Iranian Journal of Pharmaceutical Research
Volume:11 Issue: 1, Winter 2012

Pharmacoeconomics is defined as the science of identifying and comparing costs and the consequences of drug therapy in health care programs. As a sub-discipline of health economics, pharmacoeconomics, is fairly a new research discipline in the world which has come about mainly in response to economic pressures on health systems. The root of this pressure lies in the mismatch of enhanced demand for health care and pharmaceutical services on one hand, and limitations on available resources on the other.

Repeated oral administration of mexazolam, an anti-anxiety agent, may cause adverse effects such as gastric disturbance, drowsiness, and ataxia due to transiently high blood levels. Transdermal administration would avoid the systemic side effects and gastric disorders after oral administration. We have developed a matrix using ethylene-vinyl acetate (EVA), a heat-processible and flexible material, for transdermal delivery of mexazolam. Drug solubility was highest at 40% PEG-400 volume fraction. The release and permeation profiles through the rat skin were determined for 24 h using a modified Keshary-Chien diffusion cell. The drug release was increased by increasing the concentration with a linear relationship between the release rate and the square root of loading dose. Increasing temperature increased drug release from the EVA matrix. The activation energy (Ea), which was measured from a slope of log P versus 1000/T plot, was 8.64 Kcal/mol for a 1.5% loading dose. To reduce the brittleness and increase the pore of the EVA matrix, diffrent plasticizers were used. Among the plasticizers, including the citrates or the phthalate groups, diethyl phthalate showed the highest effect on the release of mexazolam. To increase the skin permeation of mexazolam from the EVA matrix, enhancers such as the fatty acids, the pyrrolidones, the propylene glycol derivatives, the glycerides, and the non-ionic surfactants were added to the EVA matrix, respectively, and skin permeation was evaluated using a modified Keshary-Chien diffusion cell fitted with intact excised rat skin. Among the several enhancers used, N-methyl-2-pyrrolidone showed the best enhancement factor. In conclusion, enhanced transdermal delivery of mexazolam through an EVA matrix containing plasticizer and a permeation enhancer could be useful in the development of a transdermal drug delivery system.

The objective of the present investigation was to develop and evaluate a contraceptive vagino-adhesive propranolol hydrochloride gel. To achieve this, various mucoadhesive polymers including guar gum (1-4% w/w), sodium alginate (4-7% w/w), xanthan gum (2-5% w/w), HPMC 4000 (3-5% w/w), Na CMC (4-7% w/w), carbomer 934 and carbomer 940 both in the range of 0.5-2.0% w/w, were dispersed in an aqueous-based solution containing the drug (1.6% w/w). The mucoadhesive properties of the gels were assessed on sheep vaginal mucosa (as model mucosa) in pH 4.5 citrate-phosphate buffer at 37°C. Formulations containing charged functional groups in their polymeric structure, showed higher mucoadhesive strengths in comparison to those composed of neutral polymers. In-vitro drug release profiles of the gels were determined in pH 4.5 citrate-phosphate buffer. Results indicated that, only formulation F13 (containing sodium alginate 6.5% w/w), could release its drug over 12 h, with a burst release at the initial phase followed by a sustained release pattern. This formulation, which showed a good mucoadhesive strength (386.97 ± 9.31 mN), was considered as the final formulation and underwent complementary tests including determination of drug content and duration of mucoadhesion. Its drug content was found to be 101.05 ± 0.106% (n = 3) and it attached to the model mucosa for more than 10 h. In conclusion, formulation F13 was considered as the most desirable formulation as it exhibited appropriate mucoadhesive properties while having the potential of providing an immediate contraceptive effect, followed by a prolonged drug release which is assumed to render longer contraceptive efficacy.

Among the numerous nanosized drug delivery systems currently under investigation, carbon nanotubes (CNTs), regardless of being single or multiple-walled, offer several advantages and are considered as promising candidates for drug targeting. Despite the valuable potentials of CNTs in drug delivery, their toxicity still remains an important issue. After the PEGylation of single-walled CNTs (SWCNTs) with phospholipid-PEG (Pl-PEG) conjugates to prepare water-dispersible nanostructures, the present study was designed to evaluate whether the functionalization with Pl-PEG derivatives could alter the cytotoxic response of cells in culture, affect their viability and proliferation. In-vitro cytotoxicity screens were performed on cultured Jurkat cells. The SWCNTs samples used in this exposure were pristine SWCNTs, Pl-PEG 2000/5000-SWCNTs at various concentrations. Jurkat cells were first incubated for 3 h at 37° C with test materials and seeded in 6-well culture plates at a given concentration. The plates were then incubated for 24, 48 and 72 h at 37° C in a 5% CO2 humidified incubator. Cell Viability and proliferation assay were performed using trypan blue exclusion test and the cell cycle kinetic status of Jurkat cells was analyzed by flow cytometry. Cell morphology was finally studied using double staining technique and a fluorescence microscope. We found that, regardless of the duration of exposure, functionalized SWCNTs were substantially less toxic, compared to pure SWCNTs and that the molecular weight of Pl-PEGs played an important role at higher concentrations. In conclusion, our noncovalent protocol seemed to be effective for increasing SWCNTs biocompatibility.

Thimerosal, which is approximately 50% mercury by weight is a preservative widely used in vaccines since the 1930’s. It meets the requirements for a preservative as set forth by Pharmacopeia challenge test and has been shown to be effective against a broad spectrum of pathogens. In July 1999, the Public Health Service agencies and vaccine manufacturers agreed that thimerosal should be reduced or eliminated in vaccines as a precautionary measure but, due to the lack of appropriate alternative, it is still extensively used in multiple dose formulations of vaccines such as hepatitis-B in developing countries. In this study the effect of the removal of thimerosal in two formulations of hepatitis B vaccines containing either aluminum hydroxide or aluminum phosphate were evaluated in Balb/c mice. These formulations were administered interperitoneally and the titer of antibody was determined by ELISA technique after 28 days. The geometric mean of antibody titer (GMT), seroconversion and seroprotection rates, ED50 and relative potency of different formulations were determined. The ED50 of thimerosal-free formulations were reduced by more than 35% in both preparations. In addition, GMT of antibody titer, seroconversion and seroprotection indicated significantly higher immunogenicity for thimerosal free formulations for both aluminum phosphate and hydroxide adjuvants.

The topical delivery of non-steroidal anti-inflammatory drugs (NSAIDS) such as Ibuprofen has been explored as a potential method of avoiding the first pass effects and the gastric irritation, which may occur when used orally. Ibuprofen is formulated into many topical preparations to reduce the adverse effects and simultaneously avoid the hepatic first-pass metabolism as well. However, it is difficult to obtain an effective concentration through topical delivery of Ibuprofen due to its low skin permeability. The aim of this study was to develop two types of nanoemulsions formulations and focused on the screening of Ibuprofen-loaded nanoemulsions and evaluating the influence of these types of nanoemulsions on the skin permeability of the drug. In both nanoemulsion formulations, oil was similar, but the surfactant and co-surfactant were different. The effect of independent variables on skin permeability parameters was evaluated using full factorial design. Results demonstrate that novel formulations were more effective as skin enhancer than traditional formulation. In case of the novel formulation, any increase in percentage of surfactant and co-surfactant had increasing effect on flux (Jss). On the other hand, the proportion of surfactant/co-surfactant (S/C) demonstrated reverse correlation with Jss. While, in traditional formulations, direct correlation was found between both variables, and Jss. Comparison between two types of nanoemulsion formulations revealed that, novel formulations were more effective as topical Ibuprofen carrier in contrast to traditional type due to lower amounts of surfactant and co-surfactant and less irritating effect.

