracts of Hypericum retusum AUCHER. The amounts of protocatechuic acid, catechin, caffeic acid and syringic acid in methanol extracts were determined by HPLC. Total phenolic content of H. retusum seed extract was found more than fruit and flower extracts. The DPPH free radical scavenging activity of flower and seed methanol extracts showed close activity versus BHT as control. Among three extract of H. retusum only flower methanol extract was exhibited considerable cytotoxic activities against to HeLa and NRK-52E cell lines. Moreover, seed methanol extract showed both acetyl and butyrl-cholinesterase inhibitory activity. The highest anti-genotoxic effects were seen 25 and 50 μg/mL concentrations. In this study, the extracts showed a strong antioxidant and anti-genotoxic effect. The seed extract was more efficiently than extracts of fruit and flowers. Our results suggest that the antioxidant and anti-genotoxic effects of extracts depend on their phenolic contents. Further studies should evaluate the in vitro and in vivo the benefits of H. retusum seed methanol extracts.
    Keywords: Hypericum retusum AUCHER, Antioxidant, cytotoxic, anticholinesterase, antigenotoxic
  • Mahdi Mojarrab, Seyed Ahmad Emami, Zahra Tayarani Najaran* Pages 221-229
    Considering multiple reports on cytotoxic activity of the Artemisia genus and its phytochemicals, in the current study A. armeniaca Lam. and the three components isolated from the plant were subjected to cytotoxic studies. Analytical fractionation of A. armeniaca aerial parts for the first time was directed to the isolation of 7-hydroxy-8-(4-hydroxy-3-methylbutoxy) comarin (armenin), 8-hydroxy-7-(4-hydroxy-3-methylbutoxy) comarin (isoarmenin) and deoxylacarol. Extracts and all compounds exhibited cytotoxic activity against apoptosis-proficient HL-60 and apoptosis-resistant K562 cells, with the lowest cytotoxic activity on normal human lymphocytes.
    Armenin as the most potent component was selected for further mechanistic study. Increased in sub-G1 peak in flow cytometry histogram of HL-60 and K562 treated cells and the cleavage of PARP in comparison with the control after treatment for 48 h verified the apoptotic activity of the armenin.
    Taken together, according to the finding of this study armenin was introduced as a novel cytotoxic compound with apoptotic activity, which is encouraging for further mechanistic and clinical studies.
    Keywords: Artemisia armeniaca, leukemic cell lines, apoptosis, coumarin-hemiterpene ether derivatives, Asteraceae
  • Seyed Hadi Mousavi *, Vahid Vazifedan, Javad Sargolzaee, Shokouhozaman Soleymanifard, Azar Fani Pakdel Pages 230-237
    Malignant tumors of head and neck carcinomas are the sixth most common type of cancer. Current systemic therapies for cancer show side effects in normal tissues and short-term efficacy due to drug resistance. Consequently, there is much interest in identifying new drugs for cancer treatment. Crocin (an active ingredient of saffron) has been shown to have cytotoxic effects on cancer cell lines. Chemo radiotherapy is the standard treatment for head and neck cancer. In the present study, the cytotoxic effects, inducing apoptosis and the radiation sensitivity of crocin were evaluated in the head and neck cancer cell line (HN-5). HN-5 cells were cultured in a DMEM medium and incubated with different concentrations of crocin (12.5-1000 µg/ml). They were exposed to 2 Gy γ-rays. Cell viability was quantified by the MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flowcytometry (sub-G1 peak). Crocin decreased cell viability in HN-5 cells in a time and concentration dependent manner. Crocin also induced a sub-G1 peak in the flowcytometery histogram of treated cells compared with the control, suggesting that apoptotic cell death is caused by its toxicity. Crocin was also shown to sensitize cells to radiation-induced toxicity and apoptosis. The simultaneous use of crocin and radiation therefore increases radiation sensitivity and cell death. Thus, after further study crocin can be considered as a potential drug and sensitizer in cancer treatment.
