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Trihexyphenidyl has a psychostimulant-like effect on mice 三苯氧胺对小鼠具有类似精神兴奋剂的作用
Zeina A.Althanoon, Loay A. Alchalaby, Farah Ramzi, Marwan M. Merkhan
Trihexyphenidyl is an antimuscarinic agent used for managing motor symptoms in Parkinson’s disease (PD). Despite its therapeutic use, trihexyphenidyl misuse and addiction have been reported. Its antimus¬carinic effect alone does not explain this abuse potential. This study investigated if trihexyphenidyl pro¬duces psychostimulant-like behavioural effects in mice related to dopamine signalling. Male and female mice received 1 or 2 mg/kg trihexyphenidyl orally before open field and forced swim tests. Trihex¬yphenidyl at 2 mg/kg increased locomotor activity, prevented by olanzapine pre-treatment. It also de¬creased forced swim test immobility time. These findings suggest trihexyphenidyl has dopamine-medi¬ated psycho-stimulant properties, providing preclinical evidence for its abuse liability. Further studies on trihexyphenidyl’s impact on dopamine neurotransmission and addiction risk are warranted.
三苯氧胺是一种抗心绞痛药,用于控制帕金森病(PD)的运动症状。尽管三苯氧胺具有治疗作用,但也有滥用和成瘾的报道。仅凭三苯氧胺的抗心律失常作用并不能解释其滥用的可能性。本研究调查了三苯氧胺是否会对小鼠产生与多巴胺信号有关的精神兴奋剂样行为效应。雄性和雌性小鼠在进行开阔地和强迫游泳测试前,分别口服1或2毫克/千克三苯氧胺。2毫克/千克的三苯氧胺会增加小鼠的运动能力,而奥氮平的预处理可以阻止这种现象。它还能缩短强迫游泳测试的静止时间。这些研究结果表明,三苯氧胺具有多巴胺介导的精神兴奋剂特性,为其滥用提供了临床前证据。有关三苯氧胺对多巴胺神经递质的影响和成瘾风险的进一步研究还很有必要。
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引用次数: 0
Aripiprazole cognitive effects on attention deficit hyperactivity disorder (ADHD) in experimental mouse model 阿立哌唑对实验小鼠注意缺陷多动障碍(ADHD)的认知影响
Halima O. Qasim, Israa M. Jabber, Sami M. Ahmed, Marwan M. Merkhan
Background: Attention deficit hyperactivity disorder (ADHD) is one of children's neurodevelopmental psychological disorders with ideal therapy obscure. Aripiprazole is an antipsychotic medication with a unique mechanism of action that enhances dopamine activity in the prefrontal cortex in turn it might executive function in ADHD patients. This study aimed to clarify the impact of aripiprazole on ADHD using a socially isolated (SI) mice model. Methods: In the current study we used early-life SI mice as models for ADHD and tested three different doses of aripiprazole on attention set-shifting performance. The socially Isolated mice are known to have impairment in attentional set-shifting. Socially housed and isolated reared mice across different doses of aripiprazole for each stage were cross-matched for comparison. Results: Socially isolated mice showed selective great deficits in interdimen¬sional discriminations and extradimensional discriminations. Aripiprazole at 3 and 6mg/kg did greatly mitigate the cognition deficits in comparison with placebo and 1 mg/kg of aripiprazole. Conclusion: The current study results emphasise the positive effect of aripiprazole on cognition. Aripiprazole has the potential to be a treatment for ADHD with a psychostimulatory effect.
