Iranian Journal of Pharmaceutical Research
Volume:15 Issue: 2, Spring 2016

Poorly water-soluble drugs often suffer from limited or irreproducible clinical response due to their low solubility and dissolution rate. In this study, organic solvent-free solid dispersions (OSF-SDs) containing telmisartan (TEL) were prepared using polyvinylpyrrolidone K30 (PVP K30) and polyethylene glycol 6000 (PEG 6000) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant by a lyophilization method. In vitro dissolution rate and physicochemical properties of the OSF-SDs were characterized using the USP I basket method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and fourier transform-infrared (FT-IR) spectroscopy. In addition, the oral bioavailability of OSF-SDs in rats was evaluated by using TEL bulk powder as a reference. The dissolution rates of the OSF-SDs were significantly enhanced as compared to TEL bulk powder. The results from DSC, XRD showed that TEL was molecularly dispersed in the OSF-SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between TEL and its carriers. The OSF-SDs exhibited significantly higher AUC0–24 h and Cmax, but similar Tmax as compared to the reference. This study demonstrated that OSF-SDs can be a promising method to enhance the dissolution rate and oral bioavailability of TEL.

Piroxicam has two different crystalline forms (known as needle and cubic forms), that they are different in physicochemical properties such as biological solubility. In the current research, using Taguchi experimental design approach the influences of five operating variables on formation of the piroxicam polymorph shapes in recrystallization were studied. The variables include type of solvent, cooling methods, type of mixture paddle, pH, and agitator speed. Statistical analysis of results revealed the significance order of factors affecting the product quality and quantity. At first using the Taguchi experimental method, the influence of process factors on the yield, particle size and dissolution rate of piroxicam powder was statistically investigated. The optimum conditions to achieve the best dissolution rate of piroxicam were determined experimentally. The results were analyzed using Qualitek4 software and it was revealed that the type of solvent and method of cooling respectively are the most important factors that affect the dissolution rate. It was also experimentally achieved that some factors such as type of agitator paddle, pH and agitation rate have no significant effects on dissolution rate.

Membrane permeability and P-glycoprotein (P-gp) efflux system are regulating factors in the drug brain penetration. Recently, some drug delivery systems have been developed to overcome these limitations. In this study, Metoclopramid has been encapsulated in PLGA nanoparticles using the emulsification/solvent evaporation technique for in vitro evaluation of the effect of PLGA nanoparticles on BBB permeability. Subsequently, prepared nanoparticles were characterized using PCS, TEM, FT-IR, DSC and XRD techniques and in vitro cell permeability of optimum formulation was evaluated using MDCK cell line as BBB model.
Data investigation showed that prepared nanoparticles have the entrapment efficiency of 50%. PCS investigation showed that prepared nanoparticles have an average size of approximately 150±14 nm and a relatively monodisperse distribution. TEM micrographs of the samples showed spherical shape and smooth surface with a particle size of nanometric range. Through DSC thermograms and XRD diffractograms analysis, it was demonstrated that there was no crystalline form of the drug in the loaded formulation.
In vitro cytotoxicity of the formulations on MDCK cell line demonstrated the greater crossing of metoclopramide in the form of nanoparticle in comparison with the free metoclopramide. Further investigation demonstrated that the PLGA nanoparticles may act as a Pgp substrate

A noninvasive method of detecting exposure of phosphatidylserine (PS) on the external surface of the plasma membrane such as nuclear imaging could assist the diagnosis and therapy of apoptosis related pathologies. The most studied imaging agent for apoptosis is Annexin V so far. Because of limitations of Annexin V other agents have been introduced such as small peptides and molecules. Radiopeptides that have affinity and bind to PS are good candidates for noninvasive imaging of apoptosis. The LIKKPF, introduced by Burtea et al, with nanomolar affinity for PS, was used as templete.
The biological properties of LIKKPF radiolabeled with Tc-99m was assessed in vitro using apoptotic Jurkat cells and in vivo using mouse model of liver apoptosis.
The radiolabeled LIKKPF with 99mTc was stable in human serum at 37C for at least 2 hr. Results showed that the radiolabeled LIKKPF has less affinity to PS compare to original phage peptide, but high enough for specific binding to apoptotic cells in vitro and in vivo.
It is concluded that the less affinity of radiolabeled LIKKPF might be attributed to hydrophobicity of peptide. The future peptides should be more hydrophobic compare to LIKKPF.

1-[4-(2-Alkylaminoethoxy)phenylcarbonyl]-3,5-bis(arylidene)-4-piperidones are a novel class of potent cytotoxic agents. These compounds demonstrate low micromolar to submicromolar IC50 values against human Molt 4/C8 and CEM T-lymphocytes and murine leukemia L1210 cells. In this study, a comparative QSAR investigation was performed on a series of 3,5-bis(arylidene)-4-piperidones using different chemometric tools to develop the best predictive models for further development of analogs with improved cytotoxicity. All the QSAR models were validated by internal validation tests. The QSAR models obtained by GA-PLS method were considered the best as compared to MLR method. The best QSAR model obtained by GA-PLS analysis on L1210, CEM and Molt4/C8 demonstrated good predictively with R2pred values ranging from 0.94-0.80. Molecular density, topological (X2A) and geometrical indices of the molecules were found to be the most important factors for determining cytotoxic properties.

