Advanced Pharmaceutical Bulletin
Year:2018 | Volume:8 | Issue:2|Papers Count:20

Human skin could be a prime target to deliver drugs into the human body as it is the largest organ of human body. However, the main challenge of delivering drug into the skin is the stratum corneum (SC), the outer layer of epidermis, which performs the main barrier function of the skin. Scientists have developed several techniques to overcome the barrier properties of the skin, which include other physical and chemical techniques. The most common and convenient technique is to use special formulation additives (chemical enhancers, CEs) which either drags the drug molecule along with it or make changes in the SC structure, thereby allowing the drug molecule to penetrate in to the SC. The main focus is to deliver drugs in the certain layers of the skin (for topical delivery) or ensuring proper percutaneous absorption (for transdermal delivery). However, skin drug delivery is still very challenging as different CEs act in different ways on the skin and they have different types of interaction with different drugs. Therefore, proper understanding on the mechanism of action of CE is mandatory. In this article, the effect of several CEs on skin has been reviewed based on the published articles. The main aim is to compile the recent knowledge on skin-CE interaction in order to design a topical and transdermal formulation efficiently. A properly designed formulation would help the drug either to deposit into the target layer or to cross the barrier membrane to reach the systemic circulation.

To describe the chemical structure and characterize physico-chemical properties of organometallic complexes it is necessary to use a complex set of analysis methods. Thus, this review has been compiled as a relevant guide which includes the most commonly used methods of analysis in the study of silver complexes with antibacterial quinolones, compounds with promising biological potential. This selection of analysis methods puts on balance the obtained data and the accessibility of the experimental approach. The steps to follow in order to obtain reliable structural information about organometallic complexes of silver, particularly the silver complexes of antibacterial quinolones, are established and presented in the review.

Emulsifiers are a large category of compounds considered as surface active agents or surfactants. An emulsifier acts by reducing the speed of chemical reactions, and enhancing its stability. Bioemulsifiers are known as surface active biomolecule materials, due to their unique features over chemical surfactants, such as non-toxicity, biodegradability, foaming, biocompatibility, efficiency at low concentrations, high selectivity in different pH, temperatures and salinities. Emulsifiers are found in various natural resources and are synthesized by Bacteria, Fungi and Yeast. Bioemulsifier’ s molecular weight is higher than that of biosurfactants. Emulsion’ s function is closely related to their chemical structure. Therefore, the aim of this paper was to study the various bioemulsifiers derived from microorganisms used in the drug and food industry. In this manuscript, we studied organisms with biosurfactant producing abilities. These inexpensive substrates could be used in environmental remediation and in the petroleum industry.

Purpose: Unique physiochemical properties of Fe2O3 nanoparticles make them great agents to serve as therapeutic and diagnostic nanoparticles (NPs). In this study, we developed gold coated Fe2O3 nanoparticles for photothermal therapy of breast cancer cells. Methods: Fe2O3 nanoparticles was prepared via microemulsion method and their surface was modified via gold. Differential light scattering (DLS) and transmission electron microscopy (TEM) methods were applied to evaluate physicochemical properties of NPs. Gold coated NP was further modified with MUC-1 aptamer as a targeting agent to increase drug delivery into the desired tissue. To evaluate cytotoxicity of prepared cells, MTT assay was employed. Targeting ability of aptamer modified NPs was assessed through confocal microscopy and flow cytometry method. Subsequently, MCF-7 and CHO cells were treated with aptamer modified NPs and were then irradiated via near infrared light (NIR) to produce heat. Results: The morphology of NPs was spherical and monodisperse with the size of 16 nm, which was confirmed via DLS and TEM. Confocal microscopy and flow cytometry results indicated that aptamer modified NPs had higher uptake compared to bare NPs. Finally, NIR exposure results revealed that higher uptake of NPs and application of NIR led to significant death of MCF-7 cells compared to CHO cells. Conclusion: To sum up, aptamer modified Fe2O3 nanoparticles showed higher uptake by cancerous cells and led to eradication of cancerous cells after exposure to NIR light.

