فهرست مطالب

Iranian Journal of Pharmaceutical Research
Volume:13 Issue: 1, Winter 2014

  • تاریخ انتشار: 1392/11/28
  • تعداد عناوین: 40
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  • Mahdi Mohammadzadeh Pages 1-2
    To create values in the working environment and to achieve the organizational aims, organizations have to manage their elements with specific alignment.In principle, different departments of organizations are put together with specific arrangements and tasks in order to create value for the stakeholders. It has been proven that creating value and the outcome of an organization has a direct relation with the strategic matching among the elements of an organization.Gordon Jock Churchman (1980) applied system to a group of elements which depend on each other interactively. Although in this definition internal organizational factors are well mentioned, the external effective factors of an organization are not notified. Mehdi Mohammadzadeh (2013) has proved the positive effects of strategic alignment between marketing and financial functions on organizational performance. A system with a thorough definition is divided into two types; Open system and Close system.
    Keywords: Management, Pharmaceutical, Turbulent
  • Mohammadreza Javadi, Ava Mansouri, Alireza Ahmadvand, Molouk Hadjibabaie, Seyed Hamid Khoee, Farzaneh Dastan, Kheirollah Gholami Pages 3-17
    Medication error (ME) is the most common preventable cause of adverse drug events which negatively affects patient safety. Inadequate, low-quality studies plus wide estimation variations in ME from developing countries including Iran, decreases the reliability of ME evaluations. To clarify sources, underreporting reasons and preventive measures of MEs, we reviewed Iran current available literature. We searched Scopus, WOS, PubMed, CINAHL, EBSCOHOST and Persian databases (IranMedex, and SID) up to October 2012. Two authors independently selected and one reviewed and extracted data. Results reported by more than 30% of studies considered as the most important topics. Finally 25 articles were included. All study designs were cross-sectional (except for two interventional studies) and in hospital settings. Nursing staff and students were the most observed populations. Individual factor, with “inadequate knowledge of medication” as its most frequent reason, were the mostly reported source of MEs. Fear and reporting process were two most important reporting barriers. The sense of being reprimanded and ignoring to report respectively were their most frequent factors. Anti-infectives were the most frequent drugs involved in MEs. Preventive measures were varied and reporting of their effectiveness was inconsistent. There are still many research gaps which need to be explored by further studies. Based on our findings, further researches may be focused on design, implementation, and evaluation of a ME reporting system as groundwork, assessing systems-related factors to ME alongside individual factors and evaluating the effectiveness of preventive measures for MEs in trials.
    Keywords: Medication errors, Source of medication errors, Reporting of medication errors, Preventive measures of medication errors, Literature review
  • Seyed Alireza Mortazavi, Yasaman Ghadjahani, Hoda Mahmoodi, Farzaneh Mehtarpour, Zahra Jaffariazar Pages 19-27
    The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of Glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were prepared by through mixing of the ingredients, followed by direct compression. All the prepared formulations were evaluated in terms of physicochemical tests, including uniformity of weight, thickness, crushing strength, friability and in-vitro drug release. Four groups of formulations were prepared. The presence of different amounts of cellulose derivatives or Carbopol 971P, alone, was studied in group A formulations. In group B formulations, the effect of adding Carbopol 971P alongside different cellulose derivatives was investigated. Group C formulations were made by including mannitol as the solubilizing agent, alongside Carbopol 971P and a cellulose derivative. In group D formulations, mini-tablets were made using Carbopol 971P, alongside two different cellulose derivative. The selected formulation (C1) contained ethyl cellulose, Carbopol 971P, mannitol and magnesium stearate, which showed almost 100% drug release over 5 h. Based on kinetic studies, this formulation was found to best fit the zero-order model of drug release. However, the Higuchi and Hixson -Crowell models also showed a good fit. Hence, overall formulation C1 was chosen as the best formulation.
    Keywords: Ocular Mini, tablet, Timolol maleate, Sustained release, Cellulose derivative, Carbopol 971P
  • Matylda Resztak, Tadeusz WŁadysŁaw Hermann, WiesŁaw Sawicki, Dorota Zuzanna Danielak Pages 29-37
    The objective of the study was to compare pharmacokinetic and pharmacodynamic parameters of gliclazide after administration of immediate (IR) and modified release (MR) tablets. The experiment included rats with both normoglyceamia and streptozocin (STZ)-induced hyperglyceamia. Several MR formulations were designed and in vitro drug release profile was assessed by a dissolution test. For the further in vivo study the most suitable formulation was chosen. For pharmacokinetic analysis concentrations of gliclazide in plasma were determined by a validated high performance liquid chromatography (HPLC) method with UV detection. Pharmacodynamic efficacy of the drug was evaluated by measuring blood glucose concentrations. Gliclazide bioavailability was totally different for two formulations in both healthy and diabetic rats based on area under the curve (AUC), time to peak concentration (tmax) and peak concentration (Cmax). Reduction of blood glucose level was significantly higher after the administration of IR than MR formulation. The highest pharmacodynamic efficacy of gliclazide was observed in the normal animals group after administration of the IR tablets, while hypoglycemic effect of the drug was diminished in animals with induced diabetes. Our study suggested that results of reduction inblood glucose level for STZ-induced groups were not comparable with pharmacodynamic effect for normal group. It may be assumed that a decrease in glycaemia in healthy subjects might not be a suitable factor for characterizing antidiabetic drugs.
    Keywords: Gliclazide, Immediate release, Modified release, Pharmacokinetics, In vitro, in vivo correlation, HPLC
  • Grissel Trujillo-De Santiago, Carlos Saenz-Collins, Lizette Garc, Iacute, A-Arellano, Mario Moises Alvarez Pages 39-48
    Contraceptive patches have become a frequently used contraceptive method. We present a mathematical model that describes the serum concentration profiles of Norelgestromin (NGMN) and Ethinylestradiol (EE) released from the contraceptive patch Ortho Evra®. We propose a simple one-compartment model based on pharmacokinetics data reported in previous studies. The model assumes a time-dependent release rate and a first order elimination rate for each of the active ingredients contained in the patch. The model was applied to noncompliance scenarios, such as total and partial detachment of the patch or prolonged use without patch replacement. The proposed model adequately describes the clinically observed evolution of NGMN and EE in serum. Predictions from the model were successfully validated using reported experimental data of serum concentrations of NGMN and EE.This simple model can be a valuable tool to predict pharmacokinetic profiles in diverse scenarios such us non-compliance situations. Alternatively, the model can be conveniently adapted to anticipate the effect of variations on patch characteristics such as differences in contact area, doses, materials, among others.
