Iranian Journal of Pharmaceutical Research
Year:2012 | Volume:11 | Issue:3|Papers Count:34

Mitochondria are unique organelles with major role in cellular function, not only as a major site of ATP production, but also by regulating energy expenditure, apoptosis signaling, and production of reactive oxygen species. They play a central role in determining the point-of-no-return for the apoptotic process. There is accumulating evidence supporting a direct link between mitochondria, oxidative stress and cell death. Although we have learned a great deal about mitochondria over the last decades, the field of mitochondrial research remains a fertile one and there is no doubt that there is still much to learn about new techniques now available.

One of the most common health problems are diseases of the cardiovascular system with a great bulk of disease burden; while a considerable number of cardiac patients undergo cardiac surgery; cardiac surgical procedures with cardiopulmonary bypass (CPB) are nowadays among the top list of surgical procedures.More than half of a century has passed since the introduction of total cardiopulmonary bypass (CPB). One of the main untoward effects of CPB is systemic inflammation; causing an “acute phase reaction” responsible for the production of other unwanted postoperative complications.The humoral and cellular components of the immune system are among the main parts of these compensatory mechanisms. There are a number of therapeutic agents used to suppress this inflammatory process.Since CPB is composed of a multitude of items, there are many studies assessing the possible methods and therapeutics for prevention or treatment of inflammation in patients undergoing CPB.According to a conventional classification, the anti-inflammatory methods are classified as either pharmacologic strategies or technical strategies. The pharmacologic strategies are those with the usage of one or more therapeutic agents; while the technical strategies are those that try to modify the CPB techniques. However, in this manuscript, the main pharmacological strategies are discussed.

The present work investigated the preparation of biodegradable beads with alginate polymer by ionotropic gelation method to improve the control release properties of the antibiotic rifampicin. Ionotropic gelation method was applied to prepare beads using calcium chloride (CaCl2) as cationic component and alginate as an anionic component. In this method, adding 0.5% w/v polyvinyl alcohol (PVA) to sodium alginate (3.0% w/v) and 2% w/v of polyvinyl pyrrolidone (PVP) to the CaCl2 solution were maintained to study the drug-loading and its released characteristics. The results showed that the addition of PVA and PVP significantly improved drug-loading, encapsulation efficiency and release characteristics. This demonstrates that the ionic gelation of alginate molecules offers a flexible and easily controllable process.

Intranasal vaccination is particularly a striking route for mucosal immunization, due to the ease of administration and the induction of both mucosal and humoral immunity. However, soluble antigens (Ag) are not sufficiently taken up after the nasal administration and need to be co-administered with adjuvants, penetration enhancers or encapsulated in particles. So, in this study, tetanus toxoid (TT) as a model Ag was entrapped in nonionic liposomes. The effect of the co-administration of Quillaja saponin (QS) as an adjuvant and cross-linked dextran microspheres (CDM) as penetration enhancer on immune responses was also studied. TT or TT+QS loaded liposomes were prepared by dehydration-rehydration method (DRV), followed by the extrusion through 400 nm filters. Some formulations were mixed with CDM. Liposomes were first characterized for their size range, mean diameter and morphology using particle size analyzer, optical and transmission electron microscopes. The volume mean diameter of liposomes was determined as 3836±179 and 624±114 nm before and after the extrusion, respectively. Structural efficiency of TT extracted from liposomes was confirmed by SDS-PAGE method. Encapsulation efficiencies of TT and QS were 44±8.50% and 60±6.02%, respectively. Rabbits were nasally immunized with various formulations and serum IgG titers and nasal lavage sIgA titers were determined by an ELISA method. TT+QS liposomes induced higher sIgA levels in comparison with TT liposomes (p<0.05), but the difference in serum IgG levels was not significant. Results indicated that neutral liposomes administered nasally, have a good potential for induction of mucosal immunity and co-encapsulation of QS and TT in liposomes improved the systemic and mucosal immune responses.

The main objective of this study was to prepare colon-specific pellets of budesonide, using pectin as film coating. Pellet cores of budesonide were prepared by extrusion / spheronization technique. Pectin, in different ratios was combined with Eudragit RS30D, Eudragit NE30D or Surelease to produce film coating. The dissolution profiles of pectin coated pellets were investigated in pH of 1.2 (2 h), pH of 7.4 (4 h) and pH of 6.8 in the absence as well as presence of rat cecal contents (18 h). Finally the selected formulation was evaluated on trinitrobenzenesulfonic acid (TNBS) induced ulcerative colitis in rat model, in comparison with conventional UC treatments. The dissolution profiles of pectin coated pellets showedthat the release of budesonide in presence of rat cecal content depended on adjuvant polymer, the ratio of pectin to polymer and film thickness. Coated pellets, prepared out of pectin and Surelease at a ratio of 1: 3 at coating level of 35% (w/w), could increase budesonide release statistically in presence of rat cecal content, while they released no drug in pH of 1.2 and 7.4. Animal experiments revealed the therapeutic efficacy of pectin/Surelease-coated pellets of budesonide in alleviating the conditions of TNBS-induced colitis model as reflected by weight gain, as well as improvement of clinical, macroscopic and microscopic parameters of induced colitis. This confirmed the ability of the optimized formulation for targeted drug delivery of budesonide to colon.

