Iranian Journal of Pharmaceutical Research

In Collaboration with School of Pharmacy, SBMU

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The IJ Pharmaceutical Research (IJPR) is a peer-reviewed multi-disciplinary pharmaceutical publication, scheduled to appear annually and serve as a means for scientific information exchange in the international pharmaceutical forum. Specific scientific topics of interest to the journal include but are not limited to: pharmaceutics, industrial pharmacy, pharmacognosy, toxicology, medicinal chemistry, novel analytical methods for drug characterization, computational and modeling approaches to drug design, bio-medical experience, clinical investigation, rational drug prescribing, pharmacoeconomics, biotechnology, nanotechnology, biopharmaceuticals, and physical pharmacy.

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    The Protective Effects of Pistacia Atlantica Gum in a Rat Model of Aluminum Chloride-Induced Alzheimer’s Disease via Affecting BDNF and NF-kB
    (Brieflands, 2024-12-31) Mohammad Mehdi Gravandi; Seyede Zahra Hosseini; Seyede Darya Alavi; Tayebeh Noori; Antoni Sureda; Roshanak Amirian; Mohammad Hosein Farzaei; Samira Shirooie
    Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, including deficits in memory and other cognitive functions. Oxidative stress and free radical damage play significant roles in its pathogenesis. This study aimed to investigate the potential anti-inflammatory and neuroprotective effects of Pistacia atlantica gum (administered at doses of 50 and 100 mg/kg for 14 days) in a rat model of AD induced by aluminum chloride (AlCl3). Behavioral changes were assessed using open field, passive avoidance, and elevated plus maze tests. Additionally, nitrite levels, nuclear factor-kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), and immunostaining were evaluated. Administration of P. atlantica gum significantly increased step-through latency in the passive avoidance test (P < 0.01 and P < 0.001), enhanced mobility in the open field test (P < 0.01 and P < 0.001), and reduced anxiety-like behaviors in the elevated plus maze (P < 0.001) compared to the AlCl3 group. Treatment with the gum partially normalized the elevated levels of NF-κB and the decreased levels of BDNF caused by AlCl3 exposure. Our findings suggest that P. atlantica gum administration may alleviate oxidative stress, neuroinflammation, and cognitive impairment in AD rats.
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    RadioLabeling of the Mutant form of Anti-PlGF Nanobody by 99mTc-Tricarbonyl
    (Brieflands, 2024-12-31) Tahereh Rezazadeh; Akram Sadat Tabatabaee Bafroee; Soraya Shahhosseini; Safura Jokar; Abolfazl Hasanramezani; Roghaye Arezumand
    Background: Molecular imaging is a highly effective method for diagnosing cancer and evaluating treatment. A molecular tracer often consists of two segments: A targeting segment, which can be antibodies, antibody fragments, or VHH (nanobody), and a detection segment, such as radioisotopes. The small size of VHH allows for excellent tissue penetration and fast clearance, resulting in minimal nonspecific background, which makes them appealing for use as imaging agents. 99m-technetium (99mTc), one of the well-known radioisotopes, is particularly useful in routine clinical imaging. Objectives: This study aims to construct 99mTc-anti-placenta growth factor (PlGF) nanobody and assess its radiochemical purity (RCP). Methods: The mutant form of anti-PlGF nanobody was expressed in E. coli TG1 and purified using Ni-NTA column affinity chromatography. The purified nanobodies were confirmed by SDS-PAGE and western blotting. A 99mTc-tricarbonyl solution was added to phosphate-buffered saline (PBS) containing the mutant nanobody for labeling, and the mixture was purified using a PD-10 column. Results: The RCP of 99mTc-tricarbonyl is > 98%. After the addition of radioisotopes to the mixture of nanobodies, purity reached 70% in 2 hours and remained constant during incubation. After purifying the labeled nanobody, activity was measured, and the highest amount of labeled nanobodies was collected in the second part. The stability of the labeled nanobody in PBS and in competition with histidine for 4 hours was checked by thin-layer chromatography (TLC). Conclusions: The findings of this study reveal that the RCP of the labeled nanobody was above 95% after 4 hours, indicating the labeled antibody's stability. These results are promising and could be utilized in future in vitro and in vivo studies.