A fast, accurate, sensitive, selective and reliable method using reversed-phase high performance liquid chromatography coupled to electrospray ionization ion trap mass spectrometry was developed and validated for the determination of finasteride in human plasma. After protein precipitation with perchloric acid, satisfactory separation was achieved on a Zorbax Eclipse® C8 analytical column using a mobile phase consisted of acetonitrile, 2 mM ammonium formate buffer (58:42, pH adjusted at 2.5 using formic acid); the flow rate was 0.25 mLmin-1 and the column oven was set to 50°C. Tamoxifen citrate was used as internal standard. This method involved the use of [M +H]+ ions of finasteride and IS at m/z 373 and 372 respectively with the selected ion monitoring (SIM) mode. The calibration curve was linear over the range of 0.1–60 ng mL−1. The limit of quantification for finasteride in plasma was 0.1 ng mL−1. The intra-day and inter-day repeatability (precision) were 2.68-13.87% and 2.14-14.69% respectively. Intra-day and inter-day accuracy were 98-101.57% and 99.7-110%. The assay method has been successfully used to estimate the pharmacokinetics of finasteride after oral administration of a 5 mg tablet of finasteride in 12 healthy volunteers.

Several modalities of drug administration have been investigated to improve bioavailability and to reduce 5-FU related toxicity. The aim of present study was to evaluate the effect of skimmed milk on the absorption and metabolism of 5-FU in rabbits, mice and dogs. It was further aimed to determine its route related toxicity in rabbits. Plasma concentration of both 5-FU and its metabolite 5-Fluoro-2-deoxyuridine (5-Fdurd) was determined using HPLC. The absorption of 5-FU co-administered with skimmed milk was significantly higher as compared to its co-administration with water in rabbits and mice (p < 0.001), whereas no significant difference was observed in dogs. The plasma concentration of 5-Fdurd a major metabolite of 5-FU was significantly higher in water group when compared with skimmed milk group in rabbits and mice (p < 0.05), whereas no significant difference was observed in dogs. Route related toxicity was also determined in rabbits. Various hematological parameters were studied at 4th and 7th day after oral and intravenous administration of 5-FU. WBCs count was significantly decreased in intravenous group as compared to control and oral groups (p < 0.001). It was concluded that co-administration of skimmed milk with 5-FU increases its absorption and reduces its metabolism. Skimmed milk also reduces 5-FU related toxicity in rabbits.

White spot lesions are observed in nearly 50% of patients undergoing orthodontic treatment. Long-lasting antibacterial properties of orthodontic cements can reduce this phenomenon. The aim of this research was to compare antimicrobial activity of three commercial glass ionomer cements with three commercial zinc phosphate cements, over time, against streptococcus mutans and candida albicans. Direct contact test (DCT) was used to evaluate the antibacterial and antifungal activity of products after 48 h and 7 days of incubation. The results demonstrated that all the cements presented antibacterial activity but the antibacterial activity of glass ionomer cements was more than that of zinc phosphate cements. Counts of C. albicans after 48 h were lower and statistically different in the GIC group in relation to the control groups. But no differences were observed between GIC and control groups at 7 days. Based on the results of this study, the antimicrobial and mainly antifungal effects of all the cements were so short.

New derivatives of 2-[2-(2-Chlorophenoxy)phenyl]-1,3,4-oxadiazole as candidates for agonistic effect on benzodiazepine receptors were synthesized. Conformational analysis and superimposition of energy minima conformers of the novel compounds on estazolam, a known benzodiazepine agonist, revealed that the main proposed benzodiazepine pharmacophores were well matched. In pharmacological evaluation, anticonvulsant activity of the compounds determined by pentylenetetrazole-induced lethal convulsion and maximal electroshock tests. The results showed that the introduction of an amino substituent in position 5 of 1,3,4- oxadiazole ring generates compound 6 that has a considerable effect. Compound 8 with a hydroxyl substituent on position 5 of 1,3,4- oxadiazole ring showed a relatively mild anticonvulsant activity, which was significantly weaker than that of diazepam and compound 6. Anticonvulsant effects of active compounds were antagonized by flumazenil, an antagonist of benzodiazepine receptors, indicating the involvement of benzodiazepine receptors in these effects.

Fibrates, as hypolipidemic drugs known as agonists of peroxisome proliferator-activated receptors, diminish inflammatory responses. Studies have shown that incorporation of a silicon atom into a drug structure improves its pharmacological potency, modifies its selectivity toward a given target, or changes its metabolic rate, in addition to increasing the lipophilicity of the compounds. A siliconized analog of clofibrate, ethyl-2-methyl-2-(4-(trimethylsilyl)phenoxy)propionate was synthesized, whereby the chlorine atom in the phenoxy ring was replaced by a trimethylsilyl group. The anti-inflammatory effects of the siliconized analog (silafibrate) were evaluated in an air-pouch model of inflammation and compared with those of clofibrate. Oral administration of both drugs produced a significant anti-inflammatory action by reducing carrageenan induced pouch leukocyte recruitment, exudates production, and granulated tissue weight. The silicon isostere of clofibrate has improved anti-inflammatory properties.

Histamine H3 receptor subtype has been the target of several recent drug development programs. Quantitative structure-activity relationship (QSAR) methods are used to predict the pharmaceutically relevant properties of drug candidates whenever it is applicable. The aim of this study was to compare the predictive powers of three different QSAR techniques, namely, multiple linear regression (MLR), artificial neural network (ANN), and HASL as a 3D QSAR method, in predicting the receptor binding affinities of arylbenzofuran histamine H3 receptor antagonists. Genetic algorithm coupled partial least square as well as stepwise multiple regression methods were used to select a number of calculated molecular descriptors to be used in MLR and ANN-based QSAR studies. Using the leave-group-out cross-validation technique, the performances of the MLR and ANN methods were evaluated. The calculated values for the mean absolute percentage error (MAPE), ranging from 2.9 to 3.6, and standard deviation of error of prediction (SDEP), ranging from 0.31 to 0.36, for both MLR and ANN methods were statistically comparable, indicating that both methods perform equally well in predicting the binding affinities of the studied compounds toward the H3 receptors. On the other hand, the results from 3D-QSAR studies using HASL method were not as good as those obtained by 2D methods. It can be concluded that simple traditional approaches such as MLR method can be as reliable as those of more advanced and sophisticated methods like ANN and 3D-QSAR analyses.

