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Insights into Novel Drug Targets in Mycobacterium tuberculosis: Where Do We Stand and Where Do We Go from Here? 对结核分枝杆菌新药物靶点的洞察:我们的立场是什么,我们将从这里走向何方?
Pub Date : 2018-09-30 DOI: 10.21608/RPBS.2018.3874.1004
Safaa M Kishk, M. Helal, M. Gomaa, I. Salama, S. Moustafa, C. Simons
Tuberculosis (TB) is the ninth leading cause of death worldwide and the leading cause from a single infectious agent, ranking above HIV/AIDS with 6.3 million new cases of TB reported in 2016. TB is an air-borne disease associated with the aerobic bacterium Mycobacterium tuberculosis (Mtb), which mainly infects the lungs. Aerosolization of diseased pulmonary secretions, by coughing, sneezing and speaking, discharge the Mtb bacilli into the atmosphere. Infected aerosol droplet nuclei sized 1-10 μm are largely trapped in the upper nasal passages or are expelled into the pharynx by the mucociliary mechanism of the lower respiratory tract and are harmlessly swallowed and digested. Infected persons may overcome the initial TB infection, resulting in the development of asymptomatic latent TB. About 10% of individuals may develop the active disease after infection; where the bacteria undergo more rapid growth and overcome the host immune system. In cases of multi-drug resistant (MDR) strains, and extreme drug-resistant (XDR) strains, treatment fails, and the bacteria propagate and attack the host, leading to death from systemic infection. Due to the increased spread of TB worldwide, both the academic and industrial communities have initiated intensive research to develop new therapeutics targeting new enzymes such as cytochrome P450s in Mtb.
结核病是全球第九大死亡原因,也是单一传染病的主要原因,排名高于艾滋病毒/艾滋病,2016年报告了630万新发结核病病例。结核病是一种与需氧细菌结核分枝杆菌(Mtb)有关的空气传播疾病,主要感染肺部。通过咳嗽、打喷嚏和说话使患病的肺部分泌物雾化,将结核分枝杆菌排放到大气中。受感染的粒径为1-10 μm的气溶胶飞沫大部分被困在上鼻道或通过下呼吸道的黏毛机制排入咽部,被无害地吞下和消化。感染者可能克服最初的结核感染,导致发展为无症状潜伏结核。约10%的人感染后可发展为活动性疾病;在那里,细菌会经历更快的生长并克服宿主的免疫系统。在多重耐药(MDR)菌株和极端耐药(XDR)菌株的情况下,治疗失败,细菌繁殖并攻击宿主,导致全身感染死亡。由于结核病在世界范围内的传播增加,学术界和工业界都开始了密集的研究,以开发针对Mtb中细胞色素p450等新酶的新疗法。
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引用次数: 0
The effect of leucine supplementation on the skeletal muscles of streptozotocin (STZ)diabetic rats 补充亮氨酸对链脲佐菌素(STZ)糖尿病大鼠骨骼肌的影响
Pub Date : 2018-09-30 DOI: 10.21608/RPBS.2018.3642.1001
Naglaa K gawada
Skeletal muscle atrophy is one of the serious and less studied diabetic complications.Leucine an essential amino acid that is transported into most mammalian cells by System L. The current study was conducted to assess the effect of leucine on diabetic skeletal muscles. Forty male Wister rats were allocated into four groups; control, Leucine-treated group was subjected to daily oral supplement of Leucine (1.35 g/kg) for 8 weeks, STZ-diabetic group was treated with single intravenous injection of STZ (45 mg/kg) and STZ-diabetic group supplemented with leucine (1.35 g/kg) for 8 weeks. Body weight and histopathological analysis of soleus muscle were evaluated. There was a significant increase in body weight of leucine group at p> 0.05. Leucine supplementation attenuated loss of soleus muscle mass observed in STZ diabetic rats. These findings may suggest protective effect of leucine against diabetic muscle loss.