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    Systematic Review of Patient Preference Studies in Non-metastatic Breast Cancer Adjuvant Medication Therapy: Attribute Selection
    (Brieflands, 2024-12-31) Ali Homayouni; Shekoufeh Nikfar; Fariborz Mokarian Rajabi; Mona Nili; Kimberly M. Kelly; Akbar Abdollahiasl
    Context: Breast cancer poses significant challenges due to its high incidence and prevalence, necessitating heightened attention. Understanding how patients prioritize different treatment options based on various attributes can assist healthcare decision-makers in maximizing patient utility. The discrete choice experiment, a conjoint method, facilitates preference elicitation by presenting different attributes and choices. This systematic review aims to identify key factors in patient preference research related to adjuvant treatment for early breast cancer characterized by hormone receptor-positive, HER2-negative status. Evidence Acquisition: PubMed, Embase, Web of Science, and Scopus were searched from 01.01.2000 to 31.03.2023. Original English articles reporting patient preferences in adjuvant breast cancer treatment were retrieved based on predefined inclusion and exclusion criteria. Included studies were examined through a narrative synthesis approach, with descriptive statistics employed for analysis. Results: Out of 1163 articles reviewed, four met the inclusion criteria and were conducted in the USA, Canada, and the Netherlands. Attributes extracted from all studies included alopecia, sensory neuropathy, motor neuropathy, myalgia/arthralgia, nausea, vomiting, fatigue, neutropenia, mucositis/stomatitis, hand-foot syndrome, diarrhea, prevention of breast cancer recurrence, osteoporosis, risk of endometrial cancer, joint and muscle pain, fluid retention, libido decrease, hot flashes, ECG monitoring, efficacy, treatment regimen, 5-year invasive disease-free survival (iDFS), dosing schedule, and treatment duration. The most frequently reported attributes were side effects, efficacy, and treatment regimen. Systematic review was commonly used to determine which attributes and levels to include. The minimum number of attributes identified per study was seven, and the maximum was 12. Sample sizes ranged from 102 to 300, with none of the studies mentioning the method of sample size estimation. Ordinary Least Squares, logistic regression, and hierarchical Bayes regression were the most frequent analysis methods. Conclusions: Side effects, 5-year iDFS, and treatment regimen are three attributes identified for conducting discrete choice experiment studies. Utilizing conjoint analysis to assess patient preferences for breast cancer treatment can aid in selecting optimal treatment regimens and improving patient adherence. Moreover, adhering to guidelines for developing experimental designs and conducting data analysis is essential for yielding robust results when employing preference elicitation methods.
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    Time-Dependent Molecular Changes Following MDMA-Induced Nephrotoxicity
    (Brieflands, 2024-12-31) Mehrdad Roghani; Ravieh Golchoobian; Maryam Mohammadian; Farzane Shanehbandpour-Tabari; Zahra Salehi; Saba Gilaki-Bisheh
    The increasing recreational use of ecstasy (MDMA) poses significant risks to human health, including reports of fatal renal failure due to its adverse renal effects. While MDMA-induced renal toxicity might result from systemic effects, there is also substantial evidence of direct harm to renal tissues by MDMA or its metabolites. The precise mechanisms underlying renal toxicity remain unclear. This study explored the impact of a single intraperitoneal dose of MDMA (20 mg/kg) on rat kidneys. Serum BUN and creatinine levels were evaluated to assess renal function, while TNF-α and TGF-β protein concentrations were measured using ELISA. mRNA levels of Bax, Bcl-xl, and Bcl-2 were quantified using quantitative RT-PCR. Additionally, apoptosis and histopathological changes in renal tissue were examined. Results showed a transient increase in serum BUN and creatinine in MDMA-treated rats. There were decreases in TNF-α and TGF-β levels in the renal tissue. Both pro-apoptotic Bax and anti-apoptotic Bcl-xl gene expressions were significantly reduced, whereas Bcl-2 expression and apoptosis did not show significant changes. No structural alterations were observed in the renal tissues. Overall, this study suggests that the renal adverse effects of MDMA may be mediated through the disruption of cytokine pathways, with notable reductions in TGF-β possibly linked to decreased TNF-α levels.
