Hasil untuk "Therapeutics. Pharmacology"

Zejian Kuang, Hongjun Luo, Hui Li et al.

Sepsis-induced myocardial dysfunction (SIMD) is a fatal complication with limited therapeutic options. Semicarbazide-sensitive amine oxidase (SSAO) contributes to oxidative stress and leukocyte recruitment, yet its role in SIMD remains unexplored. This study investigates whether hydralazine, a potent SSAO inhibitor, protects against SIMD by evaluating the involvement of SSAO inhibition. Using a murine model of LPS-induced sepsis, hydralazine was administered 30 min post-injection. Over a 7-day observation period, survival rates, cardiac function (assessed by echocardiography), and myocardial injury (evaluated via plasma biomarkers including CK, CK-MB, LDH, and AST, alongside histopathology) were monitored. Additional analyses included measurements of oxidative stress markers (T-AOC, GSH-PX, SOD, MDA, GSH), inflammatory chemokine levels using a Luminex panel, and myocardial SSAO activity via HPLC. The results demonstrated that hydralazine at doses of 5 and 10 mg/kg significantly improved 7-day survival rates from 20% to 90% and enhanced cardiac function in septic mice. It also reduced myocardial injury and histological damage while attenuating systemic inflammation through suppression of chemokine elevation. Furthermore, hydralazine boosted systemic and myocardial antioxidant capacity and normalized the sepsis-induced increase in myocardial SSAO activity, suggesting a potential mechanism for its protective effects. In conclusion, hydralazine shows robust cardioprotection in experimental sepsis by decreasing oxidative stress and inflammatory cell infiltration. The inhibition of SSAO activity may be a pivotal underlying molecular mechanism.

Kalpana Panati, Parasuraman Aiya Subramani, Venkata Ramireddy Narala

The therapeutic targeting of peroxisome proliferator-activated receptor gamma (PPARγ) for type 2 diabetes (T2D) remains a double-edged sword: while thiazolidinediones are efficacious, their severe side effects necessitate the discovery of safer modulators. We propose a novel nutrient-centred hypothesis that thiamine (vitamin B1), an essential micronutrient, may act as a natural ligand for PPARγ. To investigate this, we adopted a translational approach. Molecular docking and dynamics simulations established that thiamine forms a stable, high-affinity interaction with the PPARγ ligand-binding domain. Functionally, in 3T3-L1 adipocytes, thiamine induced adipogenesis and PPARγ-response element binding with a potency analogous to rosiglitazone, suggesting direct agonistic activity. Corroborating these mechanistic insights at the clinical level, a new meta-analysis of randomized controlled trials demonstrates that high-dose benfotiamine, a synthetic thiamine derivative, significantly improves neuropathic and vascular outcomes in T2D patients. While the contribution of thiamine’s established antioxidant effects to these clinical benefits cannot be ruled out, the synergy of computational, cellular, and human evidence provides a compelling foundation for our hypothesis. This study suggests that thiamine could act as a PPARγ ligand and serve as a safer treatment option for metabolic disorders, which needs to be tested in vivo.

Maosheng Lee, Maosheng Lee, Yanyan Tan et al.

IntroductionA traditional Chinese herbal decoction, Huoxue-Jiangtang decoction (HXJT), has been clinically prescribed to patients with type 2 diabetes mellitus (T2DM) to improve hyperglycemia and hyperlipidemia for many years. However, the potential mechanisms underlying its anti-diabetic effects remain unclear.MethodsThe aim of this study was to explore the anti-diabetic effects and underlying molecular mechanisms of HXJT in T2DM rats, which were fed with a high-fat diet (HFD) and subsequently induced with streptozotocin (STZ). HPLC-MS analysis was performed to characterize the chemical composition of HXJT and serve as a quality control measure. The T2DM rats were treated with metformin or HXJT for 8 weeks.Results and discussionTreatment with HXJT significantly reduced hyperglycemia and improved insulin resistance in T2DM rats, as revealed by multiple assessments, including fasting blood glucose (FBG), glucose tolerance, fasting insulin levels, homeostasis model assessment of insulin resistance, insulin sensitivity index analysis, and histological examination of pancreas islets. HXJT treatment decreased blood lipid profile, including total cholesterol, low-density lipoprotein cholesterol, and triglycerides, although it did not change the rats’ body weight. The Western blot results indicated that HXJT reversed the downregulation of AKT and PI3K and markedly increased glucose transporter type 4 (GLUT4) in skeletal muscles. Moreover, the levels of glycogen synthetase (GS), hexokinase, superoxide dismutase (SOD), glycogen, and muscle glycogen in the HXJT group significantly increased relative to those in untreated T2DM group, while TNF-α levels decreased observably. In conclusion, HXJT improves insulin resistance, enhances insulin sensitivity, and helps preserve glucose homeostasis. The potential molecular mechanisms are related to the activation of PI3K/AKT and GLUT4 in skeletal muscles, either directly or indirectly.

