Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences最新文献

Background: Rumex crispus L. (Polygonaceae), known as "Labada" in Turkey, was reported to be used for the treatment of gynecological diseases such as postpartum complications and infertility in folk medicine. Earlier studies on R. crispus have shown that leaf, fruit and root extracts have anti-inflammatory and antioxidant activities and are used for the treatment of tumors in the uterus. The hypothesis of this study is that R. crispus may generate potential anti-adhesive activity against complex factors such as inflammation, oxidation and fibrosis.

Objectives: We aimed to investigate the potential anti-adhesive activity of aqueous methanol extracts of leaves, fruits and roots of R. crispus.

Methods: Abdominal adhesion model was performed in 72 female Wistar Albino rats. In the first step of the experiment, the rats were divided into six groups namely, Sham, Control, Reference and Experimental Groups (consisting of three sub-groups in which R. crispus leaf, fruit and root extracts were applied at 100 mg/kg dose). The test samples were administered once to the peritoneal cavity and the rats were sacrificied at the end of the 14th day. Root extract showed prominent activity, therefore this extract was subjected to fractionation to obtain 3 fractions (30-60-100% methanol fractions) by using vacuum-liquid chromatography. In the second stage, animals were divided into 6 groups as Sham, Control, Reference and Experimental Groups (R30, R60, R100 at 100 mg/kg dose). Adhesion scoring, tissue total antioxidant and oxidant levels, histopathological and immunohistochemical (TNF-α, IL-6 and IL-8) analyzes were performed.

Results and conclusion: Adhesion scores, inflammatory cytokines and inflammation cells decreased by the application of R. crispus root extract. The fractions also showed similar anti-inflammatory effects, but R60 was found to be more effective in prevention of intra-abdominal adhesions and uterine fibrosis. R60 fraction, possessing potential bioactivity, was investigated in terms of phenolic composition by HPLC.

Background: Punica granatum L. (pomegranate) with astringent activities and Matricaria chamomilla L. (chamomile) with anti-inflammatory and antioxidant properties are natural remedies used for various skin disorders, including wound healing.

Objectives: This study was conducted to evaluate the individual and combined wound healing activity of the methanol extracts of pomegranate and chamomile flowers.

Methods: After preparing the menthol fraction of pomegranate and chamomile flowers, the content of total phenols, total tannins, and total flavonoids of fractions was measured. For standardization of pomegranate and chamomile fractions, Gallic acid and apigenin-7-O-glucoside contents of them were determined using high-performance liquid chromatography (HPLC). Moreover, their antioxidant activities were examined using DPPH and FRAP tests. The antimicrobial assay was performed against Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. Three different concentrations of methanol fraction of each plant and one combination dose of fractions were investigated for their wound healing activities in an excision wound model on the rats' dorsum. Finally, histopathological studies were done at the end of the experiment.

Results: Phytochemical examinations showed high amounts of phenolic compounds in pomegranate flowers, while chamomile flower fractions contained a high amount of total flavonoids. Both fractions, especially pomegranate, had potent antioxidant activity. The best results for wound closure were observed 7 days after wound induction. All treated groups exhibited superior wound contraction compared to their placebo at all measurement times. The combined form of pomegranate and chamomile had better wound healing properties compared to a single therapy, especially on time earlier to wound induction.

Conclusion: This study represented high antioxidant and wound healing activities for methanol fraction of pomegranate and chamomile flowers, which could be related to their high content of phytochemicals. In comparison with single herb treatment, the combined form of these two fractions in lower concentrations accelerated wound closure.