    Keywords: HN-5, Crocin, Cytotoxicity, apoptosis, Radiotherapy
  • Bahram Daraei *, Marjan Aghvami, Jalal Pourahmad, Rassoul Dinarvand Pages 249-265
    Docetaxel (DTX) is one of the most widely used drugs in oncology due to its high efficacy against several cancers. Though, its routine clinical administration, formulated in tween 80, causes serious side effects. Polylactide-co-glycolide (PLGA), biodegradable polyester synthesized and approved for human use, is employed to overcome this problem.
    In this investigation, we compare the cytotoxic mechanisms of DTX and PLGA-DTX in isolated rat hepatocytes. Cytotoxicity of DTX and PLGA-DTX were associated with reactive oxygen species formation, activation of caspases cascade, collapse of mitochondrial membrane potential (MMP), lysosomal membrane leakiness and ATP depletion. Our results also showed that CYP2E1 is involved in the oxidative stress cytotoxicity mechanism and both drugs are detoxified via phase II metabolic methylation. Furthermore, we concluded that PLGA-DTX is bioactivated by GSH. It could also potentiate hepatocyte toxicity through a mitochondrial/lysosomal toxic cross-talk. In addition to these observed differences, it is likely that mode of hepatocyte membrane penetration is different between these compounds.
    Keywords: Docetaxel, Polylactide-co-glycolide, PLGA-DTX nanoparticles, Cytotoxicity, Rat Hepatocyte, Silymarin
  • Elaheh Amini *, Mohammad Nabiuni, Javad Baharara, Kazem Parivar, Javad Asili Pages 266-276
    Ophiocoma erinaceus Muller &Troschel (Ophiocomidae) is part of the extensive group of echinoderm that contains bioactive metabolites. As, the anti cancer potential of brittle star saponin has not been reported against cervical cancer, the present study was conducted to evaluate the anticancer effect of extracted crude saponin. Saponin extraction was conducted using conventional method such as froth test, TLC, FTIR and erythrolysis assay. The Hela-S3 cervical carcinoma and HNCF-PI52 normal cells were treated with different concentrations of saponin fraction for 24 and 48 h. The cytotoxicity was examined by MTT, DAPI, AO/PI, Annexin V-FITC and flow cytometry. In addition, the apoptotic induced pathway was studied using caspase assay, evaluation of ROS generation and Bcl-2 mRNA level. Crude saponin showed cytotoxic properties in Hela-S3 cells (IC50of 23.4 µg/ml) without significant impact against normal cells. In addition, the crude saponin increased sub-G1 peak in flow cytometry histogram of treated cells, ROS generation and caspase-3 and -9 activity (IC50 of 11.10, 11.27 µg/ml). The dose dependent down regulation of Bcl-2 in treated cells demonstrated that saponin fraction can trigger intrinsic apoptotic pathway in cancer cells. This study provides valuable information about the apoptotic inducing effect of saponin fraction which can offer new insights into the anticancer potential of saponin as a promising candidate against human cervical carcinoma.
    Keywords: Ophiocoma erinaceus, echinoderm, anticancer, cervical cancer, pro-apoptotic, intrinsic pathway
  • Parina Asgharian, Fariba Heshmati Afshar, Solmaz Asnaashari, Farzaneh Lotfipour, Behzad Baradaran, Elmira Zolali, Sedigheh Bamdad Moghaddam, Abbas Delazar * Pages 277-289
    The current study was assigned to evaluate the total phenol, total flavonoid content (TPC, TFC) and antioxidant properties of extracts from the aerial parts of Scrophularia frigida (S. frigida). Extracts were also tested by preliminary phytochemical screening as well as cytotoxic activity against Artemia salina, MCF-7 (human breast carcinoma) and SW-480 (colon carcinoma) and L-929 (normal) cell lines along with antimicrobial characteristic. DPPH, MTT and Brine shrimp lethality tests and disc diffusion method were carried out to determine the biological activities of the different extracts of S. frigida. In addition, the extracts which had more potent antioxidant and antiproliferative activity were further analyzed by NMR and GC-MS. 40% methanol-water (from MeOH extract) fraction showed higher amounts of TPC, TFC and antioxidant property. Findings of the study for general toxicity effect showed that dichloromethane (DCM) and MeOH extracts had weak to moderate effects. Furthermore, DCM extract indicated the most potent anti-proliferative activity against cancer cell lines. No evidence of antibacterial activity was determined. On the other hand, analysis of the potent extract DCM in cytotoxic assay showed the presence of trans-phytol and cis-oleic acid in GC-MS. Furthermore, NMR analysis of potent methanolic fractions in antioxidant tests revealed the presence of iridoid and phenolics. Generally the results of TPC, TFC and antioxidant activity of extracts and fractions were in agreement with each other.
