فهرست مطالب

  • Volume:18 Issue: 4, 2019
  • تاریخ انتشار: 1398/09/10
  • تعداد عناوین: 25
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  • Hengameh Abdi, Atieh Amouzegar, Fereidoun Azizi * Pages 1-12

    The thionamide drugs, i.e. carbimazole and its metabolite methimazole (MMI), andpropylthiouracil (PTU) have extensively been used in the management of various forms ofhyperthyroidism over the past eight decades. This review aims to summarize different aspectsof these outstanding medications. Thionamides have shown their own acceptable efficacy andeven safety profiles in treatment of hyperthyroidism, especially GD in both children and adultsand also during pregnancy and lactation. Of the antithyroid drugs (ATDs) available, MMI isthe preferred choice in most situations taking into account its better efficacy and less adverseeffects accompanied by once-daily dose prescription because of a long half-life and similar cost.Considering the more severe teratogenic effects of MMI, PTU would be the selected ATD fortreatment of hyperthyroidism during pre-pregnancy months and the first 16 weeks of gestation.Recent studies have confirmed the efficacy and safety of long-term MMI therapy with lowmaintenance doses for GD and toxic multinodular goiter. Despite the long-term history of ATDuse, there is still ongoing debate regarding their pharmacology and diverse mechanisms of action,viz. their immunomodulatory effects, and mechanisms and susceptibility factors to their adversereactions.

    Keywords: Antithyroid, Thionamide, Methimazole, Propylthiouracil, Graves, Hyperthyroidism
  • Smoayeh Mojtabavi, Nasrin Samadi, MohammadAli Faramarzi * Pages 13-30

    It is well-known that the typical protein’s three-dimensional structure is relatively unstable in harsh conditions. A practical approach to maintain the folded state and thus improve the stability and activity of proteins in unusual circumstances is to directly apply stabilizing substances such as osmolytes to the protein-containing solutions. Osmolytes as natural occurring organic molecules typically called “compatible” solutes, based on the concept that they do not perturb cellular components. However, urea and guanidine hydrochloride (GuHCl) as denaturing osmolytes destabilize many macromolecular structures and inhibit functions. Several studies have been so far performed to explain the actual interaction of an osmolyte with a protein. The present review is aimed to achieve a collective knowledge of the progress arise in the field of osmolyte-protein interactions. The following is also an overview of the main techniques to measure protein stability in the presence of osmolytes.

    Keywords: Osmolyte, Preferential hydration, Protein structure, Protein stability, Folding state
  • Mahdi Taherian, Pariya Mahin Samadi, Hossein Rastegar, Mohammad Faramarzi, Mohammad RostamiNejad *, Mohammad Hossein Yazdi, Mostafa Rezaei Tavirani, Zeinab Yazdi Pages 31-50
    Aims

    Probiotics are viable and useful microorganisms, which are beneficial factors for human and animal health by altering their microbial flora. Most of the probiotics belong to a large group of bacteria in the human gastrointestinal tract. There are several clinical shreds of evidence that show anti-carcinogenic effects of probiotics through altering digestive enzymes, inhibition of carcinogenic agents and modulating the immune responses in experimental animals. Many studies performed to evaluate the potential effectiveness of probiotics in treating or preventing neurological diseases such as MS and novel treatment modality for T1D. The purpose of this study is to have an overview on probiotic microorganisms and to review the previous researches on the effects of probiotics on health through currently available literatures.

    Methods

    The study was performed using following keywords; Probiotics, Cancer, Immune system, Multiple Sclerosis and Diabetes mellitus. PubMed/Medline, Clinicaltrials.gov, Ovid, Google Scholar, and Reaxcys databases used to find the full text of related articles. Results and

    Conclusion

    according to the current available data on probiotics and related health-promoting benefits, it seems that, consumption of probiotics can lead to the prevention and reduction the risk of cancer, diabetes, and multiple sclerosis. Although for the better and more decisive conclusion, there is a need to larger sample size clinical studies with more focus on the safety of these biological agents and their possible beneficial effects on different population.

    Keywords: Probiotics, Cancer, Immune Responses, Treatment, Diabetes mellitus, Multiple sclerosis
  • Ensieh Khalkhal, Mostafa Rezaei Tavirani *, Mohammad RostamiNejad Pages 51-67

    Proteomics enables understanding the composition, structure, function and interactions of the entire protein complement of a cell, a tissue, or an organism under exactly defined conditions. Some factors such as stress or drug effects will change the protein pattern and cause the present or absence of a protein or gradual variation in abundances. Changes in the proteome provide a snapshot of the cell activities and physiological processes. Proteomics shows the observed protein changes to the causal effects and generate a complete three-dimensional map of the cell indicating their exact location. Proteomics is used in different biological fields and is applied in medicine, agriculture, food microbiology, industry, and pharmacy and drug discovery. Biomarker discovery, follow up of drug effect on the patients, and in vitro and in vivo proteomic investigation about the drug treated subjects implies close relationship between proteomics advances and application and drug discovery and development. This review overviews and summarizes the applications of proteomics especially in pharmacology and drug discovery.

