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Knowledge Assessment During the Medication Process Use by Older Patients on Clinical Routine: A Pilot Study. 老年患者临床常规用药过程中的知识评估:一项初步研究。
IF 1.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-02 DOI: 10.4274/tjps.galenos.2022.85054
Margarida Espírito-Santo, Tânia Nascimento, Ezequiel Pinto, M Dulce Estêvão

Objectives: The consumption of medicines has been increasing over the last decades. The lack of medication knowledge (MK) may affect the process of medication use and, consequently, may lead to negative health outcomes. This study carried out a pilot study using a new tool to assess MK in older patients in a daily clinical practice.

Materials and methods: An exploratory cross-sectional study was conducted, including older patients (≥65 years), taking two or more medicines, followed in a regional clinic. Data were collected during a structured interview, which included an algorithm for assessing MK regarding the identification of the medicines and its use and storage conditions. Health literacy and treatment adherence were also assessed.

Results: The study enrolled 49 patients, mainly between 65 and 75 years (n: 33; 67.3%) and polymedicated (n: 40; 81.6%), taking a mean of 6.9 ± 2.8 medicines per day. A lack of MK (score <50%) was observed in 15 (30.6%) participant patients. "Drug strength" and "storage conditions" were the items which presented the lowest score. MK was positively correlated with higher scores for health literacy and treatment adherence. Younger patients (age <65 years old) also had a higher MK score.

Conclusion: This study showed that the applied tool could evaluate the MK of the participants and identified specific gaps regarding MK within the process of medicine use. Further studies, with more participants, will allow the confirmation of these findings and will stimulate the development of specific strategies to improve MK, thus contributing to better health outcomes.

目的:在过去的几十年里,药品的消费量一直在增加。缺乏药物知识可能会影响药物使用过程,从而可能导致负面的健康结果。本研究开展了一项试点研究,在日常临床实践中使用一种新的工具来评估老年患者的MK。材料和方法:我们进行了一项探索性的横断面研究,纳入了在一家地区诊所服用两种或两种以上药物的老年患者(≥65岁)。数据是在结构化访谈中收集的,其中包括一种算法,用于评估关于药物鉴定及其使用和储存条件的MK。还对卫生知识普及和治疗依从性进行了评估。结果:该研究纳入了49例患者,主要年龄在65 - 75岁之间(n: 33;67.3%)和多药(n: 40;81.6%),平均每天服用6.9±2.8个药物。结论:本研究表明,所应用的工具可以评估参与者的MK,并识别出药物使用过程中MK的具体差距。有更多参与者参与的进一步研究将能够证实这些发现,并将促进制定具体战略,以改善MK,从而促进更好的健康结果。
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引用次数: 0
Folate-Mediated Paclitaxel Nanodelivery Systems: A Comprehensive Review. 叶酸介导的紫杉醇纳米递送系统:全面综述。
IF 1.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-02 DOI: 10.4274/tjps.galenos.2021.26529
Ashwini K Bawankule, Amol A Tatode, Pranali S Patil, Milind J Umekar

Paclitaxel (PTX) is used as a viable cancer medication in the chemotherapy of breast, ovarian, lung, bladder, neck, head, and esophageal tumors. The focus of this review is to survey various folate-targeting PTX-loaded nanopreparations in both research and clinical applications. There are diverse nanopreparations, including liposomes, micelles, polymeric nanopreparations, lipid nanopreparations, lipoprotein nanocarriers, and other inorganic nanopreparations for folate-associated PTX tumor targeting. Here, the folate targeting PTX-loaded nanopreparations, which have promising results in the constructive treatment of cancer by reducing toxic side-effects and/or improving effectiveness, was mainly reviewed.