背景:注意缺陷多动障碍(ADHD)是儿童神经发育性心理障碍之一,治疗效果不理想。阿立哌唑是一种抗精神病药物,其独特的作用机制可增强多巴胺在前额叶皮层的活性,进而增强多动症患者的执行功能。本研究旨在利用社会隔离(SI)小鼠模型阐明阿立哌唑对多动症的影响。研究方法在本研究中,我们使用早期SI小鼠作为多动症模型,并测试了三种不同剂量的阿立哌唑对注意力集合转移表现的影响。众所周知,社会隔离小鼠在注意集合转移方面存在障碍。将每个阶段不同剂量阿立哌唑的社会饲养小鼠和隔离饲养小鼠进行交叉配对比较。结果显示社会隔离饲养的小鼠在维间分辨和维外分辨方面表现出选择性严重缺陷。与安慰剂和1毫克/千克的阿立哌唑相比,3毫克/千克和6毫克/千克的阿立哌唑能大大缓解认知障碍。结论本研究结果强调了阿立哌唑对认知能力的积极影响。阿立哌唑有可能成为具有精神刺激作用的多动症治疗药物。
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引用次数: 0
Unrevealing the total phenols, total flavonoids, antioxidant, anti-inflammatory, and cytotoxic effects of Garden Cress seed ethanolic extracts 揭示花园芹种子乙醇提取物的总酚、总黄酮、抗氧化、抗炎和细胞毒性作用
N. T. Abdulaziz, E. Mohammed, R. Khalil, Y. Mustafa
For many years, natural bioactives have been used to treat, cure, and prevent diseases. Crude extracts from fruit seeds have been demonstrated to possess a range of advantageous biological properties, including anti-inflammatory, antioxidant, and anti-tumorous effects. In this study, the seeds of Garden Cress (Lepidium sativum, Cr) were extracted using ethanol as a solvent and two extraction techniques. These methods are microwave-facilitated extraction and successive microwave-ultrasound-assisted extraction, resulting in Cr-1 and Cr-2, respectively. These two ethanolic extracts were investigated for several biochemical characteristics, including flavonoid content, phenolic content, antioxidant, anti-inflammatory, cytotoxic, and cytoprotective effects. The first and second characteristics were computed using the colorimetric AlCl3 and Folin-Ciocalteu colorimetric methods, respectively. The antioxidant char¬acteristic was investigated against two reactive species, named hydroxyl and DPPH. Also, the total reducing power was calculated in this regard. The anti-inflammatory-reducing characteristics of the extracts were evaluated employing three inflammation-progressing enzymes. The last two characteristics were assessed using MTT-based methodology in two malignant and one healthy cellular population, respectively. The outcomes demonstrated that the extract of microwave-facilitation (Cr-1) has the highest flavonoid and phenolic contents, as well as the best antioxidant activity. Furthermore, when compared to the other one, Cr-1 showed a greater inhibitory effect on inflammation-progressing enzymes and selectivity against COX2. At the applied concentrations, neither extract, however, had any antiprolifer¬ative effect on malignant or healthy cellular lines. Moreover, the extracts had no additional influence on the ability of 5-fluorouracil (5-FU) to stop the proliferation of malignant cells. However, when the extracts were individually applied with 5-FU, the cytotoxic capability of the drug in healthy cellular populations was substantially lowered. Given these findings, the authors concluded that using Cr-1 together with 5-FU may serve as a measure of normal cellular protection.