    Keywords: Proteomics, Pharmacology, Medicine, Biomarker, drug
  • Bahare Salehi, Bilge Sener, Mehtap Kilic, Javad Sharifi Rad *, Rabia Naz, Zubaida Yousaf, Fhatuwani Nixwell Mudau, Patrick Valere Tsouh Fokou, Shahira M. Ezzat, Mahitab H. El Bishbishy, Yasaman Taheri, Giuseppe Lucariello, Alessandra Durazzo, Massimo Lucarini, Hafiz Ansar Rasul Suleria, Antonello Santini Pages 68-89

    Dioscorea species, known as “Yams,” belong to family Dioscoreaceae. This genus consists ofmore than 600 species distributed from Africa, Asia, the Caribbean’s South America, and theSouth Pacific islands. Their organoleptic properties make them the most widely used carbohydratefood and dietary supplements. The underground and/or aerial tubers represent valuable sourcesof proteins, fats, and vitamins for millions of people in West Africa. This review gives a shot ofsecondary metabolites of Dioscorea plants, including steroids, clerodane diterpenes, quinones,cyanidins, phenolics, diarylheptanoids, and nitrogen-containing compounds. This review collectedthe evidence on biological properties of description Dioscorea, including in-vitro and in-vivo studies.Dioscorea species contain promising bioactive molecules i.e. diosgenin that support their differentbiological properties, including antioxidant, hypoglycaemic, hypolipidemic, anti- antimicrobial,inflammatory, antiproliferative, androgenic, estrogenic, and contraceptive drugs. Indeed, besides itsnutrient values, Dioscorea is a potential source of bioactive substances of interest in the prevention/treatment of several diseases, and thus represents a great challenge in developing countries.However, ethnomedicinal potential should be validated and further researches on pharmacologicalproperties and phytochemical composition should be carried out. Particularly, doing some studiesto convert the preclinical results to clinical efficacy should be guaranteed.

    Keywords: Dioscorea, Food plant, Traditional use, Phytochemistry, Pharmacological activities
  • Fatemeh Shaki, Ehsan Zamani, Abdollah Arjmand, Jalal Pourahmad * Pages 90-100

    Depleted uranium (DU) is an important by product in uranium enrichment process. Due toits applications in civilian and also military activity, DU emerged as environmental pollutant.The exposure to DU can occur via external or internal pathways. In external exposure, mainlybeta radiation from the decay products contributes to DU toxicity. Internal exposure to DUis more important and can occur through ingestion of DU-contaminated water and food andinhalation of DU aerosols. There is limited information about health effects and mechanism ofDU after environmental exposure. Kidney is reported as the main target organ for the chemicaltoxicity of this metal that was reported in Persian Gulf syndrome. Alterations in behavior,some neurologic adverse effects, immunotoxicity, embryo-toxicity and hepatotoxicity wereobserved in chronic exposure to DU. Also, the increased risk of cancer was revealed inepidemiological and experimental studies. Several mechanisms were suggested for DU toxicitysuch as oxidative stress, mitochondrial toxicity and inflammation. In fact, uranium like othertoxic heavy metals can induce oxidative damage and apoptosis via mitochondrial pathway andinflammatory response. In this review, we have discussed the kinetic of DU including sourceand exposure pathway. In addition, the health effects of DU and also its toxic mechanism havebeen highlighted.

    Keywords: Depleted uranium, Toxicity, Kinetic, Mechanism, Radiation
  • Hannaneh Aghdam, Hanieh Nokhbatolfoghahaei, Arash Khojasteh * Pages 101-118

    An important field of bone tissue engineering (BTE) concerns the design and fabrication of smart scaffolds capable of inducing cellular interactions and differentiation of osteo-progenitor cells. One of these additives that has gained growing attention is metallic ions as therapeutic agents (MITAs). The specific biological advantage that these ions bring to scaffolds as well as other potential mechanical, and antimicrobial enhancements may vary depending on the ion entity, fabrication method, and biomaterials used. Therefore, this article provides an overview on current status of in-vivo application of MITAs in BTE and the remaining challenges in the field. Electronic databases, including PubMed, Scopus, Science direct and Cochrane library were searched for studies on MITAs treatments for BTE. We searched for articles in English from January-2000 to October-2019. Abstracts, letters, conference papers and reviews, In-vitro studies, studies on alloys and studies investigating effects other than enhancement of new bone formation (NBF) were excluded. A detailed summary of relevant metallic ions with specific scaffold material and design, cell type, animal model and defect type, implantation period, measured parameters and obtained qualitative and quantitative results is presented. No ideal material or fabrication method suited to deliver MITAs can yet be agreed upon, but an investigation into various systems and their drawbacks or potential advantages can lead the future research. A tendency to enhance NBF with MITAs can be observed in the studies. However, this needs to be validated with further studies comparing various ions with each other in the same animal model using critical-sized defects.