Caspase-3, one of the dominant effectors caspases, is activated in almost every model of apoptosis with various signaling pathways. Hence, inhibition of caspase-3 has become an attractive target in the treatment of neurodegenerative diseases. Caspase-3 inhibitory activities of some 1,2-benzisothiazol-3-one derivatives were modeled by quantitative structure–activity relationship (QSAR) using stepwise-multiple linear regression (SW-MLR) method. The built model was robust and predictive with correlation coefficient (R2) of 0.91 and 0.59 for training and test groups, respectively. The quality of the model was evaluated by leave-one out (LOO) cross validation (LOO correlation coefficient, Q2) of 0.80). The results indicate that the descriptors related to the electronegativity, the atomic masses, the atomic van der Waals volumes and R--CX--R Atom-centered fragments play a more significant role in caspase-3 inhibitory activity.

Multifunctional nanomaterials showed graet advantages in drug delivery. Folic acid (FA) binding protein, a glycosyl phosphatidyl inositol anchored cell surface receptor for folate, is overexpressed in several human tumors, whereas it is highly restricted in normal tissues. Therefore, in this study, FA, polyethylene glycol (PEG), and Fe3O4 nanoparticles multifunctionalized short multiwall carbon nanotubes (PEG-FA-SMWCNT@Fe3O4) were synthesized by conjugating folate, PEG, and magnetite nanoparticles with carboxylated multiwall carbon nanotubes. The prepared c-SMWCNT@Fe3O4 was characterized by X-ray diffraction (XRD) and vibrating sample magnetometer (VSM) in order to investigate crystal and magnetic properties, respectively. The images obtained by scanning electron microscopy (SEM) showed that the magnetite nanoparticles were attached to the surfaces of carbon nanotubes and SMWCNT@Fe3O4 was formed. Investigation of functional groups using Fourier transform infrared (FTIR) spectra indicated that PEG-FA was successfully linked to SMWCNT@Fe3O4.

A high performance liquid chromatographic method with ultra violet detection for simultaneous analysis of six benzodiazepines (BZDs) (chlordiazepoxide, diazepam, clonazepam, midazolam , flurazpam and lorazepam) has been developed for forensic screening of adulterated non-alcoholic drinks. Samples were analyzed after a simple procedure for preparation using pH adjustment and filtering. Isocratic elution on a C18 column (250mm × 4.6 mm, 5μm) in the temperature 45ºC with a mobile phase consisting of 15mM phosphate buffer: methanol (50:50 v/v) at a flow rate 1.4 mL/min has been done. The column eluent was monitored with a UV detector at 245 nm. This allowed a rapid detection and identification as well as quantization of the eluting peaks. Calibration curves for all drugs in the range of 0.5- 10 µg/ mL that all the linear regression and has more than 0.996. Recovery rates for the BZDs were in the range 93.7- 108.7%. The limits of detection were calculated between 0.01- 0.02 µg/ mL. Also, the limits of quantification were 0.03- 0.05 µg/mL. Within-day and between -day coefficient of variation for all BZDs at all concentrations in the range of 0.45 - 7.69 % was calculated. The procedure can provide a simple, sensitive and fast method for the screening of six BZDs in adulterated soft drinks in forensic analysis.

A fast and simple modified QuEChERS (quick, easy, cheap, rugged and safe) extraction method based on spiked calibration curves and direct sample introduction was developed for determination of benzo[a]pyrene (BaP) in bread by gas chromatography-mass spectrometry single quadrupole selected ion monitoring (GC/MS-SQ-SIM). Sample preparation includes extraction of BaP into acetone followed by cleanup with dispersive solid phase extraction. The use of spiked samples for constructing the calibration curve substantially reduced adverse matrix-related effects. The average recovery of Bap at 6 concentration levels was in range of 95–120%. The method was proved to be reproducible with relative standard deviation less than 14.5% for all of the concentration levels. The limit of detection and limit of quantification were 0.3 ng/g and 0.5 ng/g, respectively. Correlation coefficient of 0.997 was obtained for spiked calibration standard over the concentration range of 0.5-20 ng/g. To the best of our knowledge, this is the first time that a QuEChERS method is used for analysis of BaP in breads. The developed method was applied for determination of Bap in 29 traditional (Sangak) and industrial (Senan) bread samples collected from Tehran in 2014. These results showed that two Sangak samples were contaminated with BaP. Therefore, a comprehensive survey for monitoring of BaP in Sangak bread samples seems to be needed. This is the first report concerning contamination of bread samples with BaP in Iran.