    Keywords: contraceptive patch, modeling, Norelgestromin, Ethinylestradiol, pharmacodynamics
  • Poonam Inamdar, Shashikant Bhandari, Bhagyashri Sonawane, Asha Hole, Chintamani Jadhav Pages 49-65
    The urgent need of neuraminidase inhibitors (NI) has provided an impetus for understanding the structure requisite at molecular level. Our search for selective inhibitors of neuraminidase has led to the identification of pharmacophoric requirements at various positions around acyl thiourea pharmacophore. The main objective of present study is to develop selective NI, with least toxicity and drug like ADMET properties. Electronic, Steric requirements were defined using kohnone nearest neighbour- molecular field analysis (kNN-MFA) model of 3D-QSAR studies. Results generated by QSAR studies showed that model has good internal as well as external predictivity. Such defined requirements were used to generate new chemical entities which exhibit higher promising predicted activities. To check selective binding of designed NCE’s docking studies were carried out using the crystal structure of the neuraminidase enzyme having co-crystallized ligand Oseltamivir. Thus, Molecular modelling provided a good platform to optimize the acyl thiourea pharmacophore for designing its derivatives having potent anti-viral activity.
    Keywords: Anti, influenza agents, Drug design, Inhibitors, Molecular Modelling, Optimization
  • Fatemeh Khonsari, Parvin Zaker-Milani, Mitra Jelvehgari Pages 67-80
    The present study involves preparation and evaluation of gastric-mucoadhesive microparticles with Metformin Hydrochloride as model drug for prolongation of gastric residence time. The microparticles were prepared by the emulsification solvent evaporation technique using polymers of Carbomer 934p (C) and Ethylcellulose (EC). The microparticles were prepared by emulsion solvent evaporation method (O1/O2). Disc formulations were prepared by direct compression technique from microparticles. In the current study, gastric-mucoadhesive microparticles with different polymers ratios (CP:EC) were prepared and were characterized by encapsulation efficiency, particle size, flowability, mucoadhesive property and drug release studies. The best polymers ratio was 1:3 (F2) with Carbomer 934p (as mucoadhesive polymer) and ethylcellulose (as retardant polymer), respectively. The production yield microparticles F2 showed 98.80%, mean particle size 933.25 µm and loading efficiency %98.44. The results were found that microparticle discs prepared had slower release than microparticles (p > o.o5). The microparticles exhibited very good percentage of mucoadhesion and flowability properties. The release of drug was prolonged to 8 h (71.65-82.22%) when incorporated into mucoadhesive microparticles. The poor bioavailability of metformine is attributed to short retention of its dosage form at the absorption sites (in upper gastrointestinal tract). The results of mucoadhesion study showed better retention of metformine microparticles (8 h) in duodenal and jejunum regions of intestine (F1, 1:2 ratio of CP:EC). Therefore, it may be concluded that drug loaded gastric-mucoadhesive microparticles are a suitable delivery system for metformin hydrochloride, and may be used for effective management of NIDDM (Non Insulin Dependent Diabetes Mellitus).
    Keywords: Gastric, mucoadhesive, microparticle, Metformin Hydrochloride, Emulsion Solvent Evaporation technique, Ethylcellulose, Carbomer 934p
  • Massoud Amanlou, Amin Ghazi Moghadam, Maliheh Barazandeh Tehrani, Effat Souri Pages 81-86
    In this study a sensitive, simple and accurate spectrophotometric method was suggested for determination of tamsulosin in bulk powder and pharmaceutical dosage form based on the formation of an ion-pair complex between the drug and bromocresol green in a buffer solution at pH 3.5. The formed yellow color complex was extracted with chloroform and measured at 415 nm. The optimum reaction conditions such as pH, reagent amount, extracting solvent and the stoichiometry of the ion-pair complex were investigated. Under the optimized conditions, the Beer''s law was obeyed in the concentration range of 1-160 mg/mL with acceptable correlation coefficient (r2 > 0.9997) and precision (CV < 3%) and accuracy (error < 2%). The proposed method was successfully used for the determination of tamsulosin in pharmaceutical capsule with no-significant interferences of excipients.
    Keywords: Tamsulosin, Bromocresol green, Spectrophotometry, Ion, pair complex
  • Muhammad A. Abbasi, Amna Saeed, Aziz-Ur Rehman, Khalid Mohmmed Khan, Muhammad Ashraf, Syeda Abida Ejaz Pages 87-94
    The present study reports the synthesis of a series N-substituted derivatives of brominated 2-phenitidine. First, the reaction of 2-phenitidine (1) with benzenesulfonyl chloride (2) in aqueous media yielded N-(2-ethoxyphenyl) benzenesulfonamide (3), which was then subjected to bromination with bromine in the presence of glacial acetic acid to give N-(4,5-dibromo-2-ethoxyphenyl)benzenesulfonamide (4). Secondly, the product (4) on further treatment with alkyl/aryl halides (5a-l) in the presence of lithium hydride (LiH) produced twelve new derivatives of N-substituted sulfonamides (6a-l). These were characterized by 1H-NMR spectrum and screened against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase (LOX) and were found to be valuable inhibitors of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). Few of these synthesized derivatives were also active against lipoxygenase (LOX). It was concluded from this investigation that these derivatives were moderate inhibitors of cholinesterases and are also ideally suited for further structural modification to obtain more potent and less cytotoxic therapeutic agents for the treatment of Alzheimer’s disease.
    Keywords: 2, phenitidine, Sulfonamide, Bromination, Acetylcholinesterase, Bytyrylcholinesterase, Lipoxygenase, 1H, NMR
  • Akbar Mobinikhaledi, Ahmad Hamta, Mehdi Kalhor, Mehdi Shariatzadeh Pages 95-101
    Considerable attention has been focused on the synthesis of benzimidazoles due to having a broad spectrum of biological activities such as anti-parasitic, fungicidal, anti-thelemintic and anti-inflammatory activities. As a part of our research work in this area, a series of benzimidasole derivatives (3a-n) were synthesized in good to high yields by reaction of o-phenylenediamine and different aromatic aldehydes in the presence of sodium hexafluroaluminate, Na3AlF6, as an efficient catalyst at 50 ◦C. This environmentally benign and practical method offers several advantages, such as high yields, use of available catalyst, mild reaction conditions and easy workup. The antibacterial activity of these benzimidasoles was also evaluated using Staphylococcus aureus (mm) and Escherichia coli (mm) bacterial strain. All synthesized materials were characterized using IR and NMR spectroscopy as well as microanalyses data.
    Keywords: Aromatic aldehydes, Bbenzimidaazole, CatalystoPhenylenediamine
  • Radineh Motamedi, Abbas Shafiee, Mohammad Reza Rezai, Omidreza Firuzi, Najmeh Edraki, Ramin Miri Pages 103-114
    In the present work, novel 7-aryl-10, 11-dihydro-7H-chromeno [4, 3-b]quinoline-6, 8(9H, 12H)-dione derivatives were synthesized by oxidation of 7-aryl-8, 9, 10, 12-tetrahydro-7H-chromeno[4, 3-b]quinoline-6, 8-diones in the presence of silica sulfuric acid/NaNO2 with yields of 64-74%. Cytotoxic activity of synthesized compounds was assessed on three different human cancer cell lines (K562, LS180, and MCF-7). Synthesized compounds showed moderate cytotoxic activities. The most active one apeared to be 2e, containing a methoxy group on the meta position of phenyl ring (IC50 range in different cell lines: 11.1–55.7 µM). Furthermore; comparison of the cytotoxic activity of these novel oxidized derivatives with non-oxidized counterparts revealed that oxidation of dihydropyridine ring to pyridine, improves the activity especially in LS180 cell line. Conformational analysis revealed that some conformational aspects of oxidized derivatives such as orientation of C7-aryl substitute were clearly different from non-oxidized ones.
