pharmaceutical

Pharmaceutical
  • 文章类型: Journal Article
    新兴污染物,如药物和微塑料已成为一个紧迫的问题,因为它们的广泛存在和对生态系统的潜在影响。为了在多压力源背景下评估这些污染物的生态系统水平影响,我们通过在三个多月的时间内将近自然的多营养水生食物网暴露于大型中观中环境相关浓度的氟西汀和微塑料的梯度来模拟现实条件。我们测量了不同营养类群的生物量和丰度,以及生态功能,如养分利用率和分解率。为了探索潜在的群落和生态系统水平效应的潜在机制,我们还进行了行为测定,重点是运动参数作为三个物种的响应变量:大型水蚤(浮游动物猎物),Chaoborusflavicans幼虫(浮游动物的无脊椎动物中上层捕食者)和Asellusaquaticus(底栖大型无脊椎动物),利用中观宇宙中的水。我们的中观结果表明,微塑料的存在控制着浮游植物生物量的响应,由于微塑料和氟西汀之间的相互作用,具有弱的非单调剂量反应关系。然而,暴露于氟西汀引起浮游动物丰度和植物材料微生物分解率的强烈非单调剂量反应。在行为分析中,浮游动物猎物D.magna的运动表现出类似的非单调反应,主要由氟西汀诱导。它的捕食者C.flagicans,然而,显示出由微塑料和氟西汀控制的显着非单调反应。在较高的氟西汀浓度下,分解剂A.aquaticus的行为显着降低,可能导致沉积物附近分解速率降低。我们的研究表明,短期暴露后观察到的影响会导致长期暴露后更明显的生态系统水平影响。
    Emerging pollutants, such as pharmaceuticals and microplastics have become a pressing concern due to their widespread presence and potential impacts on ecological systems. To assess the ecosystem-level effects of these pollutants within a multi-stressor context, we simulated real-world conditions by exposing a near-natural multi-trophic aquatic food web to a gradient of environmentally relevant concentrations of fluoxetine and microplastics in large mesocosms over a period of more than three months. We measured the biomass and abundance of different trophic groups, as well as ecological functions such as nutrient availability and decomposition rate. To explore the mechanisms underlying potential community and ecosystem-level effects, we also performed behavioral assays focusing on locomotion parameters as a response variable in three species: Daphnia magna (zooplankton prey), Chaoborus flavicans larvae (invertebrate pelagic predator of zooplankton) and Asellus aquaticus (benthic macroinvertebrate), using water from the mesocosms. Our mesocosm results demonstrate that presence of microplastics governs the response in phytoplankton biomass, with a weak non-monotonic dose-response relationship due to the interaction between microplastics and fluoxetine. However, exposure to fluoxetine evoked a strong non-monotonic dose-response in zooplankton abundance and microbial decomposition rate of plant material. In the behavioral assays, the locomotion of zooplankton prey D. magna showed a similar non-monotonic response primarily induced by fluoxetine. Its predator C. flavicans, however, showed a significant non-monotonic response governed by both microplastics and fluoxetine. The behavior of the decomposer A. aquaticus significantly decreased at higher fluoxetine concentrations, potentially leading to reduced decomposition rates near the sediment. Our study demonstrates that effects observed upon short-term exposure result in more pronounced ecosystem-level effects following chronic exposure.