Polycyclic aromatic hydrocarbons (PAHs) are classified as persistent and carcinogenic organic pollutants. PAHs contamination has been reported in water. Many of relevant regulatory bodies such as EU and EPA have regulated the limit levels for PAHs in drinking water. In this study, 13 priority polycyclic aromatic hydrocarbons (PAHs) were determined in tap water samples of Tehran and water for injection. Dispersive liquid-liquid microextraction procedure combined with gas chromatography-mass spectrometry was used for the extraction and determination of PAHs in the samples. Under the optimized conditions, the range of extraction recoveries and relative standard deviations (RSDs) of PAHs in water using internal standard (anthracene-d10) were in the range of 71-90% and 4-16%, respectively. Limit of detection for different PAHs were between 0.03 and 0.1 ngmL-1. The concentration of PAHs in all tap water as well as water for injection samples were lower than the limit of quantification of PAHs. This is the first study addressing the occurrence of PAHs in water for injection samples in Iran using dispersive liquid-liquid microextraction procedure combined with gas chromatography-mass spectrometry.

Cyclooxygenase-2 (COX-2) has a pivotal role in the pathogenesis of the lung cancer. It is known that COX-2 negatively regulates the activity of a number of tumor suppressors, including p53. Consequently, inhibition of COX-2 signaling is anticipated to be a promising approach to stabilize p53 functionality. In this regard, we investigated the effect of COX-2 signaling blockade on p53 and COX-2 expression in A549 cells. Cell viability was assessed using MTT and protein expression was measured using Western Blot assay. Results revealed that Celecoxib dose-dependently induced growth inhibition within 24h. However, prolonged exposure to the drug up to 48h led to increase cell viability compared to the corresponding control. Western blot analyses demonstrated that Celecoxib could augment p53 expression within 24h, independently of COX-2 inhibition. In contrast, Celecoxib treatment not only returned p53 to the control level, but also strikingly induce COX-2 expression within 48h. Of further relevance, Celecoxib exposure could significantly result in MDM2 elevation at 48h. These findings represent p53 as a molecular target being interconnected with COX-2 signaling axis upon Celecoxib treatment. Moreover, our data point toward the possibility that Celecoxib treatment may not be a proper therapeutic strategy in lung cancer cells owing to its potential role in the activation of oncogenes, including COX-2 and MDM2 which seemingly confers a chemoresistance circumstance to the cell. Consequently, these results underscore intensive preclinical assessment prior to applying COX-2 inhibitors in the treatment of lung tumors.

The proliferation of hepatocellular carcinoma (HCC) cells is one of the leading causes of liver cancer mortality in humans. The inhibiting effects of matrine on HCC cell proliferation have been studied, but the mechanism of that inhibition has not been fully elucidated. Since, apoptosis plays an important role in HCC cell proliferation. We examined the apoptosis-inducing effect of matrine on tumor cells. Western blot analysis of p53,Bax, cleaved caspase-3 and myosin light chain kinase (MLCK) revealed that matrine induced tumor cell apoptosis by controlling anoikis. It activated p53, Bax-dependent caspase-3 and blocked the ECM-integrin mediated cell survival pathway through down-regulating MLCK over-expression in the liver of rats with diethylnitrosamine (DENA)-induced HCC. Our results suggest that matrine can inhibit the proliferation of HCC cells through inducing tumor cell apoptosis via activation of the p53 pathway and inhibition of MLCK overexpression. Matrine may thus be used as a potentially promising reagent to inhibit HCC cell proliferation and MLCK may be a novel target for the treatment of HCC.

In the present work we set out to investigate the neuroprotective effects of noscapine (0.5-2 µM) in presence of D-glucose on primary murine foetal cortical neurons after oxygen–glucose deprivation/24 hrs recovery. Cell viability, nitric oxide production and intracellular calcium ([ca2]i) levels were evaluated by MTT assay, the modified Griess method and Fura-2 respectively. 25 and 100 mM D-glucose could, in a concentration dependent manner, improve cell viability and decrease NO production and [ca2]i level in neuronal cells after ischemic insult. Moreover, pre-incubation of cells with noscapine, noticeably enhanced protective effects of 25 and 100 mM D-glucose compared to similar conditions without noscapine pre-treatment. In fact, noscapine attenuated NO production in a dose-dependent fashion, after 30 minutes (min) OGD, during high-glucose (HG) condition in cortical neurons. Pretreatment with 2 μM noscapine and 25 or 100 mM D-glucose, was shown to decrease the rise in [ca2]i induced by Sodium azide/glucose deprivation (chemical OGD) model. These effects were more pronounced than that of 25 or 100 mM D-glucose alone.
The present study demonstrated that the neuroprotective effects of HG after an ischemic insult were augmented by pre-treatment with noscapine. Our results also suggested that the neuroprotection offered by both HG and noscapine involve attenuation of NO production and [ca2]i levels stimulated by the experimental ischemia in cortical neurons.