    Keywords: bone tissue engineering, metallic ions, scaffolds, therapeutic ions, Drug delivery
  • Mitra Zabihi, Ava Safaroghli Azar, Ahmad Gharehbaghian, Mehdi Allahbakhshian Farsani, Davood Bashash * Pages 119-131

    The strong storyline behind the critical role of cyclin-dependent kinase (CDK) inhibitor proteinsin natural defense against malignant transformation not only represents a heroic perspective forthese proteins, but also provides a bright future for the application of small molecule inhibitorsof CDKs in the novel cancer treatment strategies. The results of the present study revealed thatthe inhibition of CDKs using pan-CDK inhibitor AT7519, as revealed by the induction of G1cell cycle arrest as well as the reduction of cyclins expression, resulted in decreased survival inacute myeloid leukemia (AML)-derived KG-1 cells, either in the context of single agent or incombination with arsenic trioxide (ATO). Apart from alterations in the expression of proliferationand apoptotic genes, the anti-survival property of AT7519 was coupled with the inhibition ofautophagy-related genes. Notably, we found that the blockage of autophagy system in KG-1cells resulted in a superior cytotoxic effect, introducing autophagy as a probable suppressor ofcell death. As far as we are aware, to date, no study has reported the contributory mechanismscorrelated with the less sensitivity of acute leukemia cells to AT7519 and our study suggested forthe first time that the activation of both PI3K and c-Myc signaling pathways could overshadow,at least partly, the efficacy of this agent in KG-1 cells. Overall, due to the pharmacologic safety ofAT7519, our study proposed this inhibitor as a promising agent for the treatment of AML eitheras a single agent or in a combined-modal strategy.

    Keywords: Acute myeloid leukemia (AML), KG-1 cells, Cyclin-dependent kinase (CDK), AT7519, Autophagy, Arsenic trioxide (ATO)
  • Maryam Sadat Hosseini, MohammadHossein Mohammadi, Rouhollah Vahabpour Roudsari, Leila Jafari, Pargol Mashati, Ahmad Gharehbaghian * Pages 132-145

    T-cell acute lymphoblastic leukemia is an aggressive hematologic malignancy which is usuallyassociated with unfavorable prognosis particularly in patients with refractory/relapsed disease.Therefore, development of novel therapeutic strategies is highly required for improving theoutcome of these patients. Although there are several studies evaluating the efficacy of proteasomeinhibitors on acute lymphoblastic leukemia of B-cell lineage, the data are still limited regardingT-cell acute lymphoblastic leukemia. Here, we tried to investigate the effects of the proteasomeinhibition by carfilzomib on the induction of apoptosis and autophagy in Molt4 cells. The effectof carfilzomib in combination with dexamethasone in Molt4, as a glucocorticoid-resistant T-cellacute lymphoblastic leukemia cell line, was also assessed. Our data showed that carfilzomib caninduce both apoptosis and autophagy in Molt4 cells. Furthermore, we found that carfilzomib isa potent inducer of reactive oxygen species production and also induces G2/M phase cell cyclearrest in Molt4 cells. Concomitant treatment with carfilzomib and dexamethasone demonstratedthat carfilzomib can synergistically enhance the cytotoxic effect of dexamethasone on Molt4cells. Furthermore, co-treatment of the cells with carfilzomib and dexamethasone increasedthe induction of autophagy as compared with each drug alone. In conclusion, our results aresuggestive of the effectiveness of carfilzomib on Molt4 cells as a model of GC-resistant T-cellacute lymphoblastic leukemia.