The social restrictions amid coronavirus disease 2019 (COVID-19) pandemic have posed a serious threat to mental health and have implications in the use of medications for mental health including antidepressants (ADs). This study investigated the trends in prescriptions and costs of various ADs in England during COVID-19 pandemic. National prescribing rates and net ingredient costs (NIC) of all ADs prescriptions during 2016 to 2020 were analyed. The total number of ADs prescriptions dispensed during COVID-19 pandemic (January to December 2020) were 78 million, 4 million more than in 2019 that costed NHS England £ 139 million more than in 2019. Sertraline, an SSRI antidepressant drug, alone accounted for an extra £113 million during 2020 than in 2019. The peak dispensing for ADs was observed in March 2020 while the total costs for AD drugs peaked in April 2020. The rising prescription costs for ADs during COVID-19 pandemic is a potential cause of concern, in particular the increasing use in adolescents and younger adults needs attention, who are at a higher risk of life-threatening adverse drug reactions.

Background: Investments in pharmaceutical companies remain challenging due to the inherent uncertainties of risk assessment.

Objectives: Our paper aims to assess the impact of the drug development setbacks (DDS) on the stock price of pharmaceutical companies while taking into account the company's financial situation, pipeline size and trend of the stock price before the DDS.

Methods: The model-based clustering based on finite Gaussian mixture modeling was employed to identify the clusters of pharmaceutical companies with homogenous parameters. An artificial neural network was constructed to aid the prediction of the positive mean rate of return 120 days after the DDS.

Results: Our results reveal that a higher pipeline size and a lower rate of return before the DDS, as well as a lower ratio of the market value of the equity and the book value of the total liabilities, are associated with a positive mean rate of return 120 days after the DDS.

Conclusion: In general, the DDS have a negative impact on the company's stock price, but this risk can be minimized by investors choosing the companies that satisfy certain criteria. Graphical abstract The higher pipeline size(spip) and lower rate of return before (srr) the drug development setback (DDS) and the Market Value of Equity/Book Value of Total Liabilities ratio (sx4) are associated with a positive mean rate of return 120 days after the DDS.

Purpose: To predict potential inhibitors of alpha-enolase to reduce plasminogen binding of Streptococcus pneumoniae (S. pneumoniae) that may lead as an orally active drug. S. pneumoniae remains dominant in causing invasive diseases. Fibrinolytic pathway is a critical factor of S. pneumoniae to invade and progression of disease in the host body. Besides the low mass on the cell surface, alpha-enolase possesses significant plasminogen binding among all exposed proteins.

Methods: In-silico based drug designing approach was implemented for evaluating potential inhibitors against alpha-enolase based on their binding affinities, energy score and pharmacokinetics. Lipinski's rule of five (LRo5) and Egan's (Brain Or IntestinaL EstimateD) BOILED-Egg methods were executed to predict the best ligand for biological systems.

Results: Molecular docking analysis revealed, Sodium (1,5-dihydroxy-2-oxopyrrolidin-3-yl)-hydroxy-dioxidophosphanium (SF-2312) as a promising inhibitor that fabricates finest attractive charges and conventional hydrogen bonds with S. pneumoniae alpha-enolase. Moreover, the pharmacokinetics of SF-2312 predict it as a therapeutic inhibitor for clinical trials. Like SF-2312, phosphono-acetohydroxamate (PhAH) also constructed adequate interactions at the active site of alpha-enolase, but it predicted less favourable than SF-2312 based on binding affinity.

Conclusion: Briefly, SF-2312 and PhAH ligands could inhibit the role of alpha-enolase to restrain plasminogen binding, invasion and progression of S. pneumoniae. As per our investigation and analysis, SF-2312 is the most potent naturally existing inhibitor of S. pneumoniae alpha-enolase in current time.

Purpose: Type 2 diabetes mellitus (T2DM) is the subject of numerous randomized controlled trials (RCTs). The validity of RCTs may be threatened by attrition bias due to the discontinuation of the study. The aim of this systematic review is to evaluate the reasons of patient's withdrawal from these RCTs.

Methods: A systematic literature search on PubMed, Cochrane Library, Web of Science, and Scopus databases was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. The aim was to obtain all relevant blinded RCTs published before January 2017 in which the effectiveness of synthetic drugs, vitamins/minerals were compared to that of placebo or active control in T2DM. The quality of RCTs was assessed using the Jadad score. The frequency of withdrawal reasons was presented based on treatments with placebo/active control, national/international level of the studies, and publication year. Meta-analysis was not performed due to the heterogeneity.