紫杉醇(PTX)是一种可行的癌症药物,用于乳腺、卵巢、肺、膀胱、颈部、头部和食道肿瘤的化疗。本文综述了各种叶酸靶向ptx负载纳米修复剂的研究和临床应用。有多种纳米修复,包括脂质体、胶束、聚合物纳米修复、脂质纳米修复、脂蛋白纳米载体和其他针对叶酸相关PTX肿瘤的无机纳米修复。本文主要综述了叶酸靶向ptx负载纳米修复剂,这些纳米修复剂通过减少毒副作用和/或提高疗效,在癌症的建设性治疗中有很好的结果。
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引用次数: 2
Stability Evaluation of the Biosimilar Monoclonal Antibody Using Analytical Techniques. 生物类似药单克隆抗体稳定性分析技术评价。
IF 1.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-02 DOI: 10.4274/tjps.galenos.2022.47690
Deniz Demirhan
ObjectivesDetermination of the drug substance (DS) and drug product (DP) stability is especially important for biosimilar monoclonal antibodies since it can affect the quality, efficacy, and safety of the drugs. The main objective of this study was to determine the stability of the biosimilar candidate (TUR01) using state-of-the-art (current) analytical techniques.Materials and MethodsAnalytical techniques used in this study were isoelectric focusing on capillary electrophoresis, capillary electrophoresis-sodium dodecyl sulfate, size exclusion chromatography-ultra-high performance liquid chromatography, binding affinity, and physicochemical and microbiological tests. DS was kept in polyethylene terephthalate copolyester, glycol modified (PETG) bottles at ≤-65.0°C and 5.0 ± 3.0°C for 18 months, where the pre-filled syringe stability study was conducted at 5.0 ± 3.0°C for 24 months and 25.0 ± 2.0°C/60% ± 5 relative humidity (RH) for 6 months. The accelerated condition for DS was accepted as 5.0 ± 3.0°C, while it was 25.0 ± 2.0°C for the DP.ResultsThe results indicated that TUR01 DS was stable when it was stored under long-term storage conditions at ≤-65°C and at 5 ± 3°C at least 18 months. Also, TUR01 DP was stable at 5 ± 3°C for 24 months and at 25 ± 2°C with 60.5% RH for 2 months without any significant changes.ConclusionState-of-the-art analytical techniques proved to be invaluable tools for evaluate the stability of the TUR01 DS and drug product.
目的:原料药(DS)和制剂(DP)稳定性的测定对单克隆生物仿制药的质量、疗效和安全性具有重要意义。本研究的主要目的是利用最新的分析技术确定候选生物类似药(TUR01)的稳定性。材料和方法:本研究使用的分析技术为毛细管电泳等电法、毛细管电泳-十二烷基硫酸钠法、粒径排除色谱-超高效液相色谱法、结合亲和法、理化和微生物学试验。DS在≤-65.0℃和5.0±3.0℃的聚对苯二甲酸乙二醇改性(PETG)瓶中保存18个月,其中在5.0±3.0℃下保存24个月,在25.0±2.0℃/60%±5相对湿度(RH)下保存6个月。DS的加速条件为5.0±3.0℃,DP的加速条件为25.0±2.0℃。结果:结果表明,TUR01 DS在≤-65℃和5±3℃条件下长期保存至少18个月,表现稳定。TUR01 DP在5±3°C条件下稳定24个月,在25±2°C条件下稳定2个月,RH为60.5%,无明显变化。结论:最先进的分析技术被证明是评估TUR01 DS和药品稳定性的宝贵工具。
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引用次数: 0
Resveratrol-Loaded Microsponge Gel for Wound Healing: In Vitro and In Vivo Characterization. 白藜芦醇微海绵凝胶用于伤口愈合:体外和体内表征。
IF 1.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-02 DOI: 10.4274/tjps.galenos.2022.93275
Vinita Chandrakant Patole, Devyani Awari, Shilpa Chaudhari

Objectives: The study was aimed to formulate resveratrol (RSV) loaded microsponges to deliver drug at the wound site and incorporate it in the Moringa oleifera Lam. (Moringaceae) gel base to provide an appropriate moist environment for wound management. RSV, a stilbenoid that activates sirtuins and cell-signaling regulators involved in the process of wound healing.