    Keywords: acute lymphoblastic leukemia, Molt4 cells, Autophagy, Apoptosis, Proteasome, Carfilzomib, Dexamethasone
  • Nazanin Ghasemi, Mojgan Bandehpour, Javad Ranjbari * Pages 146-156
    Researchers add serum to a classical medium at concentrations of 5 to 10% (v/v) to grow cellsin-vitro culture media. Unfortunately, serum is a poorly defined culture medium componentas its composition can vary considerably while serum-free cell culture media are an excellentalternative to standard serum-containing media and offer several major advantages. Advantagesof using serum-free media include a lower risk of infectious agents, lower risk of interferingcomponents, less contaminant, avoids ethical issues. According to previous studies insulin,selenium, transferrin and glucose are important component of serum that affect cell growth. Inthe present study, we optimized amount of these factors in order to serum free culture mediumfabrication. Response surface methodology (RSM) was employed for optimization of key factorsin serum free medium to enhance recombinant human GM-CSF (rhGM-CSF) production in CHOcell line. Four important process parameters including insulin concentration (0-2 g/L), transferrinconcentration (0-1 g/L), selenium concentration (0-0.001 g/L) and glucose concentration (0-5g/L) were optimized to obtain the best response of rhGM-CSF production using the statisticalBox–Behnken design. The experimental data obtained were analyzed by analysis of variance(ANOVA) and fitted to a second-order polynomial equation using multiple regression analysis.Numerical optimization applying desirability function was used to identify the optimumconditions for maximum production of rhGM-CSF. The optimum conditions were found to beinsulin concentration = 1.1 g/L, transferrin concentration = 0.545 g/L, selenium concentration =0.000724 g/L and glucose = 1. 4 g/L. Maximum rhGM-CSF production was found to be 3.5 g/L.
    Keywords: Serum free medium, RSM, optimization, GM-CSF, Key factors
  • Parvaneh Panahi Chegini, Iraj Nikokar *, Maryam Tabarzad, Sobhan Faezi, Arash Mahboubi Pages 157-168
    Recently, antimicrobial peptides have been introduced as potent antibiotics with a wide rangeof antimicrobial activities. They have also exhibited other biological activities, including antiinflammatory,growth stimulating, and anti-cancer activities. In this study, an analog of MagaininII was designed and produced as a recombinant fusion protein. The designed sequence contained24 amino acid residues (P24), in which Lys, His, Ser residues were substituted with Arg and also,hydrophobic Phe was replaced with Trp. Recombinant production of P24 in Escherichia coli (E.coli) BL21 using pTYB21, containing chitin binding domain and intein sequence at the N-terminusof the peptide gene, resulted in 1 μg mL-1 product from culture. Chitin column chromatography,followed by online peptide cleavage with thiol reducing agent was applied to purify the peptide.Antimicrobial activity was evaluated using five bacteria strains including Staphylococcus aureus,Enterococcus faecalis, Klebsiella pneumonia, E. coli, and Pseudomonas aeruginosa. DesignedAMP exhibited promising antimicrobial activities with low minimum inhibitory concentration, inthe range of 64-256 μg/mL. P24 showed potent antimicrobial activity preferably against Grampositivebacteria, and more potent than pexiganan as a successful Magainin II analog for topicalinfections. In general, further modification can be applied to improve its therapeutic index.
    Keywords: Antimicrobial peptide, Chitin binding domain, Intein linker, Recombinant production, Amino acid substitution
  • Shima Ebrahimi Khonacha, Mahyar Janahmadi, Fereshteh Motamedi * Pages 169-181
    It has been shown that brain glucose metabolism impairment, obesity, and diabetes couldlead to cognitive decline and Alzheimer’s disease (AD) pathogenesis. Kisspeptin (KP) a G-proteincoupled receptor neuropeptide, has been suggested as a link between energy balance andreproduction. Some studies have shown that the attenuation of KP signaling decreases metabolismand energy expenditure. KP mRNAs and receptors are detected in the hippocampusand cause the promotion of excitatory synaptic responses through modulation of postsynapticsignaling. The purpose of this study was to investigate the effect of KP on spatial learning andmemory and its possible neuroprotective effect on Amyloid-Beta induced cognitive impairmentusing the Morris Water Maze (MWM) task in rats. The reference and reversal spatial learningand memory have been measured in this study. Rats were injected bilaterally by Aβ1-42 (2 μg/μL) or saline as a vehicle into the hippocampal CA1 area. One week later, KP-13 (1.5 or 2 μg/μL) was injected i.c.v before or after each training session for 3 days and memory was tested24 h later. The results showed KP-13 by itself could significantly enhance spatial memoryconsolidation and retrieval, and Aβ induced reversal and reference memory impairment wassignificantly ameliorated by KP-13. In Conclusion, it seems that KP-13 as a neuropeptide hasto enhance spatial memory properties and could be a possible neuroprotective peptide on amyloid-beta induced pathology.
    Keywords: Kisspeptin, Alzheimer, Spatial memory, Morris Water Maze, Rat
  • Ghasem Haydari, SeyedJamal Hashemi Hazaveh, Bahram Daraei *, Mansour Bayat Pages 182-189

    This study focuses on optimization and validation of an Ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous analysis of 11mycotoxins: Aflatoxin B1, T-2 Toxin, Ochratoxin A, Deoxynivalenol and Zearalenone in wheat matrix. Sample extraction and cleanup procedure is based on a single extraction step using acetonitrile/water/acetic acid mixture (79.5/20/0.5 v/v/v) and rapid clean-up of samples were performed with the Myco6in1+ Immunoaffinity column. Electrospray ionization at positive mode was operated to the simultaneously analysis of selected mycotoxins in a single run time of 15 min. Multiple Reaction Monitoring (MRM) mode was selected for quantification and detection of the mycotoxins. Analysis was accepted and validated for the simultaneous quantification of 11 mycotoxins at different levels (2-150 ngg-1 for AFs, T-2 TOXIN, OTA; 20-1500 ngg-1 for ZER, HT-2 TOXIN; and 100-1500 ngg-1 for DON and FB1+B2) in wheat. Calibration curves were plotted with spiked wheat flour blank samples without internal standard. Limits of detection (LOD) ranged from 0.7 to 33.3ngg-1 and limits of quantification (LOQ) ranged from 2 to 100 ngg-1. The recoveries of selected mycotoxins were in the range of 72.2-122 %.The recoveries and repeatabilities were in accordance with the criteria determined by European Union (EU) Recommendation 519/2014.