PEGylation is a well-established technique utilized to overcome the problems related to the therapeutic applications of peptides and proteins. Reasons for the PEGylation of these biological macromolecules include reducing immunogenicity, proteolytic degradation and rapid clearance from blood circulation. Octreotide is an octapeptide analogue of naturally-occurred somatostatin. This peptide has elimination half-life of less than 2 h that requires frequent daily subcutaneous or intravenous administration. To address this issue, octreotide modification was investigated using bis-thiol alkylating PEG reagent. The required bis-thiol alkylating reagent (V) was prepared from commercially available 4-acetyl benzoic acid in five steps. Octreotide disulfide bond was mildly reduced to liberate the two cysteine sulfur atoms followed by bis-alkylation to form PEGylated peptide. The PEG modification process was monitored through the reverse phase HPLC and 1H-NMR analysis. According to the HPLC chromatograms of PEGylation reaction, the peak with 30 min retention time was identified to be PEG-octreotide. In addition, 1H-NMR analysis showed a 7.44% degree of PEG substitution.

Due to the antitumor activity of Gallium MAL complex, as well as recent findings on new targeted biomolecules in malignant cells through this complex, the development of radiolabeled gallium complex for future imaging studies was targeted. Ga-67 labeled 3-hydroxy-2-methyl-4H-pyran-4-onate (Ga-67 MAL) was prepared using freshly prepared Ga-67 chloride and 3-hydroxy-2-methyl-4H-pyran-4-onate in a sodium salt form in 25 min at 40oC. The stability of the complex was checked in final formulation and human serum for 24 h followed by the administration in Swiss mice for biodistribution studies. The complex was prepared in high radiochemical purity (>97% ITLC, >98% HPLC) and specific activity of 13-14 GBq/mmol and was stable in the presence of serum for 48 h. The partition coefficient was calculated for the compound (log p=0.40). A detailed comparative pharmacokinetic study was performed for Ga-67 cation and Ga-67-MAL. The complex is more rapidly washed out from the circulation through kidneys and liver compared to Ga-67 cation and can be an interesting tumor imaging agent due to the fact that the cold compound is undergoing clinical trials as a safe and potential therapeutic agent for cancer.

In this assay, the evaluation of lipophilicity of four ACE-inhibitors and hydrochlorothiazide (HCTZ) with RP-TLC on cellulose layers was described using three binary solvent systems. The selected ACE inhibitors had sufficiently different structures which can indicate the method suitability for their lipophilicity evaluation as the model substances in comparison with HCTZ.In addition, the linear relationship between the RM-values and composition of mobile phases was established in the current study. From the regression data of the plots, the hydrophobicity parameters, R 0M and m, were determined and C0 parameter was calculated. The correlations between the experimentally obtained hydrophobicity parameters and calculated log p values were studied. Furthermore, the obtained results were compared with those previously obtained on RP-18 modified silica gel. Very good correlation (r=0.91; water-ethanol solvent system) between the chromatographically obtained hydrophobicity parameters and calculated log p values confirmed the selection of ACE inhibitors since lisinopril and quinapril were on the opposite sites of linear relationship. The results indicate that cellulose as an easily available sorbent can be successfully used for the lipophilicity investigation of examined substances with RP-TLC.

A sensitive fluorometric method for the determination of deferiprone (DFP) based on the formation of a luminescent complex with Tb3+ions in aqueous solutions is reported. The maximum excitation and emission wavelengths were 295 and 545 nm, respectively. The effects of various factors on the luminescence intensity of the system were investigated and optimized, then under the optimum conditions, the method was validated. The method validation results indicated that the relative intensity at 545 nm has a linear relationship with the concentration of DFP in aqueous solutions at the range of 7.2×10-9 to 1.4×10-5 M, the detection and quantification limits were calculated respectively as 6.3×10-9 and 2.1×10-8 M, precision and accuracy of the method were lower than 5% and the recovery was between 100.1% and 102.3%. The results indicated that this method was simple, time saving, specific, accurate and precise for the determination of DFP in aqueous solutions. After optimization and validation, the method successfully applied for determination of DFP in tablet dosage forms. The stoichiometry of the Tb3+-DFP complex was found as 1: 3 and the complex formation constant was 1.6×1016.