    Keywords: Scrophularia frigida, antioxidant activity, cytotoxic effect, phytochemical analysis, NMR, GC-MS
  • Rasool Soltani, Hossein Fazeli, Rahim Bahri Najafi *, Alireza Jelokhanian Pages 290-296
    Antibiotic resistance is an important problem in antibiotic treatment of infections, particularly in hospitals. Tomatidine is a plant secondary metabolite with antimicrobial and antifungal effects. This study examined the possible synergistic effect tomatidine with several antibiotics against standard and clinical strains of Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli. After determining the minimum inhibitory concentrations (MICs) of antibiotics and tomatidine against the bacterial isolates using broth microdilution method, the synergistic effect between tomatidine and antibiotics was evaluated by checkerboard method and calculation of FIC indices. Tomatidine alone did not show any antimicrobial effect. However, it had synergistic effect with gentamicin and cefepime against standard and clinical isolates of S. aureus and P. aeruginosa, respectively. It also had synergistic effect with ampicillin and ciprofloxacin only against standard strains of E. faecalis and P. aeruginosa, respectively. In conclusion, tomatidine could be considered as a potential antibiotic potentiator for gentamicin, cefepime and ciprofloxacin, and ampicillin against Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis infections, respectively. However, the toxicological and pharmacological properties of tomatidine for use as a therapeutic agent remain to be determined.
    Keywords: Antibiotics, Tomatidine, Synergistic Effect, Bacteria
  • Mahboobeh Talebi *, Rasool Madani, Reza Hajihosseini, Soheila Moradi Bidhendi Pages 297-305
    The aim of this study is to investigate antibacterial effects of immunodominant proteins isolated from the venom of Naja Naja Oxiana snake against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa.
    The innate immune system is an important line of defense against bacterial diseases. Antibacterial proteins produced by snake venoms have recently attracted significant attention due to their relevance to bacterial diseases and the potential of being converted into new therapeutic agents.
    Identification of immunodominant proteins of the venom of N. Oxiana snake was performed by SDS-PAGE and western blot analysis.Identified proteins were isolated directly from preparative gel electrophoresis by Electro-elution. In the next step, antibacterial effects of immunodominant proteins were tested against several strains of clinical isolates, including S.aureus, B.subtilis and P.aeruginosa, E.coli using broth microdilution and disc-diffusion assays. In order to compare the results of the disc-diffusion assay, antibacterial effects of several antibiotics (Gentamicin, Ampicillin, Penicillin, Amoxicillin and Ciprofloxacin) were also examined using the same conditions.
    Results showed immunodominant proteins of 14, and 65kDa with high immunogenicity were very effective in inhibiting the growth of (S.aureus, B.sub) that were tested. However, they were only moderately effective in inhibiting the growth of(P.aeruginosa and E.coli). However, immunodominant proteins of 22 and 32kDa with high mmunogenicity, showed slight effectiveness in inhibiting the growth of two the Gram-positive and Gram-negative bacteria that were tested.
    To the best of our knowledge, these immunodominant proteins are novel antigens for potent antimicrobial effects against (S.aureus, B.subtilis ) and less antimicrobial effect against (E.coli, P.aeruginosa).
