Iranian Journal of Pharmaceutical Research最新文献

Background: Using sports supplements is common among athletes. The presence of anabolic steroids in sports supplements as a hormonal contaminant can increase production efficiency. Since anabolic steroids cause health problems and result in positive doping tests in athletes, it is important to investigate their presence in the supplement preparations consumed by athletes.

Objectives: This paper aims to simultaneously determine ten anabolic steroids by high-performance thin-layer chromatography (HPTLC) method in sports supplements.

Methods: Chromatographic analysis was conducted on glass silica gel 60F254 plates. The extracts loaded on silica gel plates are subjected to programed multiple development (PMD) to separate anabolic androgenic steroids (AASs). Densitometric scanning is carried out at the wavelength of 245 and 366nm. The method was validated according to the ICH guidelines.

Results: Spots at retardation factor (Rf) 0.72 (elution system 1), 0.4 (elution system 1), 0.29 (elution system 2), 0.25 (elution system 2), 0.1 (elution system 1), 0.65 (elution system 2), 0.59 (elution system 1), 0.44 (elution system 1), 0.8 (elution system 3), and 0.82 (elution system 3) values were recognized as 19-nor androstenedione, 19-nortestosterone, methyl testosterone, clostebol, stanozolol, trenbolone enanthate, oxymetholone, oxandrolone, testosterone enanthate, and nandrolone decanoate, respectively. The linear ranges were 25 - 250 μg/mL for oxymetholone, 7 - 50 μg/mL for 19-nor androstenedione, 19-nortestosterone, and oxandrolone, and 3 - 20 μg/mL for methyl testosterone, clostebol, stanozolol, trenbolone enanthate, testosterone enanthate, and nandrolone decanoate. The developed method is validated by acceptable precision (CV < 20%) and good accuracy (94% < R < 114%). The value of limit of detection (LOD) for all derivatives was in the range of 0.02 - 0.16 μg/spot (20-160 μg/g of supplement), while limit of quantitation (LOQ) was found to be in the range of 0.06 - 0.5 μg/spot (60 - 500 μg/g of supplement). Fifty sports supplement samples as real sample were collected and analyzed. None of the samples screened positive using the HPTLC method.

Conclusions: In the present study, the fast, cheap, and simple HPTLC method could be used for the multi-residue analysis of ten anabolic androgenic steroids in sports supplements.

Background: Intrauterine hypoxia (IUH) increases the risk of cardiovascular diseases in offspring. As a reactive oxygen species (ROS) scavenger, polyamine spermidine (SPD) is essential for embryonic and fetal survival and growth. However, further studies on the SPD protection and mechanisms for IUH-induced heart damage in offspring are required.

Objectives: This study aimed to investigate the preventive effects of prenatal SPD treatment on IUH-induced heart damage in newborn offspring rats and its underlying mitochondrial-related mechanism.

Methods: The rat model of IUH was established by exposure to 10% O₂ seven days before term. Meanwhile, for seven days, the pregnant rats were given SPD (5 mg.kg^-1.d^-1; ip). The one-day offspring rats were sacrificed to assess several parameters, including growth development, heart damage, cardiomyocytes proliferation, myocardial oxidative stress, cell apoptosis, and mitochondrial function, and have mitochondrial quality control (MQC), including mitophagy, mitochondrial biogenesis, and mitochondrial fusion/fission. In in vitro experiments, primary cardiomyocytes were subjected to hypoxia with or without SPD for 24 hours.

Results: IUH decreased body weight, heart weight, cardiac Ki67 expression, the activity of SOD, and the CAT and adenosine 5'-triphosphate (ATP) levels and increased the BAX/BCL2 expression, and TUNEL-positive nuclei numbers. Furthermore, IUH also caused mitochondrial structure abnormality, dysfunction, and decreased mitophagy (decreased number of mitophagosomes), declined mitochondrial biogenesis (decreased expression of SIRT-1, PGC-1α, NRF-2, and TFAM), and led to fission/fusion imbalance (increased percentage of mitochondrial fragments, increased DRP1 expression, and decreased MFN2 expression) in the myocardium. Surprisingly, SPD treatment normalized the variations in the IUH-induced parameters. Furthermore, SPD also prevented hypoxia-induced ROS accumulation, mitochondrial membrane potential decay, and the mitophagy decrease in cardiomyocytes.

Conclusion: Maternal SPD treatment caused IUH-induced heart damage in newborn offspring rats by improving the myocardial mitochondrial function via anti-oxidation and anti-apoptosis, and regulating MQC.

Background: The prevalence of drug poisoning is on the rise in Iran due to the increased public access to drugs. A national drug poisoning registry system is a suitable tool for better management, control, and prevention of drug poisoning.

Objectives: This study aimed to propose a national drug poisoning registry model for Iran.

Methods: This was an applied research conducted in two major phases. In the first phase, all sources pertaining to drug poisoning registries were reviewed, and a national drug poisoning registry model was proposed. In the second phase, this model was validated and finalized using a researcher-made questionnaire and through a two-stage Delphi technique.

