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Mechanistic insights into the pathogenesis and management of acute pancreatitis 急性胰腺炎的发病机制和治疗
Pub Date : 2022-12-01 DOI: 10.21608/aps.2023.179734.1104
Haidy E. Michel, Naglaa Gamal, M. Tadros
Acute pancreatitis (AP) is an inflammatory disorder of the pancreas; its incidence rate is increasing worldwide; it is around 34 cases per 100,000 persons /year. It may range from mild to severe cases and may be associated with morbidity and mortality mainly due to multiple organ dysfunction syndromes (MODS). Till now, there is no specific therapy for the disease and the treatment of AP is mainly supportive. Moreover, the underlying mechanisms included in its pathogenesis are not fully clear. However, it may include oxidative stress and inflammatory response, including critical mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), toll-like receptor-4 (TLR-4), nuclear factor-kappa B (NF-κB), and high-mobility group box protein1 (HMGB1). Thus, there is a pressing need for continuous search in this era to clarify different pathogenesis and the development of new treatment options for AP, also understanding the disease. While research on the human pancreas remains challenging, animal models of AP may help to elucidate the disease pathophysiology & to discover new target options for the development of new therapies. This review aims to revise several aspects related to AP diagnosis and management and to summarize different animal models of AP.
急性胰腺炎(AP)是胰腺的炎症性疾病;其发病率在世界范围内呈上升趋势;每年每10万人中约有34例。它可能从轻度到重度不等,并可能与发病率和死亡率相关,主要是由于多器官功能障碍综合征(MODS)。到目前为止,该疾病还没有特异性的治疗方法,AP治疗主要是支持性的。此外,其发病机制尚不完全清楚。然而,它可能包括氧化应激和炎症反应,包括关键介质,如白细胞介素-1β (IL-1β)、肿瘤坏死因子-α (TNF-α)、toll样受体-4 (TLR-4)、核因子-κB (NF-κB)和高迁移率组盒蛋白1 (HMGB1)。因此,迫切需要在这个时代进行持续的研究,以阐明AP的不同发病机制和开发新的治疗方案,并了解疾病。虽然对人类胰腺的研究仍然具有挑战性,但AP的动物模型可能有助于阐明疾病的病理生理学并为开发新疗法发现新的靶点选择。本文就AP诊断和治疗相关的几个方面进行综述,并对不同的AP动物模型进行综述。
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引用次数: 0
Pre-irradiation effects of ectoine on radiation-induced cardiotoxicity in female Swiss albino mice model 外托碱对瑞士雌性白化小鼠模型辐射致心脏毒性的辐照前作用
Pub Date : 2022-12-01 DOI: 10.21608/aps.2022.148701.1094
Sameh F. Nakhla, Basma Albehery, Sana Shawky, Salwa Lotfi, M. Kotb, E. El-Bassiouni, Eman El-Abd
Ectoine is a compatible solute that acts as a natural protectant. In the mice model, a single post-irradiation ectoine dose showed protective effects by modulating both inflammatory and oxidative stress pathways. The effect of ectoine has never been tested on mice cardiac tissue, thus the current study aimed to explore the pre-irradiation effect(s) of ectoine on radiation-induced cardiotoxicity. Forty female Swiss albino mice (17.6-23.1 g); controls (injected intraperitoneally for ten days with 0.2 mL saline), ectoine groups injected with 20 mg/kg of ectoine for ten days), irradiated groups (injected intraperitoneally for ten days with 0.2 mL saline then received six Gy whole body x-irradiation single dose), ectoine irradiated groups (injected with ectoine for ten days then irradiated). Animals were sacrificed on days seven, and 14 (five animals each). Hearts were examined for histological changes and immune-stained for Bax. Ectoine concentration in hearts was measured by HPLC. Serum cardiac troponin T, Total antioxidant capacity, and apoptosis-inducing factor were evaluated by mice with ready-to-use ELISA kits. Heart histological changes were documented in 40% of the 7- & 14-days post-irradiation. Ectoine concentrations (0.63 x 10 -4 mg/mg of heart weight) were higher in ectoine groups than ectoine irradiated groups (0.011 x 10 -4 mg/mg) 14-days post-treatment. Serum troponin T significantly differed between the 14 days groups ( p = 0.032). Apoptosis inducible factor significantly increased in ectoine irradiated group (at 14 days) than those of control ( p = 0.014), irradiated ( p = 0.020), and ectoine ( p = 0.033) groups. Bax showed strong to moderate immunostaining in ectoine and irradiated groups. In conclusion, Ectoine has pre-irradiation partial protective effects on heart cytotoxicity.