The aim of the present study was to synthesis a series of phthalimides based on our previous works and examine their anxiolytic properties. Using a three steps process, phthalimides were prepared from the corresponding di-methyl phthalate derivatives. Phthalic anhydride was nitrated to produce 3-nitrophthalic acid. Ring closer of either 3-nitrophthalic acid or di-methyl phthalate with urea were carried out in reflux condition. Final compounds were prepared by base catalyzed condensation of 4-methylbenzoyl chloride, benzoyl chloride and benzyl chloride with the resulting imides. From the tested compounds, only N-benzoyl 3-nitro-phthalimide was shown to produce anxiolytic activity by increasing the number of entries and time spent in open arms at 10 mg/kg.

Clinical and Epidemiological studies have shown that a diet rich in fruits and vegetables is associated with a decreased risk of cardiovascular diseases, cancers and other related disorders. These beneficial health effects have been attributed in part to the presence of antioxidants in dietary plants. Therefore screening for antioxidant properties of plant extracts has been one of the interests of scientists in this field. Different screening methods have been reported for the evaluation of antioxidant properties of plant extracts in the literature. In the present research a rapid screening method has been introduced based on cyclic voltammetry for antioxidant screening of some selected medicinal plant extracts. Cyclic Voltammetry of methanolic extracts of seven medicinal plants: Buxus hyrcana, Rumex crispus, Achillea millefolium, Zataria multiflora, Ginkgo biloba, Lippia citriodora and Heptaptera anisoptera was carried out at different scan rates. Based on the interpretation of voltammograms, Rumex crispus, Achillea millefolium and Ginkgo biloba showed higher antioxidant capability than the others while Lippia citriodora contained the highest amount of antioxidants. Cyclic voltammetry is expected to be a simple method for screening antioxidants and estimating the antioxidant activity of foods and medicinal plants.

A special type of silica-based columns has been recently introduced into the market which is called narrow-bore columns. They have lower internal volume than the standard high-performance liquid chromatography (HPLC) columns and thus reduce the solvent consumption by almost 80%. A simple, accurate and environmentally friendly reversed phase- HPLC (RP-HPLC method) which could be used in fast and high throughput analyses has been developed for the purpose of determining the sildenafil in bulk and pharmaceutical dosage forms, using narrow-bore C18 column (50 × 3.2 mm, 5 µm particle size) in isocratic mode, with mobile phase comprising of buffer (pH = 3) and acetonitrile in the ratio of 75:25 v/v. The flow rate was 0.7 mL/min and the detection was monitored through Ultraviolet detector (UV detector) at 292 nm. Clonazepam was used as the internal standard and the run time was 4 min. The proposed method has permitted the quantification of sildenafil over the linearity in the range of 30-4000 ng/mL and its percentage recovery was found to be 99-105%. Limit of quantitation (LOQ) is determined as 30 ng/mL. The intra-day and inter-day precisions were found 1.2-2.2% and 1.56-3.4% respectively. The solvent consumption was 2.8 mL per sample of which ca 0.7 mL was acetonitrile. This study shows that the application of narrow-bore column instead of the conventional reversed phase column in HPLC analyses has the advantages of shorter run time and less organic solvent consumption. This method is highly sensitive with excellent recoveries and precision and there is no need for special column and pre-column or post-column treatment of the sample. Moreover, the method is free from interference by common additives and excipients, suggesting applications in routine quality control analyses.

In chiral and non-chiral electrophoretic resolution of basic drugs, adsorption of analytes to negatively charged capillary wall could lead to poor repeatability of migration time and peak area. In addition, chiral resolutions of basic drugs are commonly performed in low pH buffers. Therefore, longer analysis time due to suppression of electroosmotic flow (EOF) is another dilemma. In this work the improvement effect of polybrene (PB), a cationic polymer, on chiral separation of a model basic drug, amlodipine (AML), was investigated. PB both as a semi-permanent coating agent and as an additive in the running buffer was utilized. Better results were obtained with PB as a buffer additive. Compare to untreated bare silica without using PB in running buffer, addition of 0.0005% PB to buffer decreased analysis time downed to 3 folds; efficiency improved up to 5 folds; limit of detection (LOD) and limit of quantification (LOQ) downed to 8 folds and within-day migration time and peak area repeatabilities, in terms of relative standard deviations (RSD) downed to 5 and 20 folds, respectively.

Developing new bone pain palliation agents is a mandate in handling end-stage cancer patients around the world. Possibly, Lu-177 ethylenediaminetetramethylene phosphonic acid (177Lu-EDTMP) is a therapeutic agent which can be widely used in bone palliation therapy. In this study, 177Lu-EDTMP complex was prepared successfully using synthesized EDTMP ligand and 177LuCl3. Lu-177 chloride was obtained by thermal neutron irradiation (4 × 1013 n.cm-2s-1) of natural Lu2O3 samples. Radiochemical purity of 177Lu-EDTMP was determined by ITLC (more than 99%). Stability studies of the final preparations in the presence of human serum were performed. The biodistribution of 177Lu-EDTMP and 177LuCl3 in wild-type rats was studied by SPECT imaging. A comparative accumulation study for 177Lu-EDTMP and 177LuCl3 was performed for vital organs up to 7 days. The complex was obtained in high radiochemical purity (more than 99%). The complex was stable in vitro in presence of human serum as well as final formulation. Significant bone uptake (> 70%) was observed for the radiopharmaceutical. Due to better physical properties of Lu-177 compared to Sm-153 and acceptable biodistribution results of the compound, 177Lu-EDTMP seemed to be an interesting new candidate for clinical trials for bone pain palliation therapy.

The edible mushrooms (basidomycetes) have high nutritional value, promote the immune system, and as a source of natural antimicrobial substances have been used to cure bacterial infections since ancient times.Various kinds of proteins with several biological activities are produced by mushrooms. In this research, in order to evaluate antibacterial activity of edible mushrooms, we isolated proteins of Agaricus bisporus and examined their effects on gr + and gr- bacteria. Protein extract of the mushroom was first discriminated by homogenation of the chopped fruiting bodies in tris buffer with pH 7.3 and then centrifuged. The Protein concentration was determined by Bradford method. Gel filtration of the proteins was performed by Sephadex G-100 using UV spectrophotometer as detector.Three fractions were collected and their purity level were defined by SDS-PAGE. In order to reach to a more purification level, isolated proteins from the G-100 column were fractionated by the DEAE ion exchange column. Antibacterial activity of total extact proteins as well as protein fractions was evaluated by the method of microdilution against gr+ and gr- bacteria. This study showed that the isolated proteins from the mushroom, Agaricus bisporus fruiting bodies were effective against Staphylococcus aureus and MRSA. The proteins of edible mushrooms like Agaricus bisporus, maybe viewed as a natural source of antibacterial agents.