    Keywords: Naja Naja, Immunodominant protein, antibacterial effect, Electro elution, Immnune system
  • Solmaz Asnaashari, Abbas Delazar, Parina Asgharian, Farzaneh Lotfipour, Sedigheh Bamdad Moghaddam, Fariba Heshmati Afshar * Pages 306-314
    The current study evaluated the general toxicity, antioxidant, antimicrobial, and cytotoxic activity of extracts obtained from the rhizomes of Eremostachys azerbaijanica (Labiatae) as well as analyzed the potent extracts using GC-MS. Extracts of E. azerbaijanica in n-hexane, dichloromethane (DCM) and methanol (MeOH) were prepared using a Soxhlet apparatus. The antioxidant activity of the extracts was evaluated for free radical scavenging activity by DPPH assay. The antimicrobial activity of samples was determined by disc diffusion and brine shrimp lethality assay (BSLA) was used to assess general toxicity. The cytotoxicity of each extract was determined by MTT assay against human colorectal adenocarcinoma (HT29), human lung carcinoma (A549) and a normal cell line (human umbilical vein endothelial cells, HUVEC).
    The MeOH extract showed significant antioxidant activity and the n-hexane and DCM extracts showed promising activity against gram-positive species when compared with amikacin as a standard. Moreover, the n-hexane extract displayed the most potent activity in general toxicity assay. The results showed that all three extracts have cytotoxicity effects against the A549 cell line. In the case of HT29 cell lines, only the DCM extract exhibited cytotoxicity. Interestingly, none of the extracts showed significant cytotoxic activity against the HUVEC cell line. The bioassay-guided identification of constituents showed the presence of fatty acids and steroids as the compounds responsible for bioactivity in the non-polar extracts.
    Keywords: Eremostachys azerbaijanica, general toxicity, Cytotoxicity, Antimicrobial, Antioxidant
  • Yacine Amar *, Boumedienne Meddah, Irene Bonacorsi, Gregorio Costa, Gaetana Pezzino, Antonina Saija, Mariateresa, Cristani, Soulef Boussahel, Guido, Ferlazzo, Aicha Tirtouil Meddah Pages 315-327
    Rosmarinus officinalis L., a medicinal herb from the labiates family, has been reported to be of potential benefit in the treatment and prevention of several diseases. In particular its phenolics have demonstrated protective effects on various types of cancer through several mechanisms. The present study aimed to determine the effects of rosemary phenolic extracts on human cell functions, with particular regard to their anti-proliferative properties in three cell types U937, CaCo-2 and the peripheral blood mononuclear cells (PBMCs). The radical scavenging and Ferric reducing abilities of the extracts have been assessed as well as their cyto-toxicity and effects on cell cycle distribution and apoptosis. About 13 compounds were identified with dominance of rosmarinic acid in the methanolic extract and phenolic diterpens in the ethyl acetate fraction (Carnosol, Carnosic acid and methyl Carnosate). The total polyphenolic content was important in the first extract with 2.589±0.005 g/100g in gallic acid equivalent compared to 0.763±0.005 g/100g. The methanolic fraction displayed higher antioxidant activity (DPPHIC50: 0.510mg/ml and FRAP: 1.714±0.068 mmol Fe2) while ethyl acetate showed pronounced antiproliferative effects (IC50: 14.85±0.20µg/ml and 14.95±2.32µg/ml respectively for U937 and CaCo-2 cells). The anti-proliferative effect was associated with a cell cycle arrest in S phase for U937 (62% of the population at 5µg/ml) with a concomitant decrease in G1 and G2/M phases. Tested extracts displayed in addition early apoptotic effects in U937 and late apoptosis in CaCo-2 cells. The obtained data indicate that the identified phenolics are at least partially responsible for the observed cytotoxicity.
