Antimetabolite

反代谢物
  • 文章类型: Journal Article
    硫唑嘌呤(AZA)在人类医学中的使用可以追溯到1975年进行的研究,该研究导致了几种药物的开发。包括6-巯基嘌呤。1958年,研究表明6-巯基嘌呤减少了针对早期施用抗原的抗体的产生,提出免疫调节作用的假设。AZA是属于表现为嘌呤类似物的药物的硫嘌呤组的前药。吸收后,它被转化为6-巯基嘌呤。随后,它可以通过各种酶途径降解成非活性化合物和与作用机理相关的生物活性化合物,这一直是评估可能的抗病毒作用的研究主题。这项研究旨在检查新陈代谢,作用机制,以及AZA及其衍生物的抗病毒潜力,通过叙述性文献综述探讨AZA对抗病毒靶点和不良反应的影响。最终,该审查将提供对抗病毒机制的见解,目前的证据表明其在体外对各种DNA和RNA病毒的有效性,并建议在体内研究,以进一步证明其抗病毒作用。
    The use of azathioprine (AZA) in human medicine dates back to research conducted in 1975 that led to the development of several drugs, including 6-mercaptopurine. In 1958, it was shown that 6-mercaptopurine decreased the production of antibodies against earlier administered antigens, raising the hypothesis of an immunomodulatory effect. AZA is a prodrug that belongs to the thiopurine group of drugs that behave as purine analogs. After absorption, it is converted into 6-mercaptopurine. Subsequently, it can be degraded through various enzymatic pathways into inactive compounds and biologically active compounds related to the mechanism of action, which has been the subject of study to evaluate a possible antiviral effect. This study aims to examine the metabolism, mechanism of action, and antiviral potential of AZA and its derivatives, exploring AZA impact on antiviral targets and adverse effects through a narrative literature review. Ultimately, the review will provide insights into the antiviral mechanism, present evidence of its in vitro effectiveness against various DNA and RNA viruses, and suggest in vivo studies to further demonstrate its antiviral effects.
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  • 文章类型: Systematic Review
    翼状胬肉是一种与紫外线有关的疾病,其特征是异常,翼形和活跃的伤口愈合过程。对于外科医生或患者来说,没有什么比翼状胬肉的复发更令人沮丧的了,并且已经研究了各种佐剂来改善这种情况。本系统综述全面总结了5-氟尿嘧啶(5-FU)作为翼状胬肉治疗的抗代谢药的有效性和安全性。对六个数据库的电子搜索进行评估,确定了34项临床研究,这些研究报告了原发性5-FU使用的复发结果,即将复发和复发性翼状胬肉。5-FU的体外和体内研究显示了人细胞中剂量和持续时间依赖性的细胞抑制作用和细胞毒性作用。5-FU相对便宜,可用,易于管理,使其对资源有限的场景具有吸引力。然而,发表的证据表明,裸露巩膜技术的复发率为11.4-60%,结膜旋转瓣3.5-35.8%,3.7-9.6%的结膜自体移植物用于术中局部5-FU,术前和术中注射14-35.8%。这种欠佳的疗效使5-FU作为翼状胬肉手术的佐剂的作用受到质疑,作者不建议使用它。相比之下,术后病灶内注射5-FU以阻止即将复发的翼状胬肉和真正复发的翼状胬肉的进展更有希望,成功率为87.2-100%和75-100%,分别。此外,5-FU作为一种治疗方式,没有手术,有效阻止81.3-96%的原发性和复发性翼状胬肉的进展。其他治疗,如局部和病灶内皮质类固醇,讨论了环孢菌素和抗VEGF药物。5-FU的并发症随着剂量的增加而增加,范围从短暂和可逆到严重和威胁视力。对于翼状胬肉,5-FU有导致巩膜变薄的倾向,角膜毒性,和移植物相关并发症。需要进行额外的随访研究以阐明最佳剂量,频率,持续时间,和5-FU注射的长期安全性。如果在翼状胬肉的管理中使用5-FU,应该小心,在选定的患者和警惕的长期监测。
    Pterygium is an ultraviolet-related disease characterized by an aberrant, wing-shaped and active wound-healing process. There is nothing quite as disheartening for the surgeon or patient as the recurrence of pterygium, and various adjuvants have been studied to ameliorate this. This systematic review provides a comprehensive summary of the efficacy and safety of 5-Fluorouracil (5-FU) as an antimetabolite agent for pterygium management. An appraisal of electronic searches of six databases identified 34 clinical studies reporting recurrence outcomes of 5-FU use in primary, impending recurrent and recurrent pterygia. In vitro and in vivo studies of 5-FU showed dose- and duration-dependent cytostatic and cytotoxic effects in human cells. 