Eun-Byul Cho, Jae-Chang Lee, Eun-Jung Kim et al.

Objectives: The present study aimed to analyze the status and needs of Korean Medicine doctors’ (KMDs) continuing professional development (CPD) and establish future improvement directions. Methods : A cross-sectional survey targeting all KMDs was conducted between October 23 to November 5, 2024, obtaining 624 responses. The questionnaire was developed to assess satisfaction with continuing education and residency training, perceived efficacy on competency development, and improvement needs. Results : While current CPD programs effectively enhanced optimal patient care competencies (highest-rated domain), approximately 40% of respondents indicated minimal improvement in social accountability and clinical management competencies. The most requested improvements were the expansion of practical training opportunities (63.0%) and curriculum improvement (37.0%). For residency training, respondents prioritized developing competency-centered curricula (65.0%) and standardized educational programs across training hospitals (63.3%). Conclusion : Findings indicate that KMDs desire increased practical training opportunities, competency-based standardized curricula, and expanded scope of practice through institutional support. Establishing competency frameworks across clinical departments and strengthening competencies required in modern healthcare environments are essential for advancing Korean Medicine practice.

Rachelle Buchbinder, Paul Glare, Claire Ashton-James et al.

Introduction The efficacy and safety of SMS text message-delivered interventions for providing pain self-management education and improving clinical pain outcomes have been demonstrated in several randomised controlled trials. However, little is known about the feasibility and effectiveness of these interventions within Australian hospital settings. The current protocol describes a trial designed to evaluate the effectiveness and implementation of an SMS text message-delivered intervention designed to support patients’ engagement with pain self-management strategies and improve clinical pain outcomes after total knee replacement surgery.Methods and analysis A hybrid, type 1 effectiveness-implementation trial will be conducted at a private hospital in Australia. Participants (n=130) will be randomised to either the intervention group (receiving a pain self-management educational video prior to surgery, plus daily SMS text message reminders for 3 weeks after surgery) or an active control group (receiving the pre-surgery video alone, without text message reminders) in addition to usual care. Effectiveness outcomes will be pain intensity (primary), opioid dose, knee function and pain-related distress and will be recorded at baseline, 3 days, 3 weeks, 6 weeks, 3 months and 6 months after surgery using self-reported surveys. Pain self-efficacy and health-related quality of life will be measured at 6 weeks, 3 months and 6 months post-surgery. Implementation outcomes (Reach, Experience, Adoption, Implementation, Maintenance) will be evaluated using mixed (qualitative and quantitative) methods. This trial represents a first step towards the translation of digitally delivered postoperative support for engaging with pain self-management in the Australian healthcare system.Ethics and dissemination The study protocol was reviewed and approved by the Austin Health Human Ethics Research Committee (Australia, HREC/110142/Austin-2024). Study results will be published in a peer-reviewed journal and presented at scientific and professional meetings.Trial registration number ACTRN12624001060538

Huina Guo, Huina Guo, YiChen Lou et al.

As a traditional Chinese medicinal herb with a long history, Codonopsis pilosula (CP) has attracted much attention from the medical community in recent years. This review summarizes the research progress of CP in the medical field in the past 5 years. By searching and analyzing the literature, and combining with Cytoscape software, we comprehensively examined the role and mechanism of action of CP in individual application, combination drug application, and the role and mechanism of action of codonopsis pilosula’s active ingredients in a variety of diseases. It also analyzes the medicinal use of CP and its application value in medicine. This review found that CP mainly manifests important roles in several diseases, such as cardiovascular system, nervous system, digestive system, immune system, etc., and regulates the development of many diseases mainly through the mechanisms of inflammation regulation, oxidative stress, immunomodulation and apoptosis. Its rich pharmacological activities and diverse medicinal effects endow CP with broad prospects and application values. This review provides valuable reference and guidance for the further development of CP in traditional Chinese medicine.

Eugene O Ohanme, Benjamin N Nwakelu, Ekene E Nwoke et al.