In this assay, edible cattle tissues from local markets of Ardabil, a Province of Iran, were examined for residues of tetracycline antibiotics (tetracycline, oxytetracycline and chlortetracycline). In total, 110 samples of triceps, gluteal muscle, diaphragm, kidney and liver were randomly obtained from the local markets of the city of Ardabil. Solid-phase extraction (SPE) and high-performance liquid chromatography (HPLC) methods were used to extract and analyze tetracycline antibiotic (TC) residues, respectively.The mean amount of total TC residues in all tested samples was 226.3±112.5 ng/g and the mean amount of the total TC residues in triceps, gluteal muscle, diaphragm, kidney and liver samples were 176.3±46.8, 405.3±219.6, 96.8±26.9, 672.4±192.0 and 651.3±210.1 ng/g, respectively. Additionally, 25.8% of muscle samples, 31.8% of liver samples and 22.7% of kidney samples contained amounts of TC residues beyond the maximum residue limit (MRLs). To reduce the TC residues found in edible cattle tissues, regulatory authorities should ensure that the cattle would undergo the proper withdrawal period from TCs before the slaughtering.

Wide range of quinazolinone biological properties including: antibacterial, anticancer, and anti-inflammatory activities encouraged us to synthesis some fused quinazolinone derivatives.Anthranilic acid was condensed with chloro acylchloride followed by dehydration to form the benzoxazinone intermediate; subsequent addition of an amine provided the fused quinazolinones. Deoxyvasicinone which was previously synthesized by a multi step complex reactions was prepared in three steps using the following procedure:LogP values of the compounds were measured using the shake flask method in octanol/water solvent system.The synthesized compounds were evaluated against six strains of bacteria (three Gram-positive and three Gram-negative) and three strains of fungi.Overall results of antimicrobial tests showed that the compounds had better bacteriostatic activity against Gram-negative bacteria. The obtained results of MBC revealed that these compounds had more significant bacteriostatic than bactericidal activities. Almost all of the screened compounds showed good activity againstC. albicans and A. niger. The obtained results of MFC indicated that these compounds had more significant fungistatic than fungicidal activities.

Considerable interest has been focused on the triazole structure, which has been known to possess a broad spectrum of biological activities such as antitumor, anti-inflammatory, antimicrobial, antiviral, and anticonvulsant activities. Before this, several heterocyclic compounds containing triazole were synthesized that had shown considerable anticonvulsant activity. As part of our continuous research in this area, we have synthesized several new 7-substituted-5-phenyl-[1,2,4] triazolo[1,5-a] pyrimidines (compounds 3a-3i, 5a-5j) through incorporating triazole moiety into the pyrimidine ring, which are expected to have the synergistic effect in dealing with the epilepsy. Their anticonvulsant activities were measured through the Maximal electroshock (MES) test. Carbamazepine and valproate were considered as positive control drugs with anticonvulsant effects [ED50=11.8 and 272 mg/Kg]. Amongst the compounds tested, compound 3f, 7-(heptyloxy)-5-phenyl-[1,2,4] triazolo [1,5-a] pyrimidine, showed potent anticonvulsant activity with ED50 84.9 mg/Kg, which was weaker than carbamazepine, but better than valproate.

The inhibitors of p53-HDM2 interaction are attractive molecules for the treatment of wild-type p53 tumors. In order to search more potent HDM2 inhibitors, docking operation with CDOCKER protocol in Discovery Studio 2.1 (DS2.1) and multidimensional hybrid quantitative structure-activity relationship (QSAR) studies through the physiochemical properties obtained from DS2.1 and E-Dragon 1.0 as descriptors, have been performed on 59 1, 4-benzodiazepine- 2, 5-diones which have p53-HDM2 interaction inhibitory activities. The docking resultsindicate that p-p interaction between the imidazole group in HIS96 and the aryl ring at 4-N of 1, 4-benzodiazepine-2, 5-dione may be one of the key factors for the combination of ligands with HDM2. Two QSAR models were obtained using genetic function approximation (GFA) and genetic partial least squares (G/PLS) based on the descriptors obtained from DS2.1 and E-dragon 1.0, respectively. The best model can explain 85.5% of the variance (R2adj) while it could predict 81.7% of the variance (R2cv). With this model, the bioactivities of some new compounds were predicted.

Helicobacter pylori (H. pylori) infection leads to different clinical and pathological outcomes in humans, including chronic gastritis, peptic ulcer disease and gastric neoplasia and even gastric cancer and its eradiation dependst upon multi-drug therapy. The most effective therapy is still unknown and prompts people to make great efforts to find better and more modern natural or synthetic anti-H. pylori agents. In this report 21 randomly selected herbal methanolic extracts were evaluated for their effect on inhibition of Jack-bean urease using the indophenol method as described by Weatherburn. The inhibition potency was measured by UV spectroscopy technique at 630 nm which attributes to released ammonium. Among these extracts, five showed potent inhibitory activities with IC50 ranges of 18-35 mg/mL. These plants are Matricaria disciforme (IC50:35 mg/mL), Nasturtium officinale (IC50:18 mg/mL), Punica granatum (IC50:30 mg/mL), Camelia sinensis (IC50:35 mg/mL), Citrus aurantifolia (IC50:28 mg/mL).