Aims: In our previous studies, we showed the inhibitory effects of Punica granatum L. flower and Rhus coriaria L. fruit water extracts on dental plaque accumulation by several bacteria, especially Streptococcus mutans (S. mutans), on orthodontic wire by in vitro assays. In this study, the anti-cariogenic properties of the extracts were evaluated by assessing their effects on expression of glycosyltransferase (gtf) genes, which are responsible for initial biofilm formation by S. mutans.
In this study, the effect of herbal extracts on expression of gtfB, C (encoding enzymes that produce water-insoluble glucans) and D (encoding enzymes that produce water-soluble glucans) genes in S. mutans growing in planktonic state was evaluated quantitatively by real-time polymerase chain reaction (PCR) method.
The minimum biofilm inhibitory concentration (MBIC) of understudied herbal water extracts significantly suppressed gtfB, C and D gene expression by 85.3 ± 7.5%, 33.3 ± 6.4% and 25 ± 14%, respectively for Punica granatum L. extract and 73.4 ± 7.3%, 93.8 ± 2.7% and 59.3 ± 9.8%, respectively for Rhus coriaria L. extract compared to the non-treated control group (P These findings suggest that Punica granatum L. and especially Rhus coriaria L. maybe used as novel, natural antiplaque agents since they inhibit specific genes associated with bacterial biofilm formation without necessarily affecting the growth of oral bacteria.

Verbascoside (acteoside), a phenyl propanoid glycoside, comprises 0.5 to 3.5% dry weight of Lippia citriodora leaves. A wide range of biological activities are attributed to verbascoside including anti-inflammatory, antioxidant, anti-bacterial, anti-tumor, anti-fungal, photoprotective as well as chelating effects. The objective of this study is to evaluate the effect of verbascoside on pregnancy outcome in mice. Timed-pregnant mice received doses of 1g/kg/day verbascoside or the vehicle control during organogenesis, intraperitoneally. Maternal body weights were measured throughout pregnancy. The litters were examined for external malformations and skeletal abnormalities. Then they were stained with Alizarin red S and Alcian blue. Maternal exposure to verbascoside throughout pregnancy did not influence the mean of maternal weight gain. Statistically significant difference was not found in mean number of implantation sites, live and resorbed fetuses between control and experiment groups. Our data demonstrate that the main component of L. citriodora, verbascoside using during organogenesis possesses no risk to fetuses. However, more research projects are needed to confirm these findings and determine the exact effects of verbascoside on human embryo development.

In this study, antioxidant and antimicrobial potentials of Usnea intermedia, U. filipendula, and U. fulvoreagens and their stictic and usnic acid contents were investigated. Antioxidant activity and total phenolic contents were evaluated in acetone, ethanol, and methanol extracts of these three species. Antioxidant activity was measured by ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)] method and total phenolic contents were measured by Folin-Ciocalteu method. High-performance liquid chromatography (HPLC) was used for the determination of lichen acids. It can be concluded from stictic and usnic acids contents that the order of solvent efficiency is acetone > ethanol > methanol and acetone > methanol > ethanol, respectively. Broth microdilution method was performed to determine the minimum inhibitory concentration (MIC) of the methanol extracts of three Usnea species. The MIC values of all the extracts ranged from 64 µg/ml to 512 µg/ml for all the bacterial strains that were tested in this study, and all the Fluoro quinolone-resistant Escherichia coli isolates (except for E101) were sensitive to the methanol extracts of the three Usnea species. This paper is the first study to determine the stictic acid content in U. intermedia and U. filipendula. Our findings indicate that these three Usnea species could be used as antioxidant and antimicrobial agents.

Free radicals play an important role in pathological processes such as aging and developing cancer; hence, natural products inhibit free radical production, and can play an important role in preventing diseases. We aimed to evaluate the scavenging activity of free radicals, reducing power, inhibition of lipid peroxidation and malondialdehyde (MDA) formation, and the antioxidant composition of rolB-transformed hairy roots and leaf callus of Catharanthus roseus. Hairy roots of the Catharanthus roseus were induced using Agrobacterium rhizogenes strain ATCC 15834 to transfer the rolB gene. Polymerase chain reaction analysis was used to identify the presence of the gene in the transformed hairy roots. Folin-Ciocalteu reagent, aluminum chloride calorimetry and high performance liquid chromatography were used to determine the content of total phenolic, flavonoid and gallic acid, respectively. To this end, we assayed the free radicals scavenging activity by 1-diphenyl-2-picrylhydrazyl (DPPH), reducing power, inhibition of lipid peroxidation and inhibition of malondialdehyde production. The results showed that phenolic, flavonoid, and gallic acid contents in the ethanol extract of the hairy roots were significantly higher (p ≤ 0.01) than those naturally found in the extracts of root, leaf, and leaf callus of C. roseus. The hairy roots extract showed the lowest IC50 for the inhibition of DPPH•. Furthermore, the ethanol extract showed the best reducing power and had the highest potential to inhibit lipid peroxidation and to form the MDA. The transformed hairy roots can be considered a rich natural source of antioxidants.