    Keywords: antioxidant activity, Antiproliferative activity, apoptosis, Cell Cycle, Rosemary extracts
  • Taghreed A. Ibrahim *, Atef Ahmed El Hela, Hala El Hefnawy, Areej M. Al Taweel, Shagufta Pervin Pages 328-337
    Family Cupressaceae is the largest coniferous plant family. Essential oils of many species belonging to family Cupressaceae are known to have several biological activities specially antimicrobial activity. The essential oils from aerial parts of Calocedrus decurrens Torr., Cupressus sempervirens stricta L. and Tetraclinis articulata (Vahl) Mast. were prepared by hydrodistillation. The chemical composition of the essential oils has been elucidated by gas chromatography-mass spectroscopy analysis. The prepared essential oils were examined against selected species of Gram-positive, Gram-negative bacteria and Candida species. Broth dilution method was used to detect minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC). Sixteen compounds were identified in the essential oils of both Calocedrus decurrens and Cupressus sempervirens L. and fifteen compounds were identified in the essential oil of Tetraclinis articulata. δ-3-Carene (43.10%), ()-Cedrol (74.03%) and Camphor (21.23%) were the major constituents in the essential oils of Calocedrus decurrens, Cupressus sempervirens L. and Tetraclinis articulata, respectively. The essential oils showed strong antimicrobial activities against the selected microorganisms in concentration range 0.02 3- 3.03 µL/mL. This study could contribute to the chemotaxonomic characterization of family Cupressaceae. In addition to, it proved that the essential oils under investigation possess potential antimicrobial properties.
    Keywords: Calocedrus, Cupressaceae, Cupressus, monoterpene, sesquiterpene, Tetraclinis
  • Ardalan Pasdaran Lashgari, Abbas Delazar, Seyed Abdulmajid Ayatollahi *, Arsalan Pasdaran Pages 338-346
    Isolated five known iridoids glycosides (Scrophuloside A, Harpagoside B, 5-hydroxyloganin, 8-O-acetylharpagide and 6-O-methyl,1-glucopyranosyl catalpol ),one phenyl ethanoid glycoside (Verbascoside) and a phenyl ethanol amine (2-(4-Chlorobenzyl amino) ethanol ) compound from the methanolic extract of aerial parts of Scrophularia oxysepala using by high performance liquid chromatography based on isocratic and liner gradients by C18 column . The structure elucidations of the isolated compounds were performed by spectroscopic methods include 1H-NMR, 13C-NMR, 2 D NMR technique such as HMBC ( in deuterated methanol as solvent) , GC-MS and UV also methanolic extract and fractions ( fractionated on solid phase extraction on C18 cartridge(Spack-C18)) of this plant was tested for free radical scavenging properties toward the 1, 1-diphenyl-1-picrylhydrazyl (DPPH), general toxicity (Brine shrimp toxicity assay) , insecticidal ( Contact toxicity insecticidal assay) and antimalarial activities (hemebiocrystallization inhibition assay).
    Keywords: Scrophularia oxysepala, phenyl ethanol amine, iridoids glycosides, radical scavenging, general toxicity, antimalarial activity, insecticidal activity
  • Ting Zhao, Yina Fan, Guanghua Mao, Weiwei Feng, Yanmin Zou, Ye Zou, Liuqing Yang *, Xiangyang Wu Pages 347-356
    Our previous study revealed that the antioxidant activity of polysaccharide (coded as FGFP) extracted from Grifola frondosa by enzymolysis treatment was significantly superior than that (coded as GFP) extracted by boiling-water. In this study, one purified polysaccharide fractions (coded as FGFP-11) was obtained from FGFP by purified using DEAE-52 column and Sephacryl S-500HR column. Results indicated that FGFP-11 with MW of 59.82 kDa consisted of mannose, glucose and galactose with a molar ratio of 1.00:16.36:5.25. Fourier Transform Infrared Spectroscopy (FTIR spectrum) of FGFP-11 was similar with that of polysaccharide extracted by boiling-water from Grifola frondosa. These indicated the enzymolysis did not destroy the polysaccharide structure. NMR spectrum showed that FGFP-11 possess α-(1→6) glycosidic bond and α-(1→3) glycosidic bond configuration. The experiment of Congo red also revealed that FGFP-11 had triple helix stereo-configuration. Moreover, the antioxidant activities of FGFP-11 were improved compared with that of GFP, especially in scavenging of hydroxyl radical and diphenyl picryl hydrazinyl (DPPH) radical.
