فهرست مطالب

Iranian Journal of Pharmaceutical Research
Volume:12 Issue: 3, Summer 2013

  • تاریخ انتشار: 1392/06/25
  • تعداد عناوین: 39
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  • Ahmad Salami, Enayatollah Seydi, Jalal Pourahmad Pages 219-220
    Nutraceuticals, mostly phytochemicals derived from dietary or medicinal plants such as soya bean, garlic, ginger, tea as well as propolis, honey and others, may have chemopreventive activities, as already suggested by epidemiologic and animal model studies. Their ability to reduce cancer incidence in these studies is likely related to apoptosis.
    Keywords: Nutraceuticals
  • Lingbin Meng, Zhongqiu Teng, Nannan Zheng, Weiwei Meng, Rongji Dai, Yulin Deng Pages 221-230
    The aim of this study was to develop a derivative of chitosan as pharmaceutical excipient used in sustained-release matrix tablets of poorly soluble drugs. A water-soluble quaternary ammonium carboxymethylchitosan was synthesized by a two-step reaction with carboxymethylchitosan (CMCTS), decylalkyl dimethyl ammonium and epichlorohydrin. The elemental analysis showed that the target product with 10.27% of the maximum grafting degree was obtained. To assess the preliminary safety of this biopolymer, cell toxicity assay was employed. In order to further investigate quaternary ammonium carboxymethylchitosan application as pharmaceutical excipient, aspirin was chosen as model drug. The effect of quaternary ammonium CMCTS on aspirin release rate from sustained-release matrix tablets was examined by in-vitro dissolution experiments. The results showed that this biopolymer had a great potential in increasing the dissolution of poorly soluble drug. With the addition of CMCTS-CEDA, the final cumulative release rate of drug rose up to 90%. After 12 h, at the grade of 10, 20 and 50 cps, the drug release rate increased from 58.1 to 90.7%, from 64.1 to 93.9%, from 69.3 to 96.1%, respectively. At the same time, aspirin release rate from sustained-release model was found to be related to the amount of quaternary ammonium CMCTS employed. With the increase of CMCTS-CEDA content, the accumulated release rate increased from 69.1% to 86.7%. The mechanism of aspirin release from sustained-release matrix tablets was also preliminary studied to be Fick diffusion. These data demonstrated that the chitosan derivative has positive effect on drug release from sustained-release matrix tablets.
    Keywords: Chitosan derivatives, Drug release rate, Aspirin, Sustained, release matrix tablet
  • Abdolhossein Moghbel, Hamideh Abbaspour Pages 231-237
    The aim of the present study was to prepare an oral tablet from liquid yogurt by reforming the physical properties for easy transportation, long-term storage and also as a complementary dairy product in case of nutrient deficiency. The liquid fresh yogurt was lyophilized at -40°C and 0.03 mTor pressure. The dry powder was homogenized by a 12 mesh size sieve. Some tests such as Carr’s compressibility index, Hausner ratio and the angle of repose were applied to evaluate the flowability of yogurt powder. Study of the deformation of particles during forcing was done by calculation of the elastic recovery index. Carr’s compressibility index percent and Hausner ratio were calculated 15 and 0.94, respectively. The range of repose angle was measured between19-20°. The elastic recovery was obtained up to 60%. Since the hardness of tablets increased by decreasing compression velocity, therefore yogurt powder might have a plastic deformation. The reduction of powder volume due to compression force was about 20% (p < 0.05). Tablets with low fat yogurt showed very good compressibility with 6-12 Strong-Cab (SC) hardness units. Producing a complementary formulated as a tablet from yogurt powder is possible and also maybe therapeutically effective against lactose-intolerance syndrome and preventing antibiotic-associated diarrhea.We suggest that for more authentic confirmation of the type of deformation, it should go through Heckel’s equation analysis, too.
    Keywords: Yogurt, Compressibility, Plastic deformation, Tablet processing, Dietary supplements, Lyophilization
  • Seyed Mahdi Hejazi, Mohammad Erfan, Seyed Alireza Mortazavi Pages 239-246
    In this work attempts were made to evaluate K+-SDS and hydrocolloid polymer-SDS interactions in flocculation of megestrol acetate dispersions to enhancetheir stability as a part of suspension formulation. Different dispersions of micronized megestrol acetate and SDS were prepared. KCl and KH2PO4 and their corresponding sodium salts were added to the dispersions and the preparations were evaluated using general physicochemical and stability tests including appearance, sedimentation volume, sedimentation rate and redispersibility. Addition of polyols and hydrocolloid polymers to the SDS containing dispersions was also investigated for possible instabilities.SDS deflocculated the initial megestrol acetate dispersions. The use of potassium salts unlike the sodium salts flocculated the dispersion particles due to precipitation reaction of potassium ions and the adsorbed SDS. Additionally the uncharged hydrocolloid polymers MC and HPMC in contrast to the ionic polymers xanthan gum and NaCMC showed incompatibility due to their interaction with SDS. K+- SDS interactions have proved useful in protein and DNA analysis studies and we found this precipitation reaction to be applicable in flocculation of pharmaceutical suspensions containing SDS.
    Keywords: KCL, SDS Precipitation Reaction, Flocculation, HPMC, SDS Interaction, Megestrol Acetate, Suspensions
  • Maryam Kazemipour, Iman Fakhari, Mehdi Ansari Pages 247-253
    Gabapentin is an anticonvulsant widely used in the treatment of epilepsy. No peculiar chromophore is available on the gabapentin moiety for direct analysis by absorption spectrophotometry. A sensitive spectrophotometric method for the determination of gabapentin in bulk, pharmaceutical formulations and human plasma has been developed. In this method, gabapentin directly derivatized with vanillin and analyzed without any extraction in bulk and pharmaceutical dosage form and in plasma samples, it was extracted with a reversed-phase solid-phase extraction (SPE) cartridge followed by derivatization with vanillin. Analysis was performed by a spectrophotometer system. The quantitation limit of gabapentin in human plasma was 0.8 mg/L. The method was linear over the concentration range of 10.0–90.0 mg/L and 0.8–10.0 mg/L for pharmaceutical dosage form and plasma, respectively. The method was precise (relative standard deviation, RSD <1.20%) and accurate (relative mean error <5.5%) for both pharmaceutical dosage form and plasma samples. Mean absolute recoveries were 94.5% for plasma.
    Keywords: Gabapentin, Spectrophotometry, Derivatization, SPE, Plasma, Vanillin
  • Marzieh Amirmostofian, Jalal Pourahmad Jaktaji, Zohreh Soleimani, Kimia Tabib, Farahnaz Tanbakosazan, Mirdavood Omrani, Farzad Kobarfard Pages 255-265
    Dacarbazine is an antitumor prodrug which is used for the treatment of malignant metastatic melanoma and Hodgkin’s disease. It requires initial activation in liver through an N-demethylationreaction. The active metabolite prevents the progress of disease via alkylation of guanine bases in DNA strands. In order to investigate the importance of imidazole ring and its dynamictautomerization in anticancer activity of dacarbazine, a pyridine analog of this drug was synthesized and the cytotoxic activity and cellular-molecular mechanisms of action for this compound were compared with those of dacarbazine. EC50 values for dacarbazine and the pyridine analog were found to be 56 M and 33 µM respectively. Both dacarbazine and the pyridine analog resulted in formation of reactive oxygen species (ROS) upon their addition to the isolated rat hepatocytes. They also decreased the mitochondrial membrane potential and causedlysosomal membrane rupture. Cytotoxicity was prevented by ROS scavengers and antioxidants. Cytotoxicity wasalso prevented by CYP450 inhibitors, lysosomalinactivators and MPT (Mitochondrial Permeability Transition Pore) blockers.