多年来,天然生物活性物质一直被用于治疗、治愈和预防疾病。从水果种子中提取的粗萃取物已被证明具有一系列有利的生物特性,包括抗炎、抗氧化和抗肿瘤作用。在这项研究中,使用乙醇作为溶剂和两种萃取技术萃取花园芹(Lepidium sativum,Cr)的种子。这两种方法分别是微波辅助萃取和微波-超声波辅助连续萃取,得到了 Cr-1 和 Cr-2。研究了这两种乙醇提取物的几种生化特性,包括类黄酮含量、酚含量、抗氧化、抗炎、细胞毒性和细胞保护作用。第一个和第二个特征分别用 AlCl3 比色法和 Folin-Ciocalteu 比色法计算。对羟基和 DPPH 两种活性物质的抗氧化特性进行了研究。此外,还计算了总还原力。利用三种炎症进展酶对提取物的抗炎还原特性进行了评估。最后两种特性分别在两种恶性细胞和一种健康细胞中使用 MTT 方法进行了评估。结果表明,微波促进提取物(Cr-1)的类黄酮和酚含量最高,抗氧化活性最好。此外,与其他提取物相比,Cr-1 对炎症进展酶的抑制作用更大,而且对 COX2 具有选择性。然而,在所使用的浓度下,这两种提取物对恶性或健康细胞系都没有任何抗增殖作用。此外,提取物对 5-氟尿嘧啶(5-FU)阻止恶性细胞增殖的能力也没有额外的影响。然而,当提取物与 5-FU 一起单独使用时,该药物在健康细胞群中的细胞毒性能力会大大降低。鉴于这些发现,作者得出结论,将Cr-1与5-FU一起使用可作为正常细胞保护的一种措施。
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引用次数: 0
The impact of surgical intervention on statographic parameters of patients with diabetic foot syndrome 手术干预对糖尿病足综合征患者统计学参数的影响
T. Tamm, I. Mamontov, Valentin Nepomnyashchy, Olha Danylova, Kostiantyn Sokol
Taking into account that the prevalence of diabetes mellitus continues to increase worldwide, secondary complications associated with this endocrine disorder are becoming increasingly common. Disruption of glucose homeostasis and hyperglycemia lead to the activation of several pathological metabolic pathways, contributing to the development of vascular insufficiency and neurodegenerative processes in the lower limbs. These processes are the causes of a condition known as diabetic foot syndrome (DFS), which requires special attention and meticulous treatment. Complications in the form of trophic ulcers of the lower limbs are one of the serious consequences of diabetes mellitus (DM) since they often lead to severe medical and social problems, including high rates of limb amputations. The purpose of the research is to investigate the redistribution of plantar pressure depending on the volume of surgical intervention in patients with diabetic foot syndrome (DFS) by measuring individual statographic parameters. The analysis of a series of parameters from statographic studies in patients with diabetic foot syndrome undergoing various volumes of surgical interventions has allowed for a comprehensive understanding of the features of vertical standing of these patients. In the course of the research, it has been revealed that as the support area of the operated foot decreases, there is an increase in body oscillation in both the sagittal and frontal planes relative to the support area. It has been proven that in cases with a normal support area of the foot, the relative body oscillation decreases.
考虑到糖尿病在全球的发病率持续上升,与这种内分泌失调相关的继发性并发症正变得越来越常见。葡萄糖稳态的破坏和高血糖会激活多种病理代谢途径,导致血管功能不全和下肢神经退行性病变。这些过程是糖尿病足综合征(DFS)的病因,需要特别关注和精心治疗。下肢营养性溃疡并发症是糖尿病(DM)的严重后果之一,因为它们通常会导致严重的医疗和社会问题,包括高截肢率。本研究的目的是通过测量各项统计参数,研究糖尿病足综合征(DFS)患者足底压力的重新分布与手术干预量的关系。通过对糖尿病足综合症患者接受不同手术干预量时的一系列静态研究参数进行分析,可以全面了解这些患者垂直站立的特点。在研究过程中发现,随着手术足部支撑面积的减少,矢状面和正面相对于支撑面积的身体摆动都会增加。事实证明,在足部支撑面积正常的情况下,身体的相对摆动会减小。
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引用次数: 0
In silico study of five new sulfonamide derivatives bearing a thiazolidine-4-one moiety: targeting carbonic anhydrase IX 含有噻唑烷-4-酮分子的五种新磺酰胺衍生物的硅学研究:靶向碳酸酐酶 IX
Zahraa Falah Naji, Noor H. Naser
Molecular docking simulations were utilized to determine the binding affinities of five compounds produced. These compounds were IVa, IVb, IVc, IVd, and IVe. Chemicals derived from thiazolidin-4-one were designed to target cancer and human carbonic anhydrase IX (PDB code: 4M2V). These chemicals were designed to target humans. Our de¬tailed sketching of the structure of the molecules was accomplished with the help of Chem Draw Ultra 12.0. To validate the compounds produced, the S. score and Rmsd values of the compounds were examined using the Molecular Operating Environment program. In contrast to acetazolamide, the proteins of the synthesized compounds had con¬siderable binding affinities with the receptor active pocket, which suggested potential activity against cancer.