    Keywords: oxidative aromatization, chromeno[4, 3, b]quinoline, cytotoxicity, conformational analysis
  • Marjan Esfahani Zade, Koroush Omidi, Joel Kauffman, Shahram Shahraki Zahedani, Ali Gudarzi, Salimeh Amidi, Farzad Kobarfard Pages 115-126
    Treatment of tuberculosis (TB) and the discovery of effective new anti tubercular drugs is one of the most urgent priorities in health organizations all around the world. In the present study, fluorinated analogs of some of the most important anti-TB agents such as p-aminosalicylic acid (PAS), thiacetazone and pyrazinamide were synthesized and tested against TB. The fluorinated analog of thiacetazone was 20 times more potent than the parent compound against M.tuberculosis H37-RV, while the fluorinated PAS was almost three times less potent than PAS. A few other halogenated analogs of thioacetazone were also synthesized and subjected to anti-TB screening tests. The best halogen substituent was found to be fluorine which has the smallest size from one hand and the strongest electronegativity from the other hand among the halogen atoms. This fact reemphasizes the unique nature of fluorine as a golden substituent in medicinal chemistry.
    Keywords: Fluorinated analogs, Anti tuberculosis drugs, Pyrazinamide, PAS, Thiacetazone
  • Bahman Nickavar, Abrisham Adeli, Azar Nickavar Pages 127-133
    The present work was designed to study the antioxidant activity and to identify the main active components of the essential oil of ajowan (Trachyspermum copticum) fruit. GC and GC-MS analyses of the essential oil showed the presence of eight compounds. The main constituents of the oil were thymol (43.7%), p-cymene (26.8%), and γ-terpinene (24.9%). The antioxidant and free radical scavenging activities of ajowan oil was evaluated by using ABTS•+ and β-carotene bleaching assays. The oil exhibited a considerable dose-dependent antioxidant activity. Antioxidant activity guided fractionation of the oil was carried out by TLC-bioautography method based on the DPPH• assay to screen and separate the main active constituents. The bioautography screening and fractionation resulted in the separation of the main antioxidant compound which was identified as thymol.
    Keywords: Trachyspermum copticum, Essential oil, Antioxidant activity, Chemical composition
  • Somayeh Baniadam, Mohammad Reza Rahiminejad, Mustafa Ghannadian, Hojjatollah Saeidi, Abdul Majid Ayatollahi, Mahmoud Aghaei Pages 135-141
    The dried plant was extracted with dichloromethane and after defatting with hexane, transferred repeatedly on silica columns using dichloromethane-hexane and ethyl acetate-hexane as mobile phases. Finally the fractions were purified by high performance liquid chromatography using a Pack-Sil column and hexane: Ethyl acetate as mobile phase. The structures of the isolated compounds included: cycloart-25-ene-3β, 24-diol (1), cycloart-23(Z)-ene-3β, 25-diol (2), cycloart-23(E)-ene-3β, 25-diol (3), and 24-methylene-cycloart-3β-ol (4) were elucidated by 13C- and 1H-NMR as well as IR and by the aid of mass fragmentation pattern and comparing with the literature. The biological effects of the compounds were done by the MTT assay on two different cancer cell lines including MDA-MB48 and MCF-7. Among these compounds, cycloart-23(E)-ene-3β,25-diol (3) was the most active compound on MDA-MB468 cell line (LD50 = 2.05 μgmL-1) and cycloart-23(Z)-ene-3β, 25-diol (2) was the most active compound on MCF-7 cell line (LD50 = 5.4 μgmL-1).
    Keywords: Euphorboa macrostegia, Cycloartane, Cytotoxicity, MDA, MB468, MCF, 7
  • Omotayo Olutola Dosumu, Patricia Onocha, Olusegun Ekundayo, Muhammad Ali Pages 143-147
    In West Africa and Nigeria in particular, many virgin plants are still waiting to be evaluated for their medicinal importance. Claims of plants with folk medicinal applications need to be evaluated and verified. Gomphrena celosioides (family – Amaranthaceae) is a weed grown in lawns and the biological activity of the extract had earlier been established. In the present study, the plant was collected, air dried, ground and soxhlet extracted with n-hexane and two compounds were isolated from the flakes that were recovered from the n-hexane extract on cooling. Column chromatography using 5% chloroform in n-hexane effected the separation. The structures of the isolated compounds were elucidated by spectroscopic analysis using IR, NMR (1H and 13C) and EI-MS. The compounds were found to be aurantiamide and aurantiamide acetate. This is the first report of isolation of these compounds in Gomphrena celosioides.
    Keywords: Amarantaceae, Gomphrena celosioides, Isolation, Aurantiamides
  • Hamid Reza Monsef, Esfahani, Ahmad Reza Shahverdi, Mohammad Reza Khorramizadeh, Mohsen Amini, Reza Hajiaghaee Pages 149-155
    Many species belonging to the Scrophularia genus have been used since ancient times as folk remedies for many medical conditions such as scrofulas, scabies, tumors, eczema, psoriasis, inflammations. The aim of this study was to characterize the matrix metalloproteinases (MMPs) inhibitor compounds of the Scrophularia striata extract by bio-guide fractionation. The aerial parts of S. striata were collected and different extracts were sequentially prepared with increasingly polar solvents. The MMPs inhibitory activity of the crude extract and its fractions were evaluated by the Zymoanalysis method. The pure compounds were purified from the active fraction by chromatography methods. Chemical structures were deduced by nuclear magnetic resonance and mass spectrometry. Two active compounds (acteoside and nepitrin) were identified by bio-guide fractionation. The inhibitory effects of nepitrin and acteoside at 20 µg/ml were about 56 and 18 percent, respectivly. The inhibitory effects of acteoside at 80 µg/ml were increased to about 73 percent. In summary, the results suggest that nepitrin effectively inhibited MMPs inhibitory activity at low concentrations, whereas acteoside showed inhibition at high concentrations.
    Keywords: Scrophularia striata, nepitrin, acteoside, wehi, 164, zymoanalysis, MMPs
  • Mohammad Sadegh Amiri, Mohammad Reza Joharchi, Mohammad Ehsan Taghavizadehyazdi Pages 157-162
    Jaundice is the commonest ailments affecting the citizens of both developed and poor Asians countries including Iran. An ethnobotanical survey of plants used by the traditional healers for the treatment of jaundice was conducted in the Mashhad city, Northeastern Iran. A total of 37 plants belonging to 32 genera and 26 families have been documented for their therapeutic use against jaundice. The plant families which contained the most commonly used species for their effects are: Fabaceae (5 species), Polygonaceae (4 sp.), Asteraceae (3 sp.), Plantaginaceae (2 sp.) and Salicaceae (2 sp.). The plants were arranged with correct nomenclature along with their common name, family, the part used and their medicinal value. The use of decoction is the most preferred method of herbal preparation. In all cases, the treatment involved oral administration of the extracts 2 to 3 times daily from a week to month till the problem disappears. Cichorium intybus, Salix alba, Cotoneaster nummularius, Descurainia sophia, Malva sylvestris, Berberis integrrima, Rumex acetosella, Phyllanthus emblica and Alhagi maurorum were repeatedly mentioned by the traditional healers as the most widely used for the treatment of jaundice in the study area. The study indicates that the local inhabitants rely on medicinal plants for treatment. This paper suggested that further clinical experimentation is needed to scientifically evaluate these widely used herbal remedies for possible bioactive effects.