    Keywords: Polysaccharide from Grifola frondosa, Enzymolysis, Purification, Characterization, Antioxidant Activities
  • Yancui Wang, Feng Liu, Zongsuo Liang *, Liang Peng, Bangqing Wang, Jing Yu, Yingying Su, Cunde Ma Pages 357-365
    The root of Ophiopogon japonicus has been used as a traditional Chinese medicine and also a functional food ingredient for a long time in China. In the present study, 17 different homoisoflavonoid compounds were identified in the root extract of O. japonicus by HPLC–DAD and LCMS/MS analyses. The antioxidant activity of the of chloroform/methanol (1:1, v/v), methanol and 70% ethanol extracts, and two major isolated homoisoflavonoid compounds (methylophiopogonanone A and methylophiopogonanone B) from O. japonicus root were investigated by various in vitro assays. Methylophiopogonanone B showed the highest antioxidant ability according to four antioxidant methods. Among the extracts, the chloroform/methanol extract which contained high amounts of homoisoflavonoids was found to exhibit the strongest antioxidant activity. The results showed that O. japonicus root can be regarded as a potential source of homoisoflavonoids and natural antioxidant.
    Keywords: Ophiopogon japonicus, Homoisoflavonoids, LCMS, MS analysis, antioxidant activity
  • Hashem Rasti, Kazem Parivar *, Javad Baharara, Mehrdad Iranshahi, Farideh Namvar Pages 366-379
    This study presents the first ever data of extracting chitin from the Chiton shell, which then converted to the soluble chitosan by soaking in the 45% NaOH solution. The obtained chitin and chitosan were characterized by the seven different methods. Antioxidant activity of the extracted chitosan was also evaluated using the two methods. The shell content was divided into calcium carbonate (90.5 %), protein (5.2%) and chitin (4.3 %). Due to the results of element analysis and 1H NMR, the final degree of deacetylation of chitosan was 90%. Surprisingly, a significant amount of Fe was accidentally found in the shell after demineralization, and removed from the solution through the filtering. Nonetheless, remained Fe in the extracted chitin and chitosan was 20 times higher than those previously reported from the shell of shrimps and crabs. Presence of this amount of Fe could describe that why the produced chitosan was darker compared to the commercial chitosan. Antioxidant activity tests showed that the IC50 of the extracted chitosan was higher than which estimated for the commercial chitosan. Antioxidant activity of the extracted chitosan is even better than the commercial version and may use in pharmaceutical industry as a source of antioxidant.
    Keywords: Chitin, Chiton, Chitosan, Persian Gulf, Antioxidant, Natural resource
  • Fatemeh Abdi *, Hamid Mobedi, Farhad Bayat, Nariman Mosaffa, Mahrokh Dolatian, Fahimeh Ramezani Tehrani Pages 380-389
    Background
    Due to its minimal systematic adverse effects, transdermal estrogen is widely used for the prevention of osteoporosis in postmenopausal women.The present meta-analysis aimed to clarify the effects of transdermal estrogen on bone mineral density (BMD) of postmenopausal women.
    Methods
    Studies were identified by searching electronic databases including Cochrane Library, MEDLINE, Embase, and CINAHL databases, and the Sciences Citation Index. Systematic review of articles published between January 1989 to February 2016.Reference lists of the included articles were also evaluated and consultations were made with relevant experts. While 132 studies included the desired keywords, only nine clinical trials met the inclusion criteria and were finally reviewed.
    Main
    Results
    The pooled percent change in BMD was statistically significant in favor of transdermal estrogen. According to the resulting pooled estimate, lumbar spine BMD one and two years after transdermal estrogen therapy was respectively 3.4% (95% CI: 1.7-5.1) and 3.7% (95% CI: 1.7-5.7) higher than the baseline values. The test for heterogeneity was not statistically significant based on the I2 heterogeneity index.
    Discussion
    One-two years of transdermal estrogen delivery can effectively increase BMD and protect the bone structure in postmenopausal women.