利用分子对接模拟确定了五种化合物的结合亲和力。这些化合物是 IVa、IVB、IVc、IVd 和 IVe。从噻唑烷-4-酮衍生出的化学物质被设计为针对癌症和人类碳酸酐酶 IX(PDB 代码:4M2V)。这些化学品的设计目标是人类。我们利用 Chem Draw Ultra 12.0 绘制了分子结构草图。为了验证化合物的有效性,我们使用分子操作环境程序检测了化合物的 S. 评分和 Rmsd 值。与乙酰唑胺相比,合成化合物的蛋白质与受体活性口袋具有可比的结合亲和力,这表明其具有潜在的抗癌活性。
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引用次数: 0
Economic perspectives in pharmaceuticals: market dynamics and pricing of medications 制药业的经济视角:市场动态和药品定价
I. Borysiuk, Mariia Shevchenko, Anna Tiutiunnyk, Polina Kovalenco, Nataliia Surtaieva
Background: Analysing the modern pharmaceutical market is crucial for making management decisions, forming strategies, and ensuring competitiveness in this sector. Aim: Determination of the impact of various economic factors of the pharmaceutical industry on market conditions and development of economically justified areas of cost formation in the pharmaceutical market. Materials and Methods: A systematic review of scientific publications in the search databases Scopus, Web of Science, Medline, and Google Scholar was conducted. Statistical research methods used are observation, index and regression analysis. The methods of benchmarking analysis and interpretation were applied. Results: A detailed examination of published works by scientists and doctors has highlighted critical problems in forming the cost of medicinal products in the pharmaceutical market. The use of medicines worldwide and in individual countries has been considered, and a trend of increasing revenue in the global pharmaceutical market has been identified. The main approaches to forming pricing models in the pharmaceutical industry have been summarised. The peculiarities of the formation of EU legislation on the registration, production, sale, and quality control of medicinal products have been highlighted. The characteristics of the functioning of reimbursement programmes in certain countries worldwide have been described. A benchmarking analysis of the pharmaceutical market economy in Ukraine and the European Union has been conducted. Conclusions: The main directions for improving pricing policy in the modern pharmaceutical market have been outlined. It has been established that the main directions for forming the cost of medicinal products are expenses on research and development, costs of goods sold and patent expenses, marketing and advertising, regulatory and permitting procedures, and market competition.
背景:分析现代医药市场对于做出管理决策、制定战略和确保该行业的竞争力至关重要。目的:确定制药业的各种经济因素对市场条件的影响,开发制药市场成本形成的经济合理领域。材料和方法:对 Scopus、Web of Science、Medline 和 Google Scholar 等检索数据库中的科学出版物进行了系统审查。使用的统计研究方法有观察法、指数法和回归分析法。采用了基准分析和解释的方法。研究结果通过对科学家和医生发表的著作进行详细研究,发现了医药市场在形成医药产品成本方面存在的关键问题。对全球和各个国家的药品使用情况进行了研究,发现了全球医药市场收入增长的趋势。总结了医药行业形成定价模型的主要方法。重点介绍了欧盟关于药品注册、生产、销售和质量控制立法的形成特点。介绍了世界上某些国家报销计划的运作特点。对乌克兰和欧盟的医药市场经济进行了基准分析。结论:概述了改进现代医药市场定价政策的主要方向。已经确定,形成医药产品成本的主要方向是研发费用、销售成本和专利费用、营销和广告、监管和许可程序以及市场竞争。
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引用次数: 0
Gynecomastia treatment with Tamoxifen or Tamoxifen followed by Letrozole: Prototype Clinical Study 用他莫昔芬或他莫昔芬后再用来曲唑治疗妇科炎症:原型临床研究
S. Zervoudis, George Iatrakis, Panagiotis Tsikouras, Panagiotis Peitsidis, Angeliki Sarella, Christos Ampatzis
Gynecomastia is very common cause of a patient’s visit to a mastology office. Gynecomastia is experienced in up to 70% of mid-puberty males and in up to 65% of middle-aged men. The treatment starts with the identification of the cause, but in most cases the patient is treated with tamoxifen, aromatase inhibitors, liposuction or surgery. Τreatment of gynecomastia is not well standarized. In our prospective study, we examined the use of tamoxifen followed by letrozole and a clinically important reduction was achieved, when compared with those who were treated only with tamoxifen. Further research needs to be conducted in order to confirm this promising protocol.