    Keywords: Ethnomedicinal, Jaundice, Traditional healers, Mashhad, Iran
  • Massoumeh Farasat, Ramazan-Ali Khavari-Nejad, Seyed Mohammad Bagher Nabavi, Foroogh Namjooyan Pages 163-170
    The antioxidant activity, contents of total phenolics and flavonoids were quantified in the methanolic extracts of four Ulva species(U.clathrata,U.linza,U.flexuosa and U.intestinalis) grown at different parts of northern coasts of the Persian Gulf in south of Iran.The seaweeds were collected from Dayyer,Taheri and Northern Ouli coasts in April 2011. Methanolic extracts of the seaweeds were assessed for their antioxidant activity using DPPH radical scavenging assay and was performed in a microplate reader. All species exhibited a DPPH radical scavenging activity, and among the species, Ulva clathrata demonstrated greater antioxidant potential with a low IC50 (0.881 mg ml-1) in comparison with the other species. Also the highest phenolic content (5.08 mg GAE g-1) and flavonoid content (30.31 mg RE g-1) were observed in U.clathrata.The phenolic and flavonoid contents showed positive correlations with the DPPH radical scavenging activity (p<0.01) and negative correlations with IC50 (p<0.01).The results suggest that these edible green seaweeds possess antioxidant potential which could be considered for future applications in medicine, dietary supplements, cosmetics or food industries.
    Keywords: Antioxidant activity, Total phenolics, Flavonoid, Seaweeds, Ulva
  • Dahong Wang, Jiangfeng Yuan, Wenyi Tao Pages 171-180
    This work was to isolate and identify the bioactive secondary metabolite which was produced by myxobacterium Stigmatella eracta WXNXJ-B, and to evaluate its antitumor and apoptosis-inducing effects. The results showed that one novel compound (molecular formula C29H25NO3) was isolated, purified by Sephadex LH-20 column chromatography and preparative RP-HPLC, and identified as 5-(6-benzyl-quinolin-3-ylmethyl)-6- phenyl-3,7-dioxa- bicycle [4.1.0] heptan-3-one (named as quinoxalone) according to its UV, IR, HRMS and NMR spectra. The compound showed strong antitumor activity on B16, HepG2, MCF-7, SGC-7901, MDA-MB231 and CT-26 six tumor cell lines in vitro. Nevertheless, it showed less cytotoxic to the mouse normal spleen cells (IC50 was 836.27 ± 13.02 µg mL-1). The cytotoxic study on HepG2 cells in-vitro showed that quinoxalone could induce the change of cell nuclear and arrested the cell division in the S and G2/M phase. Our results suggest that quinoxalone could be a potential anti-cancer agent.
    Keywords: Quinoxalone, Myxobacterium Stigmatella eracta WXNXJ, B, Structure identification, Antitumor bioactivity
  • Mehrdad Hashemi Pages 181-189
    Background & Target: Ischemia Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. In this study, the effect of pentoxyfylline on bcl2 gene expression changes and cell injury in kidney of rat following Ischemia Reperfusion were evaluated.
    Methods
    In this experimental study, 20 male wistar rats with average weight of 250-300g were selected and then were accidently divided them on two tenth group of control and treatment groups. In the control group, celiotomy was performed by ventral midline incision. The left kidney was isolated, and then both the renal artery and vein were obstructed. After 60 minutes of warm ischemia, vessel obstruction resolved and the right kidney was removed. 72 hours after reperfusion, tissue samples were taken from left kidney for Tunel assay. We used quantitative real time PCR for detection of bcl2 gene expression in treated groups and then compared them to control samples.
    Results
    In the treatment group, the cell death changes, showed lower level than the control group. The results also showed the bcl2 gene expression was declined in ischemia group as campared to PNT drug group.
    Conclusion
    The pentoxyfylline might have a role in control of apoptosis result from Ischemia- reperfusion and quantitative real-time PCR can be used as a direct method for detection bcl2 gene expression in tested samples and normal samples
    Keywords: Ischemia, Pentoxyfylline, bcl2 gene
  • Hassan Malekinejad, Masumeh Moradi, Johanna Fink-Gremmels Pages 191-198
    Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. This study designed to investigate the mechanism of cytotoxicity of MPA on the genetically engineered PC12 Tet Off (PTO) neuronal cells with p53 gene. Alamar Blue (AB) reduction showed concentration-dependent cytotoxicity of MPA on PTO cells with IC50 value of 32.32 ± 4.61 mM. The reactive oxygen species (ROS) generation following exposing the cells to MPA showed a significant (p < 0.05) increase in the ROS production and in a concentration-dependent fashion. Involvement of Caspase 3/7 proteases and Cytochrome C release in the induction of DNA fragmentation are all hallmarks of MPA-induced apoptosis in PTO cells. Our data suggest that MPA exerts an apoptotic effect on PTO cells. Moreover, the apoptotic effect of MPA attribute to the elevation of ROS generation by which might trigger the cytochrome C release and the activation of Caspase 3/7 that ultimately results in DNA fragmentation.
    Keywords: Apoptotic effect, Caspase 3, 7, Cytochrome C, Mycophenolic acid (MPA), PC12 Tet Off cells (PTO)
  • Nina Mirderikvand, Baharak Mohammadzadeh Asl, Parvaneh Naserzadeh, Fatemeh Shaki, Mohammad Shokrzadeh, Jalal Pourahmad Pages 199-206
    Although the biokinetics, metabolism, and chemical toxicity of uranium are well known, until recently little attention was paid to the potential toxic effects of uranium on reproduction and development in mammals. In recent years, it has been shown that uranium is a developmental toxicant when given orally or subcutaneously (SC) to mice. Decreased fertility, embryo/fetal toxicity including teratogenicity, and reduced growth of the offspring have been observed following uranium exposure at different gestation periods. For investigating the effects of DU on pregnant animals, three groups (control, sham and test) of NMRI mice were chosen. In test group 4mg/kg of DU were administered intraperitonealy at 11 day of gestation, in sham group only normal saline injected to interior peritoneum as indicated in the test group and in Control group which was considered as the comparison base line of our research, no injection was made. Caesarean sections were performed at 15 day of the gestation; and their placentas were examined externally. Base on our results DU caused significant external anomalies, and caused a significant decrease (p<0.05) in the weight and diameter of placentas, the number of the embryos, their body weight and crown-rump length of fetuses.
