Vidarabine

Polypropylene (PP) surgical mesh had reasonable success in repair of hernia and treatment of stress urinary incontinence (SUI); however, their use for the repair of pelvic organ prolapse (POP) resulted in highly variable results with lifelong complications in some patients. One of several factors that could be associated with mesh-related POP complications is changes in the properties of the implanted surgical mesh due to oxidative degradation of PP in vivo. Currently, there are no standardized in vitro bench testing methods available for assessing the susceptibility to oxidative degradation and estimating long-term in vivo stability of surgical mesh. In this work, we adapted a previously reported automated reactive accelerated aging (aRAA) system, which uses elevated temperatures and high concentrations of hydrogen peroxide (H₂ O₂ ), for accelerated bench-top oxidative degradation testing of PP surgical mesh. Since H₂ O₂ is highly unstable at elevated temperatures and for prolonged periods, the aRAA system involves a feedback loop based on electrochemical detection methods to maintain consistent H₂ O₂ concentration in test solutions. Four PP mesh samples with varying mesh knit designs, filament diameter, weight, and % porosity, were selected for testing using aRAA up to 4 weeks and characterized using thermal analysis, Fourier-transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) and scanning electron microscopy (SEM). Additionally, the oxidation index (OI) values were calculated based on the FTIR-ATR spectra to estimate the oxidative degradation and oxidation reaction kinetics of PP surgical mesh. The OI values and surface damage in the form of surface flaking, peeling, and formation of transverse cracks increased with aRAA aging time. The aRAA test method introduced here could be used to standardize the assessment of long-term stability of surgical mesh and may also be adopted for accelerated oxidative degradation testing of other polymer-based medical devices.

Nucleoside analogs have been widely used as antiviral, antitumor, and antiparasitic agents due to their ability to inhibit nucleic acid synthesis. Adenosine, cytidine, guanosine, thymidine and uridine analogs such as didanosine, vidarabine, remdesivir, gemcitabine, lamivudine, acyclovir, abacavir, zidovusine, stavudine, and idoxuridine showed remarkable anticancer and antiviral activities. In our previously published articles, our main intention was to develop newer generation nucleoside analogs with acylation-induced modification of the hydroxyl group and showcase their biological potencies. In the process of developing nucleoside analogs, in silico studies play an important role and provide a scientific background for biological data. Molecular interactions between drugs and receptors followed by assessment of their stability in physiological environments, help to optimize the drug development process and minimize the burden of unwanted synthesis. Computational approaches, such as DFT, FMO, MEP, ADMET prediction, PASS prediction, POM analysis, molecular docking, and molecular dynamics simulation, are the most popular tools to culminate all preclinical study data and deliver a molecule with maximum bioactivity and minimum toxicity. Although clinical drug trials are crucial for providing dosage recommendations, they can only indirectly provide mechanistic information through researchers for pathological, physiological, and pharmacological determinants. As a result, in silico approaches are increasingly used in drug discovery and development to provide mechanistic information of clinical value. This article portrays the current status of these methods and highlights some remarkable contributions to the development of nucleoside analogs with optimized bioactivity.