    Keywords: Wheat, UHPLC-MS, MS, Mycotoxins, Simultaneous, Analysis
  • Zahra Keshavarzi, Sahar Barzegari Banadkoki, Mehrdad Faizi, Yalda Zolghadri, Farshad H Shirazi * Pages 190-197
    Meat, as an important source of protein, is one of the main parts of many people’s diet. Due toeconomic interests and thereupon adulteration, there are special concerns on its accurate labeling.In this study Fourier transform infrared (ATR-FTIR) spectroscopy combined with chemometrictechniques (principal component analysis (PCA), artificial neural networks (ANNs), and partialleast square regression (PLS-R)) were employed for discrimination of pure beef meat from texturedsoy protein plus detection and quantification of texture soy protein in a mixture with beef meat.Spectral preprocessing was carried out on each spectra including Savitzki-Golay (SG) smoothingfilter, Standard Normal Vitiate (SNV), scatter correction (MSC), and min-max normalization.Spectral range 1700–1071 cm-1 was selected for further analysis. Principal component analysisshowed discrete clustering of pure samples. In the next step, supervised artificial neural networks(ANNs) were performed for classification and discrimination. The results showed classificationaccuracy of 100% using this model. Furthermore, PLS-R model correlated the actual and FTIRestimated values of texture soy protein in beef meat mixture with coefficient of determination(R2) of 0.976. In conclusion, it was demonstrated that ATR-FTIR spectroscopy along with PCAand ANNs analysis might potentially replace traditional laborious and time-consuming analyticaltechniques to detect adulteration in beef meat as a rapid, low cost, and highly accurate method.
    Keywords: Meat, Textured soy protein, Food Adulteration, Fourier-transform infrared spectroscopy, Multivariate Analyses
  • MohammadAbbas Sheikholeslami, Siavash Parvarde, Shiva Ghafghazi, Taraneh Moeinzanjani, Masoumeh Sabet Kasaei * Pages 198-207
    Background

    New evidence suggests an important role for spinal glial cells in development of opioid dependence. Curcumin, a component of the Curcuma Longa, has shown to act as a suppressor of microglial cells. The main goal of this study was to explore the attenuating effects of curcumin on morphine dependence with a focus on spinal microglial cells and inflammatory cytokines.

    Methods

    In order to induce morphine dependence in male Wistar rats, morphine was administered intraperitoneally (i.p.) once daily for 18 days in an increasing dose of 10, 20, and 40 mg/kg. Curcumin (2.5, 5, and 10 mg/kg, i.p.) was given from the days 10th to 18th. Naloxone-precipitated abstinence syndrome was used to assess behavioral symptoms of morphine dependence. Immunofluorescence staining of Iba1 and ELISA test were used to measure spinal microglial activity and inflammatory cytokines levels, respectively.

    Results

    The results showed that curcumin (2.5, 5, and 10 mg/kg) significantly decreased jumping, leaning, and diarrhea in morphine-dependent rats. In addition, the spinal concentration of TNF-α and IL-6 was reduced by curcumin (2.5, 5, and 10 mg/kg) significantly. Moreover, curcumin showed a potent attenuating effect on the number of Iba1 positive cells in rats which were subjected to morphine dependence.

    Conclusion

    In conclusion, the results of this study demonstrated that curcumin exerts a remarkable reducing effect on morphine dependence in rats. The findings showed that the therapeutic effect of curcumin on morphine dependence is mediated through the suppression of activated microglial cells and reduction of inflammatory cytokines levels in the spinal cord.

    Keywords: Morphine dependence, Withdrawal syndrome, Curcumin, Spinal cord, Microglial cells, inflammatory cytokines
  • Maryam Ranjbar Ekbatan, Mona Khoramjouy, Babak Gholamine, Mehrdad Faizi *, Shamim Sahranavard Pages 208-220
    In Iranian traditional medicine, plants belonging to Inula genus have been used for the treatment of seizure. We decided to investigate the anticonvulsant activity of seven species from this genus to find an effective remedy for seizure with less adverse effects compared to available medicines. Aqueous and methanolic extracts of Inula britannica, Inula helenium, Inula viscidula, Inula oculus-christi, Inula aucheriana, Inula thapsoides and Inula salicina were prepared and their antiepileptic activity was investigated by maximal electroshock and pentylentetrazole tests. Diazepam was used as positive control in both tests. Two extracts with the best anticonvulsant activities were selected and their sedative and hypnotic effects were evaluated using open field and righting reflex tests respectively. The effects of both extracts on memory and motor coordination were also assessed by step-through passive avoidance and rotarod tests respectively. Aqueous extract of Inula britannica and Inula viscidula showed the best activity in MES model and their ED50 was 19.5(7.9~48.5)mg/kg and 12.7(10.0~16.3)mg/kg respectively. None of the extracts showed noticeable anticonvulsant effects in the PTZ model. The active extracts showed sedative-hypnotic effects in righting reflex and open field tests. Both extracts did not affect the memory and motor coordination in the experimental model. The anticonvulsant and sedative activities of the extracts were antagonized by flumazenil, indicating that benzodiazepine receptors are probably involved in the effects. Finally, Inula britannica and Inula viscidula are good candidates for further phytochemical and mechanistic studies in order to find anticonvulsant and sedative-hypnotic agents with less adverse effect on memory and motor coordination.
    Keywords: Anticonvulsant, Pentylentetrazole, Maximal Electroshock, Inula, Hypnotic
  • Ali Karimi, Mohammad Erfan, SeyedAlireza Mortazavi *, Fatemeh Ghorbani Bidkorbeh, Behnaz Landi, Farzad Kobarfard, Farshad H.Shirazi Pages 221-236
    Purpose

    our goal is to reduce the release rate of methotrexate (MTX) and increase cell death efficiency.

    Methods

    Carboxylated multi-walled carbon nanotubes (MWCNT-COOH) were functionalized with MTX as a cytotoxic agent, FA as a targeting moiety and polyethylene amine (PEI) as a hydrophilic agent. Ultimately, MWCNT-MTX and MWCNT-MTX-PEI-FA were synthesized. Methotrexate release studies were conducted in PBS and cytotoxic studies were carried out by means of the MTT tassay.