依托碱是一种相容的溶质,作为天然保护剂。在小鼠模型中,单次辐照后异托因剂量通过调节炎症和氧化应激途径显示出保护作用。依托碱对小鼠心脏组织的影响尚未进行过实验,因此本研究旨在探讨依托碱对辐射引起的心脏毒性的辐照前作用。40只瑞士白化雌性小鼠(17.6-23.1 g);对照组(0.2 mL生理盐水腹腔注射10天)、异托碱组(20 mg/kg异托碱腹腔注射10天)、照射组(0.2 mL生理盐水腹腔注射10天,然后接受6 Gy全身x射线单剂量照射)、异托碱照射组(异托碱注射10天,然后照射)。动物在第7天和第14天献祭(每天5只)。检查心脏组织学变化和Bax免疫染色。采用高效液相色谱法测定心脏内异托因浓度。小鼠血清肌钙蛋白T、总抗氧化能力和凋亡诱导因子用即用型ELISA试剂盒进行测定。在照射后7天和14天,有40%的患者发生了心脏组织学变化。治疗14天后,依托碱组的依托碱浓度(0.63 × 10 -4 mg/mg心脏重量)高于依托碱照射组(0.011 × 10 -4 mg/mg)。14 d组间血清肌钙蛋白T差异有统计学意义(p = 0.032)。凋亡诱导因子在外托碱照射组(14 d)显著高于对照组(p = 0.014)、照射组(p = 0.020)和外托碱组(p = 0.033)。体外托碱组和辐照组Bax显示强至中度免疫染色。综上所述,依托碱对心脏细胞毒性具有局部保护作用。
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引用次数: 0
Insights into the neuroprotective properties of Biochanin-A 生物豆素a的神经保护特性研究
Pub Date : 2022-12-01 DOI: 10.21608/aps.2022.154272.1097
S. Hussein, M. Tolba, Haidy E. Michel, S. Azab
The global morbidity and mortality caused by neurological disorders are significant. Neurodegenerative disorders are anticipated to rise as the population ages because they typically manifest in mid-to-late life. The World Health Organization predicts that by 2050 two billion individuals would be 60 or older. So there is an emerging need for neuroprotective agents derived from natural sources with favorable efficacy and high safety profile. One of these natural agents is biochanin A(BIO-A), an isoflavone belonging to phytoestrogens, mainly found in red clover, soy, and chickpea, commercially available tablets. It has a wide range of pharmacological effects, such as antioxidant, anti-inflammatory, anti-apoptotic, antimicrobial, Estrogen-like, glucose and lipid metabolism modulatory, anticancer, and neuroprotective effects. BIO-A was proven to be promising when investigated in multiple models of neurological diseases such as Alzheimer’s disease and Parkinson’s disease, multiple sclerosis, stroke, brain injury, depression, anxiety, and glioblastoma. This review focuses on the possible molecular mechanisms responsible for the neuroprotective effects of BIO-A in various neurological disorders.