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    Excretion of Acebutolol and its Major Metabolite Diacetolol into Infant Blood Circulation and the Breast Milk
    (Brieflands, 2003-07-31) S. Abolfazl Mostafavi; Dora A. Stinson; Kent Dooly; Fakhreddin Jamali
    Acebutolol (AC) is a chiral β-adrenergic blocking drug, which is useful clinically as the racemate in treating hypertension and is metabolized to an equipotent chiral metabolite, diacetolol (DC). In this paper we report a case of a 32 year old woman who was receiving AC during her pregnancy and lactating time for management of hypertension. The maternal plasma level and breast milk as well as cord blood collected to see whether the drug is transferred to the fetus through the mother stereoselectively. A stereospecific high-performance liquid chromatographic (HPLC) assay was used to measure the enantiomeric concentrations of AC and DC. AC and DC enantiomers are stereoselectively excreted into the milk, although the concentrations of DC enantiomers were higher than those of AC. AC concentrations were very low in both cord artery and vein samples four hours after taking the drug however, the stereoselective concentrations of metabolite, DC, was found in these samples. In conclusion, AC and DC enantiomers are excreted in human breast milk in concentrations much higher than that in maternal plasma. Furthermore, DC was found in the infant's plasma indicating that accumulation of metabolite did occur in this infant.
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    Quercetine, a Major Flavonol Aglycon from Tanacetum balsamita L.
    (Brieflands, 2003-10-31) Bahman Nickavar; Gholamreza Amin; Nacim Mehregan
    From the aerial parts of Tanacetum balsamita L. (Compositae) a flavonol aglycon was iso-lated using chromatographic techniques. The structure of this compound was determined usingspectroscopic methods (UV, H-NMR and MS) as 3',4',5,7-Tetrahydroxy flavonol (Quercetin).
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    Preparation and Characterization of Poly-(methyl ethyl cyanoacrylate) Particles Containing 5-Aminosalicylic acid
    (Brieflands, 2005-01-31) Hashem Montaseri; MS Sayyafan; Hosnieh Tajerzadeh
    Poly-(alkylcyanoacrylate) ester particles have been used for the preparation of different formulations ranging from ophthalmic delivery systems to cancer chemotherapy carriers in clinic. The aim of this study was to prepare and characterize poly-(methyl ethyl cyanoacrylate) (PMECA) particles containing 5-aminosalicylic acid (5-ASA). PMECA particles were prepared using the inverse emulsification polymerization technique. The effects of various formulation parameters such as dispersed phase volume, polymer to drug weight ratio, and surfactant concentration on loading efficiency and size of the prepared particles were investigated. The amount of drug was determined by UV spectrophotometery at 331 nm. Morphological characteristics of particles and particle size analysis were studied by Scanning Electron Microscopy (SEM) and Laser Light Scattering techniques, respectively. The results showed that there was no linear relationship between the dispersed phase volume (DPV) and loading efficiency of 5-ASA in the range of 20-50%. Increasing polymer/drug weight ratio in the range of 1-15, enhanced the loading efficiency from 11.4 to 78.2% in a linear mode (r=0.987). Increasing the surfactant concentration in the range of 1-3% did not increase the loading efficiency of the prepared particles, and increasing the concentration to 5% even decreased the loading efficiency of particles. Laser light scattering and SEM evaluations showed that in all prepared formulations, particles were in a mixture of micro and nanospheres and micro and nanocapsules and 50 percent of particles had mean sizes in the range of 6.4-10.1 micrometer. Although our results showed significant differences in the mean particle size between some of the prepared formulations, this variation was not practically important. It was concluded that by using proper conditions, it is possible to use PMECA as a polymeric matrix for loading of 5-ASA and the other hydrophilic drugs.