Purpose: To determine the effect of natural clinoptilolite (CLN) and nano-sized clinoptilolite (NCLN) on lipid profile, food intakes (FI) and weight changes in streptozotocin (STZ) induced diabetic rats. Methods: In this experimental study, 36 rats were randomly divided into two groups: diabetic group which was injected STZ (60 mg/kg BW), and a non-diabetic group. Three days after diabetes induction, each of these groups was randomly divided into 3 subgroups of 6 animals ((1) control, (2) 1%/food CLN, (3) 1%/food NCLN). The animals were supplemented for 28 days, starting three days after STZ administration. At the end of the study, blood was drawn for biochemical assays. The weights and FIs of the rats were measured at the beginning and end of each week. Results: Our findings revealed that there was no significant change in lipid profile, 28 days after administration of STZ in diabetic rats. Low density lipoprotein (LDL) was increased slightly in diabetic rats treated with NCLN without any significant changes in other lipid profile parameters in the other groups. Weight was reduced significantly in diabetic rats. Administration of CLN and NCLN prevented further weight loss in diabetic rats. All groups treated with STZ had higher food intake during the study. Conclusion: Lack of beneficial changes in lipid profile may be attributed to short study duration, insufficient for appearance of lipid abnormalities. Given the partial improvement in weight status and lack of undesirable effects of clinoptilolite supplementation, further research is recommended in subjects with typ1 diabetes mellitus.

Purpose: The goal of this study was to improve the solubility and dissolution behavior of Raloxifene Hydrochloride (RH) using Spray Freeze Drying (SFD) technique. Methods: For achieving this goal, series of samples containing RH with polyvinylpyrrolidone (PVP) or hydroxypropyl beta cyclodextrin (HPβ CD) used as solubility enhancers were prepared and microparticles were formed via SFD. The resultant microparticles were physicochemically characterized. Morphology of the microparticles were observed using Scanning Electron Microscopy (SEM). High Performance Liquid Chromatography (HPLC) was used for analyzing the solubility and dissolution profile of the samples. Results: Fourier Transmission Infrared (FTIR) spectra showed that SFD processed compositions did not affect chemical structure of RH. SEM and Thermal Gravimetric Analysis (TGA) revealed that the fabricated spherical and highly porous microparticles were in amorphous state. SFD processed powders showed superior solubility and dissolution behavior; where, 80% of the drug was dissolved within 5 minutes. Conclusion: SFD method can be a promising alternative for enhancing the solubility of poorly water soluble compounds.

Purpose: The objective of this study was to synthesize and statistically optimize dimethyl fumarate (DMF) loaded solid lipid nanoparticles (SLNs) for better management of multiple sclerosis (MS). Methods: SLNs were formulated by hot emulsion, ultrasonication method and optimized with response surface methodology (RSM). A three factor and three level box-behnken design was used to demonstrate the role of polynomial quadratic equation and contour plots in predicting the effect of independent variables on dependent responses that were particle size and % entrapment efficiency (%EE). Results: The results were analyzed by analysis of variance (ANOVA) to evaluate the significant differences between the independent variables. The optimized SLNs were characterized and found to have an average particle size of 300 nm, zeta potential value of-34. 89 mv and polydispersity index value < 0. 3. Entrapment efficiency was found to be 59% and drug loading was 15%. TEM microphotograph revealed spherical shape and no aggregation of nanoparticles. In-vitro drug release profile was an indicative of prolonged therapy. In-vivo pharmacokinetic data revealed that the relative bioavailability was enhanced in DMF loaded SLNs in Wistar rats. Conclusion: This study showed that the present formulation with improved characteristics can be a promising formulation with a longer half-life for the better management of MS.