骨骼肌萎缩是糖尿病严重的并发症之一,但研究较少。亮氨酸是一种必需氨基酸,通过l系统运输到大多数哺乳动物细胞中。目前的研究是为了评估亮氨酸对糖尿病骨骼肌的影响。40只雄性Wister大鼠分为4组;对照组,亮氨酸治疗组每日口服补充亮氨酸(1.35 g/kg) 8周,STZ-糖尿病组单次静脉注射亮氨酸(45 mg/kg), STZ-糖尿病组补充亮氨酸(1.35 g/kg) 8周。评估体重和比目鱼肌的组织病理学分析。亮氨酸组体重显著升高(p> 0.05)。补充亮氨酸可减轻STZ糖尿病大鼠比目鱼肌质量的损失。这些发现可能提示亮氨酸对糖尿病肌肉损失的保护作用。
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引用次数: 0
Phytochemical and Biological Investigation of Narcissus pseudonarcissus Cultivated in Egypt 埃及栽培水仙的植物化学和生物学研究
Pub Date : 2018-09-30 DOI: 10.21608/RPBS.2018.3769.1002
E. Shawky, H. Hammoda, Amina Abou Donia, S. Toaima, Erii Kinoshita, H. Takayama
A phytochemical investigation of the alkaloidal content of the bulbs of Narcissus pseudonarcissus cultivated in Egypt resulted in the isolation of the alkaloid; 9-O-demethyl-7-O-methyllycorenine (5) in addition to the eight known alkaloids; homolycorine (1), 7-O-methyloduline (2), 7-O-methyllycorenine (3), hippeastrine (4), 9-O-demethylhomolycorine (6), galanthamine (7), haemanthamine (8) and lycorine. Structural determination of the isolated alkaloids was established by different spectral analyses (UV, MS, NMR and 2D-NMR). The isolation of 9-O-demethyl-7-O-methyllycorenine (5) is reported here for the first time from family Amaryllidaceae. The chemotaxonomic significance of the isolated alkaloids was also studied; six of the isolated alkaloids belong to the homolycorine series which is a distinctive feature for the section Pseudonarcissi. The alkaloids of the homolycorine series are absent from some tribes of the Amaryllidaceae, such as the Amaryllideae or Hemantheae. Moreover, all the Narcissus alkaloids of the homolycorine series display a B/C ring junction with a cis stereochemistry Furthermore, the antimicrobial activity of some isolated alkaloids has been studied. It is noteworthy that this is the first phytochemical and biological investigation to be carried out on the Amaryllidaceae plant N. pseudonarcissus grown in Egypt.
在埃及栽培的水仙(Narcissus pseudonarcissus)球茎中进行了生物碱含量的植物化学研究,分离出了其中的生物碱;9- o -去甲基-7- o -甲基番茄碱(5)以及八种已知生物碱;同质多碱(1)、7- o -甲基多碱(2)、7- o -甲基蕃茄碱(3)、海马碱(4)、9- o -去甲基同质多碱(6)、加兰他敏(7)、海毒胺(8)和石蒜碱。采用紫外、质谱、核磁共振和二维核磁共振等不同光谱分析方法对分离得到的生物碱进行了结构鉴定。9-O-demethyl-7-O-methyllycorenine(5)是首次从Amaryllidaceae中分离得到。对分离得到的生物碱的化学分类意义进行了研究;6个分离的生物碱属于同质多碱系列,这是Pseudonarcissi剖面的一个显著特征。同绿碱系列的生物碱在菊科的一些部落,如菊科或Hemantheae中不存在。水仙碱系列生物碱均呈B/C环结,具有顺式立体化学结构。此外,对部分分离生物碱的抑菌活性进行了研究。值得注意的是,这是首次对生长在埃及的amaryllidiaceae植物N. pseudonarcissus进行植物化学和生物学研究。
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引用次数: 6
Spectrophotometric method for determination of Glucosamine Sulphate in dosage forms by derivatization using Quality by Design approach 用设计质量法衍生化分光光度法测定剂型中硫酸氨基葡萄糖的含量
Pub Date : 2018-09-30 DOI: 10.21608/RPBS.2018.4273.1006
Rasha M. Ahmed, Ghada M. Hadad, A. El-Gendy, A. Ashour
A Quality by Design approach was used to develop a sensitive spectrophotometric method for determination of glucosamine Sulphate in pharmaceutical dosage forms and optimize a derivatization reaction of glucosamine with o-phthalaldhyde. This strategy was focused on derivatization process understanding and analytical method development and validation. Both of them were evaluated by applying risk assessment and Design Space tools. The scouting step was carried out by analyzing different derivatizing agents, type of buffers, pH of buffers, and time of reaction. Five critical process parameters (CPPs) were selected related to, pH of borate buffer, volume of 2-mercaptoethanol (ME), volume of o-phthalaldhyde (OPA), and the time of reaction. The effect of different levels of CPPs on critical quality attributes (CQAs) (the absorbance of derivative) was evaluated in the screening design using fractional factorial design. Using response surface methodology and contour plots the optimum values of the selected factors were determined and the design space of the method was defined. Finally, control strategy was designed and the method was validated and applied to a real sample of glucosamine dosage forms using the optimum derivatization conditions of the reaction; pH of borate buffer 10.5, concentration of buffer 0.05M, Time of reaction 10.7 minutes, volume of ME 100μL, and volume of OPA 5.1mL at room temperature. The results of the present study clearly shown that the developed method was sensitive relative to the other published spectrophotometric and HPLC methods with identification of the most significant factors affecting the derivatization reaction.