How the seeds of Delphinium staphisagria promote hair growth in humans is yet to be discovered. This lack of information leads us to the investigation of hair promoting effects of seeds of Delphinium staphisagria in vitro. Extract prepared from the Seed of Delphinium staphisagria (ESDS) - traditionally used for hair loss treatment - was selected and tested for the cytotoxic and angiogenic potential in endothelial cells (HUVECs) and human keratinocytes (HaCaT) cells. The effects of extract was determined by using in vitro colorimetric MTT [3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity assay. To identify the compounds that induce angiogenesis, we applied matrigel capillary assay in vitro using HUVECs. Vinegar and water extracts of D. staphisagria seeds significantly promoted the proliferation of human keratinocyte cells by 137, 139, 143, 149 and 147 % at the concentration of 100, 120, 200, 250 and 300 g/ml compared with vehicle –treated control, respectively at 24 h. HUVECs viability remained the same with the control group at the concentration 1, 10, 20 and 40 g/ml after 24 hours. Results demonstrated that ESDS did not cause toxicity in human keratinocytes and endothelial cells, while inducing the angiogenic activity in vitro. D. staphisagria seeds promote hair growth without overt cytotoxicity and through inducing angiogenesis. Based on the information from the traditional uses and our experimental results, D. staphisagria’s seeds appear to be a good candidate for the promotion of hair growth.

Diabetes mellitus is one of the most common causes of neuropathy. Although antioxidant and antidiabetic effects of the aqueous extract of purslane (Portulaca oleracea) (AEOP) have been demonstrated before by other researchers, we did not find any study that assessed the psychobiological effects of AEOP in diabetes induced animals. Thirty ovariectomized (OVX) female Wistar rats were randomly divided into 3 groups of control, Dia and DiaC. The latter group was orally treated by 300 mg/kg of AEOP for 35 days. Dia and DiaC groups were made diabetic by IP injection of 60 mg/kg of streptozotocin (STZ). The psychobiological effects of AEOP were assessed by Morris water maze (MWM), elevated plus maze (EPM), forced swimming test (FST) and tail pinch stressor (TPS). AEOP significantly decreased hyperglycemia (p0.05). Diabetes significantly increased their non-functional masticatory activity in TPS (p≤0.001) while it was improved in DiaC group. We showed that AEOP has significant anxiolytic effects and it can improve spatial cognitive performance, locomotor deficit and stress in diabetic OVX rats.

Leishmania antigens are weak immunogens and need to be potentiated by various adjuvants and delivery systems. Alginate microspheres as an antigen delivery system and Quillaja saponins (QS) as an immunoadjuvant have been used to enhance the immune response against Autoclaved Leishmania major (ALM). Microspheres were prepared by an emulsification technique and characterized for size, encapsulation efficiency and release profile of encapsulates. BALB/c mice were immunized three times in 3-weeks intervals using ALM plus QS loaded microspheres [(ALM)ALG], ALM encapsulated with alginate microspheres [(ALM)ALG], (ALM)ALG QS, ALM QS, ALM alone or PBS. The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection, showed by significantly (P

Retinoic acid and Rosa damascena are compounds that have considerable effects in the cellular proliferation and synthesis of extracellular matrix. The present study was designed to assess the combined effects of retinoic acid and Rosa damascena mill on wound in diabetic rats. Seventy-two rats were used in this study. Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg. Kg-1). Then, a full thickness wound was created on dorsal surface of all animals. After that, rats were divided, into three groups; control (normal saline), positive control (phenytoin ), and case (combined of 0.1% Tretinoein lotion and which concentration of Rosa damascena mill ).Afterward, wounds were evaluated macroscopically and microscopically on days 5, 10 and 15. Macroscopic and microscopic evaluations showed a significant improvement (p

Plants or natural resources have been found to be a good alternative method for nanoparticles synthesis. In this study, polyaniline coated silver nanoparticles (AgNPs) synthesized from Piper betle leaves extract were investigated for their antibacterial activity. Silver nanoparticles were prepared from the reduction of silver nitrate and NaBH4 was used as reducing agent. Silver nanoparticles and extracts were mixed thoroughly and then coated by polyaniline. Prepared nanoparticles were characterized by Visual inspection, Ultraviolet-visible spectroscopy (UV), Fourier transform infrared Spectroscopy (FT-IR), Transmission Electron Microscopy (TEM) techniques. Antibacterial activities of the synthesized silver nanoparticles were tested against Staphylococcus aureus ATCC 25923, Salmonella typhi ATCC 14028, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. UV–Vis spectrum of reaction mixture showed strong absorption peak with centering at 400 nm. The FT-IR results imply that Ag-NPs were successfully synthesized and capped with bio-compounds present in P. betle. TEM image showed that Ag-NPs formed were well dispersed with a spherical structures and particle size ranging from 10 to 30 nm. The result revealed that Ag-Extract NPs showed 32.78±0.64 mm zone of inhibition against S. aureus, whereas norfloxacin (positive control) showed maximum 32.15±0.40 mm zone of inhibition for S. aureus. Again, maximum zone of inhibition 29.55±0.45 mm was found for S. typhi, 27.12±0.38 mm for E. coli and 21.95±0.45 mm for P. aeruginosa. The results obtained by this study can’t be directly extrapolated to human; so further studies should be undertaken to established the strong antimicrobial activity of Ag-Extract NPs for drug development program.

