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Recent advances in anti-infective drug discovery最新文献

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Treatment of Chronic Hepatitis C Virus Using Direct Acting Antivirals in Geriatric Egyptian Patients. 使用直接作用抗病毒药物治疗老年埃及患者慢性丙型肝炎病毒
Pub Date : 2021-01-01 DOI: 10.2174/2772434416666210716123909
Mahmoud Elkadeem, Shoman Rabeei Shoman

Background & aims: There is high proportion of geriatric patients who acquired chronic hepatitis C virus infection. There is a shortage in evidence- based data as regards direct-acting antivirals in this group of patients. The aim was to assess safety, efficacy, and tolerability of direct acting antiviral drugs in Egyptian geriatric patients.

Methods: This prospective study was performed on 177 patients with chronic hepatitis C and administrated different regimens of direct acting antivirals. Patients were divided into two groups: Group I: patients below 65 years old (N = 143), and Group II: patients > 65 years old (N = 34). Pretreatment history taking, baseline characteristics, and investigations were done for both groups. Follow up was made to detect treatment efficacy and adverse effects.

Results: Geriatric group were found to have more comorbidities (diabetes mellitus, hypertension, and cardiomyopathy); also liver cirrhosis. Minor adverse effects occurred in both groups without significant difference included fatigue, insomnia, headache, and dizziness. Vomiting, diarrhea, and skin rash occurred in group II more than group I. Leucopenia, thrombocytopenia, jaundice, and significant anemia occurred without significant difference between both groups. Eighteen patients (25%) of 72 patients who took ribavirin had to reduce ribavirin dose or to stop it. The overall treatment response in the entire study was 97.7% without significant difference between both groups.

Conclusion: Direct acting antivirals are recommended regardless the age. These drugs are effective and tolerable in elderly patients. Attention to other comorbidities, drug-drug interactions, and follow up are recommended.

背景与目的:获得性慢性丙型肝炎病毒感染的老年患者比例较高。在这组患者中直接作用的抗病毒药物方面,缺乏基于证据的数据。目的是评估埃及老年患者直接作用抗病毒药物的安全性、有效性和耐受性。方法:对177例慢性丙型肝炎患者进行前瞻性研究,并给予不同的直接作用抗病毒药物方案。患者分为两组:I组:65岁以下患者(N = 143), II组:> 65岁患者(N = 34)。两组均进行了预处理病史、基线特征和调查。随访观察治疗效果及不良反应。结果:老年组有更多的合并症(糖尿病、高血压、心肌病);还有肝硬化。两组的轻微不良反应包括疲劳、失眠、头痛和头晕,但无显著差异。II组呕吐、腹泻、皮疹发生率高于i组。两组间白细胞减少、血小板减少、黄疸、明显贫血发生率无显著差异。72例服用利巴韦林的患者中有18例(25%)不得不减少利巴韦林剂量或停用利巴韦林。整体治疗有效率为97.7%,两组间无显著差异。结论:不论年龄,均推荐使用直接抗病毒药物。这些药物对老年患者有效且耐受性好。建议注意其他合并症、药物-药物相互作用和随访。
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引用次数: 0
Taming the Storm in the Heart: Exploring Different Therapeutic Choices Against Myocardial Inflammation in COVID-19. 驯服心中的风暴:探索COVID-19心肌炎症的不同治疗选择。
Pub Date : 2021-01-01 DOI: 10.2174/2772434416666210616124505
Abhigyan Choudhury, Suprabhat Mukherjee

Mechanism of cardiac injury in COVID-19 is a serious problem and plays critical role in mediating the severity of the disease. However, the mechanistic insights of the induction of the inflammatory signal leading to cardiac injury was poorly understood. However, few recent studies have indicated the involvement of Toll-Like Receptors (TLRs) as the major 'culprit' behind eliciting the initial signal of 'cytokine storm'. As a result, TLRs are now considered as the therapeutic targets to develop efficacious therapeutics. Herein, we present an overall summary on the mechanistic insight of cardiac injury in COVID-19 patients and the therapeutic promises of TLR-targeted therapies.