Results: Overall, 1368 articles comprising of 640,780 subjects were included. In the majority of the RCTs (75.0%), the intervention and the placebo arms were compared. Most of the included studies (96%) were classified in the high-quality category (Jadad score≥3). The highest proportion of reported withdrawal cases was found in international studies, national RCTs conducted in Japan, and RCTs published in 2011. The withdrawal reasons were reported for 91,669 (63.75%) of the total 143,794 participants who had withdrawn from these studies. The main reported reasons were "adverse effects" (24.04%), "withdraw consent" (16.10%), and "missing data" (11.08%). Variations in the reported withdrawal reasons were based on the country or published year. RCTs with triple blinded design as well as those in which anti-hyperlipidemia and anti-obesity medications were applied, showed significantly higher probability of reported the withdrawal.

Conclusion: High proportion of reported discontinuation in blinded RCTs on patients with T2DM was related to drug adverse effects. Overall, the total number and reason of drop out were unsatisfactory.

Background: Polychlorinated biphenyls (PCBs) are a group of synthetic organic chlorine compounds known as an organic pollutant in food sources, which play important roles in malignancies. The present study aimed to investigate the direct effects of prevalent PCBs in food in hormone-responsive and non-responsive cell lines.

Methods: In the current study, MCF-7, LNCap, and MDA-MB231 cell lines were treated with serial concentrations (0.001-100 μM) of PCBs for 48 h and cell viability assessment was performed using MTT assay. The best concentration then applied and the expression level of PON1 was evaluated using real-time PCR. Besides, molecular docking was performed to determine the binding mechanism and predicted binding energies of PBCs compounds to the AhR receptor.

Results: Unlike MCF-7 and LNCap cells, the viability of MDA-MB231 cells did not significantly change by different concentrations of PCBs. Meanwhile, quantitative gene expression analysis showed that the PON1 was significantly more expressed in MCF-7 and LNCap lines treated with PCB28 and PCB101. However, the expression level of this gene in other groups and also MDA-MB231cells did not demonstrate any significantly change. Also, the results of molecular docking showed that PBCs had steric interaction with AhR receptor.

Conclusions: Current results showed that despite of hormone non-responsive cells the PCBs have a significant positive effect on hormone-responsive cell. Therefore, and regarding to the existence of PCBs contamination in food there should be serious concern about their impact on the prevalence of different malignancies which certainly should result in a standard limit for this material. This study aimed to investigate the direct effects of prevalent PCBs in food in hormone-responsive and non-responsive cell lines. Cell lines were treated with serial concentrations of PCBs and cell viability assessment was performed using MTT assay. The expression level of PON1 was evaluated using real-time PCR. Molecular docking was performed to determine the binding mechanism and predicted binding energies of PBCs compounds to the AhR receptor. PCBs contamination in food there should be serious concern about their impact on the prevalence of different malignancies which certainly should result in a standard limit for this material.

Introduction: Ectopic pregnancy (EP) is an emergency condition in the gynecologic field. Methotrexate (MTX) is a drug of choice for the medical treatment of EP. Severe adverse events are rare among patients treated with MTX for this condition.

Reason for report: We describe a woman with severe multi-organ involvement experiencing about six days of instability after treatment with just a single-dose MTX for EP. This life-threatening condition is not common with a single dose of MTX. A 30-year-old healthy woman was treated medically with MTX for an EP. Three days later the patient was admitted to the emergency department of our hospital with generalized pustular rashes, alopecia, hyperpigmentation, nausea and vomiting, oral ulcers, and raised Creatinine level. Four days later due to pancytopenia, fever, and loss of consciousness, she was transferred to the intensive care unit and was intubated.