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  • 文章类型: Journal Article
    葡聚糖是在由从特定物种和菌株的微生物剂获得的酶催化的反应中合成的胞外多糖。具有不同分子量的葡聚糖多糖的产物适用于多种药物和临床用途。葡聚糖溶液具有多种特性,包括粘度,溶解度,流变学,和热性能;因此,葡聚糖已经在几个领域进行了商业应用研究。某些细菌可产生不同分子量和构型的胞外多糖葡聚糖。不同分子量的葡聚糖产品已用于多个行业,包括医学,化妆品,和食物。本文旨在概述葡聚糖在输血和临床研究中的应用及其生物合成的报道。已经总结了有关从蔗糖生物合成葡聚糖的酶催化反应以及高分子量葡聚糖分子的生物转化过程以获得不同分子量和构型的制剂的信息。
    Dextran is an exopolysaccharide synthesized in reactions catalyzed by enzymes obtained from microbial agents of specific species and strains. Products of dextran polysaccharides with different molecular weights are suitable for diverse pharmaceutical and clinical uses. Dextran solutions have multiple characteristics, including viscosity, solubility, rheological, and thermal properties; hence, dextran has been studied for its commercial applications in several sectors. Certain bacteria can produce extracellular polysaccharide dextran of different molecular weights and configurations. Dextran products of diverse molecular weights have been used in several industries, including medicine, cosmetics, and food. This article aims to provide an overview of the reports on dextran applications in blood transfusion and clinical studies and its biosynthesis. Information has been summarized on enzyme-catalyzed reactions for dextran biosynthesis from sucrose and on the bio-transformation process of high molecular weight dextran molecules to obtain preparations of diverse molecular weights and configurations.
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  • 文章类型: Journal Article
    目前,大多数报告的感染是细菌来源的;然而,这导致了围绕真菌病原体引起的感染的文献和研究的限制,它们现在正在对抗生素药物产生耐药性。在天然抗菌剂中,已观察到蜂蜜具有与伤口愈合特性相关的可证明和高度开发的抗菌和感染控制;因此,它已被纳入许多标准药物制剂。一般来说,这些产品利用纯蜂蜜样品作为产品中的生物活性成分,该产品是为方便应用而专门设计的。本文旨在回顾有关各种医用级蜂蜜产品的各种生物活性的已发表报告中的信息,包括manuka和其他来自不同花卉类型和地理区域的常规非麦卢卡类型。此外,这篇综述重点介绍了针对细菌致病菌株测试的各种类型蜂蜜产品的抗生素活性,酵母和真菌,及其在保健品配方中的应用。
    Presently, most of the reported infections are of a bacterial origin; however, this leads to a limit within the literature and research around infections caused by fungal pathogens, which are now developing resistance to antibiotic medicines. Of the natural antimicrobial agents, honey has been observed with demonstrable and highly exploitable antimicrobial and infection control related to wound healing properties; therefore, it has been incorporated into many standard pharmaceutical formulations. Generally, these products utilize a pure sample of honey as a bioactive ingredient in a product which has been purposely designed for the convenience of application. This article aims to review information available from published reports on various bioactivities of a variety of medical-grade honey products, including manuka and other conventional non-manuka types sourced from different floral types and geographical regions. Additionally, this review highlights the antibiotic activities of various types of honey products tested against pathogenic strains of bacteria, yeast and fungi, and their applications in the formulation of healthcare products.
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  • 文章类型: Journal Article
    蛋白酶,水解肽键的酶,在医学上有各种应用,临床应用,和药物开发。它们用于癌症治疗,伤口清创术,隐形眼镜清洁,朊病毒降解,生物膜去除,和纤维蛋白溶解剂。蛋白酶在心血管疾病治疗中也至关重要,强调安全的必要性,负担得起的,和有效的纤维蛋白溶解药物。蛋白水解酶和蛋白酶生物传感器越来越多地用于诊断和治疗应用。先进的技术,例如基于纳米材料的传感器,正在开发以增强灵敏度,特异性,和蛋白酶生物传感器的多功能性。这些生物传感器由于其精确性和快速性而成为疾病检测的有效工具。它们可以检测细胞外和细胞内的蛋白酶,以及基于荧光的实时和无标记检测病毒相关蛋白酶的方法。蛋白水解酶生物传感器的积极利用有望在生物医学研究中得到显着扩展。体外模型系统,和药物开发。本研究的重点是1982年至2024年间以英文发表的期刊文章和书籍。
    Proteases, enzymes that hydrolyze peptide bonds, have various applications in medicine, clinical applications, and pharmaceutical development. They are used in cancer treatment, wound debridement, contact lens cleaning, prion degradation, biofilm removal, and fibrinolytic agents. Proteases are also crucial in cardiovascular disease treatment, emphasizing the need for safe, affordable, and effective fibrinolytic drugs. Proteolytic enzymes and protease biosensors are increasingly used in diagnostic and therapeutic applications. Advanced technologies, such as nanomaterials-based sensors, are being developed to enhance the sensitivity, specificity, and versatility of protease biosensors. These biosensors are becoming effective tools for disease detection due to their precision and rapidity. They can detect extracellular and intracellular proteases, as well as fluorescence-based methods for real-time and label-free detection of virus-related proteases. The active utilization of proteolytic enzymatic biosensors is expected to expand significantly in biomedical research, in-vitro model systems, and drug development. We focused on journal articles and books published in English between 1982 and 2024 for this study.