Background: Celosia leptostachya is classified under the Amaranthaceae family. C. leptostachya possesses numerous medicinal uses. Traditional medicine practitioners exploit C. leptostachya mainly on curing illnesses such as boils, fever, snake bites, scorpion stings, eye infections, wounds and pain and most notably, epilepsy. Objectives: This study was designed to evaluate the anticonvulsant properties of the ethyl acetate (EAF) and n-hexane fractions (NHF) of C. leptostachya leaf extract in mice and determine the most active extract between EAF and NHF. Methods: The acute toxicity was carried out to determine lethal dose (LD50) using Lorke’s method. Pentylenetetrazole (PTZ), brucine and maximal electroshock (MES) were used to induce seizures in mice. We used Swinyard’s method of using an animal model of epilepsy. Thirty mice of both genders weighing 20-25 g were divided into five groups. Groups 1 and 5 are negative and positive controls, respectively. Groups 2, 3 and 4 were pre-treated with C. leptostachya extracts (100, 150 and 200 mg). Then, 30 minutes later, PTZ (90 mg/kg body weight) was administered. This method was repeated with brucine (110 mg/kg body weight). Regarding MES, after 30 minutes of administration of C. leptostachya leaf extract, an alternating current of 50 Hz and 35 mA was delivered to the animals in each group through ear-electrodes for 0.2 s. Results: Regarding MES, EAF (150 and 200 mg/kg) protected the animals against seizure, while NHF (150 and 200 mg/kg) could not prevent seizures. However, EAF and NHF (150 and 200 mg/kg) significantly decreased mean recovery time (P<0.05). In brucine-induced seizures, EAF (150 and 200 mg/kg) protected the mice against death and significantly (P<0.05) decreased mean recovery time. For PTZ-induced seizures, 200 mg/kg of EAF offered 100% protection against the mortality of mice and significantly reduced mean onset and recovering time (P<0.05).  Conclusion: Based on the results, C. leptostachya has anticonvulsant properties and EAF extract has the highest potency.

Sara Elena Rebuzzi, Giuseppe Fornarini, Alessio Signori et al.

The first-line therapy of metastatic renal cell carcinoma (mRCC) has revolutionized with the approval of immune checkpoint inhibitors (ICIs) in combination with or without tyrosine kinase inhibitors (TKIs). The choice among the many different immuno-combinations (ICI-ICI or ICI-TKI) is challenging due to the lack of predictive factors. The different shapes of the Kaplan–Meier survival curves (e.g. “banana-shaped curves”) have raised many questions on the long-term survival benefit. Here, we analyzed the factors that could have impacted the different long-term survival, including the prognostic factors distribution (IMDC score), histological factors (sarcomatoid features, PD-L1 expression), and treatment characteristics (mechanism of action, duration, discontinuation rate). This overview highlights the factors that should be considered in the first-line setting for the patients’ therapeutic choice and prognostic assessment. They are also fundamental parameters to examined for head-to-head studies and real-life, large-scale studies.

Georgios Vlasakakis, Michael T. McCabe, Yu Liu Ho et al.

Abstract Myelofibrosis is a chronic myeloproliferative disorder characterized by bone marrow fibrosis, splenomegaly, anemia, and constitutional symptoms, with a median survival of ≈6 years from diagnosis. While currently approved Janus kinase (JAK) inhibitors (ruxolitinib, fedratinib) improve splenomegaly and symptoms, most can exacerbate myelofibrosis‐related anemia, a negative prognostic factor for survival. Momelotinib is a novel JAK1/JAK2/activin A receptor type 1 (ACVR1) inhibitor approved in the US, European Union, and the UK and is the first JAK inhibitor indicated specifically for patients with myelofibrosis with anemia. Momelotinib not only addresses the splenomegaly and symptoms associated with myelofibrosis by suppressing the hyperactive JAK–STAT (signal transducer and activator of transcription) pathway but also improves anemia and reduces transfusion dependency through ACVR1 inhibition. The recommended dose of momelotinib is 200 mg orally once daily, which was established after review of safety, efficacy, pharmacokinetic, and pharmacodynamic data. Momelotinib is metabolized primarily by CYP3A4 and excreted as metabolites in feces and urine. Steady‐state maximum concentration is 479 ng/mL (CV%, 61%), with a mean AUCtau of 3288 ng.h/mL (CV%, 60%); its major metabolite, M21, is active (≈40% of pharmacological activity of parent), with a metabolite‐to‐parent AUC ratio of 1.4–2.1. This review describes momelotinib's mechanism of action, detailing how the JAK–STAT pathway is involved in myelofibrosis pathogenesis and ACVR1 inhibition decreases hepcidin, leading to improved erythropoiesis. Additionally, it summarizes the pivotal studies and data that informed the recommended dosage and risk/benefit assessment.