采用质量设计法建立了一种灵敏的分光光度法测定药品剂型中硫酸氨基葡萄糖的含量,并对氨基葡萄糖与邻苯二醛的衍生化反应进行了优化。该策略侧重于衍生化过程的理解和分析方法的开发和验证。两者都通过应用风险评估和设计空间工具进行评估。通过分析不同衍生化剂、缓冲液的种类、缓冲液的pH和反应时间,进行了寻找步骤。选择了与硼酸缓冲液pH、2-巯基乙醇(ME)体积、邻苯二醛(OPA)体积、反应时间有关的5个关键工艺参数。在筛选设计中,使用分数因子设计评估不同水平的CPPs对关键质量属性(CQAs)(衍生物吸光度)的影响。采用响应面法和等高线法确定了各因素的最优值,确定了该方法的设计空间。最后,设计了控制策略,并对该方法进行了验证,并应用于葡萄糖胺剂型的实际样品,确定了反应的最佳衍生化条件;硼酸盐缓冲液pH为10.5,缓冲液浓度为0.05M,反应时间为10.7 min,室温下,ME体积为100μL, OPA体积为5.1mL。本研究的结果清楚地表明,相对于其他已发表的分光光度法和高效液相色谱法,所建立的方法是敏感的,并确定了影响衍生化反应的最重要因素。
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引用次数: 1
Effect of Exogenous Anabolic Androgenic Steroids on Testosterone Epitestosterone Ratio and its Application on Athlete Biological Passport in Egypt 外源性合成代谢雄激素类固醇对睾酮表睾酮比率的影响及其在埃及运动员生物护照上的应用
Pub Date : 2018-09-01 DOI: 10.21608/RPBS.2018.5337.1013
hanim ameer, D. Abo-Elmatty, R. Alemany, N. Mesbah
The use of Anabolic Androgenic Steroid agents is evident within the competitive sport in senior and junior age groups, where they are taken by non-elite as well as elite participants. They are also taken in non-sporting contexts by individuals seeking to ‘improve’ their physique through an increase in muscle and/or decrease in fat mass. No accurate data is available for the prevalence of anabolic steroid misuse among athletes, studies suggest the illicit use of doping agents by athletes and non-athletes may be 1–5% in the population and greater than 50% in some groups; with the prevalence being higher in males. Many studies documented side effects and health hazards with the misusing of anabolic steroids, where these were accused as a cause of deaths among athletes. Intake of exogenous anabolic steroids disturbed the T/E ratio causing its evaluation above the normal level. This review will outline the anabolic steroids, its side effects and health impacts in both the sporting and physique development contexts. It also provides a brief review of the history of AAS as doping agents and athlete biological passport.
在高级和初级年龄组的竞技体育中,合成代谢雄激素类固醇药物的使用是显而易见的,非精英和精英参与者都服用。在非运动环境中,那些寻求通过增加肌肉和/或减少脂肪量来“改善”体质的人也会服用这种药物。运动员滥用合成代谢类固醇的发生率尚无准确数据,但研究表明,运动员和非运动员非法使用兴奋剂的比例可能在总人口中占1-5%,在某些群体中超过50%;男性患病率更高。许多研究记录了滥用合成代谢类固醇的副作用和健康危害,这些被指控是运动员死亡的原因之一。外源性合成代谢类固醇的摄入扰乱了T/E比,导致其评估高于正常水平。这篇综述将概述合成代谢类固醇,其副作用和健康的影响,在运动和体质发展的背景下。简要回顾了AAS作为兴奋剂和运动员生物护照的历史。
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引用次数: 1
HPLC determination of Metronidazole in pure form, pharmaceutical dosage form and spiked urine. 高效液相色谱法测定甲硝唑纯品、制剂剂型及加药后尿液的含量。
Pub Date : 2018-09-01 DOI: 10.21608/RPBS.2018.6184.1017
K. Afify, Randa A. Abdel-Salam, Ghada M. Hadad
A new HPLC method for the determination of Metronidazole was established. The determination was performed by using a Kinetex C18 analytical column with a gradient mobile phase system consisting of 0.05M KH₂PO4 (pH 3.5), pH adjusted with ortho phosphoric acid (mobile phase A) and Acetonitrile (mobile phase B). The flow rate was 1ml/min. and quantitation was achieved with UV detection at 230 nm, based on peak area. The retention time obtained was 5.35 ± 0.004 and the method was validated according to ICH guidelines regarding linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, robustness, and selectivity. Excellent linearity was observed for the calibration curve with an excellent correlation coefficient 0.9999. Limit of detection was 0.78 μg mL−1; limit of quantitation 2.37 μg mL−1. The developed method was found to be accurate and sensitive and is ideally suited for analysis of MTZ in pure form, pharmaceutical dosage form and spiked urine samples.