    Results

    Methotrexate release studies from these two carriers demonstrated that the attachment of PEI-FA onto MWCNT-MTX reduces the release rate of methotrexate. The IC50 of MWCNT-MTX-PEI-FA and MWCNT-MTX have been calculated as follows: 9.89 ± 0.38 and 16.98 ± 1.07 µg/ml, respectively. Cytotoxic studies on MWCNT-MTX-PEI-FA and MWCNT-MTX in the presence of an IR laser showed that at high concentrations, they had similar toxicities due to the MWCNT’s photothermal effect. Targeting effect studies in the presence of the IR laser on the cancer cells have shown that MWCNT-MTX-PEI-FA, MWCNT-MTX and f-MWCNT have triggered the death of cancer cells by 55.11±1.97 %, 49.64±2.44 %, and 37±0.70 % respectively.

    Conclusions

    The release profile of MTX in MWCNT-MTX-PEI-FA showed that the presence of PEI acts as a barrier against release and reduces the MTX release rate. In the absence of a laser, MWCNT-MTX-PEI-FA exhibits the highest degree of cytotoxicity. In the presence of a laser, the cytotoxicity of MWCNT-MTX and MWCNT-MTX-PEI-FA has no significant difference. Targeting studies have shown that MWCNT-MTX-PEI-FA can be absorbed by cancer cells exclusively.

    Keywords: Multi-walled carbon nanotubes, Photothermal, Folic Acid, Methotrexate, Polyethylenimine, Targeting effect, Cancer cell
  • Elnaz Ebrahimzadeh, SayyedAbbas Tabatabai, Roholah Vahabpour Rodsari, Zahra Hajimahdi, Afshin Zarghi * Pages 237-248

    In an attempt to identify potential new agents that are active against HIV-1, a series of novel pyridopyrimidine-5-carbohydrazide derivatives featuring a substituted benzylidene fragment were designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors. The cytotoxicity profiles of these compounds showed no significant toxicity to human cells and they exhibited anti-HIV-1 activity with EC50 values ranging from 90 to 155 M. Compound 5j bearing 4-methylbenzylidene group was found to be the most active compound with EC50 = 90 M and selectivity index, CC50/EC50 = 6.4. Molecular modeling studies indicated the capacity of compound 5j to interact with two Mg2+ cations and several residues that are important in HIV-1 integrase inhibition. These findings suggested that pyridopyrimidine-5-carbohydrazide scaffold might become a promising template for development of novel anti-HIV-1 agents.