神经系统疾病引起的全球发病率和死亡率很高。随着人口老龄化,神经退行性疾病预计会增加,因为它们通常在中老年出现。世界卫生组织预测,到2050年,60岁或以上的人口将达到20亿。因此,人们对天然来源的神经保护药物的需求日益增加,这些药物具有良好的疗效和较高的安全性。其中一种天然制剂是生物茶素A(BIO-A),一种属于植物雌激素的异黄酮,主要存在于红三叶草、大豆和鹰嘴豆的市售片剂中。它具有广泛的药理作用,如抗氧化、抗炎、抗凋亡、抗菌、雌激素样、糖脂代谢调节、抗癌和神经保护作用。BIO-A在阿尔茨海默病、帕金森病、多发性硬化症、中风、脑损伤、抑郁、焦虑和胶质母细胞瘤等神经系统疾病的多种模型中被证明是有希望的。本文就BIO-A对各种神经系统疾病的神经保护作用可能的分子机制进行综述。
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引用次数: 0
Colistin Pharmacokinetics in Pediatric Cancer Patients in Egypt 埃及儿童癌症患者的粘菌素药代动力学
Pub Date : 2022-12-01 DOI: 10.21608/aps.2022.166621.1099
Yosr Abou Sedira, L. E. El Wakeel, Mervat Mostafa Omran, I. Sidhom, S. Shouman
Colistin has been reintroduced to clinical practice after the emergence of multidrug-resistant gram-negative (MDR-GN) and the failure of other antibiotics. Pharmacokinetics and pharmacodynamic data in the pediatric population are scarce. This study aimed to highlight the pharmacokinetics of 2 colistin doses, 2.5, and 5 mg/kg/day, in febrile neutropenia pediatric cancer patients regarding patient outcomes. In a prospective, comparative study, patients suffering from MDR-GN infection were randomly recruited to receive either 2.5 or 5 mg/kg/day colistin doses. The demographic, microbiological, and treatment outcomes were collected before and after treatment. Colistin levels were determined using HPLC/MS/MS. Peak, trough, area under the concentration-time curve (AUC 24 ), and the ratio of AUC 24 to the minimum inhibitory concentration (AUC 24 /MIC) were assessed. Clinical cure was achieved in 14 (77.8%) cases in the Low-Dose (LD) group vs. 13 (81.3%) in the High-Dose (HD) group. Four (25%) patients vs. 4 (33.3%) in the LD and HD group (P= 0.69) attained an optimal plasma AUC 24 /MIC, respectively, while the therapeutic level of colistin was reached in all patients in the LD group compared to 14/16 (87.5%) in the HD group. Microbiological eradication was achieved in 93.8% and 91.6% of patients in the LD and HD groups, respectively. However, the median time to clearance was significantly lower in the LD group, 4 days vs. 7 days in the HD group (P= 0.022). In conclusion, the current study suggests that LD may be as efficacious and safe as HD in treating MDR-GN infection. However, LD colistin was associated with a shorter clearance time than HD colistin.
在出现耐多药革兰氏阴性菌(MDR-GN)和其他抗生素失效后,粘菌素已重新引入临床实践。儿科人群的药代动力学和药效学数据很少。本研究旨在强调两种剂量(2.5和5mg /kg/天)粘菌素在发热性中性粒细胞减少症儿童癌症患者中的药代动力学对患者预后的影响。在一项前瞻性比较研究中,随机招募耐多药gn感染患者接受2.5或5mg /kg/天的粘菌素剂量。在治疗前后收集人口统计学、微生物学和治疗结果。采用HPLC/MS/MS法测定粘菌素水平。测定其峰、谷、浓度-时间曲线下面积(AUC 24)和AUC 24与最低抑菌浓度(AUC 24 /MIC)之比。低剂量组14例(77.8%)获得临床治愈,高剂量组13例(81.3%)。LD和HD组分别有4例(25%)和4例(33.3%)患者达到最佳血浆AUC 24 /MIC (P= 0.69), LD组所有患者均达到粘菌素治疗水平,而HD组为14/16(87.5%)。LD组和HD组的微生物根除率分别为93.8%和91.6%。然而,LD组的中位清除时间明显较低,为4天,而HD组为7天(P= 0.022)。总之,目前的研究表明,在治疗耐多药gn感染方面,LD可能与HD一样有效和安全。然而,LD粘菌素的清除时间比HD粘菌素短。
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引用次数: 0
Direct Acting Antiviral Drugs: Pharmacokinetics and Drug-Drug Interactions 直接作用抗病毒药物:药物动力学和药物之间的相互作用
Pub Date : 2022-12-01 DOI: 10.21608/aps.2023.189971.1106
Marina Barakat, S. Wahdan, A. Awad, Ebtehal El-Demerdash Zaki
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引用次数: 0
Empirical-colistin inhalation improves ventilatory parameters and severity scoring in VAP caused by Gram-negative bacteria 经验性粘菌素吸入可改善革兰氏阴性菌引起的VAP的通气参数和严重程度评分
Pub Date : 2022-06-01 DOI: 10.21608/aps.2022.130440.1087