Five flavonoid glycosides were isolated from then -butanol soluble fraction of the ethanolic extract of Rapistrum rugosum and their structures were assigned from 1H- and 13C-NMR spectra (DEPT) with 2D NMR as quercetin-3- O-a-L-rhamnopyranoside (1), quercetin-3- O-b-D-xyloside (2), quercetin, 3-O-a- L-arabinopyranoside, 7- O-a-L-rhamnopyranoside (3), kaempferol 3- O-a-L-arabinopyranoside, 7- O-a-L-rhamnopyranoside (4) and rutin (5). The SRB cytotoxic assay was used to investigate the antitumor activities of n -butanol extract, compound 3 and its hexaacetate 3a, for the first time. Compounds 3 and 3a showed cytotoxic activity against the human cancer cell line, namely, HepG2 (hepatocellular carcinoma cell line) with IC50 (concentration of compound required to reduce cell survival by 50%) 0.86 mg/mL and 3.50 mg/mL, respectively. These results proved that compound 3, the major flavonoid of the n -butanol soluble fraction, has significant cytotoxic activity compared with the standard antitumor drug doxorubicin (0.60 mg/mL).

Gracilariopsis Persica (Rhodophyta) is one of the most abundant algae, introduced newly from the Indian Ocean. In this study, the main sterols of the algae have been isolated and identified. Separation and purification of the compounds was carried out on silica gel and sephadex LH20 column chromatography (CC) and high performance liquid chromatography (HPLC) to obtain five pure compounds 1-5. Structural elucidation of the compounds was based on the data obtained from H-NMR, 13C-NMR, DEPT and Mass spectroscopy. The separated compounds from Gp. Persica were identified as 22-dehydrocholesterol (1), cholesterol (2), stigmasterol (3), b-sitosterol (4) and fucosterol (5) based on the spectral data compared to those reported in literatures. Most of these sterols are noteworthy for their effectiveness in decreasing the plasma cholesterol, glucose and inflammation. The results of Brine Shrimp Cytotoxicity Assay indicated that the ethyl acetate extract of Gp. Persica showed a high cytotoxic effect against A. salina nauplii (LC50=4 g/mL). The methanol extract was no effective but the aqueous methanol extract was moderately effective (LC50=40 mg/mL) compared to berberine hydrochloride as a positive control (LC50=26 mg/mL).

The present study was designed to assess the cytotoxicity, anti-inflammatory and analgesic properties of methanol extract of Woodfordia fruticosa flowers. Cytotoxic activity of methanol extract of Woodfordia fruticosa flowers was tested using Artemia salina (Brine shrimp) bioassay. Two doses (400 and 600 mg/Kg) were evaluated for the anti-inflammatory activity against the carrageenan, histamine, dextran, serotonin and formaldehyde-induced rat paw edema, cotton pellet-induced granuloma and formaldehyde-induced analgesia in rats. In cytotoxicity study, extract caused 73% mortality of Brine shrimp larvae after 24 h at a concentration of 1000 mg/mL. The results of the anti-inflammatory study showed that the extract produced significant (p<0.05) decrease in paw volume in different models of paw edema. The extract also inhibited the formation of granuloma in cotton pellet-induced granuloma and reduced the frequency of formaldehyde-induced paw licking. These results showed that the methanol extract of Woodfordia fruticosa flowers have weak cytotoxic and potent anti-inflammatory compounds and justifies the traditional uses for the treatment of inflammatory conditions.

The present study was designed to investigate the immunomodulatory activity of the ethanolic extract of Tinospora cordifolia (Family: Menispermaceae) stem (climbing shrub, mango plant) at cellular level. For antioxidant study, the liver mitochondria were separated and the concentration of enzymes like lipid peroxidation (LPO), reduced glutathione (GSH), catalase (CAT) and superoxide Dismutase (SOD) were estimated; melatonin secretion characterization was carried out through SDS-PAGE. The spleen lymphocyte proliferation assay was performed through measuring its optical density at 570 nm using Elisa Reader. The cytokines viz. IL-2, IL-10 and TNF-a expression in spleen cells were determined through Real Time PCR. Tinospora cordifolia (Tc) ethanolic extract (100 mg/Kg/p.o.) increased the level of liver mitochondrial enzymes like GSH, CAT and SOD but decreased the level of LPO in liver as compared to the vehicle, SRBC and cyclophosphamide-treated groups. The secretion of melatonin via pineal gland was enhanced with Tc treatment. The extract also increased the spleen lymphocyte proliferation. In RT-PCR analysis, the expression of cytokines viz. IL-2, IL-10 and TNF-a was more in Tc -treated animals than vehicle and cyclophosphamide treatment. Hence, the study confirms the immunomodulatory activity of Tc stem through altering the concentration of antioxidant enzymes, increasing T and B cells and antibody which play an important role in immunity, enhancing the concentration of melatonin in pineal gland and increasing the level of cytokines like IL-2, IL-10 and TNF-a which plays an important role in immunity.