    Keywords: Dacarbazine, Pyridine, Cytotoxicity, Oxidative stress, Lysosome, Mitochondrial Membrane potential
  • Alireza Aliabadi, Sajad Andisheh, Zahra Tayarani-Najaran, Mona Tayarani-Najaran Pages 267-271
    Cancer is a major global problem and is the second leading cause of mortality in the developed countries.Resistance to current chemotherapeutics and high incidence of adverse effects are the two principal reasons for developing new anticancer agents. Phenylacetamide derivatives can act as potential anticancer agents. Synthesis and screening of 2-(4-Fluorophenyl)-N-phenylacetamide derivatives in present study showed that these compounds act as potent anticancer agents especially against PC3(prostate carcinoma) cell line. Compounds 2a-2c with nitro moiety demonstrated a higher cytotoxic effect than compounds 2d-2f with methoxy moiety. All compounds in this series exhibited lower activity than imatinib as reference drug. Compounds 2b (IC50 = 52 µM) and 2c (IC50 = 80 µM) were the most active compounds against PC3 cell line in comparison with imatinib(IC50 = 40 µM). Compound 2c (IC50 = 100 µM) with p-nitro substituent was the most active compound compared to imatinib(IC50 = 98 µM) in MCF-7 cell line.
    Keywords: Synthesis, Phenylacetamide derivatives, Anticancer, Cytotoxicity, MTS assay
  • Masoud Sadeghzadeh, Ghorbanali Charkhlooie, Fariba Johari Daha Pages 273-280
    Two deoxyglucose (DG) derivatives, (α,β)-2-deoxy-2-amino(ethylcarbamate)-D-glucose (ECB-DG) and (α,β)-2-deoxy-2-amino(1,2-dihydroxypropyl)-D-glucose (DHP-DG), were synthesized and radiolabeled successfully with [99mTc(H2O)3(CO)3]+ complex. [99mTc]-ECB-DG and [99mTc]-DHP-DG complexes were prepared (96% and 93% radiochemical purities respectively) by using 46 mCi of Na99mTcO4 in 1 mL saline. Radio-HPLC analysis of [99mTc]-ECB-DG at pH = 7.4, revealed that labeling with 99mTc leads to formation of one radiochemical species with tR = 381 second. Three radiochemical species, Na99mTcO4, [99mTc]-DHP-DG and [99mTc(H2O)3(CO)3]+ complexes with tR = 342 sec, tR = 567 sec and tR = 1586 sec respectively, were obtained when [99mTc]-DHP-DG complex evaluated by HPLC. Biodistribution of two complexes were studied on normal mice at 10, 30 and 60 min post-injections. Compared to the 18F-FDG, [99mTc]-ECB-DG displayed a 2.8-fold reduction in brain uptake (1.7 ± 0.2 versus 0.61% ± 0.09), whereas [99mTc]-DHP-DG just showed 1.9-fold reduction in heart uptake (2.2 ± 0.05towards 1.16±0.10) at 1 h post-injection.On the basis of our results, it seems that ECB-DG and DHP-DG analogues could be used as brain and heart imaging agent respectively.
    Keywords: 99mTc, Radiopharmaceuticals, Glucosamine derivatives, 99mTc, tricarbonyl complex, Molecular imaging
  • Ali Asadipour, Najmeh Edraki, Maryam Nakhjiri, Azadeh Yahya-Meymandi, Eskandar Alipour, Parastoo Saniee, Farideh Siavoshi, Abbas Shafiee, Alireza Foroumadi Pages 281-287
    Nitro-containing heteroaromatic derivatives structurally related to nitroimidazole (Metronidazole) are being extensively evaluated against Helicobacter pylori isolates. On the other hand, 1,3,4-thiadiazole derivatives have also demonstrated promising antibacterial potential. In present study, we evaluated anti-H. pylori activity of novel hybrid molecules bearing nitroaryl and 1,3,4-thiadiazole moieties. Anti-H. pylori activity of novel 5-(5-nitroaryl)-1,3,4-thiadiazole derivatives bearing different bulky alkylthio side chains at C-2 position of thiadiazole ring, were assessed against three different metronidazole resistant H. pylori isolates by paper disk diffusion method. Most of the compounds demonstrated moderate to strong inhibitory response especially at 25 μg/disk. The structure-activity relationship study of the compounds demonstrated that introduction of different alkylthio moieties at C-2 position of thiadiazole ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring. The promising compound of this scaffold, bearing 1-methyl-5-nitroimidazole moiety at C-5 and α-methylbenzylthio side chain at C-2 position of thiadiazole ring, showed strong inhibitory response against metronidazole resistant H. pylori isolates at 12.5 μg/disk (the inhibition zone diameter at all evaluated concentrations (12.5-100 μg/disk) is > 50 mm). Novel 5-(5-nitroaryl)-1,3,4-thiadiazole scaffold bearing different C-2 attached thio-pendant moieties with promising anti-H. pylori potential were identified. Among different nitroheterocycles, 5-nitrofuran and 5-nitroimidazole moieties were preferable for the substitution at C-5 position of 1,3,4-thiadiazole ring. Introduction of different alkylthio side chains at C-2 position of central ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring.
    Keywords: 1, 3, 4, thiadiazole, anti, Helicobacter pylori activity, Nitroheterocycle
  • Hassan Korbekandi, Zeynab Ashari, Siavash Iravani, Sajjad Abbasi Pages 289-298
    Silver nanoparticles are increasingly used in various fields of biotechnology and applications in the medicine. Objectives of this study were optimization of production of silver nanoparticles using biotransformations by Fusarium oxysporum, and a further study on the location of nanoparticles synthesis in this microorganism. The reaction mixture contained the following ingredients (final concentrations): AgNO3 (1-10 mM) as the biotransformation substrate, biomass as the biocatalyst, glucose (560 mM) as the electron donor, and phosphate buffer (pH= 7, 100 mM). The samples were taken from the reaction mixtures at different times, and the absorbance (430 nm) of the colloidal suspensions of silver nanoparticles hydrosols was read freshly (without freezing) and immediately after dilution (1:40). SEM and TEM analyses were performed on selected samples. The presence of AgNO3 (0.1 mM) in the culture as enzyme inducer, and glucose (560 mM) as electron donor had positive effects on nanoparticle production. In SEM micrographs, silver nanoparticles were almost spherical, single (25-50 nm) or in aggregates (100 nm), attached to the surface of biomass. The reaction mixture was successfully optimized to increase the yield of silver nanoparticles production. More details of the location of nanoparticles production by this fungus were revealed, which support the hypothesis that silver nanoparticles are synthesized intracellularly and not extracellularly.