Purpose: A lot of plants are available which can produce nanoparticles used in medicine, life sciences, and the pharmaceutical industry. The present study aims to introduce safe biological and eco-friendly methods for synthesizing silver nanoparticles (AgNPs) by using Saturaja rechengri Jamzad extract, which can replace traditional chemical methods. In addition, the chemical nature and antimicrobial activities were identified and accordingly the anticancer effects of AgNPs was successfully reported on colon cancer cells (HT-29). Methods: Light and ultrasound, as two green chemistry techniques were first used for AgNPs synthesis. Then, morphological and crystalline structure of AgNPs was evaluated by scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis, respectively. In addition, functional groups were determined by using the Fourier transform infrared spectroscopy (FTIR) spectrum. Further, a maximum adsorption of AgNPs was observed in UV-visible spectrum. In the next stage, antibacterial activity of green synthesized AgNPs was evaluated against two pathogenic bacteria including Escherichia coli and Staphylococcus aureus. Finally, the cytotoxicity of AgNPs on HT-29 at different concentrations and times of AgNPs was determined by MTT assay. Results: The findings indicated that the synthesis of AgNPs by ultrasonic technique leads to smaller particle size and more distribution. Based on the results of MTT test for calculating the IC50%, the anti-proliferative effects of the light and ultrasound AgNPs were observed on HT-29 cell lines depending on the dose and time. Finally, the AgNPs had the most cytotoxicity HT-29 cell lines at 100 μ g/ml concentration although the lowest toxicity effect was reported on HEK-293 cell lines at the same conditions. Conclusion: The change in the concentration, physical and chemical properties of AgNPs including the form and size of particles, and their type of covering and fields can influence the induction of cytotoxicity and morphological change in the treated cells. The present research opens a new horizon on the development of new biological and cytotoxicity agents.

Purpose: Solid lipid nanoparticles (SLNs) have been proven to possess pharmaceutical advantages. They have the ability to deliver hydrophilic drugs through lipid membranes of the body. However, the loading of such drugs into SLNs is challenging. Hydrophilic nicotinamide, a histone deacetylase inhibitor, is used to establish SLNs with enhanced encapsulation efficiency by using statistical design. Methods: The possible effective parameters of these particles’ characteristics were determined using pre-formulation studies and preliminary tests. Afterwards, the Response Surface Method (RSM) was utilized to optimize the preparation condition of SLNs. The effect of the amount of lipid, drug, surfactant, and the mixing apparatus were studied on particle size, zeta potential, and encapsulation efficiency of the obtained particles. The acquired particles were characterized in respect of their morphology, in vitro release profile, and cytotoxicity. Results: According to this study, all the dependant variables could be fitted into quadratic models. Particles of 107 nm with zeta potential of about-40. 9 and encapsulation efficiency of about 36% were obtained under optimized preparation conditions; i. e. with stearic acid to phospholipon® 90G ratio of 7. 5 and nicotinamide to sodium taurocholate ratio of 14. 74 using probe sonication. The validation test confirmed the model’ s suitability. The release profile demonstrated the controlled release profile following the initial burst release. Neither the nicotinamide nor the SLNs showed toxicity under the evaluated concentrations. Conclusion: The acquired results suggested the suitability of the model for designing the delivery system with a highly encapsulated water soluble drug for controlling its delivery.

Purpose: The current study aims the lymphatic delivery of leflunomide loaded nanostructured lipid carriers (LNLC) for the treatment of rheumatoid arthritis, mainly focussed to enhance the lymphatic delivery via chylomicron formation, improved bioavailability and reduced systemic toxicity. Methods: Melt emulsification ultra-sonication method was used to formulate the nanostructured lipid carrier (NLC) containing leflunomide. Four batches were prepared by using various concentration of surfactants (tween 80 and poloxmer 188) and lipid mixtures (stearic acid and oleic acid). All the formulations were studied for various physiochemical properties Results: The formulation with increased concentration of lipid and surfactants showed highest entrapment efficiency (93. 96 ± 0. 47%) and better drug release (90. 35%) at the end of 48 hrs. In vivo tests were carried out to determine the antiarthritic potential of the formulation in Sprague-dawley rats for a duration of 30d. The effect was evaluated by measuring the reduction in knee thickness. LNLC showed a marked reduction in inflammation compared to standard drug. Intestinal lymphatic uptake studies of LNLC were performed by intraduodenal administration and compared with leflunomide drug solution. The mesenteric lymph node was analysed by HPLC method and the concentration of drug was estimated. It showed that LNLC having highest uptake (40. 34μ g/ml) when compared with leflunomide drug solution (10. 04μ g/ml). Radiographic analysis and histopathological studies showed the formation of healthy cartilage after treatment period. Conclusion: The results suggested that LNLC has the potential to reduce the systemic toxicities associated with conventional therapy along with improved efficacy in the treatment of rheumatoid arthritis.