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  • 文章类型: Journal Article
    最近批准的药物的适应症明显少于多年前批准的药物。一个可能的原因可能是,控制自批准或启动以来的年数,最近批准的药物有较少的适应症(例如在上市时)。精准医疗和个性化医疗的作用越来越大,精准医学的目标是提供更精确的预防方法,疾病的诊断和治疗。具有较少适应症的药物可能比具有许多适应症的药物“更精确”。
    我们使用来自法国和美国两个国家的不同类型的数据来分析许多药物之间的关系,该药物的年份——即药物首次上市或批准的年份——以及它的年龄——它已经上市的年数。
    两国的所有证据都表明,控制药物年龄,与多年前批准的药物相比,最近批准的药物往往具有更少的适应症。在美国,年份的10年增长与所有药物的有效适应症数量下降10.7%有关,1989年后批准的药物的有效适应症数量下降了19.4%。在法国,药物年龄增加对适应症数量的积极影响被药物年份增加的负面影响所抵消。
    最近批准的药物与旧药物相比,不太可能是“通用技术”(甚至是多用途技术)。近几十年来,“精准医学”的相对重要性有所增加。具有较少适应症的药物可能比具有许多适应症的药物“更精确”。
    UNASSIGNED: More recently approved drugs have significantly fewer indications than drugs approved many years ago. One possible reason for this may be that, controlling for the number of years since approval or launch, more recently approved drugs have fewer indications (e.g. at the time of launch). The role of precision and personalised medicine has increased, and the goal of precision medicine is to provide a more precise approach for the prevention, diagnosis and treatment of disease. Drugs that have fewer indications may be \'more precise\' than drugs that have many indications.
    UNASSIGNED: We use different kinds of data from two countries - France and the U.S. - to analyze the relationship across many drugs between the number of indications of a drug, the drug\'s vintage - i.e. the year in which the drug was first marketed or approved - and its age - the number of years it has been marketed.
    UNASSIGNED: All the evidence from both countries indicates that, controlling for drug age, more recently approved drugs tend to have fewer indications than drugs approved many years ago. In the U.S., a 10-year increase in vintage is associated with a 10.7% decline in the effective number of indications of all drugs, and a 19.4% decline in the effective number of indications of drugs approved after 1989. In France, the positive effect on the number of indications of the increase in drug age was more than offset by the negative effect of the increase in drug vintage.
    UNASSIGNED: More recently approved drugs are less likely to be \'general-purpose technologies\' (or even multi-purpose technologies) than older drugs. The relative importance of \'precision medicine\' has increased in recent decades. Drugs that have fewer indications may be \'more precise\' than drugs that have many indications.