Date is one of the world’s oldest food-producing plants wich has always played an important role in the economy and social life. Various researchers examined chemical composition and nutritional values of edible parts of dates while limited information about chemical composition and nutritional quality of date seed is available. In this study, fatty acid composition and total tocopherol content of 14 Iranian date seed oils were studied. Statistical analysis was performed through SPSS computing package. According to the fatty acid profiles, seven fatty acids were found through nearly 50% oleic acid in seeds. Shekar cultivar by 51.40% had the maximum amount and Lasht cultivar by 33.38% had the minimum amount of oleic acid. Tocopherol content in the samples varied between 33.86 mg vit E/g oil for Shahabi2 to 10.09 mg vit E/g oil for Shekar. Tocopherol content was 1.88 and 0.61 mg respectively in one-gram seed of these two cultivars. Iranian date seed oils classified as oleic-lauric oil, had a high amount of oleic acid and could serve as a profitable source of valuable oils for industrial applications.

The side effects of synthetic antioxidants have been considered in different studies. Accordingly, there is an increasing interest toward the use of natural substances instead of the synthetic ones. In this study, the aqueous and ethanolic extracts of Pistacia vera leaves and fruits as well as hydroalcoholic extract of gum were tested for a possible antioxidant activity using in vitro methods. Deoxyribose assay, erythrocyte membrane lipid peroxidation and liver misrosomal non- enzymatic lipid peroxidation tests were used as an in-vitro model for determination antioxidant activity. The extract were evaluated at different concentratios: 25, 100, 250, 500 and 1000 mg/mL. In all procedures, all extracts showed free radical scavenging activity. The effect of ethanolic extract of P. vera fruit at 1000 mg/mL was quite similar to positive control (DMSO 20 mM) in deoxyribose method. In two other tests, the ethanolic extracts of fruits and leaves were more effective than the aqueous extracts to inhibit malondialdehyde generation. Phytochemical tests showed the presence of flavonoids and tannins in Pistocia vera extracts. The present study showed that extracts of different part of P. vera have antioxidant activity in different in vitro methods. The ethanolic extracts of leaves and fruits showed more roles for antioxidant properties and gum hydroalcoholic extract demonstrated less antioxidant effect.

Several lichen species have been used for medicinal purposes throughout the ages, and they were reported to be effective in the treatment of different disorders including tuberculosis, hemorrhoids, ulcer, dysentery and cancer. It is revealed that they may be easily accessible sources of natural drugs that could be used as a possible food supplement or in pharmaceutical industry after their safety evaluations. However, so far, the nature and/or biological roles of plenty of lichenes have not been elucidated exactly. The aim of this study was to investigate the genetic and oxidative effects of water extracts of three different lichen species; Hypogymnia physodes, Ramalina polymorpha and Usnea florida in cultured human blood cells (n=5) for the first time. All lichen species were collected from the Erzurum and Artvin provinces (in Turkey) during August 2010. The lichen extracts were added into culture tubes at various concentrations (0 to 2000 mg/L). Chromosome aberrations (CA) and micronucleus (MN) tests were used for genotoxic influences estimation. In addition, biochemical parameters (total antioxidant capacity (TAC) and total oxidative stress (TOS)) were examined to determine oxidative effects. In our in-vitro test systems, it was observed that all tested lichen extracts had no mutagenic effects on human lymphocytes. Furthermore, these extracts exhibited antioxidant properties due to the type of lichen species added to the cultures. In conclusion, these lichens can be a new resource of therapeutics as recognized in this study with their non-mutagenic and antioxidant features.

In the present study we aimed to evaluate the effects of methanolic extracts of the bulbs of Garlic (Allium sativum L., Alliaceae) and Persian shallot (Allium ascalonicum L., Alliaceae) and leaves of Sage (Salvia officinalis L., Lamiaceae), ASE, AAE and SOE respectively, on the antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) activities and on the levels of plasma lipids profiles such as triglycerides (TG), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL) in Alloxan diabetic Wistar rats.In comparison with diabetic control rats in diabetic treated rats, AAE increases the activities of SOD (65%), GPX (43%) and CAT (55%). ASE and SOE increase SOD activity by 60% and 33% respectively. ASE reduces TC (34%), SOE decreases TG (40%) and LDL (30%) and AAE reduces VLDL (24%). Metformin exhibits mild antioxidant and hypolipidemic properties. Results of quantitative phytochemical analysis show that the methanolic garlic and Persian shallot bulbs extracts contain secondary metabolites including alkaloids (3.490% and 3.430%), glycosides (18.023% and 13.301%) and saponins (0.812% and 0.752%). Methanolic sageleaves extract contains flavonoids (1.014%), glycosides (23.142%) and saponins (2.096%). The total phenolic contents of ASE, AAE and SOE were in order 4.273, 3.621 and 6.548 mg GAE/g dry weight (DW).These results suggest thatAllium sativum, Allium ascalonicum and Salvia officinalis are beneficial in the control of diabetes by noticeable antioxidant and hypolipidemic properties.