Purpose: This research is devoted to designing the synthesis of sulfanyl-substituted 3, 5-dimethylisoxazoles, which contain structural analogues of the SAM drug in the molecule. SAM (S-adenosyl-L-methionine), formed in the biosynthetic process, is used as an effective hepatoprotective drug. Complexation and hepatoprotective properties of the combinatorial series of bis(isoxazolylsulfanyl)ethane have been studied. Methods: Bis(isoxazol-4-ylmethylsulfanyl)alkanes were synthesized using the one-pot method. The structures of compounds were established by one-dimensional (1H, 13C) and two-dimensional (COSY, HCQS, HMBC) NMR spectroscopy, mass-spectrometry and Xray diffraction. The biological activity of the combinatorial series of sulfanyl derivatives of diketones, azoles and their metal complexes has been studied by in vivo method. Simulation of the animal associated processes was carried out in accordance with the principles of bioethics. Screening studies of hepatoprotective activity were carried out in a model of acute CC14 intoxication after a single injection intraperitoneally as a 50% solution in olive oil. The pharmacologically known hepatoprotective drug SAM served as a control. Results: Two-step synthesis of novel α , ω-bis(isoxazol-4-ylmethylsulfanyl)alkanes was carried out via the multicomponent reaction between 2, 4-pentandione, CH2O and α , ω-dithiols, then the resulting α , ω-bis(1, 3-diketone-2-ylmethylsulfanyl)alkanes were transformed by hydroxyl amine to obtain bis-isoxasole derivatives. Promising precursor 1, 2-bis(isoxazol-4-ylmethylsulfanyl)ethane was converted to metal complexes by interaction with PdCl2 or CuCl. The obtained compounds were found to be practically nontoxic compounds (1001 – 3000 mg/kg) according to the classification of K. K. Sidorov, but copper complex refers to low-toxic compounds substances (165 mg/kg). Compounds of sulfanyl ethane series demonstrate hepatoprotective activity. Conclusion: Palladium(II) complex being almost non-toxic possesses hepatoprotective activity comparable to the drug like SAM.

Purpose: T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common malignancies associated with T-lymphocytes, accounting for 10 to 15 percent of ALL cases in children and 25 percent in adults. Innovative therapeutic approaches that overcome ineffective treatments on tumor cells may be a potential source of improvement in therapeutic approaches. Suppression of gene expression at transfusion level is one of the important strategies in gene therapy. The expression of PTPN22 and miR-181 genes in all types of hematologic malignancies increases and is likely to contribute to the survival and death of cells by affecting a variety of signaling pathways. The purpose of this study was to determine the role of PTPN22 inhibition by siRNA, and alteration in miR-181a and miR-181b in Jurkat cell line. Methods: Jurkat cells were transfected with 80 pmol of siRNA to inhibit PTPN22. After that, expression of PTPN22 mRNA and transcript levels of miR-181a and miR-181b were measured with Real-time PCR after 48hrs. Results: Experiments demonstrated that siRNA transfection resulted in significant downregulation of PTPN22 mRNA after 48 hrs in 80 pmol dose of siRNA. Moreover, transcript levels of both miR-181a and miR-181b was decreased after transfection. Conclusion: PTPN22, miR-181a and miR-181b might be involved in progression of Jurkat cells and targeting these molecules by RNAi might confer promising tool in treatment of T-ALL.