    Keywords: Synthesis, Pyridopyrimidine-5-carbohydrazide, HIV-1 integrase, Molecular modeling, Anti-HIV-1
  • Nazanin Bagherian Rad, Mitra Rahimi * Pages 249-257
    NSAIDs are nonsteroidal anti-inflammatory drugs, thus, they will provide analgesic,antipyretic, anti-inflammatory, antiplatelet effects. Severe poisoning and death because of acuteintoxication can occur by ingestions of more than 400 mg/kg. This cross-sectional retrospectivestudy was carried out in on all patients referred to Loghman Hakim Hospital from 2011 to 2016.Grouping of our patients was based on the amount of NSAID ingestion, Type of NSAID, patient’sconscious level according to Reed Scaling criteria, suicide attempt, and gender. Data were analyzedusing the SPSS software. A P-value of 0.05 or less was considered to be statistically significant.The period prevalence of NSAID poisoning was 0.14% and the incidence was 3.816/100,000/year. The uppermost number of poisoning were seen in 2012 (20.96%). Mean age was 23.75± 9.76 years and most of the intoxications were seen in females (66.37%). Of the patients, 140(61.13%) had ingested less than 200 mg/kg, and 9.17% committed suicide having a mortality rateof 0.43%. The most common NSAIDs that had been used were Ibuprofen (73.79%). Of patients,83.4% underwent through common complications of NSAID poisoning. We find significantrelationship between the type of NSAID and higher sodium, BUN, ALT, ALP, CPK levels in men,and higher LDH level in women. Besides, we found substantial correlation between using shortactingNSAIDs and female gender, suicide action, arrival to the hospital less than 12 h, amountsunder 200 mg/kg, hospitalization longer than 12 h, and presentation of loss of consciousness.
    Keywords: Anti-inflammatory agents, Non-steroidal, Poisoning, adverse effects, Overdose
  • Amir Farrokhian, Maryam Tohidi *, Noushin Sadat Ahanchi, Davood Khalili, Mahtab Niroomand, Arash Mahboubi, Arash Derakhshi, Mohammad Abbasinazari, Farzad Hadaegh Pages 258-268
    Melatonin is widely available as over the counter product. Despite promising effects of melatonin supplementation on glycemic control, there is a significant heterogeneity between studies. The current study aimed at determining the effect of melatonin on fasting blood glucose (FBG), insulin resistance/sensitivity indices, glycosylated hemoglobin A1c (HbA1c), and high sensitivity C-reactive protein (hs-CRP) among type 2 diabetes mellitus (T2D) population during 8 weeks in a randomized, triple-blind, placebo-controlled trial. Thirty four subjects with the mean age ± standard deviation of 57.74 ± 8.57 years and 36 subjects with the mean age of 57.61 ± 9.11 years were allocated to 6 mg nightly melatonin and placebo groups, respectively. Melatonin and placebo groups were matched by age, gender, body mass index, and duration of diabetes. Also, there was no significant difference in laboratory findings except for HbA1c, which was lower in the placebo group (7.00±0.89% vs 7.60±1.47%, P=0.042). After trial completion, the increase of serum levels of melatonin was greater in the intervention than the placebo group (3.38±1.33 vs 0.94±1.28 ng/L, P=0.192). Moreover, compared to placebo group, among melatonin users, homeostasis model assessment of insulin resistance (HOMA1-IR) tended to be unfavorable at the end of follow-up [-0.51 (-1.76-0.81) vs. 0.28 (-1.24-1.74), P=0.20]; the similar trend was also shown for insulin sensitivity index (HOMA1-S) [2.33 (-3.59-12.46) vs. -2.33 (-10.61-9.16), P=0.148]. No differences were observed in FBG, HbA1C, and hs-CRP changes between the trial groups. The current study did not support the improving effect of melatonin on glucose homeostasis.
    Keywords: Melatonin, Diabetes mellitus, glycemic status, Dietary supplement, Melatonin level
  • Elham Pourheidar, Mehrdad Haghighi, Mehran Kouchek, Mir Mohammad Miri, Seyedpouzhia Shojaei, Sara Salarian, Rezvan Hassanpour, Mohammad Sistanizad * Pages 269-281
    The purpose of this study was evaluating the efficacy and safety of intravenous (IV) ampicillin–sulbactam plus nebulized colistin in the treatment of Ventilator-Associated Pneumonia (VAP) caused by MDR Acinetobacter (MDRA)in ICU patients as an alternative to IV plus nebulized colistin. In this single-blinded RCT, one group received IV colistin and another group IV ampicillin–sulbactam (16 and 12 patients from total 28 patients, respectively) for 14 days or since clinical response. Both groups received nebulized colistin by mesh nebulizer. There were no statistically significant differences between the 2 groups in baseline characteristics and previous antibiotic therapy. In follow up period, no significant difference was observed between 2 groups in rate of microbiological eradication, clinical signs of VAP improvement, survival rate and length of hospital as well as ICU stays. Although we have found no significant differences in Acute Kidney Injury (AKI) incidence between two groups, comparison of cumulative patient-days with stages 2 and 3 AKI with days with no or stage 1 AKI, according to AKIN criteria, revealed significant difference in IV colistin versus IV ampicillin–sulbactam group (p = 0.013). The results demonstrated that the high dose IV ampicillin–sulbactam plus nebulized colistin regimen has comparable efficacy with IV plus nebulized colistin in the treatment of VAP caused by MDRA,withsensitivity to colistin only, with probably lower incidence of kidney injury.
    Keywords: Acinetobacter, Acute Kidney Injury, Colistin, nebulizer, Pneumonia, Ventilator-Associated
  • Farzaneh Dastan, Jamshid Salamzadeh, Saeed Alipour Parsa, Babak Sharif Kashani, MohammadMahdi Hashempour * Pages 282-290
    Objectives

    This study aimed to investigate the efficacy of calcitriol on Ischemia-reperfusion Injury (IRI) and inflammatory biomarkers in patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) undergoing elective Percutaneous Coronary Intervention (PCI).

    Methods

    A total of 72 patients with NSTEACS were randomly divided into two groups: (1) the calcitriol-treated group, treated with three mcg intravenous calcitriol administered before PCI (n = 36), and (2) the control-treated group (n = 36). The serum high-sensitivity C-reactive protein (hs-CRP), high-sensitivity interleukin-6 (hs-IL-6), creatinine kinase (CK)-MB and cardiac troponin I (cTnI) levels were measured before PCI and 24 hours after PCI in both groups. The patients were followed up for the detection of the prevalence of major adverse cardiac events (MACE) in 180 days after PCI in both groups.

    Results

    Compared to pre-PCI, the serum hs-CRP, hs-IL-6, CK-MB, and cTnI levels were increased at 24 h after PCI (all p<0.05) in both groups. However, change in the levels of hs-CRP and hs-IL-6 were significant (p=0.04 and p=0.02, respectively). Changes in the levels of CK-MB and cTnI were non-significant (p=0.15 and p=0.39, respectively). No MACE (death, Q wave MI, target vessel revascularization, ischemic stroke) was detected in any patient in any group during a 3-month follow-up.

    Conclusion

    Administration of calcitriol in patients with non-ST-segment elevation acute coronary syndromes undergoing elective PCI can attenuate the increase in serum inflammatory biomarkers in the serum (hs-CRP and hs-IL-6) and thus decrease the inflammatory reaction caused by PCI.