    Keywords: Silver nanoparticles, Fusarium oxysporum, Optimization, Biosynthesis, Intracellular synthesis GABAA receptor
  • Mohammad Rahmati Roudsari, Sara Sohrabvandi, Aziz Homayouni Rad, Amir Mohammad Mortazavian Pages 299-305
    The combined effects of inoculation level (4 or 8-fold compared to standard inoculation) and sequence (standard inoculation before fermentation and 3-fold inoculation at the end of fermentation=1+3, Two-fold inoculation before fermentation and the same at the end of fermentation=2+2, 2+6, 4-fold before fermentation=4, 4+4, and 8) of culture inoculum containing probiotics on biochemical and microbiological characteristics of probiotic Doogh during fermentation and over 21 days of refrigerated storage (4˚C) were investigated. The probiotic microorganisms were L. acidophilus LA-5 and Bifidobacterium lactis BB-12. Overall, the treatments 8, 4 and 4+4 resulted in the highest viability at the end of fermentation as well as at early days of refrigerated storage. During the second half of cold storage period, the greatest viability of probiotics was related to the treatment 2+6. The treatment ‘8’ showed the shortest incubation time as well as the highest pH drop rate and acidity increase rate during fermentation and over the storage period.
    Keywords: Doogh, Inoculation, Probiotic, Viability
  • Xian Yang, Xue Zhang, Shui-Ping Yang, Wei-Qi Liu Pages 307-316
    In the present study, the antimicrobial tests of patchouli oil were studied by using molecular docking technology and antimicrobial test in vitro. Five biological macromolecule enzymes, required by the bacteria in the process of biosynthesis were selected as target molecules. Five antibiotics benzylpenicillin, sulfadiazine, trimethoprim, rifampicin and ciprofloxacin, which are generally acknowledged as antibacterial drugs, were selected as reference compounds. The 3 three-dimensional (3D) structures of the 5 reference compounds and 26 compounds from patchouli oil were established by using surflex-dock software (8.1). And the 3D structures of five biological macromolecule enzymes derived from Protein Data Bank (PDB). Molecular docking was carried out between the 31 chemical compounds (ligands) and the 5 enzymes (receptors) by using surflex-dock function. Furthermore, the antibacterial effects of 31 chemical compounds were investigated by the scoring function after molecular docking was completed. By comparing the scoring result of 26 compounds in patchouli oil with 5 compared components, we inferred antibacterial activity in about 26 compounds in patchouli oil. On the other hand, six frequently-used pathogenic bacteria were selected for antimicrobial test in vitro, patchouli oil and its two major compounds: (-)-patchouli alcohol and pogostone, which their contents exceeded 60% in patchouli oil samples, were selected antibacterial agents. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were also determined. Molecular docking technology and antimicrobial test in vitro proved that patchouli oil had strong antimicrobial effects. Particularly, pogostone and (-)-patchouli alcohol have potent antimicrobial activity.
    Keywords: Patchouli oil, Molecular docking, Scoring function, Antibiotic experiment in vitro, MIC, MBC
  • Muthuswamy Umamaheswari, Arumugam Madeswaran, Kuppusamy Asokkumar, Thirumalaisamy Sivashanmugam, Varadharajan Subhadradevi, Puliyath Jagannath Pages 317-323
    Allopurinol, the xanthine oxidase inhibitor, is the only drug available for the treatment of gout. We examined the xanthine oxidase inhibitory activity of some commercially available flavonoids such asepigallocatechin, acacatechin, myricetin, naringenin, daidzein and glycitein by virtual screening and in-vitro studies. The interacting residues within the complex model and their contact types were identified. The virtual screening analysis were carried out using AutoDock 4.2 and in-vitro xanthine oxidase inhibitory activity was carried out using xanthine as the substrate. In addition, enzyme kinetics was performed using LineweaverBurkplot analysis. Allopurinol, a known xanthine oxidase inhibitor was used as the standard. The docking energy ofglycitein was found to be -8.49 kcal/mol which was less than that of the standard (-4.47 kcal/mol). All the selected flavonoids were found to exhibit lower binding energy (-8.08 to -6.03 kcal/mol) than allopurinol. The docking results confirm that flavonoids showed greater inhibition of xanthine oxidase due to their active binding sites and lesser binding energies compared to allopurinol. This may be attributed to the presence of benzopyran ring in the flavonoids. In the xanthine oxidase assay, IC50 value of glycitein was found to be 12±0.86 µg/mL, whereas that of allopurinol was 24±0.28 µg/mL. All the remaining compounds exhibited IC50 values ranging between 22±0.64 to 62±1.18 µg/mL. In the enzyme kinetic studies, flavonoids showed competitive type of enzyme inhibition. It can be concluded that flavonoids could be a promising remedy for the treatment of gout and related inflammatory disorders. Further in-vivo studies are required to develop potential compounds with lesser side effects.
    Keywords: Xanthine oxidase, Flavonoids, Binding energy, Enzyme kinetics, Gout
  • Fatemeh Masjedi, Ali Gol, Shahriar Dabiri Pages 325-338
    Antidiabetic action of garlic is established in animal studies. Since all of the pervious studies have focused on the therapeutic role of garlic, this study investigated the preventive effect of garlic juice on biochemical factors and histological features in Streptozotocin (STZ)-induced diabetic rats. Forty male rats were divided into five groups (n = 8): 1-Normal group (N), 2-Normal+Garlic group (N+G) received garlic juice (1 mL/100g BW) for 6 weeks, 3-Diabetic group (D) was injected with STZ (60 mg/kg, IP), 4-Diabetic+Garlicbefore group (D+Gb) received garlic juice for 3 weeks before STZ injection and continued for another 3 weeks, 5-Diabetic+Garlic-after group (D+Ga), three days after STZ injection, they received garlic juice for 3 weeks. Serum biochemical factors were measured by the enzymatic methods and H&E stained sections of pancreas and liver were prepared for light microscopy. In diabetic rats, elevated levels of glucose, cholesterol and triglycerides, the increment of the activities of ALT and AST, increased food and water consumption were observed. The abnormal increases were significantly (p < 0.05) decreased in D+Gb groups compared to D group. In D group, scattered degeneration of the hepatocytes with lymphocytic infiltration in the portal areas, decrease of pancreatic islets numbers and diameter, atrophy of pancreatic islets were observed. These abnormal histological signs were dramatically ameliorated in D+Gb group compared to D group. In D+Ga group compared to D+Gb group slighter effects of garlic juice on histopathological and biochemical changes were seen. These results indicate that garlic juice may help in the prevention of the complications of diabetes.
    Keywords: Diabetes, Garlic, Hepatic enzymes, Histopathology, Serum lipids
  • Amir Reza Jassbi, Maryam Mohabati, Saba Eslami, Jelveh Sohrabipour, Ramin Miri Pages 339-348
    Different solvent extracts of a red algae, Hypnea flagelliformis,and two brown algae, Cystoseira myrica and Sargassum boveanum, collected from the Persian Gulf coast were subjected to different bioassays including: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay, antibacterial and antifungal activity by thin layer chromatography (TLC)-bioautography, agar disc diffusion (ADD) and nutrient-broth micro-dilution (NBMD) bioassays. The water extracts were found to have the most antioxidant activity.The antibacterial minimum inhibitory concentrations (MIC) of the active extracts were determined for the susceptible organisms, Staphylococcus aurous and Bacillus subtilis, using NBMD bioassays.The active substances were identified as free fatty acids (FFA) using gas chromatography-mass spectrometry (GC-MS) and after derivatization to their methyl esters, their concentrations were measured using GC- flame ionization detection (GC-FID). In addition to the fatty acids, fucosterol, cholesterol and 22-dehydroxychlosterol were detected as the major sterols in S. boveanum extract using GC-MS analyses.