COVID-19心脏损伤机制是一个严重的问题,在疾病的严重程度中起着关键作用。然而,诱导炎症信号导致心脏损伤的机制尚不清楚。然而,最近很少有研究表明toll样受体(TLRs)是引发“细胞因子风暴”初始信号的主要“罪魁祸首”。因此,tlr现在被认为是开发有效疗法的治疗靶点。在此,我们对COVID-19患者心脏损伤的机制以及tlr靶向治疗的治疗前景进行了全面总结。
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引用次数: 2
Investigating The Retention Potential of Chitosan Nanoparticulate Gel: Design, Development, In Vitro & Ex Vivo Characterization 壳聚糖纳米凝胶保留电位的研究:设计、开发、体外和离体表征
Pub Date : 2020-11-26 DOI: 10.2174/1574891X14666191014141558
Shreya Kaul, N. Jain, J. Pandey, Upendra Nagaich
Introduction The main purpose of the research was to develop, optimize and characterize tobramycin sulphate loaded chitosan nanoparticles based gel in order to ameliorate its therapeutic efficacy, precorneal residence time, stability, targeting and to provide controlled release of the drug. Methods Box-Behnken design was used to optimize formulation by 3-factors (chitosan, STPP and tween 80) and 3-levels. Developed formulation was subjected for characterizations such as shape and surface morphology, zeta potential, particle size, in vitro drug release studies, entrapment efficiency of drug, visual inspection, pH, viscosity, spreadability, drug content, ex vivo transcorneal permeation studies, ocular tolerance test, antimicrobial studies, isotonicity evaluation and histopathology studies. Results Based on the evaluation parameters, the optimized formulation showed a particle size of 43.85 ± 0.86 nm and entrapment efficiency 91.56% ± 1.04, PDI 0.254. Cumulative in vitro drug release was up to 92.21% ± 1.71 for 12 hours and drug content was found between 95.36% ± 1.25 to 98.8% ± 1.34. TEM analysis unfolded spherical shape of nanoparticles. TS loaded nanoparticulate gel exhibited significantly higher transcorneal permeation as well as bioadhesion when compared with marketed formulation. Ocular tolerance was evaluated by HET-CAM test and formulation was non-irritant and well-tolerated. Histopathology studies revealed that there was no evidence of damage to the normal structure of the goat cornea. As per ICH guidelines, stability studies were conducted and were subjected for 6 months. Conclusion Results revealed that the developed formulation could be an ideal substitute for conventional eye drops for the treatment of bacterial keratitis.
本研究的主要目的是开发、优化和表征硫酸妥布霉素负载壳聚糖纳米颗粒凝胶,以改善其治疗效果、角膜前停留时间、稳定性、靶向性和药物控释。方法采用Box-Behnken设计,通过3因素(壳聚糖、STPP、tween 80) 3个水平对配方进行优化。对开发的制剂进行表征,如形状和表面形貌、zeta电位、粒径、体外药物释放研究、药物包封效率、目测、pH、粘度、涂敷性、药物含量、体外经角膜渗透研究、眼耐受性试验、抗菌研究、等渗性评价和组织病理学研究。结果优化后的配方粒径为43.85±0.86 nm,包封效率为91.56%±1.04,PDI为0.254。12 h体外累积释药量为92.21%±1.71,药物含量为95.36%±1.25 ~ 98.8%±1.34。透射电镜分析显示纳米颗粒呈球形。与市场上销售的制剂相比,负载TS的纳米凝胶表现出更高的经角膜渗透和生物粘附性。通过ht - cam试验评估眼耐受性,配方无刺激性且耐受性良好。组织病理学研究显示,没有证据表明山羊角膜的正常结构受到损害。根据ICH指南,进行了为期6个月的稳定性研究。结论该制剂可作为常规滴眼液治疗细菌性角膜炎的理想替代品。
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引用次数: 4
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Recent advances in anti-infective drug discovery
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