According to the latest data from the International Diabetes Federation (IDF), the number of patients with diabetes has outpaced previously predicted growth rates and is expected to increase by 51% by 2045. Thus, the development and evaluation of the effectiveness and safety of hypoglycemic agents is an urgent task due to the high social significance of the problem. In preclinical studies there are many models of experimental diabetes mellitus in animals, both with the use of chemical inducers that cause damage to the islet apparatus of the pancreas, and with the use of diets. Accor­ding to the literature data, gerbils and degus are prone to hyperglycemia and insulin resistance when fed on standard laboratory diets, which are relatively high in calories compared to the food obtained by these animals in their natural habitat. Due to this feature the experimental induction of diabetes mellitus in these animal species can be modeled only through the use of a high-calorie diet. The purpose of this study was to test this hypothesis. Male and female gerbils of two age categories (14–20 and 40–41 weeks), as well as male and female degus, whose age was 65–70 weeks, were used as experimental animals. During the experiment the following indicators were evaluated: the concentration of glucose, cholesterol, triglycerides, creatinine, urea in blood plasma, the activity of dipeptidyl peptidase type 4 (DPP-4) and the parameters of the glucose tolerance test. Based on the totality of all experimental data a state close to pre-diabetic was established in male and female degus fed on a high-carbohydrate diet. This conclusion was made due to an increase in the activity of the DPP-4 enzyme and the presence of glucose tolerance by the 12th week of the experiment. The induction of experimental diabetes mellitus or latent diabetes mellitus using high-calorie diets failed in the majority of experimental animals (gerbils and degus) regardless of age. The obtained results are suggestive of the motivation for the use of these experimental models for the creation of experimental diabetes.

INTRODUCTION:Combination antiretroviral therapy is currently the main component of treatment for human immunodeficiency virus (HIV) infected patients. At the same time, the high mutational potential of the virus and the frequency of side effects of existing drugs dictate the need for the development and preclinical study of new, more effective and safer compounds.The aim of the study is to evaluate the specific types of toxicity of a new non-nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RNA-dependent DNA revertase) (NNRTI) based on the substance 1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil, a benzophenone derivative.MATERIAL AND METHODS:The study investigated reproductive toxicity, embryotoxicity, immunotoxicity, genotoxic (in micronucleus test in and comet assay) and allergenic properties of the test itemcompound. It was tested on three species of animals in two doses: the estimated therapeutic dose (1 TD) and its tenfold equivalent (10 TD). Taking into account the metabolic coefficients, the doses for rats (Rattus) were 9 and 90 mg/kg, for mice (Mus musculus), 21 and 210 mg/kg, and for guinea pigs (Cavia porcellus), 8 and 80 mg/kg, respectively.RESULTS AND DISCUSSION:According to the obtained results, a favorable safety profile of the tested compound was established. Negative effects on the immune system, reproductive function, the body of pregnant animals and the fetus were not observed, as well as the compound did not have genotoxic and allergenic properties.CONCLUSION:These data allows to consider the studied compound as a promising therapeutic candidate for the treatment of HIV-1 infection.

Bacterial lysates may produce immunoregulatory effects in the inflammatory diseases that are not directly caused by infectious agents; they may also stimulate the immune response against pathogens which are not a part of the lysate composition. Imudon® is a polyvalent bacterial lysate that is available in orodispersible tablets. However, the influence of this drug product on aseptic inflammation and immune defense against the infectious agents, the antigens of which are not contained in this preparation have not been studied so far. The aim of this study, therefore, was to determine the anti-inflammatory and immunomodulating effects of Imudon® using the models of aseptic lymphadenitis (in Wistar rats) and pneumococcal pneumonia (in Balb/c mice), i.e., the conditions not related to the specific components of the bacterial lysate. Lymphadenitis was induced in rats by administration of λ-carrageenan into a cervical lymph node via an open operative approach. Whereas pneumonia was induced in mice by administering Streptococcus pneumoniae suspension intranasally. The choice of pneumococcus was determined by the absence of pneumococcal antigens in Imudon®, i.e., it cannot be a direct inducer of adaptive immune response against pneumococcal infection. Imudon® was administered intragastrically as a crushed tablet suspension following a therapeutic-preventive regimen (for 14 days daily until the induction of inflammation and for 3 [in the lymphadenitis model] or 5 days [in the model of pneumonia] in three doses thereafter). In the lymphadenitis model, Imudon® demonstrated both local and systemic anti-inflammatory responses manifested in the reduced number of circulating leucocytes and lower TNFα levels and by ameliorated histological features of inflammation in the operated lymph node. In rats, the anti-inflammatory effect was most pronounced when the product was administered at a dose of 2.2 mg/kg (equivalent to a human therapeutic dose) and 6.6 mg/kg. In the model of pneumonia, administration of Imudon® at 4.44 mg/kg (equivalent to a human therapeutic dose) and 13.32 mg/kg demonstrated a trend towards increased survival rate as compared to the control group. On Day 5 after infection Imudon® (4.44 and 13.32 mg/kg) decreased significantly the severity of inflammation and bacterial titer in the lungs. The titer of anti-pneumococcal immunoglobulins A in the bronchoalveolar lavage fluid were found to be higher in the Imudon® treated group (13.32 mg/kg) compared to control group. The results of this study showed high antiinflammatory and immunomodulatory activities of Imudon® and provided an insight into the mechanisms that underlie the clinical effects of this drug in various inflammatory diseases.