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Research in Pharmaceutical Sciences - Volume:12 Issue: 2, Apr 2017

Research in Pharmaceutical Sciences
Volume:12 Issue: 2, Apr 2017

  • تاریخ انتشار: 1396/02/15
  • تعداد عناوین: 10
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  • Mina Mirian, Hossein Khanahmad, Leila Darzi, Mansour Salehi, Hojjat Sadeghi-Aliabadi Page 88
    Viral hepatitis, as an international public health concern, seriously affects communities and health system. In recent years, great strides have been taken for development of new potential tools against viral hepatitis. Among these efforts, a valuable strategy introduced new molecules called “aptamers”. Aptamers as potential alternatives for antibodies could be directed against any protein in infected cells and any components of viral particles. In this review, we will focus on recent advances in the diagnosis and treatment of viral hepatitis based on aptamer technology. In recent years, various types of aptamers including RNA and DNA were introduced against viral hepatitis. Some of these aptamers can be utilized for early and precise diagnosis of hepatitis infections and other group selected as therapeutic tools against viral targets. Designing diagnostic and therapeutic platforms based on aptamer technology is a promising approach in viral infections. The obtained aptamers in the recent years showed obvious potential for use as diagnostic and therapeutic tools against viral hepatitis. Although some modifications to increase the biostability and half-life of aptamers are underway, it seems these molecules will be a favorable substitute for monoclonal antibody in near future.
    Keywords: Dissolution rate, Nanocrystal, Nanoparticle, Nanosuspension, Nanosizing
  • Hidayat Sulistyo Sulistyo, Dhadhang Wahyu Kurniawan, Lantip Rujito Page 99
    Transfusion in the treatment of thalassemia gives rise to iron deposits in many organs. Since there are many obstacles in the use of deferoxamin (DFO) as an iron chelating agent, it is important to find another alternative therapy that can act as iron chelation. The study aims to compare the histopathological pictures of the heart and spleen in iron-induced rats after administration of DFO and nanoparticles of green tea extract. The research used experimental research design with a post-test only control group. Experimental nano green teas were divided into four treatment groups; no diet, DFO supplementation, nano green tea supplementation, and a combination of both DFO and green tea. Ferritin and glutathione peroxides were used as biochemical parameters, and histopathological pictures of the heart and spleen were recorded. The study showed that there was significant improvement in the rats receiving DFO and nanoparticles of green tea compared with the rats in the no diet group. The study also reported that nano green tea has an effect comparable to DFO.
    Keywords: Green tea, Nanoparticle, Thalassemia, Iron chelator, Transfusion
  • Farshid Hassanzadeh, Maryam Farzan, Jaleh Varshosaz, Ghadam Ali Khodarahmi, Sahar Maaleki, Mahboubeh Rostami Page 107
    In this study, poly(ethylene-co-vinyl alcohol) (EVOH) as a novel biocompatible polymeric scaffold was surface modified by succinylation to get EVOHS and further pegylated to improve structural properties using methoxypolyethylene glycol (5000 Da) succinate (PEGS) along with targeting with retinoic acid (RA) to get final modified active and passive targeted conjugate (PEGS-EVOHS-RA) to evaluate its ability in carrying and delivery of epirubicin to hepatocellular carcinoma cell lines in response to varying temperatures. In this regard, the PEGS-EVOHS-RA conjugate was prepared through the desired chemical reactions and its structure was confirmed using 1H-NMR and FT-IR spectra. The micelles were prepared from PEGS-EVOHS-RA by dialysis method. The Particle size and zeta potential were measured, and entrapment efficacy along with in vitro release efficiency in different temperatures were also studied. The structural morphology of optimized nanomicelle was studied by transmission electron microscopy micrographs. The desired final micelles were evaluated for their toxicity using MTT assay on HepG2 human hepatocellular carcinoma cell lines at normal (37°C) and elevated temperature (45 °C). The results revealed that, as the hydrophilicity of micelles increased, all characteristic properties improved. Then, these micelles can be considered as potentially effective thermo responsive delivery systems for targeted delivery of cytotoxic agents to hepatocellular carcinoma.