Medication errors are one of the important factors that increase fatal injuries to the patients and burden significant economic costs to the health care. An appropriate medical history could reduce errors related to omission of the previous drugs at the time of hospitalization. The aim of this study, as first one in Iran, was evaluating the discrepancies between medication histories obtained by pharmacists and physicians/nurses and first order of physician.
From September 2012 until March 2013, patients admitted to the post CCU of a 550 bed university hospital, were recruited in the study. As a part of medication reconciliation on admission, the physicians/nurses obtained medication history from all admitted patients. For patients included in the study, medication history was obtained by both physician/nurse and a pharmacy student (after training by a faculty clinical pharmacist) during the first 24 hours of admission.
250 patients met inclusion criteria. The mean age of patients was 61.19 ± 14.41 years. Comparing pharmacy student drug history with medication lists obtained by nurses/physicians revealed 3036 discrepancies. On average, 12.14 discrepancies, ranged from 0 to 68, were identified per patient. Only in 20 patients (8%) there was 100% agreement among medication lists obtained by pharmacist and physician/nurse. Comparing the medications by list of drugs ordered by physician at first visit showed 12.1 discrepancies on average ranging 0 to 72.
According to the results, omission errors in our setting are higher than other countries. Pharmacy-based medication reconciliation could be recommended to decrease this type of error.

So far, too little attention has been paid to total burden of healthcare associated infections (HAIs) in Iran. In present study, we aimed to assess the rate of HAIs, as well as economic burden of hospitalization and antibiotic related cost associated with HAIs at training Taleghani hospital in Iran and to compare our results with NNIS system. This research to date for the first time has tended to focus on the burden of HAIs rather than epidemiology of HAIs evaluation. The total of 474 patients was followed up in this study. Overall, the rate of HAIs was 19.2% in which ventilator associated pneumonia (VAP) was dominant HAIs and followed by UTI. Importantly, mortality rate was increased significantly at infected patients. The highest total hospitalization burden and antibiotic related cost was observed for patients with BSI. The results were demonstrated significant differences between antibiotic related cost at patients and uninfected patients. Antibiotic related absolute extra cost for HAIs was 2.09 $ per day. Estimation of direct annually HAIs associated economic burden of antibiotic and Total hospitalization was 433,382.4 $ and 705,024 $ respectively in Iran. The most obvious finding was that, a strong relationship between relatively heavy antibiotic related financial burden, higher mortality rate, longer hospitalization time and HAIs emergence on the Iranian national health system. It also reflects, more fundamentally a shift toward the need for comprehensive thinking about HAIs at ICU ward from Iran’s hospitals.

Acute Venous Thromboembolism (VTE) is a common disease associated with the significant morbidity and mortality. We reviewed clinical outcomes systematically with Dabigatran as a direct oral anticoagulants (DOAC) for treatment of acute VTE. We used Ovide, PubMed, Cochrane (CENTRAL), EMBASE, Scopus, Science Direct, LILAC(for article written not English) and also Iranian database; Magiran, Isc, Iran Medex, Iran DOC, Doaj up to May 2014 to identify randomized clinical trials of Dabigatran compared with conventional treatment for VTE. Two investigators extracted data independently.
Number of 5107 patients including two trails were selected. The risk of recurrent VTE was similar with the Dabigatran and standard treatment (Hazard Ratio, 95% confidence interval 1.09 (0.76–1.57). Dabigatran reduced the risk of minor bleeding in comparison with standard treatment; Warfarin (0.62 (0.50–0.76).
Finally- in minor bleeding - the Dabigatran seemed as effective as, and probably safer than standard treatment of acute VTE. But in some aspects such as adherence to treatment, pregnant patient, impact on quality of life, new researches are needed to be clarified.

The aim of the present study was to assess the analgesic efficacy of IV ketamine injection inaddition to nephrostomy tract infiltration of ketamine – bupivacaine on postoperative pain relief after tubeless percutaneous nephrolithotomy (PCNL).
Patients and Patients (n = 100), with renal stone who were candidates for PCNL were randomized to five groups with 20 cases in each: Group C, 10 mL of saline solution was infiltrated into the nephrostomy tract; Group B, 10 ml of 0.25% bupivacaine was infiltrated into the nephrostomy tract; Group BK1, 10 ml of 0.25% bupivacaine plus 0.5mg/kg ketamine was infiltrated into the nephrostomy tract; Group BK2, 10 ml of 0.25% bupivacaine plus 1.5mg/kg ketamine was infiltrated into the nephrostomy tract; Group K, 10 ml of saline solution containing 0.5mg/kg ketamine was intravenously administered. Post-operative pain scores were compared between groups as the primary objective. Comparison of Sedation Scores, rescue analgesic consumption, time to the first rescue analgesics administration, hemodynamic and SpO2 values were regarded as the secondary objective.
Mean VAS scores in the first 30 minutes and total analgesic consumption in the first 24 hours of post-operative period were significantly lower in groups BK1 and BK2 in comparison with the other groups (P Infiltration of ketamine plus bupivacaine provides superior analgesic effects in PCNL surgery compared with other methods.