Nourhan O. Abu-Thuraya, Lamia Elwakeel, Mohamed O. Elghoemi, Alia Abdelfattah
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引用次数: 0
Optimization of the colloidal properties of chitosan nanoparticles encapsulating alpha-arbutin 壳聚糖纳米粒包封α -熊果苷胶体性能的优化
Pub Date : 2022-06-01 DOI: 10.21608/aps.2022.121464.1081
S. Hatem, Nada ElHoffy, Reham S. Elezaby, M. Nasr, Amany Osama, S. Elkheshen
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引用次数: 1
Biologically Active Saponins of Genus Cestrum L.: A Comprehensive Review 牛蹄草属生物活性皂苷类化合物综述
Pub Date : 2022-06-01 DOI: 10.21608/aps.2022.129734.1085
Dina M. Bahgat, Haidy A. Gad, E. Elsayed, O. Eldahshan, A. Singab
Genus Cestrum L. belonging to family Solanaceae comprises from 250 to 300 species of flowering plants native to warm temperate to tropical regions of America. Shrubs of Cestrum L. species are known as Jessamines due to their highly fragrant flowers. They are planted not only for their ornamental uses but also for their valuable and diverse medicinal effects. In many African, Asian and American countries, folk medicine practitioners used different Cestrum L. species for their important ethno-pharmacological effects and diverse biological properties. In the last decades, fifty-two saponins, mainly of steroidal nucleus, have been isolated form certain Cestrum L. species and are responsible for numerous important biological activities e.g. cytotoxic, spermicidal, anti-microbial and pesticidal activities. In this updated review till 2022, we highlighted the pharmacological importance of those steroidal saponins, their biosynthetic pathway and the relation between the chemical structure and biological activity.
龙葵属属于茄科,由250至300种开花植物组成,原产于美洲暖温带至热带地区。菊花属的灌木因其芳香的花朵而被称为茉莉花。种植它们不仅是为了观赏,还因为它们有价值和多种药用作用。在许多非洲、亚洲和美洲国家,民间医学从业者使用不同的鹿茸属,因为它们具有重要的民族药理作用和不同的生物学特性。在过去的几十年里,从某些鹿茸属植物中分离到52种主要为甾体核的皂苷,它们具有细胞毒、杀精、抗菌和杀虫等重要的生物活性。在这篇更新到2022年的综述中,我们重点介绍了甾体皂苷的药理意义,它们的生物合成途径以及化学结构与生物活性的关系。
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引用次数: 1
HPLC Method for Determination of Chlorhexidine in Pharmaceutical Formulations alone and in presence of Hexamidine and p-chlorocresol, and in Spiked Human Saliva 高效液相色谱法测定药物制剂中单独氯己定、含有氯己定和对氯甲酚以及加标人唾液中氯己定的含量
Pub Date : 2022-06-01 DOI: 10.21608/aps.2022.108801.1075
Ahmed E. Sobaih, Lobna Abd El Aziz, Nancy Nassif
In the current study, a simple, reliable, and quantitative HPLC analytical method was designed to determine Hexamidine Di isethionate (HEX), Chlorhexidine Digluconate (CHX), and p-chlorocresol (CSOL) in various dosage forms including mouthwash and intimate douche in addition to chlorhexidine determination in spiked human saliva. HEX, CHX, and CSOL were determined in colored aqueous formulations without any sample pre-treatment or extraction steps. The proposed method showed linearity over a concentration range of 0.10 to 25.00 µg/mL of pure HEX, 2.00 to 30.00 µg/mL of pure CHX, and 0.10 to 30.00 µg/mL of pure CSOL and a detection limit of 0.02 µg/mL, 0.47 µg/mL & 0.03 µg/mL for HEX, CHX, and CSOL; respectively. The recoveries for Cyteal ® were 100.43 %±1.70, 99.06 %±0.69 & 98.74 %±1.06 for HEX, CHX, and CSOL; respectively, whereas, for Hexitol ® recovery was 100.79 %±1.57 for CHX. Furthermore, the proposed method has been employed to detect CHX in spiked human saliva with a recovery of 101.69%±1.38.