Drug Utilization Evaluation (DUE) studies facilitate assessing the appropriateness and rational use of medications.The goal of the present study was to evaluate Amphotericin B usage in neutropenic patients. A prospective DUE study was performed in Hematology-Oncology and Stem Cell Transplantation wards at Taleghani hospital for one-year. National comprehensive cancer network, clinical practice guidelines in oncology, American Hospital Formulary Service and other relevant medical practice and up-to dated articles were used to evaluate whether Amphotericin B is properly used according to the guidelines. All data collected by a pharmacist in daily review using information of physician and nursing records as well as laboratory findings. During the one-year study, 35 patients receiving amphotericin B were evaluated. 29 patients (82.9%) received amphotericin B due to neutropenia and fever and 6 patients had confirmed fungal infections. All of the injectable solutions of amphotericin B were appropriately prepared for intravenous infusion. In addition, for all patients, ordering (indication) of the study drug was in accordance with the guidelines. Twenty-five (71.4%) patients received an appropriate dose according to the guidelines. Duration of treatment was properly selected in 21 (60%) patients. Twenty-two (62.8%) patients developed hypokalemia as the most frequent adverse drug event. Although, preparation and indication of amphotericin B was in compliance with the current guidelines, dosage and duration of treatment were considered to be incoherent with the designed protocol used in this study. We conclude more attention should be paid to dosage and duration of treatment with amphotericin B in order to optimize its administration.

The purpose of this study was to determine the number of prescribed antibiotics being appropriately adjusted and to assess antibiotics with the highest incorrect dosing based on the patient’s renal function according to distinguished guidelines. The study was conducted at a 446-bed university hospital. One hundred and fifty patients admitted through different wards of the hospital were included in the study. Demographic data were extracted and creatinine clearance was calculated using either Cockcroft-Gault (C&G) or Modification of Diet in Renal Disease (MDRD) formula. In patients with creatinine clearances less than 50 mL/min, antibiotic dosages were compared with guideline dose recommendations to judge whether they were correctly adjusted. Two hundreds and ninety-one instructions (79.9%) of 364 antibiotic prescriptions required dosage adjustment based on the patient’s renal condition. These adjustments were rationally performed in 43.7% and 61.4% of prescriptions, according to the two guidelines used. Ciprofloxacin (29.1% of cases), and vancomycin (33.6% of cases), were the most inappropriate prescribed antibiotics in terms of dose administration. Drug dosing adjustments should be emphasized in patients with renal dysfunction. Failure to do so may lead to higher morbidity and mortality as well as therapeutic costs. Estimating creatinine clearance prior to drug ordering and use of a reliable dosing guideline is highly recommended.

The aim of the present study was to evaluate the pattern of vancomycin administration in the hematology-oncology ward of Nemazee Hospital, Shiraz, Iran. Study criteria were developed to assess the several parameters involved in vancomycin therapy. These parameters include the appropriateness of drug usage, dosage, duration of therapy, monitoring for toxicity and serum concentration monitoring. The serum concentration was measured by an automated Fluorescence Polarization Immunoassay. Clinical and preclinical parameters such as Glomerular Filtration Rate (GFR), microbial culture, antibacterial sensitivity, WBC count and fever were collected and recorded for analysis. Sixty patients were enrolled in the study, consisting of 45 males and 15 females. The age range was 15 to 68 years. In this study, 68.63% of the vancomycin used for the patients with febrile neutropenia was compatible with the Infectious Disease Society of America (IDSA) guideline. The initial dosage of vancomycin in 68.63%, rate of infusion in 100%, and dilution of vancomycin in100%, were appropriate. Inappropriate use was more evident in the continuation of vancomycin in 50% of the patients. No appropriate dosage adjustment was done for 50% of the patients with increased serum creatinine. Based on the results, the indication of vancomycin in febrile neutropenia was satisfactory. However, there were some required factors such as continuation of vancomycin, adjustment of dosage or interval, microbial culture, antibiotic sensitivity test before the first dose administration, measurement of serum concentration and monitoring which had to be revised in order to achieve an effective treatment.

To evaluate the physical and chemical stability of a suspension of mycophenolate mofetil (MMF) prepared in the hospital from commercially available MMF capsules and tablets. Extemporaneous pharmacy was used as a feasible method in this experimental study to prepare suspension form of MMF. Suspension formulations were prepared from both tablets and capsules forms of MMF. Thereafter the stability parameters such as pH, microbial control, thermal and physical stability and particle sizes were evaluated. The amount of MMF, in the suspension was measured at various time points by HPLC. The HPLC method showed that concentration of suspensions prepared from tablets and capsules were 49 mg/mL and 50 mg/mL at time 0, respectively. The effective amount of suspensions prepared from capsules was 101% at time 0, 100% after 7 days, 98% after 14 days, and less than 70% after 28 days. According to the obtained results in this study, capsule-based suspension was stable for as long as 14 days at 5°C. This formulation appears to be clinically acceptable and provides a convenient dosage form for pediatric patients and for adults during the early postoperative period.

Achillea tenuifolia Lam. (Asteraceae) afforded a dichloromethane fraction from which three known compounds β-sitosterol (compound1), 5-hydroxy, 4',6,7– trimethoxy flavone (salvigenin compound 2), and methyl-gallate (compound 3) were isolated for the first time. The structure of isolated compounds was elucidated by different spectroscopic methods. Applying the molar-ratio method, the complexation of salvigenin with Fe (III), Cu(II) and Zn(II), the most abundant type of metal ions in the body, were then evaluated. It was determined that stoichiometric ratio of salvigenin with these cations were as Fe(Salvigenin)2 (H2O)2 and Cu(Salvigenin)2(H2O)2 in methanolic solution without pH control, while zinc ions didn`t form significant complexes. The results were confirmed more, by computational molecular modeling of the structure of proposed ligand-complexes by semi-imperical PM3 calculations, which determined negative heat of formation for the complexes Fe(III) and Cu(II) ions as -689.7 and -573.5, respectively and proposed chelating affinity of salvigenin in the following order: Fe(III) > Cu(II) >> Zn(II).

The ethnobotany of the medicinal plants of Alamut region is important in understanding the cultures and traditions of Alamut people. This study documents 16 medicinal plant species, most commonly used by the indigenous people of Alamut region (Ghazvin Province), northwest, Iran. The botanical name, family name, vernacular name, part used, and the application of the plants have been provided in this paper. Alamut region was divided into different villages with the aid of maps. We recorded traditional knowledge and use of medicinal plants from herbal practitioners and village seniors in Alamut. The plants were gathered from different sites. The fully dried specimens were then mounted on herbarium sheets. We found 16 medicinal plants belonging to 11 families which were traditionally used in Alamut. Finally, we describe traditional usages by the native people in the Alamut region. The obtained results were compared with data on the herb’s clinical effects. A set of voucher specimens were deposited to the Institute of Medicinal Plants Herbarium (IMPH).

The increasing gap observed between market value and book value of many companies has taken into account towards investigating the impact of intellectual capital (IC) on business performance. IC has been widely considered as a critical tool to deliver the business successfully in an intensive competitive environment. Various models have been suggested to measure the numerous aspects of IC, i.e. the Skandia navigator, Tobin’s Q, and value added intellectual coefficient (VAIC). The aim of this study is to examine the relationship between intellectual capital and market value of pharmaceutical companies, using the VAIC developed by Ante Pulic (2000). Six-year data was obtained from audited financial reports in Iranian Exchange Stock, and used to calculate human capital, structural capital, and capital-employed efficiency of pharmaceutical companies. The results obtained using correlation and multiple regression analysis failed to support the impact of IC on market value. Practically, IC efficiency can be applied as a benchmark and strategic indicator to assess firm value. This study is a pioneering attempt in Iran to measure the impact of IC efficiency on market value using cross sectional time series data.