    Keywords: Hypnea flagelliformis, Cystoseira myrica, Sargassum boveanum, Antimicrobial activity, Antioxidants activity
  • Rym Mansour, Najoua Haouas, Amel Ben Kahla-Nakbi, Saoussen Hammami, Zine Mighri, Farouk Mhenni, Hamouda Babba Pages 349-355
    Vitis vinifera L.is a traditional Asian herb widely used for different health problems. In thepresent research, the ethanolic and the aqueous extracts of Vitis vinifera L. leaves collected fromshrub, grown in Tunisia, were prepared and evaluated for the antileishmanial activity againstLeishmani ainfantum promastigotes. The inhibitory concentration 50 (IC50) was determined andthe results showed that the etahnolic extract is more active than the aqueous one (IC50= 0.108mg/mL). Microscopic observations showed that the ethanolic extract promoted the destructionof cytoplasmic and nuclear membranes of Leishmani ainfantum promastigotes and altered theoverall shape of the cell. In order to explain the difference of antileishmanial activity betweenethanolic and aqueous extracts, anthocyanins amount was determined by spectrophotometry. Itwas found that the ethanolic extract is richer in anthocyanins than the aqueous one which canexplain the higher antileishmanial activity of the ethanolic extract.
    Keywords: Vitis vinifera L, Extraction, Leishmaniasis, Antileishmanial activity, Anthocyanins
  • Navid Abbasi Maleki, Saeid Abbasi Maleki, Reza Bekhradi Pages 357-361
    This research was done to test the effect of Rosa damascena essential oil on withdrawal signsof naloxone-precipitated morphine in male mice. Morphine dependence was induced by injection(IP) three times daily at doses of 50, 50 and 75 mg/kg, respectively, for 3 days. On day 4,after the last administration of morphine, Rosa damascena essential oil was administered atdifferent concentrations (5, 2 and 40%, IP) 30 min before administration of naloxone (5 mg/kg,IP). The following actions were taken as signs of withdrawal and records taken for jumping asa number and scores of 0 to 3 were given for incidences of grooming, teeth chattering, rearing,writing, diarrhea, wet dog shakes and climbing during a 30 min period. Results showed thatdifferent concentrations of Rosa damascena essential oil significantly reduced signs of morphinewithdrawal compared to the control group in terms of number of jumps (p < 0.05 and p < 0.01),grooming, teeth chattering, rearing, climbing, wet dog shakes and writhing, but not for diarrhea(p < 0.05). In conclusion it seems that GABAergic activity induced by flavonoids from Rosadamascena essential oil can alleviate signs of morphine withdrawal, but further studies need to bedone to better understand this mechanism.
    Keywords: Rosa damascena, Essential oil, Morphine withdrawal, GABAergic system, Mice
  • Maryam Zarringhalam, Jalal Zarringhalam, Mahdi Shadnoush, Shamsali Rezazadeh, Elaheh Tekieh Pages 363-369
    In this study, extracts and essential oils of Black and Red pepper and Thyme were tested for antibacterial activity against Escherichia coli O157:H7 andStaphylococcus aureus. Black and Red pepper and Thyme were provided from Iranian agricultural researches center. 2 g of each plant powder was added to 10 cc ethanol 96°. After 24 h, the crude extract was separated as an alcoholic extract and concentrated by distillation method. Plants were examined for determining their major component and essential oils were separated. Phytochemical analyses were done for detection of some effective substances in extracts. The antibacterial activity againstEscherichia coli O157:H7 andStaphylococcus aureus was tested and the results showed that all extracts and essential oils were effective and essential oils were more active. The extracts and oils that showed antimicrobial activity were later tested to determine the Minimum Inhibitory Dilution (MID) for those bacteria. They were also effective on the inhibition of DNase activity. This study was indicated that extracts and essential oils of Black and Red pepper and Thyme can play a significant role in inhibition of Escherichia coli O157:H7 and Staphylococcus aureus.
    Keywords: Escherichia coli O157: H7, Staphylococcus aureus, DNase activity, Black pepper, Red pepper, Thyme
  • Omid Gholami, Mahmood Jeddi-Tehrani, Mehrdad Iranshahi, Amir Hassan Zarnani, Seyed Ali Ziai Pages 371-376
    Umbelliprenin is a prenylated compound, which belongs to the class of sesquiterpene coumarins. It is extracted from dried roots of Ferula szwitsiana collected from the mountains of Golestan forest (Golestan Province, north of Iran). Induction of apoptosis in Jurkat T-CLL cells has been previously shown. In this study, effect of umbelliprenin on proapoptotic caspases (caspase-8 and -9) and antiapoptotic Bcl-2 family protein was studied. Jurkat cells were incubated with umbelliprenin. Cells were then lysed and activation of proteins was studied by Western blot analysis. In this study, we showed that umbelliprenin activates intrinsic and extrinsic pathways of apoptosis by the activation of caspase-8 and -9 respectively. Inhibition of Bcl-2 was also shown. In conclusion, umbelliprenin induced apoptosis in Jurkat cells through caspase-dependent apoptosis pathway.
    Keywords: Umbellprenin, CLL, Apoptosis, Caspase, Western blot
  • Mehrdad Roghani, Mohammad Reza Jalali Nadoushan, Tourandokht Baluchnejadmojarad, Mohammad Reza Vaez Mahdavi, Gholamali Naderi, Farshad Roghani Dehkordi, Mohammad Taghi Joghataei Pages 377-385
    Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients. In this study, the effect of chronic administration of sesame (Sesamum indicum L) seed feeding was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received sesame seed-mixed food at weight ratios of 3% and 6% for 7 weeks, one week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to PE was significantly lower in sesame-treated diabetic rats (at a ratio of 6%) relative to untreated diabetics and endothelium removal abolished this difference. Endothelium-dependent relaxation to ACh was also significantly higher in sesame-treated diabetic rats (at a ratio of 6%) as compared to diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME) significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity and sesame treatment significantly reversed the increased MDA content and restored activity of SOD. We thus conclude that chronic treatment of diabetic rats with sesame seed could in a dose- manner prevent some abnormal changes in vascular reactivity through nitric oxide and via attenuation of oxidative stress in aortic tissue and endothelium integrity is necessary for this beneficial effect.
    Keywords: Sesamum indicum L, Sesame seed, Diabetes mellitus, Streptozotocin, Aorta
  • Leila Moradabadi, Shideh Montasser Kouhsari, Mohammad Fehresti Sani Pages 385-397
    Garlic (Allium sativum L., Alliaceae), Persian shallot (Allium ascalonicum L., Alliaceae) and Sage (Salvia officinalis L., Lamiaceae) are believed to have hypoglycemic properties and have been used traditionally as antidiabetic herbal medicines in Iran. In this study, diabetes was induced by subcutaneous injection of alloxan monohydrate (100 mg kg−1) to male Wistar rats. Antidiabetic effects of methanolic extracts of the above mentioned three plants on alloxan-diabetic rats was investigated in comparison with the effects of antidiabetic drugs such as acarbose, glibenclamide and metformin by measuring postprandial blood glucose (PBG), oral glucose tolerance test (OGTT), inhibition of rat intestinal α-glucosidase enzymes activities and pancreatic Insulin and cardiac Glut-4 mRNAs expression. In short term period, hypoglycemic effects of A. sativum and A. ascalonicum showed significant reduction of PBG similar to glibenclamide (5 mg kg−1 bw) while S. officinalis significantly reduced PBG similar to acarbose (20 mg kg−1 bw). After 3 weeks of treatment by methanolic plant extracts, significant chronic decrease in the PBG was observed similar to metformin (100 mg kg−1 bw). For OGTT, S. officinalis reduced PBG in a similar way as acarbose (20 mg kg−1 bw). Intestinal sucrase and maltase activities were inhibited significantly by A. sativum, A. ascalonicum and S. officinalis. In addition, we observed increased expression of Insulin and Glut-4 genes in diabetic rats treated with these plants extracts. Up regulation of Insulin and Glut-4 genes expression and inhibition of α-glucosidaseactivities are the two mechanisms that play a considerable role in hypoglycemic action of garlic, shallot and sage.