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    The Pharmacological Effects of Odonthobuthus doriae Scorpion Venom and Its Extracted Fractions on Neuro-Muscular Transmission
    (Brieflands, 2006-04-30) Amir Jalali; Zahra Hossininasab; Zynab Ehsani; Amir-Abbas Zare; Afshin Zarghi; Hossein Vatanpour
    The effect of Odonthobuthos doriae (O.d) scorpion venom at 0/3, 1 and 3, 10 µg/ml concentrations were investigated on nerve-muscle transmission, using the Twitch tension technique. A concentration of 0.3 µg/ml caused a small change in the twitch height in response to indirect muscle stimulation, but higher concentrations (1, 3, 10 µg/ml) caused a transient augmentation in twitch response followed by a large contracture in the chick biventer cervices (CBC) preparation. This effect could be defined as a complex action of the venom, predominately presynaptic, in which its’ effects on postjunctional synapses is also maintained.
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    Development and Characterization of Bioadhesive Gel of Microencapsulated Metronidazole for Vaginal Use
    (Brieflands, 2010-07-31) Nayak Bhabani Shankar; Rout Prasant Kumar; Nayak Udaya Kumar; Bhowmik Benoy Brata
    The present study concerned with the development and characterization of metronidazole microcapsules prepared by thermal change method using different ratios (1:1, 1:2 and 1:4) of ethyl cellulose in order to select the best microcapsule formulation with a good encapsulation efficiency and drug release profile. The obtained microcapsules were discrete, spherical with free flowing properties and evaluated for particle size, shape, flow properties, wall thickness, drug encapsulation efficiency and in vitro release performance. The drug carrier interactions were investigated in solid state by FT-IR spectroscopy and scanning electron microscopy. The microcapsules with a narrow size range of 23-68 μm showed higher encapsulation efficiency. The selected microcapsule formulation, MC3 (Drug polymer ratio 1:4) was employed for gel formulation with a variety of carbopol polymers (carbopol-934, 940, 974 and 980) by mechanical stirring method in order to develop a sustained release microencapsulated metronidazole microcapsules-containing bioadhesive gel. The prepared bioadhesive gels were evaluated for pH, spreadability, extrudability, viscosity, vaginal irritation, in vitro drug release, bioadhesion, accelerated stability and in vitro drug release kinetic. In vitro experiments indicated a sustained release over 24 h and an acceptable bioadhesion quality for formulation F3. Hence, it can be concluded that the formulation F3 has potential to deliver metronidazole in a controlled and constant manner for prolong period over other formulations and can be adopted for a successful delivery of metronidazole for vaginal use.
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    Gastroprotective Effect of Hydroalcoholic Extract of Aloe buettneri
    (Brieflands, 2011-01-31) Kossi Metowogo; Kwashie Eklu-Gadegbeku; Amégnona Agbonon; Kodjo A. Aklikokou; Messanvi Gbeassor
    Aloe buettneri A. Berger is commonly used in traditional Togolese medicine to treat inflammatory and gastric ulcers. The present study examined the gastro-protection effect of the hydro-alcoholic extract of A. buettneri on mucus production and gastric pH. A gastric ulcer is induced by ethanol 95° alone (1 mL/kg body weight), after pre-treatment with indomethacin (300 mg/kg) or by utilising L-NAME (40 mg/kg IV). In addition gastric mucus was removed by scraping and subsequently weighed. The experiment focused entirely on rats that had been subjected to fasting. The hydro-alcoholic extract of A. buettneri (500 mg/kg) significantly inhibited ulcers that were induced by ethanol, indomethacin or L-NAME pre-treatment. A. buettneri was shown to increase the production of gastric mucus. Furthermore L-arginine significantly decreased the size of the induced ulcers. The results achieved in the study carried out suggest that A. buettneri posses gastro-protective properties.