The supply chain represents the critical link between the development of new product and the market in pharmaceutical industry. Over the years, improvements made in supply chain operations have focused largely on ways to reduce cost and gain efficiencies in scale. In addition, powerful regulatory and market forces have provided new incentives for pharmaceutical firms to basically rethink the way they produce and distribute products, and also to re-imagine the role of the supply chain in driving strategic growth, brand differentiation and economic value in the health continuum. The purpose of this paper is to formulate basic factors involved in risk analysis of pharmaceutical industry, and also determine the effective factors involved in suppliers selection and their priorities. This paper is based on the results of literature review, experts’ opinion acquisition, statistical analysis and also using MADM models on data gathered from distributed questionnaires. The model consists of the following steps and components: first factors involved in to supply chain risks are determined. Based on them a framework is considered. According the result of statistical analysis and MADM models the risk factors are formulated. The paper determines the main components and influenceial factors involving in the supply chain risks. Results showed that delivery risk can make an important contribution to mitigate the risk of pharmaceutical industry.

Strychnos henningsii Gilg is recommended among other remedies for the treatment of diabetes in traditional medicine of Southern Africa. The antidiabetic effect of oral administration of aqueous bark extract of the plant at 125, 250 and 500 mg/Kg body weight was investigated in diabetic rats induced with streptozotocin-nicotinamide for 15 days. The extract decreased the blood glucose level, feed and water intake as well as triacylglycerol at the three doses investigated while the best result was obtained at 250 mg/Kg. Similarly, the extract was able to lower the cholesterol level appreciably at 500 mg/Kg while the remaining doses did not have any significant effect as compared with diabetic untreated groups. In addition, the weight loss of diabetic-treated rats was markedly normalized at all doses. The glucose tolerance level of diabetic animals was effectively reduced to near normal level after 90 min of extract administration especially at the dose of 250 and 500 mg/Kg. The phytochemical screening of S. henningsii revealed the presence of flavonoids, tannins and saponins which have been reported to increase the insulin secretion. The results obtained from this study demonstrated that the aqueous extract of S. henningsii possess antihyperglycemic and antilipidemic properties and thus could prevent various complications of diabetes. Generally, this study has validated the traditional use of this plant for the treatment of diabetes mellitus.

ATP-sensitive potassium (KATP) channel openers have a relaxation effect due to the lower cellular membrane potential and inhibit calcium influx. There has been considerable interest in exploring KATP channel openers in the treatment of various diseases such as cardiovascular, cerebrovascular, and urinary system disease and premature labor. The purpose of this study was to synthesize 3,3,6,6-tetramethy l-9-aryl-octahydro-1,8-acridindiones and investigate their effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rings of rat aortic smooth muscle. In this study, four new derivatives of 3,3,6,6-tetramethy l-9-aryl-octahydro-1,8-acridindione [2a-d] were synthesized by the reaction of 5, 5-dimethyl-1,3-cyclohexanedione with an aromatic aldehyde, 2-alkylthio-1-(4-fluorobenzyl)-5-formylimidazole or 3-substituted benzaldehyde, in the presence of ammonia in methanol. Their effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rat aorta were investigated. Minoxidil was used as a standard potassium channel opener and Glibenclamide was used as a standard potassium channel blocker. The effects of compounds on KCl-induced contractile response which is an indicator of ca-channel blocking activity was also investigated and compared to that of nifedipine as a standard calcium channel blocker. Compounds 3a-d and Minoxidil relaxed the contractions exerted by using phenylephrine with the potency order as follows: Minoxidil > 3c > 3d > 3a > 3b. This effect was sensitive to the potassium channel blocker Glibenclamide. It can be concluded that these compounds act via ATP-sensitive potassium (KATP) channels. Selectivity index (SI) for these compounds and Minoxidil also shows that these compounds are selective to ATP-sensitive potassium (KATP) channels and the selectivity of compounds 3a-d is less than Minoxidil.

Cisplatin is a common chemotherapeutic agent that used for treatment of many solid cancers. Rapid identification of chemotherapy resistance is very important and may lead to effective treatment plan. Spectroscopy techniques, such as infrared spectroscopy, which are sensitive to biochemical composition of samples, have shown potentials to discriminate tissues. Developing in Fourier transform infrared (FTIR) as a diagnostic tool support conventional technique in investigating cell phenotype. By this goal three different cell lines, two cisplatin resistant OV2008-DDP (C13) and A2780-CP ovarian cell lines and one cisplatin sensitive A2780 cell line were investigated by FTIR spectroscopy. Data were subjected to principle component analysis (PCA) to obtain FTIR pattern for cisplatin resistance. Using FTIR spectroscopy on these cells in the range of 400-4000 cm-1 was shown dramatic change in cells. Results shows that Cisplatin resistance pattern is characterized in spectrum with the alteration of conformation in secondary structure of proteins and a shift toward the high wave numbers of CH2 stretching vibration. The FTIR data set between 1000 and 3000 cm-1 could be consumed as biochemical typicality spectra among resistant and sensitive cell lines while correctly classified by PCA model. Our work supports the promise of PCA analysis of FTIR data as a powerful combined approach for the development of automated methods to recognize resistant to cisplatin in experimental cell lines. One of the advantages of this tool is to investigate the resistant percent of cancer cells. Such technique may bring new tool in cancer diagnosis and stage definition in cancerous tissues.

Euphorbia wallichii a perennial herb growing mainly in Himalayas has been widely used in folk medicines for its medicinal properties. In the present study, the crude methanolic root extract (CME) and its fractions; n-Hexane Fraction (NHF), n-Butanol Fraction (NBF), Chloroform Fraction (CHF), Ethyl acetate Fraction (EAF) and Aqueous Fraction (AQF) of this plant specie were investigated for antioxidant and cytotoxic activities and phytochemical analysis. Antioxidant activity was determined by using 2,2-diphenyl-1-picryl-hydrazyl free radical (DPPH) and DNA protection assay performed on pBR322 plasmid DNA. In both these assays, promising results were obtained for CME as well as other fractions. The IC50 values for DPPH assay were in a range of 7.89 to 63.35 µg/ml in which EAF showed the best anti-oxidant potential and almost all the tested samples showed certain level of DNA protection. The cytotoxic activity was assessed by using Sulforhodamine B (SRB) assay on human cell lines; H157 (Lung Carcinoma) and HT144 (Malignant Melanoma). The IC50 values of the tested samples ranged from 0.18 to 1.4 mg/mL against H157 cell line whereas against HT144 cell line the IC50 values ranged from 0.46 to 17.88 mg/mL with NBF fraction showing maximum potential for both. Furthermore, the phytochemical analysis of CME and its fractions showed the presences of flavonoids, saponins, tannins, terpenoides and cardiac glycosides with varying concentrations.