妇科乳腺增生是患者到乳腺科就诊的常见原因。多达 70% 的青春期中期男性和多达 65% 的中年男性会出现妇科乳腺增生。治疗首先要确定病因,但在大多数情况下,患者会接受他莫昔芬、芳香化酶抑制剂、抽脂或手术治疗。妇科乳腺增生的治疗还没有很好的标准。在我们的前瞻性研究中,我们研究了在使用他莫昔芬后再使用来曲唑的情况,与仅使用他莫昔芬治疗的患者相比,来曲唑的用量减少了,这在临床上具有重要意义。我们还需要开展进一步的研究,以确认这一前景广阔的方案。
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引用次数: 0
Isolation and characterization of a tetrahydroprotoberberine alkaloid from Crassula ovata 从山苍子中分离并鉴定一种四氢小檗碱
Hawraa Kareem Al-yassery, E. Kadhim
The presence of alkaloids in Crassula ovata is a topic that is still unexplored, as there are no published studies on the matter. This study demonstrates the presence of an alkaloid compound (and its class) for the first time in Crassula ovata. The plant material was defatted with n-hexane, and a Soxhlet apparatus was used for the extraction process, while the acid-base method was used for the isolation of alkaloids from the chloroform fractions. The quaternary alkaloid was precipitated from the aqueous layer spontaneously, in high quantity. By using standard spectroscopic methods (including liquid chromatography - mass spectroscopy) we were able to clarify the structure of the precipi¬tated compound as a tetrahydroprotoberberine alkaloid based on the general fragmentation pattern of this class of alkaloids and the retro-Diels-Alder reaction; a characteristic fragmentation pathway of tetrahydroprotoberberine alka¬loids.
由于还没有公开发表过相关研究,因此有关卵叶牛肝菌(Crassula ovata)中生物碱的存在是一个尚未探索的课题。本研究首次证明了一种生物碱化合物(及其类别)存在于黄樟中。植物材料用正己烷脱脂,用索氏提取器进行提取,用酸碱法从氯仿馏分中分离生物碱。季生物碱自发地从水层中大量析出。通过使用标准光谱方法(包括液相色谱-质谱法),我们能够根据四氢小檗碱生物碱的一般碎片模式和逆-Diels-Alder反应(四氢小檗碱生物碱的特征碎片途径),明确析出化合物的结构为四氢小檗碱生物碱。
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引用次数: 0
Misuse of antibiotics in Iraq: Babylon Governorate as a model 伊拉克抗生素的滥用:以巴比伦省为范例
F. Hussein, Halla M. Hassan
The efficacy and easy access to antibiotics have led to their overuse, which allows for the development of resistance to them. This study took Babylon Governorate as a model to prove whether the above hypothesis is true or not. We aimed at exploring whether there are any restrictions for dealing with antibiotics by pharmacists in the Babylon Governorate, at identifying the distribution of pharmacies in Hillah, and at estimating the capability of the health au¬thority to control them. A total of 165 pharmacies were visited in an attempt to purchase antibiotics without a prescrip¬tion. Antibiotics were obtained from 164 pharmacies, and one pharmacy apologized because they did not have the antibiotic. Moreover, a survey was randomly distributed to different pharmacies and pharmacists asking them whether they sell antibiotics without prescriptions, and an online questionnaire was distributed to pharmacists and pharmacy students in the Babylon Governorate. The results revealed that the percentage of pharmacies that sell antibiotics without medical prescription is 98%; the remaining 2% belongs to the pharmacies that do not stock these antibiotics. We hypothesize that the main reason for this phenomenon is the chaotic distribution of pharmacies in the Governorate, and the lack of supervision by the authorities. Mapping has revealed a random distribution of pharmacies in Hillah, which is performed in an unscientific manner without taking into account whether these areas need pharmacies or not. Moreover, the lack of supervision by the Government and the health syndicates allows for antibiotics to be largely dispensed in the pharmacies without a medical prescription.