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    Cytotoxic Effect of Some 1, 4-Dihydropyridine Derivatives Containing Nitroimidazole Moiety
    (Brieflands, 2011-07-31) Ramin Miri; Katayoun Javidnia; Zahra Amirghofran; Seyyed Hossein Salimi; Zahra Sabetghadam; Savis Meili; Ahmad Reza Mehdipour
    The 1,4-dihydropyridine (DHP) derivatives are a known class of calcium channel blockers. Some derivatives of DHP showed significant cytotoxicity. It was shown that this effect may not be the result of interaction with Ca2+ channels. In this study, we performed an investigation about the intrinsic cytotoxicity of some derivatives of DHP containing nitroimidazole moiety on their C4 position on four different cancer cell lines (Raji, K562, Fen and HeLa). The result showed that these compounds had moderate-good cytotoxic activity. In addition, QSAR model shows the importance of N atom in cytotoxicity; Ca2+ channels.
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    The Effects of Berberis vulgaris Fruit Extract on Serum Lipoproteins, apoB, apoA-I, Homocysteine, Glycemic Control and Total Antioxidant Capacity in Type 2 Diabetic Patients
    (Brieflands, 2012-04-30) Farzad Shidfar; Shima Seyyed Ebrahimi; Sharieh Hosseini; Iraj Heydari; Shahrzad Shidfar; Giti Hajhassani
    Type 2 diabetes is a well-known endocrine and metabolic disorder which has reached epidemic proportions worldwide and represents a serious public health concern. Hyperglycemia and dyslipidemia are two major abnormalities which are major cardiovascular risk factors. Berberine is a major alkaloid in Berberis vulgaris fruit extract (BVFE) which have important role in regulation of serum glucose and fat metabolism in-vivo and in-vitro but its role in type 2 diabetes have not been extensively examined.
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    99mtc-Ubiquicidin [29–41], a Promising Radiopharmaceutical to Differentiate Orthopedic Implant Infections from Sterile Inflammation
    (Brieflands, 2013-04-30) Davood Beiki; Gholamali Yousefi; Babak Fallahi; Mohammad Naghi Tahmasebi; Ali Gholamrezanezhad; Armaghan Fard-Esfahani; Mostafa Erfani; Mohammad Eftekhari
    Ubiquicidin (UBI) [29-41] is a synthetic cationic antimicrobial peptide that preferentially binds to bacterial cell membrane at the site of infection. We aimed to assess diagnostic value of 99mTc-UBI [29-41] as a radiopharmaceutical in differentiation of bacterial infection from sterile inflammation in suspected orthopedic implants. Nine patients suspected for orthopedic implant infection, all males with the mean age of 41.6 ± 20.9 years, were studied. A dose of 10 MBq/Kg (range : 555-740 MBq) 99mTc-UBI [29-41] was injected intravenously. A dynamic study followed by static whole body imaging at 30, 60 and 120 min post-radiotracer injection was acquired. Periprosthetic tissue culture was considered the closest test to a gold standard for diagnosing infections and scintigraphic scans were categorized as true- or false-positive and true- or false-negative, considering the bacterial culture as the gold standard. No adverse reaction was observed during or after the radiotracer injection days. There were five true positive, four true negative and no false positive and false negative scans. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were all calculated as 100%. We found a high diagnostic accuracy for 99mTc-UBI [29-41] scintigraphy in differentiation of bacterial infection from sterile inflammation in suspected orthopedic implants. Therefore, 99mTc-UBI [29-41] scintigraphy might be potentially recommended as a safe and promising imaging modality in these settings. However, further studies on a larger number of patients and different pathologies are still needed.