Zearalenone (ZEA) mycotoxin is a potent estrogenic metabolite. It is the primary toxin causing infertility, abortion or other breeding problems. A HPLC method was validated for ZEA in foods using a monolithic column with sample clean-up on an immunoaffinity column. A certified reference material (CRM) from FAPAS (UK) was analyzed. A survey of ZEA was performed on the 72 samples of rice, bread, puffed corn snack and wheat flour collected from Tehran retail market. The average recovery and coefficient of variation in different foods ranged 92.7-107.1 and 4.9-13.8%, respectively. The amount of ZEA in corn CRM was in the acceptable range of FAPAS. The limit of quantification was 3 ng/g for rice, bread and wheat flour and 2.7 ng/g for puffed corn snack. The retention time of zearalenone was 2.6 min. All samples had contamination level lower than the maximum tolerated level of ZEA in foods in Iran. The mean intake of ZEA from all samples was much lower than the tolerable daily intake estimated by JECFA. This is the first survey on ZEA contamination in bread and rice in Iran as well as the first study on exposure assessment of Tehran population to ZEA.

The supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) represents a new thermodynamically stable formulation approach wherein it is designed to contain a reduced amount of surfactant and a water-soluble polymer (precipitation inhibitor or supersaturated promoter) to prevent precipitation of the drug by generating and maintaining a supersaturated state in-vivo. The supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) of CBZ was evaluated in-vitro and in-vivo. Three different formulations of CBZ were prepared and drug precipitation behavior, dissolution rate in-vitro and particle size distribution were evaluated. Studies on CaCO-2 permeability of three formulations were also carried out. Pharmacokinetic studies were conducted in beagle dogs with administration dose of 200mg to assess bioavailability in-vivo compared with commercial tablet. The results showed that the presence of a small amount of polymeric precipitation inhibitor (PVP) effectively sustained supersaturated state by retarding precipitation kinetics. The mean particle size after dispersion was about 33.7 nm and the release rate from S-SMEDDS was significantly higher than the commercial tablet in-vitro. S-SMEDDS formulation with precipitation inhibitor decreased impairment to cells due to a lower surfactant level compared to SMEDDS. The absorption of S-SMEDDS in-vivo resulted in about 5-fold increase in bioavailability compared with the commercial tablet and the reproducibility of plasma concentration profiles intra-individual was improved remarkably. This study demonstrates that S-SMEDDS technology provide an effective approach for improving the extent of absorption of poorly-soluble drugs with low level of surfactant.

Chloroacetaldehyde (CAA) is a chlorination by-product in finished drinking water and a toxic metabolite of a wide variety of industrial chemicals (e.g. vinyl chloride) and chemotherapeutic agents (e.g. cyclophosphamide and ifosfamide). In this research, the cytotoxic mechanisms of CAA in freshly isolated rat hepatocytes were investigated.CAA cytotoxicity was associated with reactive oxygen species (ROS) formation and glutathione depletion suggesting that oxidative stress contributed to the CAA cytotoxic mechanism. CAA-induced oxidative stress cytotoxicity markers were significantly prevented by antioxidants, ROS scavengers, mitochondrial permeability transition (MPT) pore sealing agents, endocytosis inhibitors, ATP generators and xanthine oxidase inhibitor. In our study the hepatocyte mitochondrial membrane potential was rapidly decreased by CAA which was prevented by antioxidants and ROS scavenger indicating that mitochondrial membrane damage was a consequence of ROS formation. CAA cytotoxicity was also associated with lysosomal membrane rupture. Our findings showed that at least four different intracellular sources including: metabolic enzymes cytochrome P450 and xanthine oxidase, mitochondrial respiratory chain disruption and lysosomal Haber-weiss reaction, were involved in CAA induced ROS formation and other subsequent cytotoxic events. Our other interesting finding was that the lysosomotropic agents prevented CAA induced mitochondrial membrane potential collapse and mitochondrial MPT pore sealing agents inhibited lysosomal membrane damage caused by CAA. It can therefore be suggested that there is probably a toxic interaction (cross-talk) between mitochondrial and lysosomal oxidative stress generating systems, which potentiates each organelle damage and ROS formation in CAA- induced hepatotoxicity.

The present study was aimed to evaluate the therapeutic potential of Pimpinella tirupatiensis (Pt) by assaying the activities of selective mitochondrial enzymes in streptozotocin induced diabetic rats. Diabetic rats showed a significant (p < 0.01) reduction in the activities of oxidative enzymes Succinate dehydrogenase (SDH), Malate dehydrogenase (MDH), Glutamate dehydrogenase (GDH) and isocitrate dehydrogenase (ICDH). Lactate dehydrogenase (LDH) activity was significantly (p < 0.01) increased in diabetic rats. The daily oral treatment of Pimpinella tirupatiensis ethyl alcohol extract (750 mg/kg body weight/day) to diabetic rats for 30 days reversed the above changes in a significant (p < 0.01) manner. From our observations, we conclude that administration of Pt altered the activities of oxidative enzymes, thereby suggesting its role in mitochondrial energy production. The obtained results were compared with Glibenclamide, a standard anti diabetic drug. Thus, the modulatory effects of Pt on altering these enzymes activities afford a promise for widespread use for treatment of diabetes in the future.

Considering the growing trend of laryngeal surgeries and the need to protect the airway during and after surgery, among several therapeutic regimens to induce sedation, two regimens of propofol-fentanyl and propofol-midazolam were compared in microlaryngeal surgeries. Forty ASA I-II class patients undergoing microlaryngeal surgeries and referring routinely for postoperative visits were randomly recruited into two groups. For all the patients, 0.5 mg/Kg of propofol was used as bolus and then, 50 mcg/Kg/min of the drug was infused intravenously. For one group, 0.03 mg/Kg bolus of midazolam and for the other group, 2 mcg/Kg bolus of fentanyl was administered in combination with propofol. Ramsay system was used in order to evaluate the effect of the two drugs in inducing sedation. The need for additional dose, blood pressure, heart rate, arterial blood oxygen saturation, and also recovery time and adverse effects such as nausea/vomiting and recalling intra-operative memories, were assessed. The patients in the two groups were not statistically different regarding the number of patients, age, sex, preoperative vital signs, the need for additional doses of propofol, systolic blood pressure and mean systolic blood pressure during laryngoscopy. However, mean systolic blood pressure 1 min after removal of laryngoscope returned faster to the baseline in midazolam group (p < 0.01). Mean heart rate returned sooner to the baseline in fentanyl group following removal of stimulation. Besides, heart rate showed a more reduction following administration of fentanyl (p < 0.02). Mean arterial blood oxygen saturation during laryngoscopy significantly decreased in fentanyl group (p < 0.05) compared to the other group. The time it took to achieve a full consciousness was shorter in midazolam group (p < 0.01). Nausea/vomiting was significantly more prevalent in fentanyl group while the patients in midazolam group apparently experienced more of amnesia, comparatively (p < 0.01). Inducing laryngeal block and local anesthesia using propofol-midazolam regimen is not only associated with a more rapid recovery and less recalling of unpleasant memories, but also better in preventing reduction of arterial oxygen saturation during laryngoscopy compared with propofol-fentanyl regimen.