    Keywords: Calcitriol, Ischemia-Reperfusion Injuries, Percutaneous Coronary Interventions, Revascularization, inflammation, Biomarkers
  • Zahra Jafari, Majid Emtiazy, Farnaz Sohrabvand, Daryush Talei, Laleh Oveidzadeh, Mahboobeh Abrishamkar, Mohammad Kamalinejad * Pages 291-301
    Primary dysmenorrhea is a common gynecological disorder in women of reproductive age. Despite the effective treatments such as nonsteroidal anti-inflammatory drugs and oral contraceptives, researchers have always been looking for alternative drugs due to the adverse effects and limited efficacy of conventional medications. Glycyrrhiza glabra L. (G. glabra), commonly known as Licorice, has been applied for a long time as a plant with multiple therapeutic potencies in Traditional Persian Medicine (TPM). This study was designed to evaluate the effect of the G. glabra on primary dysmenorrhea. Sixty patients with moderate and severe dysmenorrhea were randomly divided into two groups; one group received 400 mg Ibuprofen tablets every 8 hours and placebo syrup and the other received 5 cc of G. glabra syrup two times a day and placebo tablets. The patients took the drugs from the first day of menstruation to fifth for two consequent cycles. The primary pain intensity and its changes evaluated in each group and compared between two groups.
    Results
    The reduction of pain intensity was 5.85 (±3.11) in the G. glabra group compared with 6.92 (±1.87) in the Ibuprofen group (p < 0.001). No significant difference detected between the two groups (p = 0.151). No serious side effects were reported during the study.
    Conclusion
    This study suggests that we can use G. glabra to relieve the pain in patients with primary dysmenorrhea; although studies with a larger sample size may lead to more comprehensive perceptions about the efficacy of G. glabra.
    Keywords: Primary dysmenorrhea, Glycyrrhiza glabra L, Traditional Persian Medicine, Licorice, Ibuprofen
  • Ali Tafazoli, Simin Dadashzadeh, Mahshid Mehdizadeh, Sayeh Parkhideh, Maria Tavakoli Ardakani * Pages 302-314

    Allogeneic hematopoietic stem cell transplantation (AHSCT) is a major method of treatmentfor different hematologic and congenital disease. Graft versus host disease (GvHD) is a lifethreateningadverse effect of AHSCT. Cyclosporine is the most important and common agentfor GvHD prophylaxis. Because of variable and unpredictable pharmacokinetics of cyclosporinethat produces different responses in each patients group and clinical setting, there are still lots ofuncertainties about its optimal method of administration and monitoring of this drug. Frequentblood samples in eight different times were taken for cyclosporine quantification in twentyAHSCT recipients and pharmacokinetic parameters determined in both intravenous (IV) and oraladministration and monitoring parameters assessed accordingly. Of pharmacokinetic parametersmean ± SD area under concentration – time curve (AUC), clearance, and half-life were estimatedto be 5492 ± 1596 ng.h/mL, 19.44 ± 6.61 L/h, and 11.8 ± 5.4 h for IV and 7637.7 ± 2739.8 ng.h/mL, 19.42 ± 6.62 L/h, and 11.16 ± 5.9 h for oral administration, respectively. Appropriate oral tointravenous dosing ratio found to be about 1.6. Of monitoring parameters, C0.5 h and C6 showedthe highest coefficient of determination for regression between single points and total area undercurve. Evaluation of pharmacokinetic parameters derived from concentration versus time curveshowed that the appropriate oral/IV is 1.6 for maintenance GvHD prophylaxis for outpatientscould be helpful. Cyclosporine plasma concentration at 0.5 and 6 h after IV administrationshowed the highest correlation with AUC of this drug.

    Keywords: cyclosporine, Pharmacokinetics, hematopoietic stem cell transplantation, graft versus host disease, Oral, Intravenous
  • Bahram Fariborz Farsad, Farzaneh Dastan, Jamshid Salamzadeh, Zahra Moghadamnia, Raha Eskandari, Fanak Fahimi * Pages 315-320
    Warfarin is a critical medication that is broadly used for the treatment and prevention ofthromboembolic disorders. Due to warfarin’s narrow therapeutic index, it is crucial that patientsfollow an appropriate dosage regimen. Patient knowledge is one of the most important factorsto safe and effective use of warfarin. Due to the obvious risks of anticoagulants administration,evaluating patients’ awareness seems to be crucial. The purpose of this article was to evaluatethe effects of intervention by an informative pamphlet on knowledge and adherence of patientswho consumed warfarin. Two-hundred and fifty patients receiving warfarin were assigned tothe study. They were asked to fill in the questionnaire. Then patients were provided with aneducational pamphlet. In the second interview, patients filled the questionnaire again. Obtaineddata were assessed and analyzed by Excel software and SPSS version 18.0. Out of 250 patientswho entered the study, 150 patients attended for the second interview. Data analysis revealedthat out of 13 explanatory factors, only patients’ literacy level and income were the predictorswhich inversely correlated with the patients’ adherence (r = -0.44; p = 0.00040). Our educationalintervention had a positive impact on patients’ knowledge regarding anticoagulation (p < 0.0001).Our findings revealed that a written informative pamphlet could effectively increase patients’anticoagulation knowledge. Since, poorly literate patients had a lesser level of knowledgebefore and after educational intervention, it is recommended to develop appropriate educationalprograms especially designed for this group of patients.
    Keywords: warfarin, Anticoagulation knowledge assessment, Anticoagulants, Thromboembolic disorders, Adherence, Patient education, Pamphlet