Stav Brown, Audree B. Tadros, Giacomo Montagna et al.

PurposePatients undergoing axillary lymph node dissection (ALND) for breast cancer face a high risk of lymphedema, further increased by high body mass index (BMI) and insulin resistance. GLP-1 receptor agonists (GLP-1RAs) have the potential to reduce these risk factors, but their role in lymphedema has never been investigated. The purpose of this study was to determine if GLP-RAs can reduce the risk of lymphedema in patients undergoing ALND.MethodsAll patients who underwent ALND at a tertiary cancer center between 2010 and 2023 were reviewed. Patients with less than 2 years of follow-up from the time of ALND were excluded. Race, BMI, radiation, chemotherapy history, pre-existing diagnosis of diabetes, lymphedema development after ALND, and the use of GLP-1RAs were analyzed. Multivariate logistic regression analysis was performed to assess if there was a significant reduction in the risk of developing lymphedema after ALND. A sub-group analysis of non-diabetic patients was also performed.Results3,830 patients who underwent ALND were included, 76 of which were treated with. GLP-1 RAs. The incidence of lymphedema in the GLP-1 RA cohort was 6.6% (5 patients). Compared to 28.5% (1,071 patients) in the non-GLP-1 RA cohort. On multivariate regression analysis, patients who were treated with GLP-1 RA were 86% less likely to develop lymphedema compared to the non-GLP-1 RA cohort (OR 0.14, 95% CI 0.04–0.32, p &lt; 0.0001). A BMI of 25 kg/m 2 or greater was a statistically significant risk factor for developing lymphedema with an odds ratio of 1.34 (95% CI 1.16–1.56, p &lt; 0.0001). Diabetes was associated with lymphedema development that closely approached statistical significance (OR 1.32, 95% CI 0.97–1.78, p = 0.06). A subgroup analysis solely on non-diabetic patients showed similar results. The odds of developing lymphedema were 84% lower for patients without diabetes treated with GLP1-RAs compared to those who did not receive GLP-1 RAs (OR 0.16, 95% CI 0.05–0.40, p &lt; 0.0001).ConclusionGLP1-RAs appear to significantly reduce the risk of lymphedema in patientsundergoing ALND. The mechanism of action may be multifactorial and not limited to weight reduction and insulin resistance. Future prospective analysis is warranted to clarify the role of GLP-1RAs in reducing lymphedema risk.

Beverly A. Teicher

Jiarui Mi, Xia Wu, Xiaoyin Bai et al.

Abstract Novel druggable targets are warranted for inflammatory bowel disease (IBD) treatment. We aimed to identify novel circulating proteins with causal associations with the risk of IBDs and provide potential therapeutic targets for IBD treatment. We performed a two‐sample Mendelian randomization (MR) study to explore the associations of 55 circulating biomarkers on the risk of IBD, Crohn's disease (CD), and ulcerative colitis (UC) by leveraging the summary statistics from large genomewide association studies and protein quantitative trait loci studies. The individual estimate was pooled together by meta‐analyses to estimate the causal effects of each outcome. In univariable MR, we identified several circulating proteins showed potential correlation with IBD, UC, and CD. Of note, we observed that a genetically proxied increased level of suppression of tumorigenicity 2 (ST2) was associated with an elevated risk of IBD (odds ratios [ORs] 1.133, 95% confidence interval [CI] 1.091–1.176, p < 0.0001), CD (ORs 1.188, 95% CI 1.103–1.281, p < 0.0001), and UC cohorts (ORs 1.087, 95% CI 1.050–1.125, p < 0.0001). Additionally, we observed a consistent positive correlation between the level of CSF‐1 and the increased risk of IBD in individual MR, with statistically significant causal associations in the meta‐analyses with ORs equal to 1.217 (IBD, 95% CI 1.115–1.328, p < 0.0001), 1.223 (CD, 95% CI 1.082–1.382, p = 0.0013), and 1.179 (UC, 95% CI 1.055–1.317, p = 0.0037). This study provided evidence for potential casual associations between circulating ST2 and CSF‐1 levels, and increased risks of IBD, UC, and CD, implicating potential treatment targets for IBD and subtypes.

Hirofumi Nagai, Tsutomu Shimada, Yoshimitsu Takahashi et al.