Numerous studies have been focused on natural anticarcinogenic agents. Many antioxidants have been identified as anticarcinogens. Antimutagens have also been proposed as cancer chemopreventive agents. The use of natural products as anticancer has a long history that began with traditional medicine. The aim of this study was to evaluate cytotoxicity and antioxidant activity of twenty-three plant species of Leguminosae family from different regions of Iran. Twenty-three plant species of Leguminosae family were collected in May-June 2009 from different regions of Iran.Methanol extracts of these species were tested through the brine shrimp lethality assay in order to detect potential sources of novel cytotoxic compounds. The total antioxidant activity was evaluated with DPPH free radical-scavenging method. The extracts of twelve species showed moderate cytotoxicity against brine shrimp (LC50 between 30 and 50 μg/mL). The extracts of Taverniera spartea and Tephrosia persica showed significant cytotoxicity (LC50 < 30 μg/mL) with LC50 values of 0.34 and 2.43 μg/mL, respectively, whereas the positive control, thymol showed a LC50 value of 1.37 μg/mL. The chloroform fractions of the latter two species were subjected to the brine shrimp lethality assay with LC50 values of 113.79 and 1.23 μg/mL, respectively. In comparing antioxidant capacities, Gleditschia caspica and Taverniera spartea showed significant antioxidant activity (IC50 < 50 μg/mL) with LC50 values of 14.54 and 20.32 μg/mL, respectively. It could be seen among 23 tested plant species that Taverniera spartea had the most cytotoxic and antioxidant activity and was the best candidate for these effects. Further investigations are necessary for chemical characterization of the active compounds and more comprehensive biological assays.

The imbalance between pro-oxidants and anti-oxidants leads to generation of oxygen/nitrogen free radicals which are implicated in several neurodegenerative diseases. Fagonia arabica is an ethno-pharmacologically important Ayurvedic herb known to have many medicinal properties like anti-inflammatory, analgesic and antipyretic effects. However, its antioxidant potential has not been investigated so far. The present study was designed to investigate the antioxidant potential of F. arabica and its neuroprotective effect on chemical ischemia induced in PC12 cells. Chemical ischemia was induced through exposing the cells to uncoupler of oxidative phosphorylation sodium azide (5.0 mM) and competitive inhibitor of glycolysis 2-deoxy-glucose (2.0 mM) for 2 h followed by 24 h reperfusion with normal culture medium. Total polyphenolic content (TPC) and antioxidant potential of the herb was measured using DPPH and ABTS•+ scavenging and ferric ion reducing antioxidant potential (FRAP) assays; its effect on neuroprotection and energy metabolism was also studied. The ischemic injury was characterized by impaired energy status as indicated by decreased ATP levels in the cells, accompanied by increased lactic acid content. Both the changes favourably responded to F. arabica and offered considerable neuroprotection from ischemia and helped to maintain the cellular viability and mitochondrial integrity of the cells. F. arabica showed considerable amount of TPC and antioxidant activity. This study reveals the antioxidant potential of F. arabica and its protective efficacy against ischemia/reperfusion mediated cell death. F. arabica thus can be considered for further studies for the development of the prophylactic or therapeutic agent for the treatment of ischemic stroke.

Low glucose condition induces neuronal cell-death via intracellular mechanisms including mitogen-activated protein kinases (MAPK) signaling pathways. It has been shown that low glucose medium decreases neuronal survival in cerebellar granule neurons (CGNs). In this study, we have examined the activation of JNK, p38kinase and ERK1/2 pathways in low glucose medium in CGNs. The CGNs were prepared from new-born (P-2 and P-5) rats and cultured in Dulbecco′s Modified Eagle′s Medium high (DMEM-HIGH) glucose supplemented with Fetal Bovine Serum (FBS) 10% for 7 days. The glucose deprivation was induced through replacing the culture medium with the low glucose (5 mM) medium. The MAPK pathways activation was evaluated through phospho specific antibodies using western blot. The viability of cells was measuring using MTT assay. The results indicated that low glucose reduces the cell survival and brain-derived neurotrophic factor (BDNF) elevates the cell viability in CGNs. The basal c-Jun N-terminal kinase (JNK) activity was high in CGNs and glucose deprivation for 24 h had increased phospho-JNK level to 2-fold compared to basal. BDNF treatment reduced the basal JNK activity within 30 min but had no effect in longer incubations. BDNF also blocked the low glucose-induced JNK activation. In addition, CGNs exhibited high p38 phosphorylation in low glucose medium in 48 h. These results demonstrated that in sustained low glucose conditions, CGNs had high activity of stress-activated MAPK which could induce cellular damage. Moreover, BDNF can prevent JNK and p38 activation in stress conditions and increase cell viability. Our results suggest that in sustained stress conditions, inhibition of JNK and/or p38 pathways might protect neurons from damage in low glucose conditions.

Human serum albumin (HSA) is an important protein that carries variety of substances like some hormones and drugs in blood. Pharmacological studies of the interaction of many drugs and HSA are reported during several decades, specially recently years. Interaction of cortisol and fluoxetine hydrochloride (FLX) (as a common anti-stress drug) with HSA (as their carrier in blood) has been studied separately by using different spectroscopic techniques. Here, considering the increment of anti-stress drugs consumption, conformational change of HSA in presence of cortisol and FLX in 50 mM tris buffer, at pH = 7.5 and 37°C, is investigated via pH meter, UV absorption and fluorescence spectroscopy and circular dichroism methods. pH meter findings indicate that the acid denaturation of HSA in the presence of drug and cortisol occurs in the similar manner and this pattern is different relative to the denaturation of HSA in the absence of two reagents. The results of the other techniques consistent with the pH meter findings show that FLX effects on the physiochemical properties of HSA are as that of Cortisol. In-vivo study in Rats confirms in-vitro findings which means blood cortisol level increased in the presence of FLX. Experimental results indicate that FLX and cortisol alter the structural aspects of HSA in similar manner, so, this findings lead to the following reasonable “FLX is a competitive ligand for the binding of cortisol to HSA. Binding of FLX to HSA interferes to the interaction of cortisol-HSA.”

In the present study, we have investigated the effects of silymarine on depression and the possible role of serotonergic system in these effects. The rats were anesthetized intraperitoneally with ketamine hydrochloride and placed in a Stoelting stereotaxic instrument. A stainless steel guide cannula (22-gauge) was implanted in the third ventricular region. The third ventricular region was infused by means of an internal cannula (27-gauge), terminated 1 mm below the tip of the guide cannula. Forced swimming test was used for evaluating the depression. The results obtained from this study showed that oral administration of silymarin (35, 70, 140 and 280 mg/rat) for two weeks increased the immobility time in forced swimming test, indicating an increase in depression level of the treated rats. Intra-third-ventricle (Intra-TV) infusion of 5HT1A receptor agonist 8-OH-DPAT (25 and 10 ng/rat) decreased the immobility time indicating an anti-depression effect, while injection of 5HT1A receptor antagonist NAN190 (0.25, 0.5 and 1 µg/rat) had no significant effect on immobility time. An effective dose of 8-OH-DPAT (10 ng/rat) co-administered with silymarin (140 and 280 mg/rat) decreased the depressogenic effects of silymarin. These results showed that the depressogenic effects of silymarin may be modulated via 5HT1A receptor of serotonin.