5-FU is relatively inexpensive, available, and easy to administer, making it attractive for resource-limited scenarios. However, the published evidence demonstrates a recurrence rate of 11.4-60% with the bare scleral technique, 3.5-35.8% with conjunctival rotational flaps, 3.7-9.6% with conjunctival autografts for intraoperative topical 5-FU, and 14-35.8% for preoperative and intraoperative injections. This suboptimal efficacy brings the role of 5-FU as an adjuvant for pterygium surgery into question and the authors do not recommend its use. In contrast, postoperative intralesional injections of 5-FU to arrest progression in impending recurrent pterygium and true recurrent pterygia were more promising, with success rates of 87.2-100% and 75-100%, respectively. Furthermore, 5-FU as a treatment modality, without surgery, effectively arrested progression in 81.3-96% of primary and recurrent pterygia. Other treatments such as topical and intralesional corticosteroids, cyclosporine and anti-VEGF agents are discussed. Complications of 5-FU increase with higher doses and range from transient and reversible to severe and sight-threatening. For pterygium, 5-FU has a predilection for causing scleral thinning, corneal toxicity, and graft-related complications. Additional study with extended follow-up is needed to elucidate the optimal dose, frequency, duration, and long-term safety of 5-FU injections. If 5-FU is used in the management of pterygium, it should be with caution, in selected patients and with vigilant long-term monitoring.
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  • 文章类型: Journal Article
    BACKGROUND: 5-Fluorouracil (5-FU) is an antimetabolite chemotherapy used for a variety of solid tumors. It has the potential to cause a wide spectrum of cardiotoxicity, ranging from asymptomatic electrocardiographic changes to cardiomyopathy and subsequent cardiac failure. Main body of the abstract: We present two descriptive cases of new-onset severe cardiomyopathy induced by 5-FU followed by a review of the literature.
    CONCLUSIONS: Our case series emphasizes the importance of early recognition of this rare complication and prompt cessation of 5-FU, as cardiac dysfunction in this context is potentially reversible.
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  • 文章类型: Journal Article
    Hydroxyurea (HU) is being used for patients with transfusion-dependent β-thalassemia major (β-TM) as well as non transfusion-dependent β-TM. As controversy exists regarding efficacy and safety of HU, we searched the published literature on efficacy, effectiveness and toxicity of HU in patients with β-TM. The research sources we used were: Medline, SID, PubMed, Scopus, Request, Web of Knowledge, Springer, Ovid, Cochrane searched up to October 2012. Using search terms sensitive to studies of clinical trials combined with searches on terms related to thalassemia and HU. We selected studies on randomized trials, quasi experimental trials (before and after design), case reports (with 1-5 cases), side effect studies in patients with β-TM, studies related to the mechanism of action and toxicity when used in patients with other hemoglobinopathies. We researched studies in English and Persian. Eligible articles were reviewed by two independent reviewers. Patient\'s characteristics, duration of trial, outcome and side effects were extracted. The main outcomes were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic, Tau(2) and I(2). Subgroup analyses were performed and the statistics data (STATA) software used. More than 500 articles were reviewed. No randomized clinical trial was found. Seventeen trials with before and after designs were found, 16 case reports (1-5 cases), 19 articles for mechanism of action and 16 studies for side effects were published from 1969 to October 2012. Hemoglobin levels after treatment showed modest but significant increase in non transfusion-dependent β-TM (p < 0.0001) and in transfusion-dependent β-TM (p < 0.0001).
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