Materials and methods: Microsponges were prepared by oil in oil emulsion solvent diffusion method by optimizing the independent variables; drug: polymer ratio and volume of internal phase solvent and their effects on entrapment efficiency and particle size. Formulation batches were evaluated for drug content, production yield, entrapment efficiency, and in vitro drug release. The microsponges were further incorporated into M. oleifera gum gel, which was then evaluated for spreadability, viscosity, ex vivo diffusion study and in vivo studies using an excision wound model in rats.

Results: Scanning electron microscopy revealed spherical and porous nature of the microsponges in vitro-release study of the optimized batch of RSV microsponges showed 80.88% drug release within 8 h. Differential scanning calorimetry results revealed no drug and polymer interaction during the formation of microsponges. An ex vivo diffusion study through goat skin revealed sustained release of RSV through porous microsponges embedded in the gel base at the wound site. An in vivo study performed using an excision wound model showed wound healing and closure within day 8. Histopathology showed increased re-epithelization and reduced ulceration in RSV microsponge gel-treated group compared with sham operated.

Conclusion: RSV microsponge gel delivered the drug at the wound site and the gel base provided a moist environment and influenced cell adhesion, thereby promoting faster wound healing.

目的:制备白藜芦醇(resveratrol, RSV)载药微海绵,并将其掺入辣木中。(辣木科)凝胶基为伤口处理提供适宜的湿润环境。RSV是一种苯乙烯类化合物,可以激活sirtuins和参与伤口愈合过程的细胞信号调节因子。材料与方法:通过优化自变量,采用油中油乳化溶剂扩散法制备微海绵;药物:聚合物比、内相溶剂体积及其对包封效率和粒径的影响。对制剂批次进行药物含量、产率、包封效率和体外药物释放度评价。将微海绵进一步掺入油橄榄胶凝胶中,对其涂抹性、黏度、体外扩散研究和大鼠切除伤口模型的体内研究进行评价。结果:扫描电镜显示微海绵具有球形和多孔的性质,体外释放研究表明,优化后的RSV微海绵在8 h内药物释放率为80.88%。差示扫描量热法结果显示微海绵在形成过程中没有药物与聚合物的相互作用。通过山羊皮肤的体外扩散研究发现,RSV通过包埋在伤口凝胶基中的多孔微海绵持续释放。使用切除伤口模型进行的体内研究显示伤口在第8天愈合和闭合。组织病理学结果显示,与假手术组相比,RSV微海绵凝胶治疗组再上皮增加,溃疡减少。结论:RSV微海绵凝胶在创面给药,凝胶基底提供湿润环境,影响细胞粘附,促进创面更快愈合。
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引用次数: 1
Genistein Enhances TRAIL-Mediated Apoptosis Through the Inhibition of XIAP and DcR1 in Colon Carcinoma Cells Treated with 5-Fluorouracil 染料木黄酮通过抑制XIAP和DcR1增强5-氟尿嘧啶诱导的结肠癌细胞凋亡
IF 1.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-02-23 DOI: 10.4274/tjps.galenos.2023.69649
T. Çal, S. Aydın Dilsiz, H. Canpınar, Ülkü Ündeğer Bucurgat
Objectives: Colorectal cancer is one of the most common cancers in the world. However, surgical intervention and chemotherapy provide only limited benefits for the recovery and survival of patients. The anti-carcinogenic effect of genistein has attracted attention due to epidemiological studies showing that soybean consumption is associated with a decrease in incidence of cancer. There are limited studies on the effects of genistein in colorectal carcinoma cells. We aimed to investigate the cytotoxic, genotoxic, and apoptotic effects of genistein in SW480 and SW620 colon adenocarcinoma cells treated with 5-fluorouracil, the basis of chemotherapy, and TRAIL ligand, the mediator of apoptosis, both alone and in combination. Materials and Methods: The cytotoxicity and genotoxicity were determined by MTT assay and comet assay, respectively. The apoptotic effects were evaluated by RT-PCR assay, with the additional use of Annexin