Buthotus schachis one of the most dangerous scorpions in tropical part of Iran. The effects of its crude venom at 1, 3, 10 mg/mL and its obtained fractions by gel filtrations were investigated on neuromuscular transmission. CBC and MHD indirectly and directly stimulated preparations techniques were used to study their possible pre or post junctional activities. At 3 and 10 mg/mL (not at 1 mg/mL), BS venom caused initiall increase in twitch height followed by blockage due to large contraction that responded gradually at the same time. Contracture responses to exogenous Ach (1-2 mM, 30 sec) and Carb (30-40 mM, 60 sec) in the presence of the venom were not increased which does show no anticholinstrease effects. Furthermore Contracture response to KCl (20-40 mM, 30 sec) does changed exposure to venom in CBC preparations. On the other hand the effects of the venom in response to directly stimulated preparations was shallower than in indirect stimulated preparations. So in agreement with KCL response BS venom affects mostly prejunctionally to facilitate the neurotransmitter release rather than postjunctionally effects. To access bioactive components, seven fractions were collected by gel filtrations techniques. Among the fractions F6, LD50=21 mg<F4, LD50=35.5 mg<Venom LD50=84 mg per mice were more toxic respectively. Both fractions show the same effects but stronger than venom on twitch height responses in indirectly stimulated CBC preparations.Finally, according to our results venom as well as fractions F4 and F6 act mostly prejunctionally on Ach release. More attempt is carrying out to study their effects on ion channel activities.

The study was aimed at evaluating the antioxidant activity of hydroalcoholic solution extracts of Urticadioica L. (UD), Malva neglecta Wallr. (MN) plants and their mixture. In this study, flower (UDF), root (UDR), seed (UDS) and leaf (UDL) parts of UD and flower (MNF) and leaf (MNL) parts of MN were used. The antioxidant properties of hydroalcoholic extracts and their mixture were evaluated using different antioxidant tests such as total antioxidant activity, reducing power, superoxide anion radical scavenging, hydrogen peroxide scavenging, free radical scavenging, and metal chelating activity for comparison. In addition, total phenolic compounds in the extracts of both plants were determined as catechin equivalent. The various antioxidant activities were compared to natural and synthetic standard antioxidants such as BHA, BHT and a-tocopherol. According to FTC method, the both extracts exhibited strong total antioxidant activity. At the concentration of 100 mg/mL, Hydroalcoholic extracts of UDS, UDR, UDF, UDL, MNF, MNL, and UD-MN showed 81.7%, 79.8%, 78.3%, 76.4%, 77.3%, 74.1%, and 80.7%, respectively. Comparable, 100 mg/mL of standard antioxidants BHA, BHT and a-tocopherol exhibited 66.2%, 70.6%, and 50.1% inhibition on peroxidation of linoleic acid emulsion, respectively. In addition, UD-MN showed strong superoxide anion radical scavenging activity comparable with UDR, UDF, UDL, MNF, and MNL. Based on the findings, plants mixture was commonly found to have synergistically higher antioxidant activity.

Four known flavonoids: quercetin 3-O -b-D-rutinoside (Q3Rut), myricetin 3- O -b-D-galactopyranoside (M3Gal), quercetin 3- O -b-D-galactopyranoside (Q3Gal) and quercetin 3- O -b-D-glucopyranoside (Q3Glc), for the first time were isolated from aerial parts of Euphorbia microsciadia. The chemical structure of them was elucidated on the basis of 1 and 2 D-NMR spectra and different spectroscopic techniques. The immunomodulatory activities of isolated compounds were compared using standard T-cell proliferation assay. These data showed that lymphocyte suppression activity of flavonoids (1-4) were comparatively lower than prednisolon as a standard drug. Immunosuppressive activity of flavonoids with hydroxyl groups at both 3′-and 4′-positions in their B-ring (Q3Gal) were more than those with 3′-, 4′-and 5′-hydroxyl substitution (M3Gal). In these compounds, Q3Gal showed the most inhibitory activity, whereas M3Gal showed the least lymphocyte antiprolifeartive activity.