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  • 文章类型: Journal Article
    制药污染物,一组新出现的污染物,近年来引起了极大的关注,它们从水生环境中的去除已经得到解决。在目前的研究中,开发了一种新的基于海绵的移动床生物膜反应器(MBBR),以去除化学需氧量(COD)和药物化合物布洛芬(IBU)。构建了一个30升的中试规模MBBR,从德黑兰南部污水处理厂的第一个澄清池的废水中连续进料。控制的操作参数是pH值在自然范围内,溶解氧为1.5-2mg/L,平均悬浮混合液悬浮固体(MLSS),混合液挥发性悬浮固体(MLVSS)为1.68±0.1g/L和1.48±0.1g/L,分别。水力停留时间(HRT)(5h,10h,15h),填充率(10%,20%,30%),和初始IBU浓度(2mg/L,5mg/L,评估了10mg/L)的去除效率。这项研究的结果表明,COD的去除效率范围为48.9至96.7%,在HRT为10h时观察到最佳去除效率,20%的填充率,初始IBU浓度为2mg/L同时,IBU去除率从25%到92.7%,在相同的HRT和填充比下观察到最高的去除效率,尽管初始IBU浓度为5mg/L。将HRT从5小时延长至10小时可显着提高COD和IBU的去除。然而,从10小时进一步延长至15小时,对COD和IBU的去除效率略有提高,甚至在某些情况下,去除效率下降。根据获得的结果,选择20%的填充率作为最佳状态。将IBU的初始浓度从2mg/L增加到5mg/L通常可以改善COD和IBU的去除,而从5到10mg/L的增加导致COD和IBU去除率下降。本研究还优化了反应器的效率COD和IBU去除通过使用响应面法(RSM)与HRT的独立变量,填充率,和初始IBU浓度。在这方面,二次模型被发现是显著的。利用中央复合设计(CCD),HRT为10小时时的最佳运行参数,21%的填充率,确定IBU的初始浓度为3mg/L,实现最高的COD和IBU去除效率。本研究表明,基于海绵的MBBR是一种有前途的COD和IBU去除技术。
    Pharmaceutical pollutants, a group of emerging contaminants, have attracted outstanding attention in recent years, and their removal from aquatic environments has been addressed. In the current study, a new sponge-based moving bed biofilm reactor (MBBR) was developed to remove chemical oxygen demand (COD) and the pharmaceutical compound Ibuprofen (IBU). A 30-L pilot scale MBBR was constructed, which was continuously fed from the effluent of the first clarifier of the Southern Tehran wastewater treatment plant. The controlled operational parameters were pH in the natural range, Dissolved Oxygen of 1.5-2 mg/L, average suspended mixed liquor suspended solids (MLSS), and mixed liquor volatile suspended solids (MLVSS) of 1.68 ± 0.1 g/L and 1.48 ± 0.1 g/L, respectively. The effect of hydraulic retention time (HRT) (5 h, 10 h, 15 h), filling ratio (10%, 20%, 30%), and initial IBU concentration (2 mg/L, 5 mg/L, 10 mg/L) on removal efficiencies was assessed. The findings of this study revealed a COD removal efficiency ranging from 48.9 to 96.7%, with the best removal efficiency observed at an HRT of 10 h, a filling ratio of 20%, and an initial IBU concentration of 2 mg/L. Simultaneously, the IBU removal rate ranged from 25 to 92.7%, with the highest removal efficiency observed under the same HRT and filling ratio, albeit with an initial IBU concentration of 5 mg/L. An extension of HRT from 5 to 10 h significantly improved both COD and IBU removal. However, further extension from 10 to 15 h slightly enhanced the removal efficiency of COD and IBU, and even in some cases, removal efficiency decreased. Based on the obtained results, 20% of the filling ratio was chosen as the optimum state. Increasing the initial concentration of IBU from 2 to 5 mg/L generally improved COD and IBU removal, whereas an increase from 5 to 10 mg/L caused a decline in COD and IBU removal. This study also optimized the reactor\'s efficiency for COD and IBU removal by using response surface methodology (RSM) with independent variables of HRT, filling ratio, and initial IBU concentration. In this regard, the quadratic model was found to be significant. Utilizing the central composite design (CCD), the optimal operating parameters at an HRT of 10 h, a filling ratio of 21%, and an initial IBU concentration of 3 mg/L were pinpointed, achieving the highest COD and IBU removal efficiencies. The present study demonstrated that sponge-based MBBR stands out as a promising technology for COD and IBU removal.