    Keywords: Nanomicelles, PEGylation, Thermo-responsive, Poly(ethylene-co-vinyl alcohol) (EVOH), Cytotoxicity
  • Fatemeh Shaki, Yaghoub Shayeste, Mohammad Karami, Esmaeil Akbari, Mahdi Rezaei, Ramin Ataee Page 119
    Oxidative stress and mitochondrial dysfunction are the main suggested mechanisms for neurodegenerative diseases. In this study, we have evaluated the effects of epicatechin (EC) on mitochondrial damage induced by homocycteine (Hcy) using isolated rat hippocampus mitochondria in vivo. EC (50 mg/kg) was gavaged daily for a period of 10 days, starting 5 days prior to Hcy (0.5 μmol/μL) intra hippocampus injection in rats. Mitochondria were isolated from brain by different centrifuge techniques. Mitochondrial function was assayed by MTT test. Also, mitochondrial swelling and oxidative stress markers, such as reactive oxygen species (ROS), lipid peroxidation and glutathione (GSH), were assayed. Hcy induced mitochondrial dysfunction and swelling. Increase in ROS formation, lipid peroxidation, and decreased GSH were observed after Hcy treatment in isolated brain mitochondria. Furthermore, oral administration of EC significantly decreased the lipid peroxidation and ROS levels and also increased GSH levels. Also, EC treatment significantly improved mitochondrial function. As EC indicated protective effects against oxidative stress and mitochondrial damage induced by Hcy, it is suggested for further trials for prevention or treatments of neurodegenerative disorders such as Alzheimer disease.
    Keywords: Epicatechin, Homocycteine, Oxidative stress, Mitochondria, Neurodegenerative
  • Rahim Bahri-Najafi, Abolfazl Mostafavi, Naser Tavakoli, Somayeh Taymouri, Mohammad-Mehdi Shahraki Page 128
    In the current study, floating dosage form containing acyclovir was developed to increase its oral bioavailability. Effervescent floating tablets containing 200 mg acyclovir were prepared by direct compression method with three different rate controlling polymers including Hydroxypropyl methylcellulose K4M, Carbapol 934, and Polyvinylpyrrolidone. Optimized formulation showed good floating properties and in vitro drug release characteristics with mean dissolution time and dissolution efficacy of about 4.76 h and 54.33%, respectively. X-ray radiography exhibited that the tablet would reside in the stomach for about 5 ± 0.7 h. After oral administration of floating tablet containing 200 mg acyclovir, the Cmax, Tmax, and AUC0–∞ of optimized gastroretentive formulation were found to be 551 ± 141 ng/mL, 2.75 ± 0.25 h and 3761 ± 909.6 ng/mL/h, respectively.
    Keywords: Acyclovir, Floating tablet, HPLC, X-ray radiography
  • Akram Ahangarpour, Ali Akbar Oroojan, Layasadat Khorsandi, Seyedeh Asma Najimi Page 137
    D-galactose induces pancreatic disorder along with aging mouse model. Vitex agnus-castus (VAC) has potential pancreatic protective effect. Hence, this study was designed to evaluate the hypoglycemic and pancreas protective effects of VAC hydroalcoholic extract in D-galactose-induced aging female mice. In the present experimental study, 72 adult female Naval Medical Research Institute (NMRI) mice (weighing 30–35 g) were divided into 6 groups of control, VAC hydroalcoholic extract, D-galactose, D-galactose VAC hydroalcoholic extract, aged, aged VAC hydroalcoholic extract. The aged model was prepared by subcutaneous injection of D-galactose for 45 days and, VAC hydroalcoholic extract was gavaged twice a day in the last 7 days. 24 h after the last drug and extract administrations, serum samples and pancreatic tissues were removed to evaluate experimental and histological determinations. Serum glucose level decreased in VAC, D-galactose and, aged-treated groups compared to the control (P
    Keywords: Vitex agnus-castus, Pancreas, D-galactose, Aged mouse
  • Mohammadreza Amirsadri, Mohammad Javad Sedighi Page 144
    Aspirin is one of the certified medicines commonly used for the secondary prevention of myocardial infarction (MI). Aspirin side effects and gastrointestinal bleeding, in particular, have arisen debates on its use for the primary prevention of MI. The present research evaluates the cost-effectiveness of the use of aspirin in the primary prevention of MI among Iranian men with average cardiovascular disease (CVD) risk, using Markov modeling technique. The incremental cost-effectiveness ratios (ICERs) estimated to be 864 USA dollars (USD) per quality-adjusted life years (QALY) gained and 782 USD per life years gained (LYG) for each patient in the base-case scenario (public tariffs and no discounting). This research proves cost-effectiveness of the use of aspirin in the primary prevention of MI in targeted population, since the assessed ICERs are quite under the recommended threshold by WHO which is one gross domestic product (GDP) per capita ($5315.1 for Iran in 2015).
