The assessment of dose-response is an essential part of drug development in terms of the determination of a drug's effective dose, finding the safety endpoint, estimation of the pharmacokinetic profile, and even validation of drug activity, especially for therapeutic agents with a principally novel mechanism of action. Drugs based on released-active forms of antibodies are a good example of such a target. In this study, the efficacy of the antiviral drug Anaferon for children (released-active form of antibodies to interferon-gamma) was tested in a dose-dependent manner (at doses of 0.13, 0.2, 0.4, 0.8 ml/mouse/day) in a murine model of acute pneumonia induced by influenza virus pandemic strain A/California/07/09 (H1N1). Administration of the drug at the two highest doses led to: a reduction in the virus infectious titer in lung tissue up to 4.2 lgEID50/20 mg of tissue; infected animals' life prolongation up to 6.7 days; an increase in the survival rate of up to 40% and a decrease in morphological signs of inflammation when compared to the control animals. In this study, the dose-response effect of Anaferon for Children was demonstrated on mice for the first time. This finding is especially important for drugs with a principally novel mechanism of action like drugs based on released-active forms of antibodies. J. Med. Virol. 89:759-766, 2017. © 2016 Wiley Periodicals, Inc.

In preliminary ELISA studies where released-active forms (RAF) of antibodies (Abs) to interferon-gamma (IFNg) were added to the antigen-antibody system, a statistically significant difference in absorbance signals obtained in their presence in comparison to placebo was observed. A piezoelectric immunosensor assay was developed to support these data and investigate the effects of RAF Abs to IFNg on the specific interaction between Abs to IFNg and IFNg. The experimental conditions were designed and optimal electrode coating, detection circumstances and suitable chaotropic agents for electrode regeneration were selected. The developed technique was found to provide high repeatability, intermediate precision and specificity. The difference between the analytical signals of RAF Ab samples and those of the placebo was up to 50.8%, whereas the difference between non-specific controls and the placebo was within 5%–6%. Thus, the piezoelectric immunosensor as well as ELISA has the potential to be used for detecting the effects of RAF Abs to IFNg on the antigen-antibody interaction, which might be the result of RAF’s ability to modify the affinity of IFNg to specific/related Abs.

This text is aimed to provide the readers with detailed information about phenomenon of released-activity and reply on the specific risen questions.

No abstract

Bladder cancer is one of the most severe and common diseases of genitourinary organs. According to WHO statistics, bladder cancer is the tenth in cancer morbidity structure and the 13th in cancer mortality structure in the world. In Russia, bladder cancer is 11th in cancer morbidity structure and 16th in cancer mortality structure. In most cases, bladder cancer is diagnosed at 6574 years of age. The 5-year survival rate for stage IV bladder cancer is about 15%. Early detection, correct staging, and management of the patient influence the prognosis and further quality of life. This review shows detection and staging methods of bladder cancer, staging categories based on multiparametric magnetic-resonance imaging with the use of Vesical Imaging-Reporting and Data System (VI-RADS). Illustrations and a brief overview of alternative visualization methods of bladder lesions, and new approaches in assessment of digital medical images, radiomics and radiogenomics, are presented. In the future, these methods should help to determine the biological characteristics of the tumor without taking a biopsy.