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  • 文章类型: Journal Article
    人类相关微生物对药物暴露的生存策略主要在真正的病原体暴露于抗生素的背景下进行研究。人们不太了解非致病性微生物和宿主相关共生群落与人类接触的各种药物和外源性物质的生存策略。复杂群落中微生物共生的生活方式提供了多种方式来适应不同的药物诱导的压力。这里,我们回顾了在个体和社区水平暴露于药物(抗生素和非抗生素)时肠道共生所采用的反应和生存策略.我们还讨论了影响药物暴露后恢复和建立新社区结构的因素。这些生存策略是肠道微生物组稳定性和恢复力的关键。最终影响宿主的整体健康和福祉。
    Survival strategies of human-associated microbes to drug exposure have been mainly studied in the context of bona fide pathogens exposed to antibiotics. Less well understood are the survival strategies of non-pathogenic microbes and host-associated commensal communities to the variety of drugs and xenobiotics to which humans are exposed. The lifestyle of microbial commensals within complex communities offers a variety of ways to adapt to different drug-induced stresses. Here, we review the responses and survival strategies employed by gut commensals when exposed to drugs-antibiotics and non-antibiotics-at the individual and community level. We also discuss the factors influencing the recovery and establishment of a new community structure following drug exposure. These survival strategies are key to the stability and resilience of the gut microbiome, ultimately influencing the overall health and well-being of the host.
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  • 文章类型: Journal Article
    福特巴替尼是成纤维细胞生长因子受体的强大抑制剂,阻止其磷酸化并随后导致各种细胞系中细胞活力的降低。福特巴替尼被批准作为几种疾病的有效治疗药物,包括非小细胞肺癌和乳腺癌。在这里,一种新型的选择性荧光探针被创建用于在各种基质中进行氟替替尼定量,包括药物制剂和人血浆。该技术主要取决于通过与三甲胺和溴乙酰溴反应将futibatinib化学转化为荧光产物。产生的荧光探针在248nm激发时在338nm处显示最大发射峰。该方法提供了0.120ng/mL的低检测限,并在1-200ng/mL的范围内保持了线性浓度依赖性关系。灵敏度高,通过该方法证明了在药物制剂和加标血浆基质中氟替替尼定量的准确性和精密度,根据ICH要求进行了验证。
    Futibatinib is a powerful inhibitor of fibroblast growth factor receptors that impedes its phosphorylation and subsequently leading to a reduction in in cell viability across various cell lines. Futibatinib was approved for initial use as an effective treatment for several diseases, including non-small cell lung cancer and breast cancer. Herein, a novel selective fluorescence probe was created for futibatinib quantification in various matrices, including pharmaceutical formulation and human plasma. The technique primarily depends on futibatinib\'s chemical conversion into a fluorescent product through a reaction with trimethylamine and bromoacetyl bromide. The created fluorescent probe exhibits maximum emission peak at 338 nm upon excitation at 248 nm. The method provided a low detection limit of 0.120 ng/mL and maintained a linear concentration-dependent relationship across the range of 1-200 ng/mL. High sensitivity, accuracy and precision were demonstrated for futibatinib quantification in pharmaceutical formulation and spiked plasma matrix by the method, which was validated in accordance with ICH requirements.