V FITC, mitochondrial membrane potential, caspase 3, 8 and 9 activity, reactive oxygen species assay kits. Results: According to our findings, genistein, 5-fluorouracil and TRAIL had synergistic apoptotic effects as a result of DR5 up-regulation, ROS production, and DNA damage, which was mediated by increased caspase 3, 8 and 9 activity and decreased mitochondrial membrane potential. Conclusion: The applied combinations of these compounds may contribute to the resistance problem that may occur in the treatment of colorectal cancer, with the decrease in DcR1 and XIAP genes.
目的:癌症是世界上最常见的癌症之一。然而,手术干预和化疗对患者的康复和生存只有有限的益处。染料木黄酮的抗癌作用引起了人们的关注,因为流行病学研究表明,食用大豆与癌症发病率的降低有关。关于染料木素在结直肠癌细胞中的作用的研究有限。我们的目的是研究染料木黄酮在单独或联合使用化疗基础5-氟尿嘧啶和凋亡介质TRAIL配体处理的SW480和SW620结肠癌细胞中的细胞毒性、基因毒性和凋亡作用。材料与方法:分别用MTT法和彗星法测定细胞毒性和遗传毒性。通过RT-PCR测定评估细胞凋亡作用,并额外使用膜联蛋白V FITC、线粒体膜电位、胱天蛋白酶3、8和9活性、活性氧测定试剂盒。结果:根据我们的研究结果,染料木黄酮、5-氟尿嘧啶和TRAIL具有协同凋亡作用,这是DR5上调、ROS产生和DNA损伤的结果,这是由胱天蛋白酶3、8和9活性增加和线粒体膜电位降低介导的。结论:应用这些化合物的组合可能导致治疗癌症时可能出现的耐药性问题,DcR1和XIAP基因减少。
{"title":"Genistein Enhances TRAIL-Mediated Apoptosis Through the Inhibition of XIAP and DcR1 in Colon Carcinoma Cells Treated with 5-Fluorouracil","authors":"T. Çal, S. Aydın Dilsiz, H. Canpınar, Ülkü Ündeğer Bucurgat","doi":"10.4274/tjps.galenos.2023.69649","DOIUrl":"https://doi.org/10.4274/tjps.galenos.2023.69649","url":null,"abstract":"Objectives: Colorectal cancer is one of the most common cancers in the world. However, surgical intervention and chemotherapy provide only limited benefits for the recovery and survival of patients. The anti-carcinogenic effect of genistein has attracted attention due to epidemiological studies showing that soybean consumption is associated with a decrease in incidence of cancer. There are limited studies on the effects of genistein in colorectal carcinoma cells. We aimed to investigate the cytotoxic, genotoxic, and apoptotic effects of genistein in SW480 and SW620 colon adenocarcinoma cells treated with 5-fluorouracil, the basis of chemotherapy, and TRAIL ligand, the mediator of apoptosis, both alone and in combination. Materials and Methods: The cytotoxicity and genotoxicity were determined by MTT assay and comet assay, respectively. The apoptotic effects were evaluated by RT-PCR assay, with the additional use of Annexin V FITC, mitochondrial membrane potential, caspase 3, 8 and 9 activity, reactive oxygen species assay kits. Results: According to our findings, genistein, 5-fluorouracil and TRAIL had synergistic apoptotic effects as a result of DR5 up-regulation, ROS production, and DNA damage, which was mediated by increased caspase 3, 8 and 9 activity and decreased mitochondrial membrane potential. Conclusion: The applied combinations of these compounds may contribute to the resistance problem that may occur in the treatment of colorectal cancer, with the decrease in DcR1 and XIAP genes.","PeriodicalId":23378,"journal":{"name":"Turkish Journal of Pharmaceutical Sciences","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2023-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42116508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deiodinase Type III Polymorphism (Rs1190716) Affects The Therapeutic Response to Levothyroxine Short Title: Deiodinase Type III Gene and Hypothyroidism 脱碘酶III型多态性(Rs190716)对左旋甲状腺素治疗反应的影响