本研究设计了一种简单、可靠、定量的高效液相色谱分析方法,用于测定人唾液中不同剂型(包括漱口水和冲洗液)中的异乙酸己定(HEX)、二光酸氯己定(CHX)和对氯甲酚(CSOL)。HEX, CHX和CSOL在有色水溶液中测定,无需任何样品预处理或提取步骤。该方法在纯HEX、CHX和CSOL的浓度范围分别为0.10 ~ 25.00µg/mL、2.00 ~ 30.00µg/mL和0.10 ~ 30.00µg/mL呈线性关系,HEX、CHX和CSOL的检测限分别为0.02µg/mL、0.47µg/mL和0.03µg/mL;分别。Cyteal®的加样回收率分别为100.43%±1.70、99.06%±0.69、98.74%±1.06;而CHX的Hexitol®回收率为100.79%±1.57。该方法可用于人唾液中CHX的检测,回收率为101.69%±1.38。
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引用次数: 1
Effect of adding exogenous acyl homoserine lactone signal to Pseudomonas aeruginosa premature culture and prediction of signal binding domain in Rhamnolipids RhlA enzyme 添加外源性酰基同丝氨酸内酯信号对铜绿假单胞菌过早培养的影响及鼠李糖脂RhlA酶信号结合域的预测
Pub Date : 2022-06-01 DOI: 10.21608/aps.2022.128953.1084
Masarra M. Sakr, Ghadir S. El-Housseiny, Noha M. Elsayed
The hierarchy of the quorum-sensing system plays a crucial role in Pseudomonas (P.) aeruginosa virulence and the production of important industrial bacterial products like rhamnolipids and proteases. In this study, the effect of adding exogenous acyl-homoserine lactone synthetic signal to the premature culture of P. aeruginosa on the production of protease and rhamnolipids was investigated. At the early exponential phase, induction of rhamnolipid production showed a more rapid response than protease production. Prediction of the 3D structure of the acyltransferase RhlA enzyme, which is the first key enzyme in rhamnolipid synthesis, was then done using the I-Tasser program to investigate the possible protein structure that might influence the response to N-acyl-homoserine lactone (AHL) presence. With a good C-score, 3D modeling showed RhlA to have AHL binding pocket where ten ligand binding site residues were elucidated in the protein. Multiple sequence alignment revealed low homology with LuxR proteins. Although conserved residues were depicted from the alignment, they were different from the ligand-binding residues suggesting that AHL binds to RhlA with a different mechanism than LuxR proteins. After further bioinformatics analysis, we found that RhlA binds to AHL in a mechanism similar to the lactonase enzyme. In conclusion, the in silico domain and protein alignment analysis revealed an AHL binding site in the RhlA enzyme protein structure.
群体感应系统的层次在铜绿假单胞菌的毒力和重要的工业细菌产品如鼠李糖脂和蛋白酶的生产中起着至关重要的作用。本研究研究了在铜绿假单胞菌早培养中添加外源酰基-同丝氨酸内酯合成信号对其蛋白酶和鼠李糖脂产量的影响。在早期指数阶段,诱导鼠李糖脂的产生比蛋白酶的产生反应更快。然后使用I-Tasser程序对鼠李糖脂合成中的第一个关键酶——酰基转移酶RhlA酶的三维结构进行预测,以研究可能影响对n -酰基-高丝氨酸内酯(AHL)存在的反应的可能的蛋白质结构。3D建模显示,具有良好C-score的RhlA具有AHL结合袋,其中在蛋白质中阐明了10个配体结合位点残基。多重序列比对显示与LuxR蛋白同源性较低。虽然从比对中描绘了保守残基,但它们与配体结合残基不同,这表明AHL与RhlA结合的机制与LuxR蛋白不同。经过进一步的生物信息学分析,我们发现RhlA以类似于内酯酶的机制与AHL结合。总之,硅结构域和蛋白质比对分析在RhlA酶的蛋白质结构中发现了AHL结合位点。
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引用次数: 0
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Archives of Pharmaceutical Sciences Ain Shams University
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