Results: The focus of national drug poisoning activities and registry management reached the 100% consensus of experts at the Drug and Poison Information Center of the Food and Drug Organization (Ministry of Health and Medical Education). Goals, data sources, registry system structure, data set, standards, data exchange, registry features, and processes of the proposed model also achieved unanimous expert consensus.

Conclusions: Given the importance of a national drug poisoning registry in gathering, storing, analyzing, and reporting the data of patients, it is essential to provide a framework for evaluating and controlling drug poisoning and for generating valuable data for decision-making. The model proposed herein can offer the information infrastructure for designing and implementing such a system.

Background: A large number of new substances have insufficient biopharmaceutical properties for oral administration caused by their slow dissolution rate and poor solubility.

Objective: The purpose of our experiment was to improve the physicochemical properties of a hydrophobic drug, quercetin, by the nanomilling approach.

Methods: Quercetin nanosuspensions were prepared using a wet-milling method followed by lyophilization. Stabilizer type and ratio, drug content, milling time, and bead size were identified as critical variables, and their impacts on quercetin particle size were assessed. The optimized nanocrystal was characterized by its morphology, crystallinity, molecular interactions, saturation solubility, and dissolution properties.

Results: At optimized process conditions of milling at 500 rpm for 18 cycles of grinding with 0.3 - 0.4 mm zirconium oxide beads, minimum particle size, and PDI values were 281.21 nm and 0.22, respectively. Nanocrystals showed rod-like nanostructures, and XRD scans confirmed a decrease in drug crystallinity. The optimized formulation showed increased solubility and dissolution rate, as well as good physical stability.

Conclusions: Particle size reduction by media milling technique was an efficient method for the solubility enhancement of hydrophobic drugs.

Background: The supply chain of pharmaceuticals and medical devices takes on critical importance regarding group purchasing, given its contribution to a country's healthcare system. One of the primary loops in this chain is the pharmacy as a supplier of goods to consumers and a buyer of goods from distributors.

Objectives: Given the importance of proper and productive preparation, this study examined the structure of aggregated procurement of drugs and medical supplies in public pharmacies.

Methods: This study used a qualitative method and interviews to collect the necessary data. Fourteen experts and specialists in the public pharmacy field were interviewed and selected using the purposive sampling method. Finally, the textual data were analyzed using efficient thematic analysis.

Results: According to experts, the organizational structure for aggregated procurement of medicines and medical supplies in Iran's public pharmacies can take the form of a headquarters structure, a virtual structure, and a semi-centralized virtual structure. The main requirements for these structures are software infrastructure, a productive workforce, and improved storage methods.

Conclusions: According to the majority of experts, the most desirable structure for implementing aggregated procurement in hospital pharmacies is the headquarters structure. The aggregated procurement process can reduce pharmacy costs and increase financial reserves and profitability if adequately implemented and equipped with the necessary infrastructure.

The COVID-19 pandemic has prompted researchers to find treatments and vaccines to control SARS-CoV-2. There are some hypotheses about the benefit of respiratory virus vaccines, like MMR, for COVID-19 pneumonia severity, morbidity, and mortality. The influenza vaccine is one of the most frequently used respiratory virus vaccines covered by one of the Iranian insurance institutes. We have a symmetrical group of participants that have received this vaccine that could be compared with each other. We compared 3,379 persons aged 20 - 75 years for the effect of the influenza vaccine on COVID-19 mortality. We ultimately found that it does not affect mortality caused by COVID-19 pneumonia, but it can decrease the hospitalization cost in people over 65 years with a history of chronic disease.

Background: Curcumin, a compound derived from the root of the Curcuma longa, has been confirmed as an anticancer, chemoprotective, and gene/protein regulatory agent. Nanoformulation of curcumin has been developed to increase its targeting efficiency, solubility, controlled release, and physical and chemical stability.

Objectives: This study investigated the effect of new nano-type curcumin, oleic acid-derived dendrosome (OA400 nanoparticles), on the expression of E6 and E7 human papillomavirus oncogenes and P53 and Rb factors in the HeLa cell line. After preparing nano-curcumin by mixing OA400 nano-carrier and curcumin, its effect was considered on the human cervical cancer cell line (HeLa cell line RRID: CVCL_003) and normal fibroblast cells.

Methods: MTT assay and flow cytometry were used to evaluate cell viability and apoptosis. Furthermore, real-time RT-PCR and western blot analyses assessed RNA and protein expression of E6, E7, P53, and Rb. Statistical analyses were performed by GraphPad Prism 7 software.

Results: The nanoformulation of curcumin could reduce the expression of E6 and E7 oncogenes and increase P53 and Rb tumor suppressors in HeLa cancerous cells at 15 μM concentration; however, it had no significant effect on the viability of normal fibroblast cells. On the other hand, curcumin altered the expression of these genes at a 50-μM concentration. Gene and protein expression analysis indicated the up-regulation of P53 and Rb factors and the down-regulation of E6 and E7 under the influence of nano-curcumin treatment more than curcumin.