抗生素的功效和容易获得性导致了抗生素的过度使用,从而产生了抗药性。本研究以巴比伦省为模型,以证明上述假设是否属实。我们旨在探讨巴比伦省的药剂师在处理抗生素时是否存在任何限制,确定希拉省药店的分布情况,并估计卫生部门对其进行控制的能力。我们共走访了 165 家药店,试图在没有处方的情况下购买抗生素。共从 164 家药店获得了抗生素,其中一家药店因没有抗生素而道歉。此外,我们还向不同的药店和药剂师随机发放了一份调查问卷,询问他们是否出售无处方抗生素,并向巴比伦省的药剂师和药学专业学生发放了一份在线问卷。结果显示,无处方销售抗生素的药店比例为 98%,其余 2%的药店不销售此类抗生素。我们推测,造成这种现象的主要原因是该省药店分布混乱,当局缺乏监管。摸底调查显示,希拉省的药店分布比较随意,没有考虑到这些地区是否需要药店,这种分布方式是不科学的。此外,由于政府和卫生集团缺乏监督,药房在很大程度上可以在没有医生处方的情况下配发抗生素。
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引用次数: 0
In vitro study of the antibacterial effects of the Cydonia oblonga extract 楙提取物抗菌作用的体外研究
N. Hindi, Baraa Hamid Hadi, Lubna Abdul Muttalib Al-Shalah, Ahmed Saleem Abbas
Cydonia oblonga is effective against many infections and has medicinal properties that are useful in the treatment of many other diseases. The aim of this study was to elucidate the antimicrobial activity (in the form of anti-adherence and anti-biofilm formation) of the aqueous Cydonia oblonga extract. The biological activity of the extract was compared to that of imipenem. All bacterial isolates of Gram-positive and Gram-negative bacteria assessed were found to be susceptible to the Cydonia oblonga extract and the zone of inhibition ranged from 24 to 34 mm. Most bacterial isolates were resistant to the antibiotic, and some bacterial isolates were sensitive to imipenem. The adherence and biofilm formation inhibitory activities in the presence of the aqueous extract of Cydonia oblonga were found to be moderate or elevated in most of the Gram-negative bacteria assessed. According to our findings, the aqueous Cydonia oblonga extract displays great effectiveness (and promise) against many pathogenic bacterial isolates.
Cydonia oblonga 对多种感染有效,其药用特性可用于治疗许多其他疾病。本研究的目的是阐明水性 Cydonia oblonga 提取物的抗菌活性(以抗粘附和抗生物膜形成的形式)。该提取物的生物活性与亚胺培南的生物活性进行了比较。结果发现,所有被评估的革兰氏阳性和革兰氏阴性细菌分离物均对长爪苣苔提取物敏感,抑菌区范围为 24 至 34 毫米。大多数细菌分离物对抗生素具有耐药性,一些细菌分离物对亚胺培南敏感。我们发现,在长叶楙水提取物存在的情况下,对大多数革兰氏阴性细菌的粘附和生物膜形成的抑制活性为中等或较高。根据我们的研究结果,Cydonia oblonga 水提取物对许多致病性细菌分离物显示出巨大的效力(和前景)。
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引用次数: 0
期刊
Review of Clinical Pharmacology and Pharmacokinetics - International Edition
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