IF 1.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-12-28 DOI: 10.4274/tjps.galenos.2022.04876
A. H. Mohmmed, Suzanne Jubair, B. Khalaf
Objectives : Levothyroxine (LT4) is the commonly used treatment for hypothyroidism. Deiodinases enzymes control the metabolism and homeostasis of thyroid hormones (THs). Deiodinases type III (DIO3) gene encodes deiodinase type 3 enzyme (D3), the genetic polymorphisms of this gene could affect the levels of THs and then the response to LT4 treatment. This study aims to investigate the single nucleotide polymorphism (SNP), rs1190716; C>T, of DIO3 as a candidate genetic variant that might affect the clinical response to LT4 treatment. Materials and Methods: Two hundred Iraqi hypothyroid female patients who were aged 40 years or older were enrolled in this cross-sectional study. All of them were already on the LT4 treatment for at least 4 months. Thyroid hormones (thyroxin (T4), triiodothyrionine (T3), revers riiodothyrionine (rT3) and diiodothyrionine (T2)) were estimated. Allele specific-polymerase chain reaction technique was performed to detect the rs1190716; C>T SNP. Results: The genotypes distribution of rs1190716; C>T SNP was 10 (4.5%) for the wild type (CC), 50 (22.7%) for the heterozygous mutant type (TC), and 160 (72.7%) for the homozygous mutant type (TT). The patients were divided into three groups according to their genotypes. Significant differences were found in the levels of T4, T3 and T2 among the groups of the patients (P=0.019, P=0.039, P= 0.032, respectively) Conclusion: The rs1190716; C>T SNP could affect the activity of the D3 enzyme and the metabolic homeostasis of the THs, therefore rs1190716; C>T SNP could have an impact in the therapeutic response to LT4 in Iraqi female patients with primary hypothyroidism. Regarding the DIO3 gene, this is a novel finding, hence further studies are needed to conform it.
目的:左旋甲状腺素(LT4)是甲状腺功能减退症的常用治疗方法。脱碘酶控制甲状腺激素(THs)的代谢和稳态。脱碘酶III型(DIO3)基因编码脱碘酶3型(D3),该基因的遗传多态性可能影响THs水平,进而影响对LT4治疗的反应。本研究旨在研究单核苷酸多态性(SNP)rs1190716;C> DIO3的T作为可能影响对LT4治疗的临床反应的候选基因变体。材料和方法:200名年龄在40岁或以上的伊拉克甲状腺功能减退症女性患者被纳入这项横断面研究。所有患者均已接受LT4治疗至少4个月。甲状腺激素(甲状腺素(T4)、三碘甲状腺激素(T3)、反三碘甲状腺素(rT3)和二碘甲状腺激素。应用等位基因特异性聚合酶链反应技术检测rs1190716;C> T SNP。结果:rs1190716的基因型分布;C> 野生型(CC)的T SNP为10(4.5%),杂合突变型(TC)为50(22.7%),纯合子突变型(TT)为160(72.7%)。根据基因型将患者分为三组。T4、T3和T2水平在各组间存在显著差异(分别为P=0.019、P=0.039、P=0.032)。结论:rs1190716;C> T SNP可以影响D3酶的活性和THs的代谢稳态,因此rs1190716;C> T SNP可能对原发性甲状腺功能减退的伊拉克女性患者对LT4的治疗反应产生影响。关于DIO3基因,这是一个新的发现,因此需要进一步的研究来证实它。
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引用次数: 0
Cell Therapy and Investigation of Angiogenesis of Fibroblastswith Collagen Hydrogel on the Healing of Diabetic Wounds 胶原水凝胶对成纤维细胞治疗及血管生成的研究
IF 1.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-12-28 DOI: 10.4274/tjps.galenos.2022.62679
Abbas Zabihi, Sanaz Pashapour, M. Mahmoodi