    Keywords: Diabetes, Glut, 4, Insulin, OGTT, PBG
  • Zhen-Qiu Zhang, Wei Liu, Li Zhuang, Jing Wang, Shuai Zhang Pages 399-409
    The aim of this study was to investigate the pharmacokinetic profiles of baicalin, wogonoside, baicalein and wogonin after oral administration of pure baicalin, Radix scutellariae and Scutellariae-Paeoniae couple extracts were administered and the pharmacokinetics profiles were compared between normal and ulcerative colitis rats. The plasma concentrations of the four flavonoids were determined by using a simple and rapid high-performance liquid chromatography method. All the rats were divided randomly into two groups (ulcerative colitis and normal groups). Each group contained three subgroups: pure baicalin, Radix scutellariae and Scutellariae-Paeoniae couple extracts subgroup. Each group received oral administration of pure baicalin, Radix Scutellariae and Scutellariae-Paeoniae couple extracts at the same dose of 200 mg/kg baicalin. The results showed that wogonoside, possibily as a methylated product of baicalin, was found in plasma after oral administration of pure baicalin or formulas to rats. Baicalin and wogonoside demonstrated bimodal phenomenon. Baicalin and wogonoside in Scutellariae-Paeoniae couple extract had shown better absorption than which in pure baicalin and Radix Scutellariae extract. Whether oral administration of pure baicalin, Radix Scutellariae or Scutellariae-Paeoniae couple extracts, ulcerative colitis rats showed better absorption than normal rats. For example AUC(0–t) of baicalin were: (41.46 ± 0.62), (59.12 ± 6.42) and (104.87 ± 0.86) (μg/mL)·h in UC groups vs (17.77 ± 0.66), (28.04 ± 4.06) and (49.01 ± 4.61) (μg/mL)·h in normal groups, respectively. The pharmacokinetics properties of the four flavonoids differed between ulcerative colitis and normal rats, including AUC(0–t) and Cmax (p < 0.05).
    Keywords: Baicalin, Wogonoside, Baicalein, Wogonin, Pharmacokinetic
  • Morahem Ashengroph, Iraj Nahvi, Jahanshir Amini Pages 411-421
    For all industrial processes, modelling, optimisation and control are the keys to enhance productivity and ensure product quality. In the current study, the optimization of process parameters for improving the conversion of isoeugenol to vanillin by Psychrobacter sp. CSW4 was investigated by means of Taguchi approach and Box-Behnken statistical design under resting cell conditions. Taguchi design was employed for screening the significant variables in the bioconversion medium. Sequentially, Box-Behnken design experiments under Response Surface Methodology (RSM) was used for further optimization. Four factors (isoeugenol, NaCl, biomass and tween 80 initial concentrations), which have significant effects on vanillin yield, were selected from ten variables by Taguchi experimental design. With the regression coefficient analysis in the Box-Behnken design, a relationship between vanillin production and four significant variables was obtained, and the optimum levels of the four variables were as follows: initial isoeugenol concentration 6.5 g/L, initial tween 80 concentration 0.89 g/L, initial NaCl concentration 113.2 g/L and initial biomass concentration 6.27 g/L. Under these optimized conditions, the maximum predicted concentration of vanillin was 2.25 g/L. These optimized values of the factors were validated in a triplicate shaking flask study and an average of 2.19 g/L for vanillin, which corresponded to a molar yield 36.3%, after a 24 h bioconversion was obtained. The present work is the first one reporting the application of Taguchi design and Response surface methodology for optimizing bioconversion of isoeugenol into vanillin under resting cell conditions.
    Keywords: Bioconversion process parameters, Vanillin production, Psychrobacter sp. CSW4, Optimization, Taguchi design, Response surface methodology
  • Nima Razzaghi-Asl, Ahmad Ebadi, Najmeh Edraki, Sara Shahabipour, Ramin Miri Pages 423-436
    One of the most important targets in Alzheimer disease is Beta site amyloid precursor protein cleaving enzyme-1 (BACE-1). It is a membrane associated protein and is one of the main enzymes responsible for amyloid β (Aβ) production. Up to now, a considerable number of peptidic and non-peptidic inhibitors of BACE-1 have been developed. Recently, small molecule BACE-1 inhibitors have attracted the attention of scientists, because peptidic inhibitors have many pharmacokinetic problems. In the present study, several small molecule BACE-1 inhibitors were extracted from Brookhaven Protein Databank (PDB) and subjected to dissection analysis to achieve constructing fragments. Atom type, hybridization, and bond order were considered for generated constitutional fragments (simplified structures). AutoDock version 4.2 was applied to dock various chemical fragments into BACE-1 active site. The benefits of such studies have been well revealed in previous reports. On the basis of obtained binding affinities, fragment-based ligand efficiency (LE) indices were estimated. These theoretical binding efficiencies were applied to further elucidate the key structural features of BACE-1 inhibitors. Typical results of the study were elucidated and we suggested the ways these findings might be beneficial to guide rational bioactive molecular developments. Our study confirmed that the evaluation of ligand-receptor interactions in terms of ligand efficiency indices (binding energy per atom and pKi per MW) could be a helpful strategy in structure-based drug discovery (SBDD) strategies.
    Keywords: Alzheimer, BACE, 1, Docking, Ligand efficiency
  • Mansour Rismanchian, Niloufar Khodaeian, Lida Bahramian, Mohammad Hosein Fathi, Hojjat Sadeghi-Aliabadi Pages 437-443
    The cytotoxicity of the biomaterials is a key issue that should be addressed prior to pre-clinical applications. This study was designed to evaluate and compare the cytotoxixity of two forms of bioactive glasses:nanopowder:andmicropowder. Human HGF1-PI53 gingival fibroblast cells were used to evaluate the cytotoxicity of 0.5, 1, 1.5, 2, 5, 10, 15 and 20 mg/mL concentrations of the two bioactive glasses via MTT assay. The results were statistically analyzed using analysis of variance and Tukey''s test. A p-value less than 0.05 was considered statistically significant. Results showed that two bioactive glasses hadstatistically significant differences at 5, 10, 15 and 20 mg/mL concentrations (p-value < 0.05) and there was no correlation between time and cell cytotoxicity of bioactive glasses (p-value > 0.05), using t-test and Spearman’s correlation coefficient. We conclude that that cytotoxicity of nanopowder bioactive glass atconcentrations ≤ 2 mg/mL was similar to micropowder bioactive glass at 24 and 48 h, however, it is more cytotoxic atconcentrations ≥ 5 mg/mL in the first 48 h of applications.