Aminoglycosides are still widely used for treatment of gram-negative sepsis in critically ill patients. The most reported electrolyte abnormalities related to these drugs are hypokalemia, hypomagnesemia, and hypocalcemia. In this study potential benefit of atorvastatin in prevention of amikacin-induced electrolytes imbalances has been evaluated. In this trial 44 patients were assigned to the atorvastatin or placebo group based on the simple randomization method. Atorvastatin group received amikacin with dose of 15 mg/kg/day in two equal divided doses every 12h as intravenous infusion during 30 minutes and atorvastatin 40 mg tablet as daily oral dose for 7 days. Patients in the placebo group received same dose of amikacin and placebo tablet (Placebo group) for at least 7 days. Serum electrolytes (sodium, potassium, calcium, phosphor and magnesium) concentrations, blood urea nitrogen and serum creatinine levels were measured at day 0 and end of the study. Baseline mean±SD of serum potassium concentration in the atorvastatin and placebo group was 4.07± 0.37 and 4.15 ± 0.53 meq/l respectively (p=0.88). Serum potassium concentration remained unchanged at the end of the study in the atorvastatin group (P=0.61) but significantly decreased from 4.15 ± 0.53 to 3.80 ± 0.55 meq/l in the placebo group at day 7(P = 0.02). In this pilot study, atorvastatin as 40 mg daily oral dose prevented renal potassium loss during course of amikacin therapy in the critically ill patients. In the future well designed randomized clinical trials with adequate sample size, renoprotective effects of statins should be examined.

Factor XIII deficiency (FXIIID) is an extremely rare hemorrhagic disorder with a prevalence of 1/3-5 million. Management of disease is performed by fresh frozen plasma (FFP), Cryoprecipitate (CP) or FXIII concentrate (Fibrogammin P®). Our objective was to assess safety and effectiveness of Fibrogammin P® in patients with FXIIID. For this purpose we designed this long-term follow up study on a large group of patients with FXIIID.
This prospective study was conducted on 213 patients with FXIIID since 2009 to 2013. Administrated dose for Fibrogammin P® according to clinical situations of patients ranged from 10 to 26 IU/kg every 4 – 6 weeks. All patients in 6-month intervals were checked for human immunodeficiency virus (HIV), hepatitis A, B and C viruses (HAV, HBV, HCV).
Twelve percent of participants had at least one ICH episode until 2008 but after administration of Fibrogammin P® did not have any major bleeding or episode of ICH, except in one patient. We also had 7 females with recurrent miscarriage that were managed successfully with a dose of 10 to 26 IU/kg every 4 – 6 weeks. This dose also was quite successful in management of major and minor surgery. None of the participants showed allergic reaction during treatment. A total of 7155450 IU of Fibrogammin P® were infused but nobody was positive for HIV, HAV, HBV, and HCV. We found that Fibrogammin P® is a safe and effective therapeutic choice in management of FXIIID.

Labor pain is one of the most tiresome types of pain. So human has been seeking to allay this pain until now. Administration of a suitable agent such as Entonox during labor is very beneficial for childbirth outcomes. Entonox can be administered in two ways: intermittently and continuously. The aim of this study is to demonstrate whether continuous method is as safe as intermittent method? This randomized clinical trial was performed in Mobini Hospital, Sabzevar, Iran. One hundred admitted women for vaginal delivery were included in this study. Fitted patients were randomly divided into two equal groups. After thorough training, the patients used Entonox during active phase of labor. Fifty parturients used it intermittently and 50 others used it continuously. Then, maternal adverse effects, satisfaction and labor progression were registered and compared in two groups. Statistical Analysis was performed by spss17 software, t-test and chi square test. The maternal side effects of Entonox had no significant difference in two groups (p