INTRODUCTION: A diabetic ulcer is a common disease in diabetic patients. Due to antibiotic resistance, new therapeutic alternatives are being considered in diabetic foot patients to reduce complications and mortality. This study aimed to evaluate the effect of collagen hydrogel on wound healing process in diabetic rats. METHODS: Diabetic wounds were induced with streptozotocin in all 42 male Wistar rats. The rats were divided into four groups: (a) treated with fibroblast cells, (b) collagen hydrogel, (c) collagen cultured with fibroblast cells, and (d) control group. Microscopic and histological (H&E staining and Mason trichrome staining), measurement of wound surface with Image J, skin density and thickness by the ultrasound probe, and skin elasticity with cutometer tool was used to evaluate the wound healing in a days , 14, and 21 after the treatment. RESULTS: The results showed that the treatment of diabetic wounds with fibroblast cells cultured in collagen hydrogel greatly reduces inflammatory responses in the skin tissue and significantly accelerates the healing process. Also, 21 days after the start of treatment, skin elasticity, thickness and density were higher in the collagen + fibroblast group than in the control group.
简介:糖尿病性溃疡是糖尿病患者的常见病。由于抗生素耐药性,新的治疗方案正在考虑糖尿病足患者,以减少并发症和死亡率。本研究旨在探讨胶原水凝胶对糖尿病大鼠创面愈合过程的影响。方法:采用链脲佐菌素诱导42只雄性Wistar大鼠糖尿病创面。将大鼠分为四组:(a)成纤维细胞组,(b)胶原水凝胶组,(c)成纤维细胞培养胶原组,(d)对照组。采用显微和组织学(H&E染色和Mason三色染色)、Image J创面测量、超声探头皮肤密度和厚度、刀具皮肤弹性评估治疗后1天、14天、21天创面愈合情况。结果:胶原水凝胶培养成纤维细胞治疗糖尿病创面可显著降低皮肤组织炎症反应,显著加快创面愈合进程。治疗21 d后,胶原+成纤维细胞组皮肤弹性、厚度和密度均高于对照组。
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引用次数: 0
A Cross-Sectional Survey of Knowledge, Attitude, and Practices Regarding Influenza Vaccination Among Jordanians Aged 18–64 With Chronic Diseases 约旦18-64岁慢性病患者流感疫苗接种知识、态度和实践的横断面调查
IF 1.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-12-28 DOI: 10.4274/tjps.galenos.2022.61798
Ola A Bdair, Izzeddin A. Bdair, Esraa Gogazeh, Ola Al-fawares, M. Alwadi, Rawan Badaineh, Fatima Al-tarawneh
Background : Influenza is a frequent infectious disease that can be prevented and is linked to significant mortality and morbidity. The most economical way to prevent influenza is through vaccination, although this method is not widely used. This study aimed to assess the seasonal influenza vaccination rates and the knowledge and attitudes of Jordanian adults with chronic illnesses toward the influenza vaccine. Methods : A cross-sectional design was employed. A 26-item online survey was utilized to gather data about the patients' knowledge of and attitudes toward the influenza vaccine as well as their status as influenza vaccine recipients. Results : A total of 19% of the 564 study participants had an influenza vaccination. The majority (81%) of individuals reported inconsistent vaccination uptake. The most important factor affect vaccination is the belief the flu is not a threat (39%) and they were not advised by their doctors about the vaccination (32%). Participants with no health insurance and with public insurance had a lower level of vaccination in comparison with private insurance (p = 0.008). Conclusions : The adult population of Jordan with chronic diseases have subpar immunization rates. Also revealed is a blatant misunderstanding about the value of routine influenza vaccination. These findings emphasize how urgently the public needs to be made aware of the effectiveness of the influenza vaccine.
背景:流感是一种可以预防的常见传染病,与显著的死亡率和发病率有关。预防流感最经济的方法是接种疫苗,尽管这种方法没有被广泛使用。本研究旨在评估季节性流感疫苗接种率以及患有慢性病的约旦成年人对流感疫苗的知识和态度。方法:采用横断面设计。利用一项26项在线调查收集了有关患者对流感疫苗的知识和态度以及他们作为流感疫苗接种者的状况的数据。结果:564名研究参与者中,共有19%的人接种了流感疫苗。大多数(81%)的人报告疫苗接种率不一致。影响疫苗接种的最重要因素是认为流感不是威胁(39%),医生也没有建议他们接种疫苗(32%)。与私人保险相比,没有健康保险和有公共保险的参与者的疫苗接种水平较低(p=0.008)。结论:约旦患有慢性病的成年人口的免疫接种率较低。还暴露出对常规流感疫苗价值的公然误解。这些发现强调了公众迫切需要意识到流感疫苗的有效性。