Our previous studies revealed an inhibitory effect of ICD-85 (Venom derived peptides) on breast cancer cell line MDA-MB231. ICD-85 was also confirmed byin-vivo studies to suppress the breast tumor in mice. However, the exact mechanism of ICD-85 was unknown. Hence, the present study was undertaken to assess the mechanism of ICD-85 effect as an anti-proliferative agent of cancer cells. The effect of ICD-85 on proliferation of HL-60 cancer cells was determined by using the MTT assay. The morphological changes of ICD-85 treated HL-60 cells were observed under transmission electron microscope (TEM). DNA fragmentation analysis was also carried out using gel electrophoresis. ICD-85 induced the marked inhibition of HL60 cell proliferation with an IC50-value of 0.04 mg/mL following 24 h of incubation. ICD-85 treated cells when compared with untreated cells, showed nuclear material condensation, endoplasmic reticulum dilation, mitochondria swelling or degradation, increased cytoplasmic vacuoles, reduction or disappearance in cytoplasmic process and decreased nuclear/cytoplasmic ratio was observed. The characteristic DNA ladder formation of ICD-85-treated cells in agarose gel electrophoresis confirmed the results obtained through the electron microscopy. The results of the present study indicated that ICD-85 inhibited the cancer cell proliferation by inducing cell apoptosis.

The role of inflammation has been shown in the pathogenesis of epilepsy, while glucocorticoids and adrenaline have anti-inflammatory effects. The aim of the present study was to investigate the effects of adrenaline, prednisolone, and indomethacin on caffeine-induced epilepsy (epileptiform activity) in rats and to examine the mechanism of the pro-epileptic effect of indomethacin. The adrenalectomized rats that had been given only adrenaline (the control group) did not die; however, adrenaline did not prevent the adrenalectomized rats which were given prazosin, phenoxybenzamine, yohimbine, metoprolol, and propranolol from dying. In the rats given propranolol+adrenaline, the rate of death was 100%, while this rate was 50% in the groups receiving prazosin+adrenaline, phenoxybenzamine+adrenaline, and metoprolol+adrenaline. The rate was 75% in the group given yohimbine+adrenaline. Prednisolone increased the degree of convulsion in adrenalectomized rats. Over-reduction in the blood catecholamine level made epileptogenesis more severe. It was observed that adrenaline pressed epileptogenesis via its own receptors (a- 1, a- 2, b- 1, b- 2). It was also revealed that all of the adrenergic receptors were responsible due to antiepileptic activity; b- 2 receptors played the most important role. It was observed that both acute and chronic indomethacin administration reduced the catecholamine levels. The situation in which acute administration of indomethacin did not affect epileptogenesis might originate from the fact that the structure of indomethacin did not significantly increase the corticosterone level.

A selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/ MS) method was developed for the determination of berberine, palmatine and jatrorrhizine in rat plasma. Target compounds, together with the internal standard (metronidazole), were extracted from rat plasma samples by protein precipitation with acetonitrile-methanol (1: 2, v/v). Chromatography was carried out using a C18 column (150 × 4.6mm, 5mm) under isocratic elution with water (containing 0.3% formic acid) -acetonitrile (30: 70, v/v). The mass spectrometric detection was performed by selected reaction monitoring (SRM) mode via electrospray ionization (ESI) source operating in positive ionization mode. The method was linear over the concentration range of 0.2-100 ng/mL for all components. The intra- and inter-day precision values were less than 14.7% and the deviations were within±9.0%. The validated method was applied to the comparative pharmacokinetic studies of berberine, palmatine and jatrorrhizine after oral administration of Rhizoma coptidis and Zuojinwan. The results indicated that the pharmacokinetics of berberine, palmatine and jatrorrhizine were significantly different between different groups.

Clindamycin is a lincosamide antibiotic which is approved for the treatment of Anaerobic, Streptococcal and Staphylococcal infections. There has been an increased interest in the use of clindamycin since it achieves high intracellular levels in phagocytic cells, high levels in bone and appears to have an antitoxin effect against the toxin elaborating strains of streptococci and staphylococci. Clindamycin is considered as a bacteriostatic antibiotic, while it is bactericidal against some strains of Staphylococci, Streptococci and Anaerobes such as B. fragilis. Its major disadvantage is its propensity to cause antibiotic-associated diarrhea. In spite of expanded use of clindamycin in bone infections, the adverse reactions of this antibiotic are minor. Polyarthritis is a rare adverse effect of this antibiotic.In this case report, we studied a 75-year-old male patient with past history of drop attack and subdural hematoma who developed skull osteomyelitis after the surgery. After two weeks of intravenous antibiotic therapy, wound discharge was stopped and the patient was discharged from the hospital with the maintenance oral antibiotic therapy including clindamycin 300 mg q8 h, ciprofloxacin 500 mg q12 h and rifampin 600 mg fasting.Six days after the beginning of oral antibiotics, right wrist monoarthritis was developed. It was unresponsive to nonsteroidal anti-inflammatory drug and improved after decreased doses of clindamycin. As best as we know, monoarthritis was not reported with clindamycin previously.