Conclusions: These data indicate the potential of curcumin-loaded OA400 nanoparticles to be considered as a treatment option in cervical cancer investigations.

Background: Drug resistance in breast cancer is an unsolved problem in treating patients. It has been recently discussed that lysosomes contribute to the invasion and angiogenesis of cancer cells. There is evidence that lysosomes can also cause multi-drug resistance. We analyzed this emerging concept in breast cancer through computational and systems biology approaches.

Objectives: We aimed to identify the key lysosome-related genes associated with drug-resistant breast cancer.

Methods: All genes contributing to the structure and function of lysosomes were inquired through the Human Lysosome Gene Database. The prioritized top 51 genes from the provided lists of Endeavour, ToppGene, and GPSy as prioritization tools were selected. All lysosomal genes and 12 breast cancer-related genes aligned to identify the most similar genes to breast cancer-related genes. Different centralities were applied to score each human protein to calculate the most central lysosomal genes in the human protein-protein interaction (PPI) network. Common genes were extracted from the results of the mentioned methods as a selected gene set. For Gene Ontology enrichment, the selected gene set was analyzed by WebGestalt, DAVID, and KOBAS. The PPI network was constructed via the STRING database. The PPI network was analyzed utilizing Cytoscape for topology network interaction and CytoHubba to extract hub genes.

Results: Based on biological studies, literature reviews, and comparing all mentioned analyzing methods, six genes were introduced as essential in breast cancer. This computational approach to all lysosome-related genes suggested that candidate genes include PRF1, TLR9, CLTC, GJA1, AP3B1, and RPTOR. The analyses of these six genes suggest that they may have a crucial role in breast cancer development, which has rarely been evaluated. These genes have a potential therapeutic implication for new drug discovery for chemo-resistant breast cancer.

Conclusions: The present work focused on all the functional and structural lysosome-related genes associated with breast cancer. It revealed the top six lysosome hub genes that might serve as therapeutic targets in drug-resistant breast cancer. Since these genes play a pivotal role in the structure and function of lysosomes, targeting them can effectively overcome drug resistance.

Background: Overexpression of programmed cell death ligand 1 (PD-L1) in tumor cells and subsequent interaction with the programmed cell death protein 1 (PD-1) in tumor-infiltrating T cells cause an immune evasion of the tumor from cytotoxic T-cells. Therefore, inhibiting such interaction by a recombinant PD-1 can hinder tumor growth and extend the survival rate.

Methods: The mouse extracellular domain of PD-1 (mPD-1) was expressed in E. coli BL21 (DE3) strain and purified using nickel affinity chromatography. The binding ability of the purified protein to human PD-L1 was studied using ELISA. Finally, the tumor-bearing mice were used to evaluate the potential antitumor effect.

Results: The recombinant mPD-1 showed a significant binding capacity to human PD-L1 at the molecular level. The tumor size significantly decreased in the tumor-bearing mice after the intra-tumoral injections of mPD-1. Moreover, the survival rate increased significantly after eight weeks of monitoring. The histopathology revealed the necrosis in the tumor tissue of the control group compared to the mPD-1 received mice.

Conclusions: Our outcomes propose that interaction blockade between PD-1 and PD-L1 is a promising approach for targeted tumor therapy.

Background: Polypharmacy is a significant patient safety concern.

Objectives: This study aims to estimate the prevalence of polypharmacy, its continuity and associated factors, and common medication classes among a large outpatient population in East Azerbaijan province, Iran.

Methods: A retrospective prescription data analysis was performed. The cohort included all ≥ 20 years old subjects with at least one prescription filled during the main three-month study period (2020 March 1 - 2020 May 31). Polypharmacy was defined as being exposed to more than four different medications during the main study period, and continuous polypharmacy was defined as being exposed to more than four medications during both the main study period and follow-up period (2020 October 1 - 2020 December 31). The frequency and prevalence of polypharmacy, along with predictive factors, were estimated. We performed multivariate logistic regression and estimated odds ratios (ORs) to investigate the risk factors for polypharmacy.

Results: 307,820 patients included (mean age 49.8 years, 62.9% female, mean drug use 3.7 (SD = 2.6). Polypharmacy was observed in 28.3% (CI: 28.1 - 28.4), of which 36.6% experienced continuous polypharmacy. The odds of being exposed to polypharmacy increased with being female, increasing age, and exposure to chronic conditions. The groups of medications most utilized by polypharmacy patients were those indicated for gastro-esophageal reflux diseases, beta-blocking agents, antidepressants, blood glucose-lowering drugs, and antithrombotic agents.

Conclusions: Strategies should be formulated to inform healthcare policymakers and providers about the magnitude of the polypharmacy phenomenon, associated factors, and the common medication classes involved.