    Keywords: Aspirin, Primary prevention, Cardiovascular diseases, Markov chain, Cost-effectiveness
  • Faezeh Safdari, Mohammad Rabbani, Ali Hosseini-Sharifabad Page 154
    Potassium bromide (KBr), an old antiepileptic agent, is illegally used in pharmaceutical or food industries to improve the product appearance. KBr has been proven to influence several pathways which are important in memory formation. Therefore, the present study aimed to evaluate the effect of KBr on spatial working memory using object recognition task (ORT). Rats received a single dose of KBr (50, 100 or 150 mg/kg), per oral, in acute treatment. KBr long term effects were also studied in animals receiving 50 mg/kg/day of KBr for 28 consecutive days. At the end of treatments, animals underwent two trials of ORT, five min each. In the first trial (T1), animals encountered with two identical objects for exploration. After 1 h, the animals were exposed to a familiar and an unfamiliar object (T2). The exploration times for discrimination (D) and recognition (R) as well as the frequency of exploration for any objects were determined. Acute administration of 150 mg/kg of KBr significantly decreased the discrimination and recognition indices (RI and DI) (P
    Keywords: Potassium bromide, Acute, Long term, Spatial working memory, Object recognition task
  • Seyed Ahmad Emami, Rezvan Yazdian-Robati, Mohammad Sadeghi, Javad Baharara, Elaheh Amini, Farzaneh Salek, Zahra Tayarani-Najaran Page 160
    Nepeta satureioides Boiss. has been used in traditional medicine of eastern countries and is famous for its medicinal properties. The aim of this study was to evaluate the effect of methanol (MeOH), n-hexane and dichloromethane (CH2Cl2) fractions of the extract on melanin synthesis and oxidative stress in B16F10 melanoma cell line. The B16F10 cell line viability after treatment with increasing concentrations of different fractions of the plant (5-60 µg/mL) was measured using MTT assay. The inhibitory effect on synthesis of melanin, mushroom tyrosinase activity, cellular tyrosinase and oxidative stress were determined by the colorimetric and fluorometric methods. The data showed that at concentrations below 60 µg/mL, fractions did not show significant toxicity on melanoma cells. The amount of melanin synthesis by MeOH and CH2Cl2 fractions and mushroom tyrosinase activity by the MeOH fraction declined in B16F10 cells. In addition to the capacity of MeOH, n-hexane and CH2Cl2 fractions in decreasing the amount of reactive oxygen species (ROS) in melanoma cells, all fractions revealed remarkable antioxidant activity. The melanogenesis inhibitory and antioxidant effects of N. satureioides on B16F10 cells may suggest this plant as a new pharmaceutical agent in reducing skin pigment and skin aging in cosmetic industry.
    Keywords: Melanogenesis, Tyrosinase, Melanoma, Nepeta satureioides Boiss, Lamiaceae
  • Mahsa Ghavim, Khalil Abnous, Fatemeh Arasteh, Sahar Taghavi, Maryam Sadat Nabavinia, Mona Alibolandi, Mohammad Ramezani Page 168
    For high-throughput production of recombinant protein in Escherichia coli (E. coli), besides important parameters such as efficient vector with strong promoter and compatible host, other important issues including codon usage, rare codons, and GC content specially at N-terminal region should be considered. In the current study, the effect of decreasing the percentage of GC nucleotides and optimizing codon usage at N-terminal region of human growth hormone (hGH) cDNA on the level of its expression in E. coli were investigated. Mutation in cDNA of hGH was performed through site-directed mutagenesis using PCR. Then, the mutant genes were amplified and cloned into the expression vector, pET-28a. The new constructs were transformed into the BL21(DE3) strain of E. coli and chemically induced for hGH expression. At the final stage, expressed proteins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), scanning gel densitometry, and western blot. SDS-PAGE scanning gel densitometry assay and western blot analysis revealed higher expression level of hGH by using the two new expressions constructs (mutant genes vectors with decreasing GC content and optimized-codon usage at N-terminal of cDNA) in comparison with wild gene expression vector. Obtained results demonstrated that decreasing the GC nucleotide content and optimization of codon usage at N-terminal of the hGH cDNA could significantly enhance the expression of the target protein in E. coli. Our results highlight the important role of both 5´ region of the heterologous genes in terms of codon usage and also GC content on non-host protein expression in E. coli.
    Keywords: GC content, Codon usage, Escherichia coli, Recombinant human growth hormone, pET-28a