    Keywords: Nanopowder, MTT assay, HGF1, P153 cell line
  • Tan Li, Hong Chen, Xin Mei, Na Wei, Bo Cao Pages 445-455
    Contact hypersensitivity (CHS) mouse model induced by 2, 4-dinitrofluorobenzene (DNFB) is thought to be a T helper 1 (Th1)-dominant response and used for investigating anti-inflammatory and immunosuppressive agents. However, it is hardly used for screening large-scale drugs because of the large number of animals and complex mechanisms involved in-vivo. In this study, we focused on whether T lymphocytes from CHS mouse model could maintain the state of immune response in-vitro and explored a suitable time for drugs screening. The results showed that CD4+ T cells of CHS mice were higher compared with those in normal group. The expression of T-bet and GATA3 showed a Th1 shift and the levels of interleukin (IL)-2 and IL-4 also showed similar trend. Furthermore, IL-6 produced by T lymphocytes from CHS mice had a high level too. Then, we detected the effects of dexamethasone (DEX), cyclosporine A (CsA) and mycophenolate mofetil (MMF) on T lymphocytes in-vitro, and the data displayed that these immunosuppressive drugs could all inhibit the proliferation of T lymphocytes significantly. These findings suggested that T lymphocytes from CHS mice could mimic a similar immune response in-vitro, and it’s also a suitable method for screening anti-inflammatory and immunosuppressive agents.
    Keywords: Immunoregulation, Delayed hypersensitivity, T lymphocytes, in, vitro
  • Somayeh Assadian Narenji, Nasser Naghdi, Shahrbanoo OryanÞ, Keyhan Azadmanesh Pages 457-469
    Hippocampus is essentially involved in learning and memory processes, and is known to be a target for androgen actions. The high density of the androgen receptors in hippocampus shows that there must be some relationship between androgens and memory. Androgen effects on spatial memory are complex and contradictory. Some evidence suggests a positive correlation between androgens and spatial memory. While some other reports indicated an impairment effect. The present study was conducted to assess the effect of 3α diol on spatial discrimination of rats. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and then received 3α diol (0.2, 1, 3 and 6 μg/ 0.5 μL/side), indomethacin (1.5, 3 and 6 μg/ 0.5 μL/side), indomethacin (3 μg/ 0.5 μL/side) + 3α diol (1μg/ 0.5 μL/side), 25-35 min before training in Morris Water Maze task. Our results showed that injection of 3α diol (1, 3 and 6 μg/ 0.5 μL/side) and indomethacin (3 and 6 μg/ 0.5 μL/side) significantly increased the escape latency and traveled distance to find hidden platform. It is concluded that intra CA1 administration of 3α diol and indomethacin could impair spatial learning and memory in acquisition stage. However, intra hippocampal injection of indomethacin plus 3α diol could not change spatial learning and memory impairment effect of indomethacin or 3α diol in Morris Water Maze task.
    Keywords: Androgens, Spatial memory, 3α diol, indomethacin, Morris water maze, GABAA receptor
  • Mojtaba Ziaee, Mohammad Ali Eghbal, Jafar Rahmani, Mohammad Ghaffarzadeh, Mohammad Bolourtchian, Arash Khorrami, Alireza Garjani Pages 471-481
    Silicon is the element very similar to carbon, and bioactive siliconized compounds have therefore received much attention. Siliconization of a compound enhances its biological activities. In the present study the hypolipidemic effect and toxicity of clofibrate and its siliconized analog, silafibrate, were compared. The experiments were performed in hypercholesterolemicWistar rats. Animals received high fat diet with 62.75% normal chow, 2% cholesterol, 0.25% cholic acid, 15% lard oil, 10% wheat flour and 10% sucrose.Silafibrate(40 mg/kg/day) produced a predominant reduction in the serum levels of total cholesterol (28.4%, p < 0.001), triglycerides (62%, p < 0.0001) and low-density lipoproteins (27%, p < 0.001) being more effective than the reference drug clofibrate (20%, 40%, 14.5%; p < 0.05). Similarly, it increased the total antioxidant levels in serum by 40% (p < 0.05). Simultaneously, treatment with silafibrate also reduced the malondialdehyde(MDA) concentration by 41% (p < 0.05). LD50 of silafibrate, given orally,was greater than 2000 mg/kg body weight inalbino mice while LD50 for clofibrate was calculated to be 1220 mg/kg. Thirty-day subacute toxicity was also evaluated with oral daily dose at 25, 50 and 100 mg/kg body weight in Wistarrats. No significant changes in body weight, food intake, behavior, mortality, hematology, blood biochemistry, vital organ weight were detected. The results of this study indicate that the effectiveness and safety of thehypolipidemic drug, clofibrate, were enhanced remarkably by replacing chlorine atom in its phenoxy ring with trimethylsilyl.
    Keywords: Clofibrate, Siliconizedanalog, Silafibrate, Hypolipidemicdrug, Toxicity
  • Fariborz Keyhanfar, Manzumeh Shamsi Meymandi, Gholamreza Sepehri, Ramin Rastegaryanzadeh, Gioia Heravi Pages 483-493
    The development of combination therapy is a coherent approach in severe pain treatment. The present study investigated the antinociceptive effect of pregabalin alone and in combination with tramadol in acute pain modeling. Therefore, three groups of male mice received either pregabalin (1 to 400 mg/Kg), tramadol (10 to 80 mg/Kg) or their combination intraperitoneally. Then latency time, maximum possible effect (%MPE) and area under curve (AUC) were calculated in tail flick test. The antinociceptive indexes were significantly increasedin10, 100 and 200 mg/kg ofpregabalin while tramadol showed dose-dependentantinociception (effective dose 50% was 54 to 79 mg/Kg). The antinociceptive effect of 100 mg/Kg of pregabalin (%MPE = 35±4%) was similar to that of 50 mg/Kg of tramadol. The combination of non-analgesic doses (10 mg/Kg) of tramadol and pregabalin did not increase %MPE and AUC, but the co-administration of 30 mg/Kg of tramadol with pregabalin (10 mg/Kg) increased all antinociceptive indexes significantly compared to the controls and with each drug alone. In conclusion, pregabalin showed a comparable antinociceptive effect to tramadol. The increase in analgesic effect was observed after the combination of low analgesic doses of tramadol with pregabalin, while the combination of non-analgesic doses of each drug reversed the interaction to antagonism. Therefore to increase the analgesic effect in pain management, more attention should be paid to respecting right proportion of drug combination. Further studies that specify the mechanism(s) and statement of interaction are needed to expand these findings to clinical applications.
    Keywords: Pregabalin, Tramadol, Combination, Antinociception, Tail flick
  • Soyar Sari, Mehrdad Hashemi, Reza Mahdian, Kazem Parivar, Mehdi Rezayat Pages 495-501
    Ischemia-reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. Ischemia-reperfusion brain injury initiates an inflammatory response involving the expression of adhesion molecules and cytokines. Twenty–four male Wistar rats (250-300 g body wt) were used in this study. The animals were divided into four groups of 6 rats each: I: Control group that was subjected to ischemia-reperfusion, II: Ischemia-reperfusion group that was subjected to all surgical procedures, III: Drug group that received pentoxifylline (200, 400 and 600 mg/kg) 60 min before and after ischemia and IV: Vehicle group that received saline. Seventy two h after ischemia-reperfusion, the hippocampus was taken for studying the changes in bcl-2 gene expression. We used quantitative real-time PCR for the detection of bcl-2 gene expression in ischemia and drug groups and then compared them to normal samples. The results showed the gene dosage ratio of 0.66 and 1.5 for ischemia group and the drug groups, respectively. The results also showed the bcl-2 gene expression declined in ischemia group as compared to the drug group. Furthermore, we observed a significant difference in the bcl-2 gene expression between ischemia and drug groups. These findings are consistent with anti-apoptotic properties of bcl-2 gene. Furthermore this method provides a powerful tool for the investigators to study brain ischemia and respond to the treatment drugs with anti-apoptotic agents.