Purpose: In Persian traditional medicine, application of Mummy material has been advised since hundred years ago for treatment of different diseases as bone fracture, cutaneous wounds and joint inflammation. Regarding to the claim of indigenous people for application of this material in the treatment of joint inflammation, the present study was designed to evaluate whether Mummy can revoke the inflammatory responses in chondrocytes stimulated with interleukin 1-β (IL-1β ). Methods: Isolated chondrocytes at the second passage were plated in 50 ml conical tubes at density of 1x106 for pellet culture or were plated in T75 culture flasks as monolayer. Cells in both groups were treated as control (receiving serum free culture medium), negative control (receiving IL-1β (10ng/ml for 24 hr)) and IL-1β pre-stimulated cells which treated with Mummy at concentrations of 500 and 1000μ g/ml for 72hrs. After 72 hrs, to evaluate whether Mummy can revoke the inflammatory response in chondrocytes, cell in different groups were prepared for investigation of gene expression profile of collagen II, Cox-2, MMP-13, C-Rel and P65 using real-time RT-PCR. Results: Treatment of chondrocytes with IL-1β (10ng/ml) resulted in a significant increase in expression level of Cox-2, MMP-13, C-Rel and P65 in pellet culture system, while treatment of IL-1β-stimulated choncrocytes with Mummy at both concentrations of 500 and 1000μ g/ml inhibited the expression level of above mentioned genes. Compared to the pellet culture, Mummy did not affect expression level of genes in monolayer condition. Conclusion: The obtained data from this investigation revealed that Mummy can be used as a potent factor for inhibiting the inflammatory responses induced by IL-1β in chondrocytes probably through inhibition of NF-қ B subunits activation.

Purpose: Mesenchymal stem cells (MSCs) play an important role in the proliferation and differentiation of hematopoietic stem cells (HSCs) in the bone marrow via cell-to-cell contact, as well as secretion of cytokines and microvesicles (MVs). In this study, we investigated the effect of mesenchymal stem cell-derived microvesicles (MSC-MVs) on erythroid differentiation of umbilical cord blood-derived CD34+ cells. Methods: In this descriptive study, CD34+ cells were cultured with mixture of SCF (10 ng/ml) and rhEPO (5 U/ml) cytokines in complete IMDM medium as positive control group. Then, in MV1-and MV2-groups, microvesicles at 10 and 20 μ g/ml concentration were added. After 72 hours, erythroid specific markers (CD71 and CD235a) and genes (HBG1, GATA1, FOG1 and NFE2) were assessed by flow cytometry and qRT-PCR, respectively. Results: The expression of specific markers of the erythroid lineages (CD71 and GPA) in the presence of different concentration of microvesicles were lower than that of the control group (P<0. 001). Also, the expression of specific genes of the erythroid lineages (NFE2, FOG1, GATA1, and HBG1) was investigated in comparison to the internal control (GAPDH). Among all of them, HBG1 and FOG1 genes were significantly decreased to the control group (P<0. 0001) but GATA1 and NFE2 gene expressions was not significant. Conclusion: The results of this study showed that MSC-MVs decrease the erythroid differentiation of umbilical cord blood-derived CD34+ cells. Therefore, MSC-MVs play a key role in the regulation of normal erythropoiesis.