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引用次数: 2
Development and Full Validation of a Novel Liquid Chromatography Electrochemical Detection Method for Simultaneous Determination of Nine Catecholamines in Rat Brain 一种同时测定大鼠脑中9种儿茶酚胺的新型液相色谱-电化学检测方法的建立和充分验证
IF 1.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-12-28 DOI: 10.4274/tjps.galenos.2022.06606
Saniye Özcan, Murat Kozanlı, Aysun Geven, Nafiz Öncü Can
INTRODUCTION: Chemical neurotransmission, managed by neurotransmitters, has a crucial role in brain processes such as fear, memory, learning, and pain, or neuropathologies such as schizophrenia, epilepsy, anxiety/depression, and Parkinson’s disease. The measurement of these compounds is to elucidate the disease mechanisms and evaluate the outcomes of therapeutic interventions. However, this can be quite difficult due to various matrix effects and the problems of chromatographic separation of analytes. In the current study; for the first time, an optimized and fully validated fully according to FDA and EMA Bioanalytical Validation Guidance HPLC-EC method was developed for the simultaneous analysis of nine neurotransmitter compounds which are dopamine (DA), homovanilic acid (HVA), vanilmandelic acid (VA) serotonin (SER), 5-hydroxyindole-3-acetic acid (5-HIAA), 4-hydroxy-3-methoxyphenylglycol (MHPG), norepinephrine (NE), 3,4 dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) and simultaneously determined in rat brain samples. METHODS: The separation was achieved with 150 mm × 4.6 mm, 2.6 μm F5 Kinetex (Phenomenex, USA) column isocratically, and analysis was carried out HPLC equipped with DECADE II electrochemical detector. RESULTS: The method exhibited good selectivity and correlation coefficient values for each analyte’s calibration curves were >0.99. The detection and quantification limits ranged from 0.01 to 0.03 ng/mL and 3.04 to 9.13 ng/mL, respectively. The stability of the analytes and method robustness were also examined in detail in the study, and the obtained results are also presented statistically. DISCUSSION AND CONCLUSION: The developed fully validated method has been successfully applied to real rat brain samples and important results have been obtained. In the rat brain sample analysis, the least amount of SER and the highest amount of NA were found.
导读:由神经递质控制的化学神经传递在诸如恐惧、记忆、学习和疼痛等大脑过程或精神分裂症、癫痫、焦虑/抑郁和帕金森病等神经病理中起着至关重要的作用。这些化合物的测量是为了阐明疾病机制和评估治疗干预的结果。然而,由于各种基质效应和分析物的色谱分离问题,这可能相当困难。在目前的研究中;根据FDA和EMA生物分析验证指南,首次建立了一种优化的HPLC-EC方法,用于同时分析多巴胺(DA)、香草酸(HVA)、香草酸(VA)、血清素(SER)、5-羟基吲哚-3-乙酸(5-HIAA)、4-羟基-3-甲氧基苯基乙二醇(MHPG)、去甲肾上腺素(NE)、3,4二羟基苯乙酸(DOPAC)和3-甲氧基酪胺(3- mt),同时测定大鼠脑样品。方法:采用150 mm × 4.6 mm, 2.6 μm F5 Kinetex (Phenomenex, USA)柱等柱分离,配备DECADE II型电化学检测器进行HPLC分析。结果:该方法具有良好的选择性,各分析物的标度曲线相关系数均为0.99。检测限为0.01 ~ 0.03 ng/mL,定量限为3.04 ~ 9.13 ng/mL。研究中还对分析物的稳定性和方法的稳健性进行了详细的检验,并对所得结果进行了统计分析。讨论与结论:本方法已成功应用于实际大鼠脑样品,并获得重要结果。在大鼠脑样品分析中,发现SER含量最少,NA含量最高。
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引用次数: 0
Advantages and Disadvantages of Two In Vitro Assays in Evaluating Aromatase Activity: "A Cell-Based and a Cell-Free Assay". 评价芳香酶活性的两种体外测定法的优缺点:“基于细胞和无细胞测定法”。
IF 1.7 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2022-12-21 DOI: 10.4274/tjps.galenos.2021.85530
Elif İnce Ergüç, Senem Özcan Sezer, Hande Gürer Orhan