    Keywords: Depleted uranium, Morphology, Mouse fetus, Embryotoxicity
  • Lamia Mhadhebi, Amel Mhadhebi, Jacques Robert, Abderrahman Bouraoui Pages 207-220
    Seaweeds have caused an emerging interest in the biomedical area, mainly due to their contents of bioactive substances which show great potential as anti-inflammatory, anti-microbial, anti-viral and anti-tumoral drugs. Despite the diversity in quality and quantity of the Mediterranean Tunisian coast flora, with its large contains of marine organisms and seaweeds, most of them have not yet been investigated for pharmacological and biological activities. Anti-oxidant, anti-inflammatory and anti-proliferative effects of the aqueous extracts (AQ) of three brown seaweed respectively, Cystoseira crinita (AQ-Ccri), Cystoseira sedoides (AQ-Csed) and Cystoseira compressa (AQ-Ccom) were investigated. Anti-oxidant activity was evaluated using the DPPH assay. Total phenolic contents were measured using Folin–Ciocalteu method. The anti-inflammatory activity of these extracts was determined in-vivo, using carrageenan induced rat paw oedema assay. The anti-proliferative activity was studied on normal cells (MDCK and rat fibroblast) and cancer (A549, MCF7 and HCT15) cell lines by the ability of the cells to metabolically reduce MTT formazan dyes, in comparison to a reference drug the Cisplatin. Results demonstrated that AQ-Ccri, AQ-Csed and AQ-Ccom extracts exhibited significant radical scavenging activity. AQ-Ccom extract had the highest total phenolic content. AQ-Ccri, AQ-Csed and AQ-Ccom extracts exhibited significant anti-inflammatory activity in a dose dependent manner by comparison to reference drugs. Moreover, AQ-Ccri, AQ-Csed and AQ-Ccom extracts showed an important anti-proliferative activity against both Human tumor cell lines HCT15 and MCF7. These pharmacological efficacies of these AQ- extracts of Cystoseira were positively correlated with their total phenol content and their good anti-oxidant activity. The purification and the determination of chemical structures of compounds of these active aqueous extracts are under investigation. It could have a promising role in the future medicine and nutrition when used as drug or food additive.
    Keywords: Anti, oxidant activity, Anti, proliferative activity, Anti, inflammatory activity, Cystoseira
  • Liang Ni, Wei-Yong Shi Pages 221-226
    In this study, we measured the composition and free radical scavenging activity of several species of nuts, namely, Torreya grandis, Carya cathayensis,and Myrica rubra. The nut kernels of the aforementioned species are rich in fatty acids, particularly in unsaturated fatty acids, and have 51% oil content. T. grandis and C. cathayensis are mostly produced in ZheJiang province. The trace elements in the kernels of T. grandis and C. cathayensis were generally higher than those in M. rubra, except for Fe with a value of 64.41 mg/Kg. T. grandis is rich in selenium (52.91−68.71 mg/Kg). All three kernel oils have a certain free radical scavenging capacity, with the highest value in M. rubra. In the DPPH assay, the IC50 of M. rubra kernel oil was 60 μg/mL, and OH was 100 μg/mL. The results of this study provide basic data for the future development of the edible nut resources in ZheJiang province.
    Keywords: Kernel, Free radical, Torreya grandis, Carya cathayensis, Myrica rubra
  • Reza Sedaghat, Mehrdad Roghani, Mohsen Khalili Pages 227-234
    Parkinson disease (PD) is the most common movement disorder with progressive degeneration of midbrain dopaminergic neurons for which current treatments afford symptomatic relief with no-prevention of disease progression. Due to the neuroprotective property of the Nigella sativa bioactive compound thymoquinone (TQ), this study was undertaken to evaluate whether TQ could improve behavioral and cellular abnormalities and markers of oxidative stress in an experimental model of early PD in rat. Unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were daily pretreated p.o. with TQ at doses of 5 and/or 10 mg/Kg three times at an interval of 24 h. After 1 week, apomorphine caused contralateral rotations, a reduction in the number of neurons on the left side of the substantia nigra pars compacta (SNC) was observed, malondialdehyde (MDA) and nitrite level in midbrain homogenate increased and activity of superoxide dismutase (SOD) reduced in the 6-OHDA lesion group. TQ pretreatment significantly improved turning behavior, prevented loss of SNC neurons,and lowered level of MDA. These results suggest that TQ could afford neuroprotection against 6-OHDA neurotoxicity that is partly due to the attenuation of lipid peroxidation and this may provide benefits, along with other therapies, in neurodegenerative disorders including PD.
    Keywords: Thymoquinone, Parkinson's disease, 6, hydroxydopamine, Oxidative stress
  • Firouz Faedmaleki, Farshad H. Shirazi, Amir Salarian, Hamidreza Ahmadi Ashtiani, Hossein Rastegar Pages 235-242
    Nano-silver (AgNP) has biological properties which are significant for consumer products, food technology, textiles and medical applications (e.g. wound care products, implantable medical devices, in diagnosis, drug delivery, and imaging). For their antibacterial activity, silver nanoparticles are largely used in various commercially available products. Thus, the use of nano-silver is becoming more and more widespread in medicine. In this study we investigated the cytotoxic effects of AgNPs on liver primary cells of mice, as well as the human liver HepG2 cell. Cell viability was examined with MTT assay after HepG2 cells exposure to AgNPs at 1, 2, 3, 4, 5, 7.5, 10 ppm compared to mice primary liver cells at 1, 10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration-dependent decrease of cell viability in both cells. IC50 value of 2.764 ppm (µg/ml) was calculated in HepG2 cell line and IC50 value of 121.7 ppm (µg/ml) was calculated in primary liver cells of mice. The results of this experiment indicated that silver nanoparticles had cytotoxic effects on HepG2 cell line and primary liver cells of mice. The results illustrated that nano-silver had 44 times stronger inhibitory effect on the growth of cancerous cells (HepG2 cell line) compared to the normal cells (primary liver cells of mice). which might further justify AgNPs as a cytotoxic agents and a potential anticancer candidate which needs further studies in this regard.
    Keywords: Silver nanoparticle, HepG2 cell line, Primary liver cells of mice, MTT assay, Cell viability, Nanotechnology
  • Payam Khazaeli, Mohammad Karamuzian, Shohreh Rohani, Behnam Sadeghirad, Nima Ghalekhani Pages 243-251
    Background
    Minoxidil has been reported to inhibit in vitro fibroblast proliferation and lysyl hydroxylase activity, a key enzyme in collagen biosynthesis. These in-vitro effects proposed minoxidil to be a potential antifibrotic agent. The present study aimed to investigate the effects of minoxidil gel on wound healing procedure in a second-degree burn model in rats.
    Materials And Methods
    Wistar rats were anesthetized and a second-degree burn was induced on the back of Wistar rats using a heated 2 cm diameter metal plate. Experimental groups received 2% or 5% topical minoxidil gel, dexpanthenol or sliver sulfadiazine. Histological parameters including collagen content, angiogenesis, number of preserved follicles and necrosis along with tensile strength of burn wound area were assessed on days 3, 7, 14 and 21 post-injury.
    Results
    Microscopic evaluation of specimens collected from sample animals were consistent and showed a second-degree burn. Main histological findings regarding minoxidil topical usage showed that collagen content and tensile strength of burned area did not differ between groups. However, minoxidil increased the number and diameter of blood vessels significantly compared with other groups.