Abstract Background Gefitinib and erlotinib, are epidermal growth factor receptor tyrosine kinase inhibitors, and are currently recommended for non-small cell lung cancer stage IV in the elderly and in patients with decreased performance status in the Japanese Lung Cancer Society Guideline, but they occasionally caused severe hepatotoxicity requiring postponement or modification of treatment. However, little is known about the risk factors for hepatotoxicity in patients receiving gefitinib and erlotinib. In this study, we investigated the factors influencing hepatotoxicity in Japanese non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib monotherapy. Methods Japanese patients with NSCLC who started gefitinib or erlotinib monotherapy from January 2005 to December 2017 at Kanazawa University Hospital or Kanazawa Medical University Hospital were included in this study. Factors affecting hepatotoxicity were retrospectively investigated by multiple logistic regression analysis. Results A total of 102 patients who received gefitinib and 95 patients who received erlotinib were included in the analysis. In the gefitinib group, a body mass index (BMI) ≥ 25 was associated with an increased risk of hepatotoxicity (OR = 4.571, 95% CI = 1.486–14.056, P = 0.008). In the erlotinib group, concomitant use of acid-suppressing medications (AS), namely proton pump inhibitors or histamine-2 receptor antagonists, was associated with a reduced risk of hepatotoxicity (OR = 0.341, 95% CI = 0.129–0.900, P = 0.030). Conclusions BMI ≥ 25 in patients treated with gefitinib increased the risk of hepatotoxicity. In contrast, AS combination with erlotinib reduced the risk of hepatotoxicity. Thus, because different factors influence the risk of hepatotoxicity, monitoring for adverse events should take into account patient background factors and concomitant medications.

Rajeev K. Singla, Rajeev K. Singla, Adriana Gibara Guimarães et al.

Lu Yang, Lu Yang, Liping Bi et al.

Liver fibrosis is a progressive liver damage condition caused by various factors and may progress toward liver cirrhosis, and even hepatocellular carcinoma. Many studies have found that the disfunction in metabolism could contribute to the development of liver fibrosis. Geniposide, derived from Gardenia jasminoides J. Ellis, has been demonstrated with therapeutic effects on liver fibrosis. However, the exact molecular mechanisms of such liver-protection remain largely unknown. The aim of this study was to explored the effect of geniposide on metabolic regulations in liver fibrosis. We used carbon tetrachloride (CCl4) to construct a mouse model of liver fibrosis and subsequently administered geniposide treatment. Therapeutic effects of geniposide on liver fibrosis were accessed through measuring the levels of hepatic enzymes in serum and the pathological changes in liver. We also investigated the effects of geniposide on inflammatory response, oxidative stress and apoptosis in liver. Furthermore, serum untargeted metabolomics were used to explore the metabolic regulatory mechanisms behind geniposide on liver fibrosis. Our results demonstrated that geniposide could reduce the levels of hepatic enzymes in serum and ameliorate the pathological changes in liver fibrosis mice. Geniposide enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased methane dicarboxylic aldehyde (MDA) levels in liver. Geniposide treatment also decreased the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-a) in liver tissue homogenate. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining demonstrated that geniposide could reduce the apoptosis of hepatocytes. Geniposide increased the protein expression of B-cell lymphoma-2 (Bcl-2) and downregulated the protein expression of Bcl-2 Associated X (Bax), cleaved-Caspase 3, and cleaved-Caspase 9. Serum untargeted metabolomics analysis demonstrated that geniposide treatment improved the metabolic disorders including glycerophospholipid metabolism, arginine and proline metabolism, and arachidonic acid (AA) metabolism. In conclusion, our study demonstrated the protective effects of geniposide on liver fibrosis. We found that geniposide could treat liver fibrosis by inhibiting oxidative stress, reducing inflammatory response and apoptosis in the liver, and modulating glycerophospholipid, and arginine, proline, and AA metabolism processes.

Christoph Helma, David Vorgrimmler, Denis Gebele et al.

This study compares the accuracy of (Q)SAR/read-across predictions with the experimental variability of chronic lowest-observed-adverse-effect levels (LOAELs) from in vivo experiments. We could demonstrate that predictions of the lazy structure-activity relationships (lazar) algorithm within the applicability domain of the training data have the same variability as the experimental training data. Predictions with a lower similarity threshold (i.e., a larger distance from the applicability domain) are also significantly better than random guessing, but the errors to be expected are higher and a manual inspection of prediction results is highly recommended.