Objectives: Aromatase is an enzyme that catalyzes the conversion of androgens to estrogens. While inhibition of aromatase is a useful approach for treating breast cancer, it may also have toxicological consequences due to its endocrine disrupting/modulating effect. In this study, sensitivity and performance of two in vitro assays -a cell free and a cell-based- for evaluating aromatase activity were investigated by testing known aromatase inhibitors and partial validation of the methods was performed. Advantages and disadvantages of these methods are also discussed.

Materials and methods: Aromatase activity was evaluated via two in vitro models; direct measurement with a cell-free assay using a fluorescent substrate and recombinant human enzyme and indirect evaluation with a cell-based assay where cell proliferation was determined in estrogen receptor positive human breast cancer cells (MCF-7 BUS) in the absence of estrogen and the presence of testosterone.

Results: In the cell-free direct measurement assay, reference compounds ketoconazole and aminoglutethimide have been shown to inhibit the aromatase enzyme with half-maximal inhibitory concentration (IC50) values concordant with literature. In cell-based indirect measurement assay, only ketoconazole dose-dependently inhibited cell proliferation with 3.47 x 10-7 M IC50. Inter-assay and intra-assay reproducibility of both methods was found to be within acceptable deviation levels.

Conclusion: Both methods can be successfully applied. However, to evaluate the potential aromatase activity of the novel compounds in vitro, it seems better to perform both the cell-based and the cell-free assays that allows low-moderate biotransformation and eliminate cytotoxicity potential, respectively.

目的:芳香化酶是一种催化雄激素转化为雌激素的酶。虽然抑制芳香化酶是治疗乳腺癌的一种有效方法,但由于其内分泌干扰/调节作用,也可能产生毒理学后果。在这项研究中,通过测试已知的芳香酶抑制剂,研究了两种体外测定法(无细胞法和基于细胞法)评估芳香酶活性的灵敏度和性能,并对方法进行了部分验证。讨论了这些方法的优缺点。材料与方法:采用两种体外模型评价芳香酶活性;使用荧光底物和重组人酶的无细胞测定法直接测量,以及使用基于细胞的测定法间接评估,在雌激素受体阳性的人乳腺癌细胞(MCF-7 BUS)中,在缺乏雌激素和存在睾丸激素的情况下测定细胞增殖。结果:在无细胞直接测定法中,对照物酮康唑和氨酰硫胺对芳香酶有抑制作用,半数最大抑制浓度(IC50)值与文献相符。在以细胞为基础的间接测量实验中,仅酮康唑剂量依赖性抑制细胞增殖,IC50为3.47 × 10-7 M。两种方法的测定间和测定内的重复性均在可接受的偏差范围内。结论:两种方法均可成功应用。然而,为了在体外评估新化合物潜在的芳香酶活性,似乎更好的方法是分别进行基于细胞和无细胞的实验,这两种实验分别允许中低生物转化和消除细胞毒性潜力。
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Turkish Journal of Pharmaceutical Sciences
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