建立了测定甲硝唑含量的高效液相色谱法。色谱柱为Kinetex C18,梯度流动相为0.05M KH₂PO4 (pH为3.5),以邻位磷酸(流动相a)和乙腈(流动相B)调节pH,流速为1ml/min。根据峰面积,在230 nm处进行紫外检测定量。获得的保留时间为5.35±0.004,并根据ICH指南对该方法进行了线性、检出限(LOD)、定量限(LOQ)、精密度、准确度、鲁棒性和选择性等方面的验证。线性良好,相关系数为0.9999。检出限为0.78 μg mL−1;定量限2.37 μ mL−1。结果表明,该方法准确、灵敏,适用于纯MTZ、药物剂型和加标尿样的分析。
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引用次数: 1
A Brief review of Circulating MicroRNAs and Essential Hypertension 循环microrna与原发性高血压的研究综述
Pub Date : 2018-09-01 DOI: 10.21608/RPBS.2018.5986.1016
Heba K. Badawy, Noha Mesbah, D. Abo-Elmatty
Essential hypertension is a chronic medical condition affecting thousands of people worldwide. It is polygenic and multi-factorial disease resulting from the interaction between genetic and environmental factors. Essential hypertension is implicated in cerebrovascular, cardiovascular and renal diseases. MicroRNAs are considered endogenous, non-coding regulators of gene expression by targeting specific mRNAs for degradation and/ or translational repression. MicroRNAs participate in a variety of developmental processes as metabolism, cell proliferation, and apoptosis. Many studies have reported the possibility of using miRNAs as new biological markers for polygenic diseases as cancer, stem cell aging, coronary heart disease, and essential hypertension. The stability of these miRNAs as miRNA let-7e, miRNA 296-5p, miRNA 605, and miRNA 623 in biological fluids makes them amenable to detection and quantification. This review summarizes the mechanisms by which miRNAs can control normal cellular processes and gene expression and the association of some circulating miRNAs with the incidence of different diseases, particularly essential hypertension.
原发性高血压是一种影响全世界成千上万人的慢性疾病。它是遗传因素和环境因素相互作用的多基因、多因素疾病。原发性高血压与脑血管、心血管和肾脏疾病有关。MicroRNAs被认为是内源性的非编码基因表达调节剂,通过靶向特定mrna进行降解和/或翻译抑制。microrna参与多种发育过程,如代谢、细胞增殖和细胞凋亡。许多研究报道了使用mirna作为癌症、干细胞老化、冠心病和原发性高血压等多基因疾病的新生物标志物的可能性。这些miRNA如miRNA let-7e、miRNA 296-5p、miRNA 605和miRNA 623在生物体液中的稳定性使它们易于检测和定量。本文综述了mirna控制正常细胞过程和基因表达的机制,以及一些循环mirna与不同疾病,特别是原发性高血压发病率的关系。
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引用次数: 1
Recent Analytical Approaches in Quality Control of Cannabis sativa L. and Its Preparations 大麻及其制剂质量控制的最新分析方法
Pub Date : 2018-09-01 DOI: 10.21608/RPBS.2018.5518.1014
E. Ibrahim, Ghada M. Hadad, R. A. Salam, A. Ibrahim, Safwat Ahmed, M. Radwan, W. Gul, M. Elsohly
Cannabis sativa L. is annually herbal plant belonging to the family Cannabaceae gaining more and more attention all over the world, due to its long historical clinical practice and its recent legalization either for recreational or medicinal uses. The quality control of the plant is a critical for its legalization and globalization. This review deals with the recent analytical methods (years 2015-2018) in the quality control of Cannabis, including the traditional chromatographic methods like HPLC, LC/MS/MS, UPLC, GC/FID, and GC/MS; and spectrophotometric, including FT-IR, NIR and NMR techniques as well as the most recent advanced techniques. The comprehensive methods, such as fingerprint and multi-component quantification are emphasized; hyphenated techniques, like HPLC, LC/MS/MS, GC/FID, GC-MS, LC-NMR, chemometric methods. In few words, the analysis and quality control of cannabis biomass, extracts and/or preparations is moving towards an integrative and comprehensive direction, in order to better address the inherent holistic nature of cannabis.