    Keywords: Menopause, Bonemineral, density, Transdermal, estrogen
  • Iman Karimzadeh *, Behrooz Heydari, Hossein Khalili, Esfandiar Shojaei, Abdolrasool Ebrahimi Pages 390-398
    Background/
    Objective
    The aim of the present preliminary study was to assess the demographic, clinical, paraclinical, microbiological, echocardiographic, and therapeutic profile as well as in-hospital outcome of patients with infective endocarditis at a referral center for various infectious diseases in Iran.
    Methods
    Required demographic, clinical, plausible complications and paraclinical data were collected from patients’ medical charts. Echocardiographic findings were obtained by performing transthoracic and/or transesophageal echocardiography as clinically indicated. In addition, details of management modalities and in-hospital outcome of patients were recorded.
    Results
    During a 3-year period, 55 patients with definite or possible diagnosis of Infective endocarditis were admitted to the ward. Twenty one (38.2%) patients were injection drug users. Staphylococcus aureus and S. epidermidis were the most commonly isolated microorganisms. Management modalities of Infective endocarditis included antimicrobial therapy alone (48 cases) and the combination of antimicrobial therapy and surgery (7 cases).
    Conclusion
    The rate of negative blood culture in our cohort is high. S. aureus and S. epidermidis were the most commonly isolated microorganisms from positive blood cultures. Congestive heart failure was the most frequent infective endocarditis complication as well as indication for surgery. In-hospital mortality rate of patients was unexpectedly low.
    Keywords: Infective endocarditis, clinical presentation, treatment, outcome
  • Naeemeh Yousefi, Arash Rashidian*, Fatemeh Soleymani Pages 399-403
    Overuse of injections is a common problem in many low-income and middle income countries. While cultural factors and attitudes of both physicians and patients are important factors, physicians› financial intensives may play an important role in overprescribing of injections. This study was designed to assess the effects of providing injection services in physicians› ambulatory offices on prescribing injectable medicines. This cross-sectional study was conducted in Tehran in 2012 -2013and included a random sample of general physicians, pediatricians and infectious disease specialists. We collected data on the provision of injection services in or in proximity of physician offices, and obtained data from physicians› prescriptions in the previous three-month period. We analyzed the data using ANOVA, Student›s t-test and linear regression methods. We obtained complete data from 465 of 600 sampled physicians. Overall 41.9% of prescriptions contained injectable medicines. 75% of physicians offered injection services in their offices. Male physicians and general physicians were more likely to offer the services, and more likely to prescribe injectables. We observed a clear linear relationship between the injection service working hours and the proportion of prescriptions containing injectables (p-value
    Keywords: rational use of medicines; injection medicines; survey; developing countries; outpatient care
  • Armaiti Salamati Sharifabad *, Soheyla Mashouf, Faraz Mojab Pages 404-409
    This study evaluated the effects of inhalation of Lavender essential oil on vital signs in ICU open-heart surgery. This study is a clinical single-blind trial. The study was conducted on 40 patients who had open-heart surgery in the Cardiac ICU of two Hospitals of Tehran University of Medical Sciences, 2012. Criteria included: full Consciousness, lack of hemorrhage, lack of heart rate reduction and hypotension, spontaneous breathing ability and not using synthetic opioids within 2 hours before extubation. After extubation, the patient's vital signs (include: BP, HR, CVP, SPO2, RR) were measured. Then, a cotton swab which was impregnated with 2 drops of Lavender essential oil 2% was placed in their oxygen mask, and they got breath for 10 minutes. Thirty minutes after aromatherapy, their vital signs were measured again. After that the rate of patient’s vital signs before and after aromatherapy were compared. The statistical paired t-test showed that there was a significant difference in systolic blood pressure (p > 0.001), diastolic blood pressure (p = 0.001) and heart rate (p = 0.03) before and after the intervention. Although, the results did not show any significant difference in respiratory rate (p = 0.1), SpO2 rate (p = 0.5) and Central venous pressure (CVP) (p = 0.2) before and after inhaling Lavender essential oil. Therefore, the aromatherapy effectively reduced blood pressure and heart rate in patients admitted to the ICU open-heart surgery and can be used as an independent nursing intervention for reducing BP and HR.
    Keywords: Aromatherapy, Lavender, Control of Pain, Open-heart surgery