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    Synergistic Effect and Mechanism of Cineole and Terpineol on In-vitro Transdermal Delivery of Huperzine A from Microemulsions
    (Brieflands, 2013-04-30) Jun Shi; Wen-Juan Cong; Yi-Ming Wang; Qing-Fei Liu; Guo-An Luo
    The aim of the present study was to investigate the influence and the mechanisms of cineole and terpineol on the in-vitro transdermal delivery of huperzine A from microemulsions, and their potential synergistic effect on the permeation enhancement. The transdermal delivery of huperzine A from microemulsions with different concentrations of cineole and terpineol through the rat abdominal skin was determined by Franz-type diffusion cells. The partition coefficient of huperzine A between the full thickness skin and microemulsion was determined. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was carried out to analyze the effects of cineole and terpineol on the biophysical properties of the stratum corneum (SC) and the mechanisms of permeation enhancement. These results indicated that cineole and terpineol could synergistically increase the transdermal delivery of huperzine A from microemulsions through increasing the partition and diffusion coefficients of huperzine A. ATR-FTIR studies further validated the synergistic effect and revealed that the enhancing mechanisms were due to increasing the disorderliness and fluidity of SC lipid alkyl chains, disrupting the structure of keratin in SC, and extracting SC lipids. In conclusion, cineole and terpineol, acting synergistically to enhance the transdermal delivery of huperzine A from microemulsions, might provide an alternative permeation enhancer combination for the transdermal delivery of huperzine A.
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    Isolation, Purification, Characterization and Effect upon HepG2 Cells of Anemaran from Rhizome Anemarrhena
    (Brieflands, 2013-10-31) Qian-Qian Jiang; Yun-Ping Zhao; Wen-Yuan Gao; Xia Li; Lu-Qi Huang; Pei-Gen Xiao
    The rhizome of Anemarrhena asphodeloides is used as food and traditional Chinese medicine for its hypoglycemic effect. The aim of this study was to investigate the isolation, purification and hypoglycemic activity of Anemaran as the active component. The influence factors (isolation duration, ratio of residuals to water and extracting times) during the isolation process were evaluated. The optimal conditions for NA and AA were extraction temperature 90ºC and 100ºC, duration 1h and 1.5 h, extraction time 3 and 3, and the solid–liquor ratio 1:20 and 1:15, respectively. Neutral and acid Anemaran (NA and AA) were isolated from the rhizome of Anemarrhena asphodeloides. Five fractions of NA-1, NA-2, NA-3, AA-1 and AA-2 were obtained after crude neutral and acid Anemaran purified through DEAE- 52 cellulose anion-exchange column. The characterizations of Anemaran and its different fractions were both analyzed by Fourier transform infrared spectroscopy (FT-IR) and scanning electron micrographs (SEM). Structural properties of different fractions were examined by FT-IR. Strong characteristic absorption peaks were observed at around 1744 cm−1and 1650 cm−1 caused by the C=O group of uronic acids, and the band between 1440 cm−1 and 1395 cm−1 associated with the stretching vibration of C–O of galacturonic acid. Neither the crude neutral, nor the acid anemaran significantly inhibited the growth of HepG2 cells in-vitro, which indicated the low cytotoxicity of the anemaran. Furthermore, both neutral and acid anemaran showed hypoglycemic effect. The hypoglycemic effect of neutral anemaran was much higher than that of acid anemaran.