    Discussion
    Although minoxidil improved the process of wound-healing, our results did not support the proposed idea of its usage as an antifibrotic agent. However, to reject its possible effects as an antifibrotic agent, more objective animal models should be developed and studied.
    Keywords: Minoxidil, Topical gel, Angiogenesis, Second, degree burn, Wound healing
  • Akram Ranjbar, Mohammad Sharifzadeh, Jamshid Karimi, Heidar Tavilani Tavilani, Maryam Baeeri Baeeri, Tavakol Heidary Shayesteh, Mohammad Abdollahi Pages 253-262
    Anti-oxidant effects of propofol (2, 6-diisopropylphenol) were evaluated agains carbon tetrachloridet CCl4 -induced oxidative stress in rat liver. 30 male rats were equally divided in to 6 groups (5 rats each). Group I (control), while Group II was given CCl4 (3 mL /Kg/day, IP). Animals of Groups III received only propofol (10 mg/Kg/day, IP). Group IV was given propofol+ CCl4. Group V was administered vitamin E (alpha-tocopherol acetate 15 mg/Kg/day, SC). Animals of Group VII received alpha-tocopherol acetate + CCl4 once daily for two weeks. After treatment, blood and liver mitochondria were isolated. Anti-oxidant enzymes activity such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and oxidative stress marker such as reduced glutathione (GSH) and lipid peroxidation (LPO) concentration were measured. Oxidative stress induced with CCl4 in liver mitochondria was evident by a significant increase in enzymatic activities of GPx, SOD, and LPO and decreased of GSH and vailability of mitochondria. Propofol and vitamin E restored CCl4-induced changes in GSH, GPx, SOD and LPO in blood and liver mitochondria. CCl4 decreased viability of mitochondria that was recovered by propofol and vitamin E. It is concluded that oxidative damage is the mechanism of toxicity of CCl4 in the mitochondria that can be recovered by propofol comparable to vitamin E.
    Keywords: Propofol, Liver mitochondria, Oxidative stress, Rat, CCl4
  • Mahsima Khoshneviszadeh, Soheil Ashkani-Esfahani, Mohammad Reza Namazi, Ali Noorafshan, Bita Geramizadeh, Ramin Miri Pages 263-269
    Wounds and wound healing have always been one of the most important subjects that experimental researches were dedicated to. Simvastatin has been used for long as a common lipid lowering agent which was reported to have some pleiotropic effects such as antioxidation, anti-inflammation and immunomodulation. In this study we aimed to determine the effect of simvastatin on wound healing process in laboratory rats by means of stereological and histopathological analyses. 36 male Sprague-Dawley rats (220 ± 20 g) with a 1 cm2 circular full-thickness wound on their back were divided into three groups: SS group that received a gel with 2% concentration of simvastatin; UW group that received no treatment but daily irrigation with normal saline; Base group that was treated with the gel base. Duration of the study was 12 days and at the end, wound closure rate, grade of inflammation, granulation-tissue formation, ulceration, epithelization, fibroblast proliferation, collagen-bundles synthesis, and vascularization were determined. Outcome of this study revealed that Simvastatin improves the wound healing by its anti-inflammatory and epithelization induction effect as well as statistically significant induction of fibroblast proliferation and collagen bundle synthesis which were reported by our stereological and histopathological investigations. Results of the present study demonstrated that topical Simvastatin enhances the wound healing process through affecting different aspects of tissue regeneration; however, further researches are needed to find the exact mechanism, advantages and disadvantages of this chemical agent.
    Keywords: Simvastatin, Wound healing, Stereology, Reepithelization
  • Jamshid Salamzadeh, Naghmeh Foroutan, Hamid Reza Jamshidi, Hamid Reza Rasekh, Ali Rajabzadeh, Arash Foroutan, Mohsen Nafar Pages 271-278
    Objectives
    The present study aimed to provide an estimation of the current financial burden of renal transplantation therapy for insurance organisations.
    Methods
    An Excel-based model was developed to determine the treatment costs of current clinical practice in renal transplantation therapy (RTT). Inputs were derived from Ministry of Health and insurance organizations` database, hospital and pharmacy records, clinical trials and available literature. A one-way sensitivity analysis and Monte-Carlo simulation were performed to illustrate total cost changes made by cost components and to test the reliability of model probabilities respectively.
    Results
    According to the model, 2200 patients received RTT in the study year which resulted in the first year total treatment cost of almost $14,000,000. These costs corresponded to annual total cost per patient of almost $6500 for the payers.
    Conclusion
    According to the results of the study, treatment cost per patient in RTT is almost $6500 for the payers in Iran. Although RTT is almost fully reimbursed by government in Iran, an improvement in insurance decision making especially regarding new effective immunosuppressive drugs is quite necessary for controlling growing trends of OOP expenditures in these patients. The present study aimed to improve efficiency in budget allocation by providing insurance decision makers with an estimation of financial impact of current clinical practice in RTT, making it possible for them to compare current financial burden of the disease with the future cost burden of including newly submitted drugs to their formulary in RTT and also provided practical policy making recommendations in the end.
    Keywords: Cost, Renal transplantation therapy, Insurance, Policy making, Budget
  • Zahra Nasiri-Toosi, Simin Dashti-Khavidaki, Mohsen Nasiri-Toosi, Ali Jafarian, Hossein Khalili, Shirinsadat Badri, Sima Sadrai Pages 279-282
    Tacrolimus, a cornerstone of immunosuppressive therapy in solid organ transplantation, has a narrow therapeutic range with considerable inter-individual and intra-individual pharmacokinetic variability. To date, there is no information on the pharmacokinetics of tacrolimus in Iranian liver transplant recipients. This study was designed to determine pharmacokinetic properties of orally administered tacrolimus in Iranian adult liver transplant recipients. Tacrolimus doses and steady state whole blood trough concentrations as well as patient demographic and clinical data were obtained retrospectively using the 30 included patients’ medical records. Pharmacokinetic parameters were estimated by using a nonlinear mixed effect model program (Monolix version 3.1). Absorption rate constant was fixed at two hours-1. Drug apparent clearance (CL/F), apparent volume of distribution (Vd/F), and elimination half life (t½β) were calculated. The administered dose of tacrolimus to the patients ranged from 0.02 to 0.14 mg/Kg/day. Tacrolimus blood trough concentrations varied widely within the range of 1.8 to 30 ng/mL. The mean values of CL/F, Vd/F, and t½β were found to be 9.3 ± 0.96 L/h, 101 ± 29 L, and 7.5 hours, respectively. The pharmacokinetics of tacrolimus was highly variable among our patients. CL/F, Vd/F, and t½β of tacrolimus in this study were comparable to reported values from Italian heart transplant patients but somewhat different from reported ones from other solid organ transplant populations.