Purpose: Adipose tissue derived stem cells (ASCs) and chondrocytes are best cells for articular cartilage regeneration. Chondrocyte with peri-cellular matrix (PCM) is called chondron provides ideal microenviroment than chondrocytes. We aimed to evaluate the regenerative effects of intra-articular injection of ASCs co-cultures with chondron in induced osteoarthritis (OA). Methods: ASC, from the peri-renal fat of male rat and chondron from primary newborn rat hyaline cartilage were isolated. ASCs were cultured for at least three passages in vitro. Six weeks after OA induction, rats were randomly distributed in five groups of control, osteoarthritic, ASC, chondron and co-cultured. ASCs (107), chondrons (107) and combination of chondrons and ASCs (107) were injected into intra-articular space of the rat knee. The effect of treatments was evaluated by macroscopic and microscopic examinations. The expression levels of collagen type Ι Ι was studied by immunohistochemistry. Results: Macroscopic appearance of the co-cultured group, showed much enhanced articular cartilage regeneration compared to ASC and chondron groups. H&E showed evidence of repair site of articular surface without erosion and fibrillation versus OA group which showed thin layer of hyaline cartilage over tidemark and spontaneous fibrocartilage formation. Metachrom atic regions stained with toluidine blue were larger in treatment groups versus OA group. Strong intensity of type Ι Ι collagen staining was observed in co-culture group compared to other groups. Conclusion: Co-culture of chondrons and ASCs increased articular hyaline cartilage formation and provides a useful tool to improve limitations of each of applied cells in this model.

Purpose: Despite a proposed role for oxidative stress in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), antioxidant approaches have not been sufficiently investigated in human NAFLD management. Resveratrol has been reported to possess a wide range of biological functions, including antioxidant activities. This study aimed to evaluate the effects of resveratrol supplementation on oxidative/anti-oxidative status in patients with NAFLD. Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 60 patients with NAFLD (males and females) aged 20 to 60 years, and body mass index (BMI) of 25-35 kg/m2. Subjects were randomly assigned to receive a daily dose of 600 mg resveratrol (2×300 mg pure trans-resveratrol capsules; n=30) or placebo capsules (n=30) for 12 wk. Fasting blood samples, anthropometric measurements, and dietary intakes were collected for all patients at baseline and at the end of the trial. Oxidative stress was evaluated by measurement of serum malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), and erythrocyte superoxide dismutase (SOD) as well as glutathione peroxidase (GSH-Px) activities. Changes in the outcomes were analyzed using analysis of covariance (ANCOVA). Results: Resveratrol supplementation did not significantly affect neither serum MDA, ox-LDL, and TAC levels, nor erythrocyte SOD and GSH-Px activities, compared to placebo group (All P>0. 05). Moreover, changes in serum levels of liver enzymes (ALT, AST, GGT, and ALP) were not significant in neither of the study groups (All P>0. 05). Conclusion: Resveratrol supplementation did not modify oxidative/anti-oxidative status in patients with NAFLD.

Purpose: Diabetic hearts are resistant to cardioprotection by ischemic-postconditioning (IPostC). Protection of diabetic hearts and finding related interfering mechanisms would have clinical benefits. This study investigated the combination effects of vildagliptin (Vilda) and IPostC on cardioprotection and the levels of autophagy and mitochondrial function following myocardial ischemia/reperfusion (I/R) injury in type-II diabetic rats. Methods: Diabetes was established by high fat diet/low dose of streptozotocin and lasted for 12 weeks. The diabetic rats received Vilda (6 mg/kg/day, orally) for one month before I/R. Myocardial regional ischemia was induced through the ligation of left coronary artery, and IPostC was applied immediately at the onset of reperfusion. The infarct size was assessed by a computerised planimetry and left ventricles samples were harvested for cardiac mitochondrial function studies (ROS production, membrane potential and staining) and western blotting was used for determination of autophagy markers. Results: None of Vilda or IPostC but combination of them could significantly reduce the infarct size of diabetic hearts, comparing to control (P<0. 001). IPostC could not significantly affect p62 expression level in diabetic hearts, but pre-treatment with Vilda alone (p<0. 05) and in combination with IPostC (p<0. 01) more significantly decreased p62 expression in comparison with corresponding control group. The expression of LC3B-II and LC3BII/LC3BI as well as mitochondrial ROS production were decreased significantly in treatment groups (p<0. 001). Mitochondrial membrane depolarization was significantly higher and mitochondrial density was lower in untreated diabetic I/R hearts than treated groups (p<0. 001). IPostC in combination with vildagliptin prevented the mitochondrial membrane depolarization and increased the mitochondrial content more potent than IPostC alone in diabetic hearts. Conclusion: Combination of vildagliptin and IPostC in diabetic hearts was a well-working strategy to reduce myocardial I/R damages by restoring mitochondrial membrane potential and ROS production and modulating the autophagic activity in I/R hearts.