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    Anxiolytic-Like and Sedative Effects of Alcea Aucheri (Boiss.) Alef. Flower Extract in the Laboratory Rat
    (Brieflands, 2017-10-31) Tajmah Mombeini; Hamid Gholami Pourbadie; Mohammad Kamalinejad; Soroush Mazloumi; Ahmad Reza Dehpour
    The present study was conducted to investigate the possible anxiolytic and sedative of an acute administration and 4-day repeated dosing of an aqueous extract of flowers of Alcea aucheri (Boiss.) Alef. (EFA)in rats subjected to the elevated plus-maze (EPM), open-field, and horizontal wire tests. All drugs were administered intraperitoneally. Phytochemical screening confirmed the presence of phenolic compounds, flavonoids, and polysaccharides in the extract. Repeated dosing of EFA (at dose of 35 mg/kg) significantly increased percentage of time spent on open arms and of open arms entries, and also decreased percentage of time spent on closed arms and of closed arms entries; compared with saline control, 24 h after treatment. In addition, repeated dosing of EFA (at dose of 175 mg/kg) significantly increased open arm activity 48 h after treatment, versus saline group. This effect was also observed following acute administration of EFA at 175 mg/kg. In open field, acute administration of EFA at doses of 17.5, 35, 70, 175, 350, and 700 mg/kg induced a statistically significant and dose-dependent decrease in locomotor activity, compared with saline control. ED50 value for EFA-induced decrease in locomotor activity was 194 mg/kg. Furthermore, unlike diazepam; EFA didn´t decrease the percent of the rats grasping the wire.
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    Efficacy and Safety of Two Different Enoxaparin Doses for Thromboprophylaxis in Non-critically Ill Patients: A Randomized Controlled Trial
    (Brieflands, 2022-12-31) Ilad Alavi-Darazam; Kimia Forouhar; Omid Moradi; Ali Saffaei; Sara Asadi; Zahra Sahraei
    Background: Recently, a few studies based on anti-factor Xa activity levels have propounded doubtful and sub-prophylactic levels by the usual dose of enoxaparin in surgical and critically ill patients. In this study, we assessed two doses of enoxaparin in adult non-critically ill patients. Methods: Patients were randomly assigned into two groups of intervention and control. While the intervention group received enoxaparin with a daily dose of 60 mg, the control group received enoxaparin 40 mg. Anti-factor Xa activity was measured based on the peak steady-state levels. The level of 0.2 to 0.4 IU/mL was considered as a prophylactic goal. All individuals were followed for bleeding or thromboembolic events during admission. Results: The mean levels of anti-factor Xa were 0.29 ± 0.13 IU/mL in the control group (n = 31) and 0.44 ± 0.19 IU/mL in the intervention group (n = 29). More patients in the control group had an optimal level of anti-factor Xa compared to the patients in the intervention group (62.1% vs. 29%). No adverse outcomes were detected in any of the groups. Conclusions: Enoxaparin dose of 60 mg daily provided anti-factor Xa level higher than desired in most patients. In non-critically ill patients, the dose of 40 mg is the proper dose for thromboprophylaxis.
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    Designing and Expression of Recombinant Chimeric Spike Protein from SARS-CoV-2 in Escherichia coli and Its Immunogenicity Assessment
    (Brieflands, 2023-12-31) Sahar Karimi; Shahram Nazarian; Fattah Sotoodehnejadnematalahi; Roohollah Dorostkar; Jafar Amani
    Since December 2019, the world has been grappling with an ongoing global COVID-19 pandemic. Various virus variants have emerged over the past two years, each posing a greater threat than its predecessors. The recent appearance of the omicron variant (B.1.1.529) has raised significant alarm within the field of epidemiology due to its highly contagious nature and rapid transmission rate. The omicron variant possessed mutations in the key receptor-binding domain (RBD) region, the S region, and these modifications have shown a notable impact on the strain's susceptibility to neutralizing antibodies. Developing safe and efficient vaccines to prevent a future severe acute respiratory outbreak of coronavirus syndrome 2 (SARS-CoV-2) is significant. Viral surface spike proteins are ideal targets for vaccines. This study aimed to find a multi-subunit chimeric vaccine. After conducting bioinformatics analysis, the recombinant spike (RS) protein of SARS-CoV-2 was deliberately designed and subsequently produced using E. coli expression systems. The immunogenicity of RS and neutralizing antibody responses were evaluated on immunized BALB/c mice. There was a significant difference in antibody titers between RS-immunized mice and control groups. The endpoint of the serum antibody titer of mice immunized with our chimeric protein was 2.5 times higher than that of the negative control. The chimeric construct could present multiple antigens simultaneously, influentially affecting immunization. Sera from mice vaccinated by RS could recognize the SARS-CoV-2 virus and neutralize antibodies. Our chimeric peptide could bind to antibodies in the serum of patients infected with different serotypes of the SARS-CoV-2 virus, such as alpha, delta, and omicron variants. The results indicated that the RS protein would be a potential novel antigenic candidate for subunit vaccine development and could be used as a useful alternative to generate diagnostic serological tests for SARS-CoV-2 infection.