    Keywords: Ischemia, reperfusion, Apoptosis, bcl, 2, Real, time PCR
  • Mohammad Sistanizad, Mehran Kouchek, Mohammad Miri, Reza Goharani, Mehrdaad Solooki, Ladan Ayazkhoo, Masoumeh Foroumand, Majid Mokhtari Pages 503-509
    Development of antibiotic resistance in Intensive Care Units (ICUs) is a worldwide problem. The purpose of this study was to evaluate the effect of an antibiotic stewardship program (ASP) by carbapenems restriction on gram-negative antimicrobial resistance in ICU. The study was designed in a 21 bedded general ICU of a teaching hospital with two wings (one and two) in Tehran, Iran. Carbapenem prescription in ICU1 was restricted to only the culture proven multi-drug-resistant bacteria with the absence of sensitivity to other antimicrobial agents. Carbapenem had to be prescribed by a trained ICU physician with close consultation with infectious disease specialist and the clinical pharmacist posted in ICU. Post-prescription reviews and de-escalations were carried out by the same team on regular basis. Restriction policy was commenced in January 2011 in ICU1. All documented infections and resistance patterns of isolated pathogens were recorded in both ICUs during two periods of 6 months before and 9 months after restriction policy implementation. During this study bacterial growth was detected in 51.5% of 1601 samples. Carbapenem administration was decreased from 6.86 to 2.75 DDD/100 patients day (60% decreases) pre-restriction and post-restriction respectively. Significant increase in sensitivity of pseudomonas to imipenem was observed in ICU1 comparing with pre-restriction period six months post restriction (p = 0.000). Sensitivity of Klebsiella and Acinetobacter to imipenem did not change significantly during the study period.
    Conclusion
    Our study demonstrated that restriction of carbapenems can increase sensitivity of P. aeroginosa to imipenem.
    Keywords: carbapenem, antibiotic resistance, intensive care, Pseudomonas spp
  • Mitra Korani, Seyed Mehdi Rezayat, Sepideh Arbabi Bidgoli Pages 511-519
    Silver nanoparticles (Ag NPs) have been widely used as new potent antimicrobial agents in cosmetic and hygienic products. Present study compares the tissue levels of Ag NPs in different organs of Guiana Pigs quantitatively after dermal application and analysis the morphological changes and pathological abnormalities on the basis of the Ag NPs tissue levels. Before toxicological assessments,the size of colloidal nanosilver was recorded by X-Ray Diffraction and Transmission Electron Microscope tests and the sizes of samples were recorded in sizes less than 100 nm. For toxicological evaluation, male guinea pigs were exposed to three concentrations of Ag NPs (100, 1000 and 10000 ppm) according to acute pretests for further assessments in subchronic model in a period of 13 weeks. A close correlation between dermal exposure and tissue levels of Ag NPs was found (p < 0.05) and tissue uptakes happened in dose dependent manner with the following ranking: kidney>muscle>bone>skin>liver>heart >spleen. In histopathological studies, severe proximal convoluted tubule degeneration and distal convoluted tubule were seen in the kidneys of the middle and high-dose animals. Separated lines and marrow space narrow were determined as two major signs of bone toxicities which observed in three different dose levels of Ag NPs. Increased dermal dose of Ag NPs caused cardiocyte deformity, congestion and inflammation. The three different Ag NPs concentration gave comparable results for several endpoints measured in heart, bone and kidney, but differed in tissue concentrations and the extent of histopathological changes. It seems that Ag ions could be detected in different organs after dermal exposure, which has the potential to provide target organ toxicities in a time and dose dependent manner.
    Keywords: Ag NPs, Nanosilver, Cardiotoxicity, Osteotoxicity, Nephrotoxicity, sub, chronic dermal toxicity, Silver nanoparticles
  • Zeinab Khazaei Koohpar, Mehrdad Hashemi, Reza Mahdian, Kazem Parivar Pages 521-527
    3, 4- Methylenedioxymethamphetamine (MDMA or «Ecstasy») is a psychoactive and hallucinogenic drug of abuse. MDMA has been shown to produce neurotoxicity both in animals and humans. Recently, the vasodilator drugs such as pentoxifylline is one of the new strategies which have been considered as neuroprotector. In this study effect of pentoxifylline on bcl-2 gene expression changes in hippocampus of rat following long- term use of ecstasy was investigated. 30 male Wistarrats weighing 250-300g were randomly divided into 5 groups: control (normal), sham (MDMA injection), experimental 1 (MDMA and then PTX injections), experimental 2 (PTX injection and after 1 week, MDMA injection) and vehicle (saline injection) groups. All drugs were injected intraperitoneally. Two weeks later, the hippocampi were removed for studying the changes in bcl-2 gene expression. We used quantitative real time PCR for detection of bcl-2 gene expression in treated groups and then compared them to control samples. The results showed the gene dosage ratio of 0. 49, 0. 78 and 1. 17 for sham, experimental 1 and experimental 2 groups, respectively. The results also showed the bcl-2 gene expression declined in sham group as compared to the experimentalgroups. Furthermore, we observed a significant difference in the bcl-2 gene expression between sham and experimental 2 groups. We conclude that quantitative real time PCR could be used as a direct method for the detection of bcl-2 gene expression in tested and normal samples.
    Keywords: Ecstasy, Hippocampus, Pentoxifylline, bcl2, Real, time PCR
  • Seyedeh-Atefeh Mirshafa, Mohammad Azadbakht, Nematollah Ahangar Pages 529-535
    Asperugo procumbents L. has been used in Iranian traditional medicine for the refreshing, tranquillizing and mood elevating activities. The present study was undertaken to evaluate the antidepressant and sedative-hypnotic potential of acute administration of the hydroalcoholic extract of this plant in mice.Additionally, the effects of flumazenil on the hypnotic activity of the extracts were evaluated. None of the doses of the extract could significantly reduce immobility time in comparison with control group in antidepressant tests. In hypnotic test, 250 and 400 mg/kg doses significantly increased pentobarbital-induced sleeping time compared to vehicle.All of the doses of the extract significantly reduced the latency to sleep in comparison to the vehicle. Flumazenil reversed the augmented effects of extracts in pentobarbital-induced hypnotic test.The results of the present study indicate the low antidepressant and good sedative-hypnotic effects of the hydroalcoholic extract of Asperugo procumbens aerial parts in mice. Central benzodiazepine receptors are involved in the sedative-hypnotic effects of this plant.