Outcome: After 38 days of hospitalization, treatment was successful with leucovorin and supportive care and the patient's symptoms and clinical manifestations were regressed.

Background: In recent era, pH sensitive polymeric carriers that combines the materials engineering and medicine is gaining researcher's attention as they maximizes drug concentration at site of absorption and reduces side effects for e.g. orally administered cetirizine HCl (CTZ HCl) upsets the stomach and furthermore shows high intestinal absorption. Thus, development of pH sensitive hydrogels with sufficient mechanical strength will be good candidate to address this issue.

Methods: Here, we developed pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum (IA-g-poly(AM)/sterculia gum) semi-interpenetrating network (semi-IPN) by free radical polymerization technique for intestinal delivery of CTZ HCL.

Results: Optimized formulation (I5) with 6% w/w IA showed negligible swelling at pH 1.2, and maximum swelling at pH 7.4. Solid state characterization of optimized formulation showed successful development of semi-IPN structure and incorporation of drug without any noticeable drug-carrier interaction. In vitro release study showed biphasic pH dependent release of CTZ HCl, where initial burst release was observed at acidic pH followed by sustained release at basic pH. Acute oral toxicity and histopathological studies confirmed the non-toxic nature of IA-g-poly(AM)/sterculia gum.

Conclusion: Conclusively, developed biocompatible semi-IPN hydrogels with sufficient pH sensitivity and mechanical strength could serve as a potential carrier for intestinal delivery of CTZ HCL to maximize its absorption and reduce side effects.

Background: Breakthrough pain (BTP) is an important challenge in treatment and requires a rapid onset of action for pain control. BTP should be adequately controlled with a stable dose of a short-acting oral opioid. So far, no drug is available for the treatment of BTP in cancer patients in Iran, so we designed the first study in Iran to investigate the effect of sublingual fentanyl in relief of pain episodes in these patients.

Objective: The purpose of this study was to evaluate the efficacy and safety of sublingual fentanyl in the treatment of breakthrough pain in cancer patients.

Method: This study was a randomized double-blind placebo-controlled clinical trial in cancer patients with breakthrough pain (at least 1-4 episodes of acute pain with moderate to severe pain daily) referred to the pain clinic of Akhtar and Masih Daneshvari hospitals in 2019. The study consisted of two stages: 100 patients were selected by simple, non-random sampling and entered the open-label titration phase. The primary efficacy endpoint was the sum of pain intensity difference over 30 min post-administration. Secondary efficacy endpoints included pain intensity difference (PID) and pain relief (PR) throughout the 60-min post-dose assessment period. In the double-blind study, patients were randomly divided into two groups of placebo (n=50) and intervention (sublingual fentanyl tablet) (n=50). For evaluation of efficacy, 10 episodes were treated in each group and the results were recorded by the patient. (Clinical trial registration: IRCT20131124015515N8).

Results: A total of 100 patients entered the titration phase, primary efficacy of sublingual fentanyl was 3.5±0.6 and secondary efficacy of sublingual fentanyl (60 min, after treatment) was 0.3±0.6 which was statistically significant. In the titration phase, the treatment success rate was 100%. In the double-blind phase of the study, the pain intensity in multiple episodes showed a significant improvement at 15, 30, 45, and 60 min after drug administration (P=0.0001). The intensity of pain in each episode was significantly decreased compared to the next episode (P=0.0001). The mean frequency of pain episodes in the sublingual fentanyl group showed a significant decrease (P=0.0001). The most common adverse drug events in the titration phase were drowsiness (20%), dizziness (7%), and nausea 4%, and in the double-blind phase only drowsiness (12%). (Cancer Research Center, Shahid Beheshti University of Medical Sciences, Survey).

Conclusion: Sublingual fentanyl appears to be effective for patients with rapid-onset analgesia, has short-acting duration, is effective medication, safe, and well tolerated. It is a suitable choice in Iranian patients with chronic cancer-related pain controlled suffering from acute pain episodes related to cancer.