大麻是一种一年一度的草本植物,属于大麻科,由于其悠久的历史临床实践和最近的合法化,无论是娱乐还是药用,它在世界各地越来越受到关注。大麻的质量控制是大麻合法化和全球化的关键。综述了大麻质量控制的最新分析方法(2015-2018年),包括HPLC、LC/MS/MS、UPLC、GC/FID、GC/MS等传统色谱方法;以及分光光度法,包括FT-IR, NIR和NMR技术以及最新的先进技术。重点介绍了指纹图谱、多组分定量等综合方法;联用技术,如HPLC, LC/MS/MS, GC/FID, GC-MS, LC- nmr,化学计量方法。简而言之,大麻生物量、提取物和/或制剂的分析和质量控制正朝着综合和全面的方向发展,以便更好地处理大麻固有的整体性。
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引用次数: 2
Synthesis and Antimicrobial Evaluation of Novel Hydrazones and 1,3,4-Oxadiazoles Incorporating Bumetanide Derivatives 含布美他胺衍生物的新型腙和1,3,4-恶二唑的合成及抗菌评价
Pub Date : 2018-09-01 DOI: 10.21608/RPBS.2018.23373
I. Salem, S. Mostafa, Osama I. El-Sabbag, T. Ibrahim, Ahmed Abdulrahmanf, M. M. Bendary
The aim of this study is to synthesize new benzenesulfonamide derivatives that possess antibacterial activity using Bumetanide as a precursor of benzenesulfonamide. A novel series of hydrazones containing benzenesulfonamides (4a-i) and 1,3,4 oxadiazole containing benzenesulfonamides (5a-e) were prepared and their antibacterial and antifungal activities were measured using microplate broth assay against Gram-positive: Staphylococcus aureus, Gram-negative: Escherichia coli and Pseudomonas aeruginosa and Fungi: Aspergillus fumigates and Candida albicans. The results showed that some of the prepared compounds exhibit a good to excellent activity against the mentioned bacteria, however all the series showed no activity against fungi. Among the series, Compound (4i) demoed an excellent antibacterial activity better than that of the standard reference (Sulfamethoxazole) against Escherichia coli, while compounds (4c, 4e, 4g) showed good activity against all tested bacterial strains equals to Sulfamethoxazole activity. Moreover, compounds (4g, 5d) exert an antimicrobial activity equals to that of Sulfamethoxazole against Pseudomonas aeruginosa, while compounds (4a, 4b, 4c, 4f, 4g, 4h) exhibit similar activity to Sulfamethoxazole against Escherichia coli.
本研究的目的是利用布美他尼作为苯磺酰胺的前体合成具有抗菌活性的苯磺酰胺衍生物。制备了一系列新的含苯磺酰胺(4a-i)和含1,3,4恶二唑(5a-e)的苯磺酰胺腙,并采用微孔板培养液法测定了它们对革兰氏阳性菌金黄色葡萄球菌、革兰氏阴性菌大肠杆菌和铜绿假单胞菌以及真菌:烟熏曲霉和白色念珠菌的抑菌活性。结果表明,部分化合物对上述细菌具有较好的活性,但对真菌均无活性。其中化合物(4i)对大肠杆菌的抑菌活性优于标准参比物(磺胺甲恶唑),化合物(4c、4e、4g)对所有被试菌株的抑菌活性与磺胺甲恶唑的抑菌活性相当。此外,化合物(4g, 5d)对铜绿假单胞菌的抑菌活性与磺胺甲恶唑相当,而化合物(4a, 4b, 4c, 4f, 4g, 4h)对大肠杆菌的抑菌活性与磺胺甲恶唑相似。
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引用次数: 1
Review article on nanoemulsions and nanostructured lipid carriers 纳米乳剂和纳米结构脂质载体的研究进展
Pub Date : 2018-09-01 DOI: 10.21608/rpbs.2018.5223.1011
Samar H. Faheim, A. Gardouh, A. Nouh, M. Ghorab
{"title":"Review article on nanoemulsions and nanostructured lipid carriers","authors":"Samar H. Faheim, A. Gardouh, A. Nouh, M. Ghorab","doi":"10.21608/rpbs.2018.5223.1011","DOIUrl":"https://doi.org/10.21608/rpbs.2018.5223.1011","url":null,"abstract":"","PeriodicalId":21118,"journal":{"name":"Records of Pharmaceutical and Biomedical Sciences","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84351024","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: 2
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