    Keywords: Liver transplantation, Pharmacokinetics, Tacrolimus
  • Ali Hassan Rahmani, Amir Jalali, Mohammad Hassan Alemzadeh, Ansari, Mina Tafazoli, Fakher Rahim Pages 283-289
    This study was done to determine whether high or low dose of anti-snake venom (ASV) is better in coagulopathy in victims of envenoming by vipers. This retrospective study was conducted on the 154 patients (Mean age ± SD, Range) of viper snake bites who were referred to the emergency ward of Razi Hospital, Ahvaz, Iran over 2 years period (2004 - 2006). According to the treatment dosage the patients were divided in two groups include group 1 (78 cases), low dose regimen and group 2 (76 cases), high dose one. In group 1, the treatment was performed by administration of 4 to 6 vials of ASV through intravenous infusion. In group 2, the patients were given 5 to 10 vials of ASV as an initial dose. In low dose regimen, the number of received packed red blood cell was higher (14 vs. 3) in comparison with high dose group. The number of ASV vials the patients received was 5.5and 21.06 in group 1 and 2, respectively (5.5 ± 1.7 vs. 21.06 ± 10.89; p < 0.01). The difference in frequency of coagulopathy complications, and need for using packed red blood cell were statistically significant (96.2% and 17.9% in group 1 vs. 34.2% and 3.9% in group 2, p < 0.01). It seems that cautious usage of high dose of ASV (10 - 20 vials) without very special concerns about the cost, dose, and without hazardous side effects is essential for the routine management of sever snake envenoming.
    Keywords: bite, Anti, snake venom, Iranian snakes, Coagulopathy complication
  • Shadi Baniasadi, Fanak Fahimi, Maryam Habibi, Roodabeh Haghgoo, Masoumeh Karimi Gamishan, Fatemeh Dabaghzadeh, Maryam Farasatinasab, Shadi Farsaei, Afshin Gharekhani, Hamidreza Kafi, Iman Karimzadeh, Ali Kharazmkia, Farhad Najmeddin, Naemeh Nikvarz, Mohammad Bagher Oghazian, Haleh Rezaee Pages 291-297
    Detection of adverse drug reactions (ADRs) in hospitals provides an important measure of the burden of drug related morbidity on the healthcare system. Spontaneous reporting of ADRs is scare and several obstacles to such reporting have been identified formerly. This study aimed to determine the role of clinical pharmacy residents in ADR reporting within a hospital setting.Clinical pharmacy residents were trained to report all suspected ADRs through ADR-reporting yellow cards. The incidence, pattern, seriousness, and preventability of the reported ADRs were analyzed. During the period of 12 months, for 8559 patients, 202 ADR reports were received. The most frequently reported reactions were due to anti-infective agents (38.38%). Rifampin accounted for the highest number of the reported ADRs among anti-infective agents. The gastro-intestinal system was the most frequently affected system (21.56%) of all reactions. Fifty four of the ADRs were reported as serious reactions. Eighteen of the ADRs were classified as preventable. Clinical pharmacy residents'' involvement in the ADR reporting program could improve the ADR reporting system.
    Keywords: Adverse drug reaction, Clinical pharmacist, Hospital, Pharmacovigilance, Spontaneous reporting
  • Sedigheh Ayati, Fatemeh Vahidroodsari, Farnoosh Farshidi, Masoud Shahabian, Monavar Afzal Aghaee Pages 299-304
    We want to compare the efficacy and safety of vaginal versus sublingual misoprostol for cervical ripening and induction of labor. This randomized clinical trial was performed on 140 women with medical or obstetric indications for labor induction. The patients were randomly divided into two groups: vaginal and sublingual administration of misoprostol. In first group, 25 µg misoprostol was placed in the posterior fornix of the vagina and second group received 25 µg misoprostol sublingually, every 6 hours for 24 h. Maternal and neonatal outcomes were analyzed. There was no significant difference in the demographic characteristics between two groups. The main indication for cesarean section in both groups was fetal distress, followed by absence of active labor progress. Evaluation of cesarean indication was not significantly different in two groups; including fetal distress, absence of active labor, uterine over activity and failure to progress. The maternal complication in sublingual group included residual placenta (2%), tachysystole (2%), vomiting (12%), atoni (3.3%) and abdominal pain (5.5%), although there was no significant difference between two groups. Sublingual misoprostol is as effective as vaginal misoprostol for induction of labor at term. However, sublingual misoprostol has the advantage of easy administration and may be more suitable than vaginal misoprostol.
    Keywords: Induction of labor, Misoprostol, Vaginal, Sublingual
  • Sara Zeighami, Molouk Hadjibabaie, Asieh Ashouri, Amir Sarayani, Seyed Hamid Khoee, Sarah Mousavi, Mania Radfar, Ardeshir Ghavamzadeh Pages 305-312
    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for hematological disorders. Cyclosporine (CsA) is one of the major immunosuppressive agents for the prophylaxis against graft versus host disease (GvHD). In this retrospective study, we evaluated the effects of CsA serum levels on the incidence of acute GvHD and transplant outcomes. 103 adult patients received Hematopoitic Stem Cell Transplantation(HSCT) in the Hematology-Oncology, Bone Marrow Transplantation center at Shariati Hospital in Tehran, Iran. All participants received prophylactic regimen of cyclosporine plus methotrexate. CsA dose titration was done according to patients'' serum levels and drug toxicity. Serum levels tested on the twice weekly basis in first 4 weeks after transplantation.Acute GvHD (grades II-IV) developed in 44 patients (43%, 95%CI: 33%-52%). The median time to ANC and PLT recovery was 13 days (range: 9-31 days) and 16 days (range: 0-38 days), respectively. Univariate analysis of risk factors related to aGvHD (grade II-IV) development showed a higher risk of incidence of aGvHD (grades II-IV) for patients having the lowest blood CSA concentration (<200ng/ml) in the third weeks after transplantation (36% vs. 12%, P=0.035). The only risk factors related to incidence of aGvHD grades III-IV was also blood CsA concentration at 3rd week post transplant (15% vs. 3%, P=0.047). The CsA concentration at 3rd week was not related to disease free survival and overall survival (P=0.913 vs. P=0.81) respectively. Higher CsA serum levels in the third week post HSCT significantly decreased incidence of acute GvHD.
    Keywords: Hematopoietic stem cell transplant, Graft versus host disease, Cyclosporin
  • Nima Babhadiashar, Masoud Sotoudeh, Ebrahim Azizi, Jafar Bashiri, Reza Didevar, Reza Malekzadeh, Mohammad Hossein Ghahremani Pages 313-318
    Various substances in cigarette smoke including nicotine have been shown to promote/induce cancer cell proliferation. Since cotinine has a longer half life and stability in the blood, it has become the preferred biomarker for cigarette smoking exposure. Seventy-three gastric cancer patients were included in this study. The tumor tissues were stained with H and E for pathological evaluation. The cotinine levels were measured in urine using a competitive ELISA. Tumors were 90% adenocarcinoma with 63% intestinal and 37% diffuse subtypes. Tumors were poorly (45.2%) or moderately differentiated (41.1%) and localized mainly (77%) in the upper part of stomach. The levels of cotinine were significantly different between smoker (283.83 ± 178.10 ng/mL) and non-smoker (39.28 ± 113.34 ng/mL) groups (p < 0.001). However, there is no-significant correlation between tumor characteristics and cotinine level in smoker patients. Cotinine level correlates with smoking in gastric patients, however, correlation with the tumor features has not been observed.