Linezolid (LZD), severed as the first oxazolidinone antibiotic, was active against multidrug-resistant gram-positive strains. LZD can induce thrombocytopenia, anemia and leukocytopenia. Currently, reports on pure red cell aplasia (PRCA) cases induced by LZD are relatively rare [4-7]. In this paper, we reported a patient with PRCA twice induced by LZD. A 37-year-old man was diagnosed with myelodysplatic syndrome (MDS) and underwent allo-HSCT from an unrelated donor with ABO blood type- and leukocyte antigen (HLA)-matching. After HSCT for 2 years, the patient suffered from refractory fever and headache. He was first treated with empirical antifungal agent and antibiotics for central nervous system (CNS) infection, but then changed to LZD therapy for little effect. Twenty-eight days after LZD treatment, the symptom improved significantly but the hemoglobin declined to 70 g/L and the reticulocyte level was only 0.23%. The LZD therapy was stopped and the fever and headache symptoms reoccurred 1 week latter. Then, erythropoietin (EPO) and halved dosage of LZD were used for treatment. The CNS infection and the anemia symptom relieved gradually and the level of hemoglobin and reticulocyte declined again. After blood transfusion, the half dose of LZD was sustained without anaemia recovery. In summary, patients with anemia, myelosuppressants history or potential abnormal proliferation of T cells may suffer PRCA with long term LZD treatment. The monitoring of complete blood count and reticulocyte count were necessary during LZD therapy. If the clinical condition permits, LZD dosage reduction and blood transfusion should be considered.

Previous studies had shown that sub-inhibitory concentrations of silver sulphadiazine (AgSD) stimulated the production of Toxic Shock Syndrome Toxin-1 in certain strains (responder strains) of Staphylococcus aureus and that protease production was also affected. No changes were detected in other strains (non-responders).
Extracellular proteins from eleven responder and non-responder strains grown with and without AgSD were separated by SDS PAGE.
There were three classes of response, responder strains that showed enhancement of synthesis of certain proteins, non-responder strains that showed no change and responder strains that showed a general decrease in exoprotein production in the early stages of growth.
The results showed that the effects of AgSD were complex and that S. aureus strains were heterogenous with respect to their response to sub-inhibitory concentrations of AgSD.

We aimed to investigate the effects of dietary combination of honey and Ardeh on chemotherapy-induced complications in patients with acute myeloid leukemia (AML).
A total of 107 AML patients who underwent chemotherapy for at least 30 consecutive days were recruited to this double-blind randomized placebo-controlled clinical-trial which was conducted in the Imam Reza and Ghaem teaching hospitals (Mashhad, Iran). They were divided into two age and sex-matched groups: 58 treated and 49 untreated patients. A combination of 50 grams of honey and 150 grams of Ardeh was added to the treated group’s diet for 30 consecutive days, three times each day; while the untreated group received their regular diet.Both groups received their standard medication for AML as well. After one month, they were all examined and lab tests were done on them by an internist and laboratory technicians who were blinded to the subject allocations.
Mean value of WBC count in treated group was significantly lower than that of untreated group. Duration of fever and admission in the hospital due to fever were both significantly lower in the treated group (P=0.014, P=0.032 respectively).
Total gastrointestinal complications were significantly less in the treated group one month after therapy with the special honey and Ardeh compound. No unusual or unexpected side effects were observed. Honey and Ardeh are easily accessible materials that can be helpfully administered in AML patients receiving chemotherapy, since their useful effects in ameliorating gastrointestinal complications and reducing fever and neutropenia in AML patients have been shown.

Nowadays, bypassing agents such as recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrates (aPCC) are used to treat bleeding episodes in the Hemophilia patients with inhibitors. AryoSeven® is an Iranian biogeneric rFVIIa with homogeneity of efficacy and the nature to NovoSeven in a comparative trial. The current clinical trial aimed to evaluate the cost-effectiveness of FEIBA and AryoSeven® by Decision Analytic Model according to the Iranian healthcare system. An open label, multi-center, cross-over clinical trial was designed. Patients were categorized into 3 groups based on their prior tendency to one or none of the products. To determine the premium therapeutic strategy, the Incremental cost-effectiveness ratio (ICER) was calculated. Protocol F led to more treatment success in group F than the other groups (P= 0.03). Also, there was a significant statistical difference between the mean of effectiveness scores in the groups using protocol F (P = 0.01). The effectiveness of protocol F and A were 89% and 72%, respectively. ICER cost US$ 5,146 to manage an episode of bleeding to get one more unit of effectiveness using FEIBA VS. AryoSeven. Although the results showed that AryoSeven was more cost-effective compared to FEIBA, the two strategies were undominated. In other words, both medicines can be applied in the first line of the treatment if the cost of FEIBA was reduced. The present clinical trial was registered at IRCT website, under ID No.2013020612380N1.

Administration of antenatal corticosteroids to pregnant women with imminent delivery of a newborn at 24 to 34 weeks of gestation represents one of the most important advances in perinatal medicine in the past 25 years1,2. A single course of antenatal steroid has been associated with a decrease in acute neonatal systemic morbidity and mortality after preterm birth reducing the risk of respiratory distress syndrome and intraventricular haemorrhage (IVH)2,3. We advance the hypothesis that prenatal dexamethasone exposure may not protect preterm infants against IVH down-regulating the expression of survivin that plays a key role in the protection of brain cells against insult-induced apoptosis. Research studies are needed to better define whether antenatal betamethasone may be the best alternative therapy for antenatal prevention of IVH and whether dexamethasone may sensitize immature brain to IVH involving dose timing and treatment regimen.