Veera Mohan Rao M, Rameswarudu M

Background: Peak expiratory flow rate (PEFR) assesses the overall functional status of the respiratory system. Aims and Objectives: The aim of this study was to observe the PEFR in school going healthy children, in a town located in the southern part of India. To illustrate the relation among the age, height, weight, and PEFR in the school going children. Materials and Methods: 119 school going healthy boys were selected randomly, aged between 5 and 16 years. Anthropometric parameters, namely, height and weight of the subjects were measured to the nearest reading with minimal clothes on and without footwear using stadiometer and weighing machine, respectively. Subjects were divided into five groups: Group I with a height range of 101-120 cm, Group II with 121-130 cm; Group III with 131-140 cm; Group IV with 141-150 cm; and Group V with 151-160 cm. PEFR was measured using the pocket flow meter and wrights flow meter. Results: Mean PEFR values with standard deviation in the five groups with pocket flow meter and with wrights flow meter are Group I: 159 ± 18.3 and 118 ± 22.5, Group II: 227 ± 31.0 and 204 ± 31.8, Group III: 253 ± 52.0 and 234 ± 51.2, Group IV: 309 ± 43 and 296 ± 40.9, and Group V: 368 ± 51.0 and 343 ± 47.7. Correlation coefficient was also calculated between the height and PEFR, measured with pocket flow meter in all the five groups; 0.64, 0.68, 0.25, 0.47, and 0.69 from Groups I to V. Conclusion: PEFR is increased with the increasing in height of the subjects. [Natl J Physiol Pharm Pharmacol 2017; 7(4.000): 363-365]

S. N. Tolpygina, S. Yu. Martsevich

The main differences between original and generic drugs as well as registration criteria for generics are described. Possible reasons of discrepancy in bioequivalence and therapeutic equivalence of original and generic drugs are reviewed. The examples of such a discrepancy as a result of comparative clinical trails (enalapril maleate) are discussed. Approaches to planning of comparative trails on drug therapeutic equivalence are presented.

Fabiana Rossi Varallo, Helaine Carneiro Capucho, Cleópatra Silva Planeta et al.

Purpose: Potentially Inappropriate Medications (PIM) use in elderly people may be responsible for the development of Adverse Drug Reaction (ADR) which, when severe, leads to hospital admissions. Objectives: to estimate the prevalence of elderly who had used PIM before being admitted to hospital admission and to identify the risk factors and the hospitalizations related to ADR arising from PIM. Methods: A descriptive and cross-sectional study was performed in the internal medicine ward of a teaching hospital (Brazil), in 2008. With the aid of a validated form, patients aged ≥ 60 years, with length of hospital stay ≥ 24 hours, were interviewed about drugs taken prior to the hospital admission and the complaints/reasons for hospitalization. Results: 19.1% (59/308) of older patients had taken PIM before hospital admission and in 4.9%; there were a causal relation between the PIM taken and the complaint reported. PIM responsible for admissions were: amiodarone, amitriptyline, cimetidine, clonidine, diazepam, digoxin, estrogen, fluoxetine, lorazepam, short-acting nifedipine and propranolol. 47.0% of the clinical manifestations of PIM-related ADR were: dizziness, fatigue, digoxin toxicity and erythema. Only polypharmacy was detected as a risk factor for the occurrence of ADR of PIM (p = 0.02). Conclusion: PIM use in elderly people is not a risk factor for ADR-related hospital admission. Probably, severe ADR, which lead to hospitalizations of older people, can be explained by idiosyncratic response or the predisposition of these patients to develop adverse drug events, whether or not drugs are classed as PIM. Key-words: potentially inappropriate medication (PIM), older people, adverse drug reaction (ADR), hospital admission, pharmacovigilance

Gh Karimi, M Saradeghi Keisari

Background: Depression is one of the most psychiatric disorders that there are many treatments for it. Milk thistle is a plant which has many pharmacologic effects such as antioxidant, anti-inflammatory and anticancer. It is reported that silymarin (main component of milk thistle) increase the concentration of some neurotransmitter in brain. Objective: Evaluation of the antidepressant effect of aqueous and ethanolic extracts of milk thistle. Methods: We investigated the antidepressant effect of aqueous (0.72, 1.26, 1.80 g/kg) and ethanolic (0.24, 0.42, 0.6 g/kg) extracts using modified forced swimming test in mice. Results: The ethanolic extract did not have any effect on the duration of immobility of mice. However, the aqueous extract significantly reduced the duration of immobility versus the control group. Conclusion: Aqueous extract of milk thistle showed antidepressant effect in animal model.