    Keywords: Gastric cancer, cigarette smoking, Cotinine
  • Taher Entezari-Maleki, Azita Hajhossein Talasaz, Mojtaba Salarifar, Molouk Hadjibabaie, Mohammad Reza Javadi, Ali Bozorgi, Yaser Jenab, Mohammad Ali Boroumand, Kheirollah Gholami Pages 319-327
    Low plasma level of vitamin D is linked to the increased risk of cardiovascular diseases such as hypertension, diabetes, dyslipidemia and peripheral vascular diseases. Vitamin D deficiency is a worldwide problem that involves Iranian population. To the best of our knowledge, this was the first investigation on venous thromboembolism (VTE) subjects that assessed the correlation of vitamin D level with plasma P-selectin, hs-CRP, and risk factors of thrombosis. In this prospective study, patients with diagnosis of acute deep vein thrombosis and or pulmonary eboembolism were enrolled. All patients’ clinical data, demographics and risk factors of thrombosis were evaluated. Plasma level of P-selectin and hs-CRP were measured by ELISA method. Radio immune assay method was used to determine plasma level of 25-hydroxy vitamin D. In this study, 60 subjects were included. The mean ± SD plasma 25-hydroxy vitamin D level (25(OH) D) of participants was 21.4 ± 14.6 ng/mL. The vitamin D deficiency was reported in 60% of patients. No significant relation was found between the plasma 25(OH)D level and P-selectin and hs-CRP. In multiple regression analysis, there was a significant relationship between the level of 25(OH)D and the patients’ age (beta = 0.452; p = 0.001), diabetes (beta = 0.280; p = 0.036) and positive family history of cardiovascular diseases (beta = 0.373; p = 0.003). Vitamin D deficiency is a frequent problem in Iranian VTE patients. Moreover, Plasma level of vitamin D is not associated with increase level of P-selectin and hs-CRP in VTE patients.
    Keywords: D deficiency, DVT, PE, VTE, P, selectin, Hs, CRP, Thrombosis risk factors
  • Bing Li, Yujin Wang, Yun Zhang, Meili Liu Pages 329-336
    In the current study, the effects of ethanol (EtOH) on toxicokinetics of methamphetamine (MA) and its metabolite amphetamine (AP) were investigated. A single dose of MA hydrochloride at 15 mg/Kg was given intragastrically, either alone (MA group; n = 8) or in conjunction with 3 g/Kg EtOH (MA+EtOH group; n = 8) to rabbits. In placebo group, normal saline only was given (placebo group; n = 4). Plasma and urine samples were collected and analyzed by gas chromatography/mass spectrometry (GC/MS) for MA and AP. Toxicokinetic parameters of MA and AP were determined using WinNonlin. Our results showed that toxicokinetic profiles of MA and AP in the two experimental groups were both fitted to an open two-compartment model with first-order kinetics. These were not affected by co-administration of EtOH. However, concomitant intake of EtOH significantly increased MA plasma absorption constant (Ka) and maximum concentration (Cmax). The Ka of MA was increased from 0.679/h ± 0.023/h to 0.964/h ± 0.033/h (P < 0.05, the mean Cmax from 1.408 mg/L ± 0.072 mg/L to 1.676 mg/L ± 0.135 mg/L (P < 0.05), whereas the Tmax was significantly decreased from 1.620 h ± 0.062 h to 1.259h ± 0.033h (P < 0.05). In contrast, no significant difference was observed on MA elimination. Furthermore, the plasma AP area under the curve (AUC0-30 h) increased from 5.281 mg/h/L ± 0.264 mg/h/L to.13.052 mg/h/L ± 0.956 mg/h/L and Cmax increased from 0.315 mg/L ± 0.010 mg/L to 0.423 mg/L ± 0.042 mg/L (P < 0.01). Taken together, co-administration of EtOH with MA significantly accelerated MA absorption and subsequent metabolism to AP, but did not have significant effect on MA elimination.
    Keywords: Methamphetamine, Amphetamine, Ethanol, Toxicokinetics
  • Ali Farhoudian, Mandana Sadeghi, Hamid Reza Khoddami Vishteh, Babak Moazen, Monir Fekri, Afarin Rahimi Movaghar Pages 337-344
    Iranian crack is a new form of narcotic substance that has found widespread prevalence in Iran in the past years. crack only nominally resembles crack cocaine as it is widely different in its clinical signs. Thus the present study aims to quantify the chemical combination of this drug. The samples included 18 specimen of crack collected from different zones of Tehran, Iran. All specimens were in the form of inodorous cream solid powdery substance. TLC and HPLC methods were used to perform semi-quantitative and quantitative analysis of the components, respectively. The TLC analysis showed no cocaine compound in the specimens while they all revealed to contain heroin, codeine, morphine and caffeine. All but two specimens contained thebaine. None of the specimens contained amphetamine, benzodiazepines, tricyclic antidepressants, aspirin, barbiturates, tramadol and buprenorphine. Acetaminophen was found in four specimens. HPLC revealed heroin to be the foundation substance in all specimens and most of them contained a significant amount of acetylcodeine. The present analysis of the chemical combination of crack showed that this substance is a heroin-based narcotic which is basically different from the cocaine-based crack used in Western countries. Studies like the present one at different time points, especially when abnormal clinical signs are detected, can reveal the chemical combination of the target substance and contribute to the clinical management of its acute or chronic poisoning.
    Keywords: Substance use, Heroin, Crack Cocaine, Iranian crack, Kerack, TLC, HPLC
  • Naficeh Sadeghi, Mohammad Reza Oveisi, Behrooz Jannat, Mannan Hajimahmoodi, Abdolazim Behfar, Masoomeh Behzad, Narges Norouzi, Morvarid Oveisi, Behzad Jannat Pages 345-349
    Apart from the breast milk, infant formula and baby weaning food have a special role in infant diet. Infants and young children are very susceptible to amount of trace elements. Copper and zinc are two elements that add in infant food. Lead and cadmium are heavy metals that enter to food chain unavoidably. DPASV is a benefit and applicable method for measurement of trace elements in food products. In this study, concentration of zinc, copper, lead and cadmium in four brands of baby food (rice and wheat based) and powder milk was analyzed with DPASV and polarograph set. Total Mean SE of zinc, copper, lead and cadmium in baby foods (n=240) were 11.86 1.474 mg/100g, 508.197 83.154 µg/100g, 0.445 0.006, 0.050 0.005 mg/kg respectively. Also these amount in powder milk (n=240) were 3.621 0.529 mg/100g, 403.822 133.953 µg/100g, 0.007 0.003, 0.060 0.040 mg/kg respectively. Zinc level in baby food type I was higher than lablled value (P = 0.030), but in other brands was not difference. Concentration of copper in all of samples was in labeled range (P > 0.05). In each four products, level of lead and cadmium were lower than the standard limit (P<0.05). Amount of zinc and lead in baby food I, had difference versus other products. Concentration of zinc, cadmium in baby food type I, was higher than type II (P= 0.043, 0.001 respectively). Concentration of lead and cadmium in baby food type II, was higher than infant formulas, but are in standard limit.
    Keywords: lead, cadmium, zinc, copper, baby weaning food, powder milk, voltammetry