    Keywords: Depression, Asperugo procumbens L, Forced swimming test, Tail suspension test, Hypnotic test
  • Parvaneh Adimi, Seyed Jamal Hashemi, Mahmood Mahmoudi, Hossein Mirhendi, Mohammad Reza Shidfar, Masood Emmami, Ali Rezaei-Matehkolaei, Mohsen Gramishoar, Parivash Kordbacheh Pages 537-545
    Dermatophyte fungi are the etiologic agents of skin infections commonly referred to as ringworm. These infections are not dangerous but as a chronic cutaneous infections they may be difficult to treat and can also cause physical discomfort for patients. They are considered important as a public health problem as well. No information is available regarding the efficacy of antifungal agents against dermatophytes in Tehran. Therefore, in this study we evaluated the efficacy of 10 systemic and topical antifungal medications using CLSI broth microdilution method (M38-A). The antifungal agents used included griseofulvin, terbinafine, itraconazole, ketoconazole, fluconazole, voriconazole, clotrimazole, ciclopiroxolamine, amorolfine and naftifine.Fifteen different species of dermatophytes which were mostly clinical isolates were used as follows; T. mentagrophytes, T. rubrum, E. floccosum, M. canis, T. verrucosum, T. tonsurans,M. gypseum, T. violaceum, M. ferruginum,M. fulvum, T. schoenleinii, M. racemosum, T. erinacei,T.eriotriphon and Arthrodermabenhamiae. The mean number of fungi particles (conidia) inoculated was 1.25 ×10⁴ CFU/mL. Results were read after 7 days of incubation at 28 °C. According to the obtained results,itraconazole and terbinafine showed the lowest and fluconazole had the greatest MIC values for the most fungi tested. Based on the results, it is necessary to do more research and design a reliable standard method for determination of antifungal susceptibility to choose proper antibiotics with fewer side effects and decrease antifungal resistance and risk of treatment failure.
    Keywords: Antifungal susceptibility, Dermatophyte, Microdilution method, Minimum inhibitory concentration (MIC)
  • Talia Mazidi, Mohammad-Reza Rouini, Mohammad-Hossein Ghahremani, Simin Dashti-Khavidaki, Mahboob Lessan-Pezeshki, Farrokh Lagha Ahmadi, Jamshid Salam-Zadeh, Ali Mandegary, Kheirollah Gholami Pages 547-556
    There are wide individual differences in pharmacokinetic parameters of mycophenolate mofetil (MMF) among transplanted patients. Some studies have shown that single nucleotide polymorphisms (SNPs) of the Uridine Diphosphate Glucuronosyl Transferase1A9 (UGT1A9) are responsible for these differences in early days after transplantation. Therefore it was decided to evaluate the influence of UGT polymorphism on MMF pharmacokinetics among stable Iranian transplant patients. This was a cross sectional study from March 2008 through December 2008 in Imam Khomeini Hospital affiliated to the Tehran University of Medical Sciences in Iran. Blood samples were taken from 40 de novo stable Iranian renal transplant patients taking 2 g MMF daily with SrCr£1.4 mg/dL with at least 3 months history of transplantation. Appropriate PCR and HPLC methods were used for the determination of SNPs and their impact on MPA pharmacokinetics. T-275A polymorphism occurred in 15% of patients, UGT1A9*3 occurred in 2.5% of patients. Carriers of T-275A polymorphism had significant lower MPA AUC 0-12 in comparison with non-carriers or wild type (73.3±17.8 mg/h/mL vs. 110.8±31.1 mg/h/mL, p = 0.006). There was no significant difference in AUC 6-12 between the two groups although carriers of T-275A SNP had lower MPA AUC 6-12 (22.4±4.5 mg/h/mL vs. 26.8±10.2 mg/h/mL, p=0.24). Cmax was lower in the carriers of (20.2±9.0 mg/mL vs. 37.2±12.5 mg/mL, p=0.004). There was no significant difference in C0 between two groups. (3.0±1.2 mg/mL vs. 3.9±1.6 mg/mL, p=0.1). This study in Iranian stable transplanted patients shows that carriers of T-275A polymorphism had significantly lower MPA exposure compared to non-carriers.
    Keywords: UGT, Polymorphism, Mycophenolate mofetil, Renal transplantation
  • Xingguang Zhang, Xiaofeng Lv, Yanqi Zhang, Xiumin Jiao, Bin Chen Pages 557-562
    Osteoporosis is a systemic skeletal disease and there is a close relationship between the sympathetic nervous system (SNS) and bone metabolism. Leptin has been shown to regulate bone formation and bone resorption via the SNS. However, the effect of SNS on leptin signaling has not been clearly understood. In the present study, we studied the effect of propranolol on ovariectomy-induced osteoporosis of rat. The results showed propranolol could increase the bone mass of ovariectomized rat. Propranolol could also up-regulate the level of peripheral leptin and the level of leptin receptor in ovariectomized rat hypothalamus. Our results indicate the effect of propranolol on ovariectomy-induced osteoporosis may be exerted, at least partly, through the regulation of leptin signaling and there may be an interaction between the SNS and leptin on the regulation of bone metabolism.
    Keywords: Propranolol up, regulates Leptin in Ovariectomized Rat
  • Valiollah Babaeipour, Seyed Abbas Shojaosadati, Nader Maghsoudi Pages 563-572
    Tuning recombinant protein expression is an approach which can be successfully employed for increasing the yield of recombinant protein production in high cell density cultures. On the other hand, most of the previous results reported the optimization induction conditions during batch and continuous culture of recombinant E. coli, and consequently fed-batch culture have received less attention. Hence, in this research induction conditions for the over-production of recombinant interferon-γ including the amount of inducer, induction time and post-induction duration during chemical induction were optimized. E. coli BL21 (DE3) (pET3a-hifnγ) was used to over-express human interferon-gamma (hIFN-γ) in an exponential fed-batch procedure with a maximum attainable specific growth rate of 0.55 h-1 at the beginning of feeding and 0.4 h-1 in induction time. The factors were considered as the amount of inducer (IPTG) in the range of 0.565- 22 mg g-1 L-1 at seven levels, cell density at induction time as 53, 65 and 75 g (dry cell weight) L-1, induction duration at different intervals of 3, 4, and 5 h after induction time. The final concentration of biomass and interferon gamma reached to 127 g L-1 (DCW) and 51 g (hIFN-γ) L-1 after 17 h, and also the final specific yield and overall productivity were obtained 0.4 g (hIFN-γ) g-1 DCW and 3 g (hIFN-γ) L-1 h-1, respectively, which are the highest amounts of reported specific yield and productivity for recombinant proteins production.
    Keywords: Human interferon, γ Fed, Batch, Escherichia coli, Specific growth rate, Induction condition
  • Mehdi Mohammadzadeh, Farimah Rahimi, Forough Rahimi, Seyed Mohammad Aarabi, Jamshid Salamzadeh Pages 573-577
    Funding combination is the most important issue for the companies while they know the amount of required capital. Companies should be careful regarding the appliance of financial providing methods compatible with the investment strategy of company and profitability. This study seeks to examine the relationship between the capital structure and the profitability of pharmaceutical companies in Iran. For this purpose, top 30 Iranian pharmaceutical companies defined as study samples and their financial data were gathered for the period of 2001-2010. In this study, the net margin profit and debts to asset ratio were used as indicators of profitability and capital structure, respectively and sales growth was used as a control variable. Results showed that there was significant negative relationship between the profitability and the capital structure which means that the pharmaceutical companies have established a Pecking Order Theory and the internal financing has led to more profitability.
    Keywords: Capital Structure, Profitability, Pharmaceutical industry, Iran