ACV

Suicide gene therapy using herpes simplex virus-thymidine kinase (HSV-TK)/ganciclovir (GCV), has been extensively tested for the treatment of glioma. Our previous study showed that exogenous wild type p53 (wt-p53) enhanced the anti-tumor effect of HSV-TK/GCV therapy. However, the use of GCV is hindered by its low penetration to the brain and its toxicity when used at higher dose. In the present study, we used another pro-drug, acyclovir (ACV), and examined the therapeutic efficacy of HSV-TK/ACV combining with wt-p53 in C6 glioma cells. We observed that wt-p53 combined with HSV-TK/ACV resulted in the super-additive anti-tumor effect in vitro. Exogenous wt-p53 significantly enhanced the sensitivity of TK positive C6 cells to ACV in vitro. Our in vivo experiment demonstrated that the effect of wt-p53 and HSV-TK/ACV combination therapy was better than that of HSV-TK/ACV alone. The survival time of tumor-bearing rats treated with wt-p53 in combination with HSV-TK/ACV was also significantly prolonged than those treated with HSV-TK/ACV alone. These results suggest that wt-p53 can enhance the therapeutic efficacy of HSV-TK/ACV both in vitro and in vivo. These findings are considerably valuable with the respect of using less toxic ACV as prodrug. This novel strategy could provide benefit to HSV-TK/prodrug gene therapy.

Acyclovir (ACV) is an effective and selective antiviral drug, and the study of its toxicology and the use of appropriate detection techniques to control its toxicity at safe levels are extremely important for medicine efforts and human health. This review discusses the mechanism driving ACV's ability to inhibit viral coding, starting from its development and pharmacology. A comprehensive summary of the existing preparation methods and synthetic materials, such as 5-aminoimidazole-4-carboxamide, guanine and its derivatives, and other purine derivatives, is presented to elucidate the preparation of ACV in detail. In addition, it presents valuable analytical procedures for the toxicological studies of ACV, which are essential for human use and dosing. Analytical methods, including spectrophotometry, high performance liquid chromatography (HPLC), liquid chromatography/tandem mass spectrometry (LC-MS/MS), electrochemical sensors, molecularly imprinted polymers (MIPs), and flow injection-chemiluminescence (FI-CL) are also highlighted. A brief description of the characteristics of each of these methods is also presented. Finally, insight is provided for the development of ACV to drive further innovation of ACV in pharmaceutical applications. This review provides a comprehensive summary of the past life and future challenges of ACV.

Background:Blunted cyclic variation of heart rate (CVHR), measured as a decrease in CVHR amplitude (Acv), predicts mortality risk after acute myocardial infarction (AMI). However, Acv also can be reduced in mild sleep apnea with mild O2desaturation. We investigated whether Acv's predictive power for post-AMI mortality could be improved by considering the effect of sleep apnea severity.Methods:In 24-hr ECG in 265,291 participants of the Allostatic State Mapping by Ambulatory ECG Repository project, sleep apnea severity was estimated by the frequency of CVHR (Fcv) measured by an automated algorithm for auto-correlated wave detection by adaptive threshold (ACAT). The distribution of Acv on the Acv-Fcv relation map was modeled by percentile regression, and a function converting Acv into percentile value was developed. In the retrospective cohort of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study, consisting of 673 survivors and 44 non-survivors after AMI, the mortality predictive power of percentile Acv calculated by the function was compared with that of unadjusted Acv.Results:Among the ALLSTAR ECG data, low Acv values appeared more likely when Fcv was low. The logistic regression analysis for mortality in the ENRICHD cohort showed c-statistics of 0.667 (SE, 0.041), 0.817 (0.035), and 0.843 (0.030) for Fcv, unadjusted Acv, and the percentile Acv, respectively. Compared with unadjusted Acv, the percentile Acv showed a significant net reclassification improvement of 0.90 (95% CI, 0.51-1.42).Conclusions:The predictive power of Acv for post-AMI mortality is improved by considering its relation to sleep apnea severity estimated by Fcv.

Dementia linked with cognitive impairments is the most prominent indication of Alzheimer's disease (AD). In the current investigation, we have examined the streptozotocin- (STZ) induced cellular toxicity in mouse neuroblastoma (N2A) cells, and Zn with the high-fat diet- (HFD) induced neurotoxicity in mouse brain. These cells and animals were pretreated with apple cider vinegar (ACV), Chrysin, and Rivastigmine to examine their protection against cellular toxicity and neurotoxicity. Experiments have affirmed that pretreatment of ACV, Chrysin, and Rivastigmine has displayed protective outcomes in MTT reduction, tau phosphorylation, amyloid aggregation, attenuated memory impairment as well as oxidative stress, and protected cholinergic hippocampal neurons from degeneration. ACV showed better antioxidant and neuroprotection potential as compared with Chrysin and Rivastigmine. So the existence of excitatory/inhibitory enzymatic activity and higher antioxidant potential indicate that ACV, as a food beverage in a regular diet, could be promising and effective against neurological complications such as AD. PRACTICAL APPLICATIONS: In the Urban lifestyle, HFD and stress are the critical factors of various chronic and prevalent diseases, including diabetes, obesity, cardiovascular, and neurodegenerative disorders like AD. We are already familiar with the multiple benefits of ACV, such as weight loss, antimicrobial activity, diabetes, skin disorders. So in the current research work, we have gauged the effectiveness of ACV against neurological complications in comparison with a synthetic flavonoid (Chrysin) and an anti-Alzheimer's drug (Rivastigmine). To enhance the pragmatic orientation of our results, we have used the ACV in our study, which is readily available in the market for domestic consumption. All the cellular, biochemical, behavioral, and histopathological data revealed that ACV had high antioxidant potential. Our findings suggest that the addition of ACV as a food additive in the daily diet may reduce the threat of multiple neurodegenerative diseases. Therefore, our study could be the precursor of a new pharmacological therapeutic approach via ACV toward cognitive impairments associated with Alzheimer's disease.