Purpose: Gemfibrozil (GEM) apart from agonist activity at peroxisome proliferator-activated receptor-alpha (PPAR-α ) has antioxidant and anti-inflammatory properties. Accordingly, the present study was designed to investigate the protective effect of GEM on acute liver toxicity induced by acetaminophen (APAP) in mice. Methods: In this study, mice divided in seven groups include, control group, APAP group, GEM group, three APAP groups pretreated with GEM at the doses of 25, 50 and 100 mg/kg respectively and APAP group pretreated with N-Acetyl cysteine. GEM, NAC or vehicle were administered for 10 days. In last day, GEM and NAC were gavaged 1 h before and 1 h after APAP injection. Twenty four hours after APAP, mice were sacrificed. Serum parameters include alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver tissue markers including catalase enzyme activity, reactive oxygen species (ROS), malondialdehyde and reduced glutathione (GSH) levels determined and histopathological parameters measured. Results: GEM led to significant decrease in serum ALT and AST activities and increase in catalase activity and hepatic GSH level and reduces malondialdehyde and ROS levels in the liver tissue. In confirmation, histopathological findings revealed that GEM decrease degeneration, vacuolation and necrosis of hepatocytes and infiltration of inflammatory cells. Conclusion: Present data demonstrated that GEM has antioxidant properties and can protect the liver from APAP toxicity, just in the same pathway that toxicity occurs by toxic ROS and that GEM may be an alternative therapeutic agent to NAC in APAP toxicity.

Purpose: Ascorbyl palmitate (AP) is a widely used food additive in food industry. In this study, AP was evaluated for potential cyto-genotoxicity on Human Umbilical Vein Endothelial Cells (HUVECs). Methods: MTT assay and flow cytometry analysis was used for cytotoxicity evaluation, while genotoxicity was carried out using DAPI staining assays and real time PCR. Results: The growth of HUVECs was decreased upon treatment with AP in dose-and timedependent manner. Early/late apoptosis percentage in HUVECs treated with this additive was detected using flow cytometry analysis. Also morphology of DAPI stained HUVECs clearly showed chromatin fragmentation. Furthermore, real time PCR results showed that AP induces apoptosis by up-regulation of caspase-3, 9 and down-regulation of Bcl-2 ratio. Conclusion: The present results indicated that AP has capability to induce apoptosis in HUVECs and its better to make a thorough analysis about its extensive application in food industry.

Purpose: Cucurbita maxima Duchense (C. maxima) has been widely used in China and Mexico as a hypoglycemic plant for controlling blood glucose in diabetic patients. Furthermore, in northwest of Iran, this plant is used traditionally for controlling of diabetes. We examined the effect of C. maxima pulp besides insulin on control of hyperglycemia in diabetic patients admitted to Intensive care unit (ICU). Methods: Twenty critically ill patients who were admitted to the ICU were enrolled in this study. 5g lyophilized powder of C. maxima was administrated every 12 hours for 3 days. Moreover, blood glucose level and insulin dose were measured every 1-4 hours during 3 days before administration and 3days at the time of C. maxima administration. Results: The average of glucose level in 3 days before C. maxima administration was 214. 9 ± 55. 7 mg/dl, while in 3 days during C. maxima administration it was decreased to 178. 4 ± 36. 1 mg/dl (P<0. 001). Additionally, the average insulin dose during 3 days before intervention was 48. 05 ± 36. 5 IU and during the 3 days of C. maxima administration was decreased to 39. 5 ± 27. 8 IU (P=0. 06). Conclusion: It seems that C. maxima may decrease high blood glucose level fast and effective in diabetic critically ill patients.