Background Awareness of pharmacists about counterfeit drugs is necessary for health improvement in community. The purpose of the present study is to assess the knowledge and measure the professional attitude and practice of Iranian pharmacist about counterfeit drugs. In August 2008, a knowledge, attitude and practice (KAP) study was performed in a national sample of 794 pharmacists who participated in an Iranian Pharmacist Association congress. A questionnaire was prepared to collect Demographic and professional characteristics, Knowledge, attitude and practice of pharmacists regarding counterfeit drugs. The mean percent of participants who answer each practice questions correctly is 13.62% and none of questions have more than 14.7% of correct answer, while the participants’ attitude towards the subject is at high level. None of demographic factors represented a significant relationship with knowledge and the only related parameters with attitude, were age and gender. Increasing age of pharmacists resulted in attitude improvement (p=0.013) and women›s attitudes were better than men (p=0.05).The only related parameters with practice, were the number of working hours per a week and attitude. Increasing the number of working hours per a week, resulted in decreasing the desirable practice (p=0.041) and attitude also had a direct relationship with practice (p=0.011). Conclusion The most important finding in the present study was the pharmacists› low knowledge and practice level about counterfeit drugs, while their attitude towards this subject was at a high level. The results point out the need for designing and implementing educational programs.

3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins), are effective serum cholesterol-lowering agents which also have anti-inflammatory properties. The objective of this study was to evaluate the effect of atorvastatin on bronchial hyperresponsiveness.Adult patients (age 14 to 65 years) with bronchial hyperresponsiveness (BHR) diagnosis based on the spirometry with methacholine challenge test were entered into the study. The study was conducted in the National Research Institute of Tuberculosis and Lung Disease. Patients were randomized to receive either atorvastatin 20 mg/day or placebo for 4 weeks. Spirometric parameters were determined at baseline and at completion of the study. Twenty two patients with the age of 32.95±10.30 years completed the trial.Changes in airway responsiveness categories (moderate to severe, mild, borderline, normal) after the intervention were not significant in atorvastatin group as in placebo group (p-value=0.131 for atorvastatin group and p-value=0.305 for placebo group). Also, changes in methacholine solution number (different concentrations of methacholine) which caused at least 20% decrease in FEV1 were not significant between groups (p-value=0.089). Although we could not find a significant difference, the patients’ fall in FEV1 in atorvastatin group was observed in higher concentrations of methacholine. Median before treatment versus after treatment in atorvastatin group was 1 versus 4 mg/mL, while those were 2 versus 1 mg/mL in placebo group.This study showed a better but not significant hyperresponsiveness control in the treatment group. The result might be presented more pronounced, if we could increase the sample size.

Gabapentin seems to be a safe and well tolerated medication for treating heroine dependence. This study examined the efficacy of gabapentin for relieving withdrawal-related pain due to heroin use.Sixty men were recruited from an inpatient psychiatric ward of Fatemieh hospital in Semnanand randomized to receive either placebo (n=30) or gabapentin (1800 mg/day) (n=30) for 7 days. Subjective Opioid Withdrawal Scale (SOWS) was measured as a self-administered scale for grading body pain at baseline, and on days 1, 2, 3, 4, 6, and 7.Mean of pain score had a significant decrease trend in both gabapentin and placebo groups. Pain severity during the most of detoxification duration was significantly lower in gabapentin group compared with the placebo group.It is suggested that gabapentin may have an effective role in removing heroin withdrawal-related pain.

Export and the readiness to export constitute the first step of international marketing, which are affected by both internal and external factors of firms. One of the most important internal factors is the presence of skilled personnel. The purpose of this study was to define the relationship between staff qualification and encouragment with the readiness level of Iranian pharmacuetical firms for engagement in export marketing.The research was based on a single case study on a basket of seven leading domestic firms. For the bias reduction, questionnaires as well as interviews with managers were used.The performance of the studied factor was lower than the desired level for export readiness and there was much scope for improvement in staff qualifications to achieve such readiness.The results of this research enable small and medium-sized pharmaceutical companies to evaluate their staff qualification levels needed for export readiness and to detect their shortcomings in order to improve them.

The present study was designed to explore the flavonoid contents and the radical scavenging activities of 50% ethanol extracts of leaves, stems, rachis and roots of Dryopteris erythrosora. The total flavonoid contents in various parts were determined as: stems > roots > rachis > leaves. All extracts from different parts of D. erythrosora showed strong bioactivities. The DPPH free radical scavenging abilities of extracts were determined as: stems > root > rachis >> leaves. This trend is reciprocal proportion to the total flavonoid contents in leaves, stems, rachis and roots of D. erythrosora extracts. The superoxide anion scavenging abilities of ethanol extracts were determined as: stems > leaves > rachis > root. It illustrated that there are strong superoxide anion scavengers in D. erythrosora. It is worth to separate and identify these components in future.