The aim of this research was to investigate the Cyclooxygenase-2 (COX-2) selective inhibition effect on haloperidol-induced catatonia. In this study, the effect of orally, acutely and Sub-chronically administrations of compound 11b [1-(phenyl)-5-(4-methylsulfonylphenyl)-2-ethylthioimidazole] (2, 4 and 8 mg/kg), a newly selective COX-2 inhibitor, was investigated against the haloperidol-induced catatonia phenomenon comparing to the standard drug scopolamine (1 mg/Kg) followed by microdialysis analysis of Striatum dopaminergic neurotransmission. The results showed a great potency for compound 11b in improvement of catalepsy followed by enhancing the dopaminergic neurotransmission p < 0.05. In addition, our statistical analysis showed that the protective effect of compound 11b against haloperidol-induced catatonia was both dose- and time-dependent. These findings are additional pharmacological data that suggest the effectiveness of compound 11b in treatment of schizophrenic drug overdoses and also Parkinson’s disease (PD) affiliated rigidity.

Possessing putative hypolipidemic effects, Teucrium polium (TP) have been traditionally used as a medicinal plant in Iran. The aim of the present study was to investigate this effect on the sucrose-induced insulin resistance male rat model. Thirty Wistar male rats weighting 180 ± 20 g were divided into five groups of six each. Four groups were given sucrose 50% in drinking water for 10 weeks. In 8th week of treatment, three groups of them were randomly selected and treated with Teucrium polium (T. polium) ethyl acetate extract (50, 100 and 200 mg/Kg for two weeks). Control animals were fed using normal rat chow. After ten weeks, blood samples were collected from the heart. Blood Glucose, insulin, leptin, lipid content and fasting insulin resistance index (FIRI) as well as liver and muscle glycogen and lipid contents were determined. Final data were analyzed by ANOVA and post-hoc Tukey’s test. Liver glycogen contents and blood levels of glucose and insulin were significantly increased in high sucrose (HS) group compared with control group. A significant decrease was observed in blood glucose and insulin levels, FIRI, serum total lipid, triglyceride and VLDL-c as well as the liver triglyceride level, muscle and liver glycogen contents in 100 and 200 mg/Kg of TP-treated groups compared with HS group. Leptin level was significantly decreased in 50 and 100 mg/Kg groups compared with HS group. The treatment with T. polium ethyl acetate extract (TP-EAE) induced a dose-dependent reduction in serum, liver and muscle triglyceride (TG) and liver glycogen content levels, as well as serum insulin. These effects may be attributed, in part, to the hypolipidemic effect of TP flavonoids; otherwise, the hepatoprotective and antioxidant activity of TP-EAE may improve the liver function and reverse harmful sucrose effects.

Scorpion venom toxicity is of major concern due to its influence on human activities and public health. We investigated the in-vitro process of cell death caused by two Iranian scorpions Odontobuthus doriae and Bothutus salceyi venom on human cell lines. The aim of this study was to provide further information about triggering cell death and suggestion of methods for the elimination of unwanted cells such as tumor cells. The cytotoxicity and apoptosis induced by effect of scorpion venoms on five established eukaryotic cell lines are analyzed on different human cell lines. All cultured cell lines were incubated with varying doses of scorpion venom for 24 h at 37°C. Control culture was treated with an equal amount of SFM. The percentage of cell survival was measured using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) colorimetric assay. Our data demonstrated that Bothutus saulcyi, does not show cytotoxic effect on any of the used cell lines. Odontobuthus doriae, however, has resulted a dose dependent cytotoxic effect with maximum at 1 ug/mL on 1321N1 glioma like cell line. Then the cytotoxic venom of O. doriae was fractionated using Sephadex G50 gel chromatography. The toxic fractions on mouse used to Cytotoxicity assay on 1321 N1 cell line and data demonstrated that, the fraction F3 showed a dose dependent Cytotoxicity assay. Further studies to explode the mode of action of these venoms are recommended and purification of the toxic fraction should be done.

A fiber coating from polyaniline (PANI) was electrochemically prepared and employed for Solid phase micreoextraction (SPME). The PANI film was directly electrodeposited on the platinum wire surface using cyclic voltametry (CV) technique. The same method was applied for the preparation of SPME fiber coated by polyaniline multiwalled carbon nanotubes (PANI/MWCNTs) composite. The concentration of sulfuric acid for electropolymerization was 0.1 M in the presence of 0.045 M aniline in aqueous solution. For the electrodeposition of PANI/MWCNT composite, 4 µg/mL of MWCNTs was dispersed into the solution. Film coating was carried out on the platinum wire by repetitive cycling of potentials between 0 and 1.0 V at the scan rate of 0.05 V/s. The applicability of these coatings were assessed through employing a laboratory-made SPME injecting device and gas chromatography with mass spectrometry (GC-MS) for the extraction of palmitic acid and oleic acid from chloroform. The developed method proved to be simple and easy, offering high reproducibility. Both PANI coated and PANI/CNT coated probes had the ability to concentrate palmitic acid and oleic acid on their coating and produced strong signals in GC-MS chromatograms. In the meantime, PANI/CNT coated SPME probes produced signals which were stronger than those produced by PANI coated SPME probes. The amount of extracted palmitic acid and oleic acid from chloroform by the PANI/MWCNTs coating was about 6 and 12 times higher than the amount extracted by plane PANI SPME fibers respectively. It could be suggested that the composite material with CNTs has both an increased surface area and an elevated absorptive capacity which leads to this overall increase in extracted palmitic acid and oleic acid.

Ischemia reperfusion injury (IR injury) is a common problem in clinical conditions. Researches have frequently revealed that ATP- sensitive potassium (KATP) channels and nitric oxide plays a role in protection against ischemic injury in skeletal muscle. The present study aimed at evaluating the possible link between this two pathways. Sixty-eight male wistar rats, were pretreated with saline, diazoxide (KATP opener; 45 mg/Kg, IP), glibenclamide (KATP inhibitor; 5 mg/Kg), or L-NAME (iNOS inhibitor; 20 mg/Kg, IP) before 3 h ischemia and 2 h reperfusion. Activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and the level of malondialdehyde (MDA) and expression of iNOS were measured in muscle tissue. Tissue MDA content was significantly increased by IR (p < 0.001). Diazoxide significantly decreased the IR-induced elevation of tissue MDA level (p < 0.05) and Glibenclamide increased MDA (p < 0.05 vs. IR group). L-NAME inhibited the effect of diazoxide on decreasing MDA (p < 0.01 vs., diazoxide+IR group) and IR decreased the activity of SOD and CAT (p < 0.01), while pretreatment with diazoxide increased activity of SOD and CAT (p < 0.01). Glibenclamide decreased SOD and CAT activity after IR (p < 0.05). L-NAME pretreatment in diazoxide-treated rats abolished the effect of diazoxide on increasing the activity of SOD and CAT (p < 0.05 vs. Diaz+IR). Expression of iNOS was increased by IR (p < 0.01 vs. Sham group). Diazoxide significantly decreased iNOS expression after IR (p < 0.05 vs. IR). L-NAME significantly decreased iNOS expression after IR (p < 0.01) in diazoxide-treated rats (p < 0.01 vs. Diaz+IR).