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    Effectiveness of Fluconazole for Suppressive Maintenance Therapy in Patients with RVVC: a Randomized Placebo-Controlled Study
    (Brieflands, 2009-10-31) Forouzan Bolouri; Nasrin Moghadami Tabrizi; Fatemeh Davari Tanha; Azra Azmoodeh; Saeed Emami; Mehraban Falahati; Somaye Sharifynia; Maliheh Safavi; Abbas Shafiee; Alireza Foroumadi
    Recurrent vulvovaginal candidiasis (RVVC) is seen in 5% of women with Candida vaginitis. Use of fluconazole as prophylactic treatment has been suggested for RVVC. The aim of the present study was to evaluate the efficacy of fluconazole suppressive therapy in RVVC patients, as a randomized, placebo-controlled, double-blind prophylactic study. Among the 330 women with acute symptomatic vulvovaginal candidiasis referred to Mirza-kouchak Khan gynecology hospital, 64 eligible subjects with RVVC were enrolled. Then, all of them were treated with fluconazole (150 mg orally every 3 days, for three doses). This was followed by microscopical and clinical examination. Next, patients were randomly divided into two groups. In the fluconazole group (n = 32), patients received fluconazole 150 mg, per week for 6 months and in the control group (n = 32) they received placebo. All the patients were revisited on a monthly basis and at the end of treatment, as well as 3 and 6 months after treatment. At the end of treatment, the frequency of positive culture in fluconazole group was significantly lower than the placebo group (25% vs. 62.5%, P = 0.05). Furthermore, the rate of clinical recurrence was significantly lower in the fluconazole group,with respect to the placebo group (18.8% vs. 50%, P = 0.017). However, following band 6 months after treatment, patients who received fluconazole maintenance therapy had a non-significant differences, compared to the placebo group, based on the rate of clinical recurrence or the frequency of positive cultures. Resistance to fluconazole (MIC ≥ 64) was comparable between groups. Despite the fact that fluconazole is well tolerated by the patients, suppressive treatment with fluconazole in RVVC patients had an insufficient effect on prevention from recurrence of clinical signs and the improvement of vaginal mycological status in long term (3-6 months after treatment).
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    Design, Synthesis and Anticonvulsant Activity of 2-(2-Phenoxy) phenyl- 1,3,4-oxadiazole Derivatives
    (Brieflands, 2013-03-31) Sayyed Abbas Tabatabai; Saoka Barghi Lashkari; Mohammad Reza Zarrindast; Mohammadreza Gholibeikian; Abbas Shafiee
    Benzodiazepines are useful drugs for treatment of sleep disorders, anxiety, seizure cases and skeletal muscle cramps. Some derivatives of 2-(2-Phenoxy) phenyl-1, 3, 4-oxadiazole were synthesized as benzodiazepine receptor agonists. Conformational analysis and superimposition of energy minima conformers of the compounds on estazolam, a known benzodiazepine agonist, reveal that the main proposed benzodiazepine pharmacophores were well matched. Anticonvulsant activity of the synthesized compounds, determined by pentylenetetrazole-induced lethal convulsion test, showed that the introduction of an amino substituent in position 5 of 1,3,4- oxadiazole ring generates compound 9 which has a respectable effect. The results are in agreement with SAR of benzodiazepine receptor ligands since the elimination of electronegative substituent in position 2 of phenoxy ring or position 4 of phenyl ring reduces the anticonvulsant activity.