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  • 文章类型: Journal Article
    全球对源自自然资源的环保产品的需求不断增加,这刺激了对生物材料的深入研究。在这些材料中,纳米纤维素是一种高效的选择,由源自木质纤维素生物质的紧密堆积的纤维素原纤维组成。纳米纤维素拥有卓越的属性组合,包括高比表面积,令人印象深刻的机械强度,丰富的羟基易于改性,以及无毒,可生物降解,和环保属性。因此,纳米纤维素已被广泛研究用于高级应用。本文提供了来自不同天然来源的纳米纤维素的各种来源的全面概述,并概述了可用的广泛的生产方法。此外,它深入研究了纳米纤维素在生物医学和制药行业中的广泛用途,揭示了它在这些领域的潜在作用。此外,它强调了纳米纤维素复合材料及其应用的重要性,同时也解决了必须克服的关键挑战,以实现纳米纤维素的广泛利用。
    The increasing global demand for eco-friendly products derived from natural resources has spurred intensive research into biomaterials. Among these materials, nanocellulose stands out as a highly efficient option, consisting of tightly packed cellulose fibrils derived from lignocellulosic biomass. Nanocellulose boasts a remarkable combination of attributes, including a high specific surface area, impressive mechanical strength, abundant hydroxyl groups for easy modification, as well as non-toxic, biodegradable, and environmentally friendly properties. Consequently, nanocellulose has been extensively studied for advanced applications. This paper provides a comprehensive overview of the various sources of nanocellulose derived from diverse natural sources and outlines the wide array of production methods available. Furthermore, it delves into the extensive utility of nanocellulose within the biomedical and pharmaceutical industries, shedding light on its potential role in these fields. Additionally, it highlights the significance of nanocellulose composites and their applications, while also addressing key challenges that must be overcome to enable widespread utilization of nanocellulose.
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  • 文章类型: Journal Article
    沉积物中的潜在有毒元素(PTEs)可能对环境和公共卫生造成极大危害。这项研究旨在评估伊洛林制药行业周围沉积物中PTEs的人类和生态风险,尼日利亚。物理化学参数和铅(Pb)的浓度,铬(Cr),镉(Cd),钴(Co),砷(As),在潮湿和干燥季节从七个位置收集的沉积物样品中分析了镍(Ni)。还进行了标准的二维主成分分析(PCA)和风险评估。Pb的浓度,Co,Ni,Cr,Cd,沉积物中的含量为0.001至0.031毫克/千克,0-0.005mg/kg,0.005-0.012mg/kg,0.001-0.014mg/kg,0.005-0.024mg/kg,和0.001-0.012毫克/千克,分别。发现总PTEs含量的平均浓度按浓度降序排列:Pb>Cd>Ni>Cr>As>Co。PCA显示,在其他位置以及排放点获得的样品中,一些PTE高度集中。各地区的危险指数大多<1,表明几乎没有可能的非癌效应。然而,砷和镍增加的终生癌症风险很高,需要引起注意.生态风险评价表明,铅和砷是所有地区的主要PTEs污染物。该研究确定了沉积物中的PTE谱,并强调了持续监测和采取行动以阻止对当地环境和公共卫生的长期负面影响的必要性。
    Potentially toxic elements (PTEs) in sediment can be highly hazardous to the environment and public health. This study aimed to assess the human and ecological risks of PTEs in sediments around a pharmaceutical industry in Ilorin, Nigeria. Physicochemical parameters and the concentrations of lead (Pb), chromium (Cr), cadmium (Cd), cobalt (Co), arsenic (As), and nickel (Ni) were analyzed in sediment samples collected from seven locations in the wet and dry seasons. Standard two-dimensional principal component analysis (PCA) and risk assessments were also conducted. The concentrations of Pb, Co, Ni, Cr, Cd, and As in the sediments ranged from 0.001 to 0.031 mg/kg, 0-0.005 mg/kg, 0.005-0.012 mg/kg, 0.001-0.014 mg/kg, 0.005-0.024 mg/kg, and 0.001-0.012 mg/kg, respectively. The mean concentrations of the total PTEs content were found in decreasing order of concentration: Pb > Cd > Ni > Cr > As > Co. PCA showed that some of the PTEs were highly concentrated in samples obtained at other locations as well as at the discharge point. The Hazard Index was mostly <1 across locations, indicating little to no probable non-cancerous effect. However, the incremental lifetime cancer risk for arsenic and nickel was high and required attention. The ecological risk assessment showed that lead and arsenic were the major PTEs pollutants in all locations. The study identifies PTEs profiles in sediments and emphasises the necessity of continual monitoring and action to stop long-term negative impacts on the local environment and public health.
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