The perinatal (prenatal and early neonatal) period is a critical stage for hypothalamic programming of sexual differentiation as well as for the development of energy and metabolic homeostasis. We hypothesized that neonatal treatment with antidiabetic drug biguanide metformin would positively modify regulation of growth hormone -IGF-1 -insulin signaling pathway slowing down aging and improving cancer preventive patterns in rodents. To test this hypothesis male and female 129/Sv mice were s.c. injected with metformin (100 mg/kg) at the 3rd, 5th and 7th days after birth. Metformin-treated males consumed less food and water and their body weight was decreased as compared with control mice practically over their entire lifespan. There were no significant differences in age-related dynamics of food and water consumption in females and they were heavier than controls. The fraction of mice with regular estrous cycles decreased with age and demonstrated a tendency to decrease in the females neonatally treated with metformin. Neonatal exposure to metformin practically failed to change the extent of hormonal and metabolic parameters in blood serum of male and female mice. In males, neonatal metformin treatment significantly increased the mean life span (C20%, P < 0.05) and slightly increased the maximum life span (C3.5%). In females, the mean life span and median in metformin-treated groups were slightly decreased (¡9.1% and ¡13.8% respectively, P > 0.05) in comparison to controls, whereas mean life span of last 10% survivors and maximum life span were the same as in controls. Almost half (45%) of control male mice and 71.8% male mice neonatally exposed to metformin survived up to 800 d of age, the same age was achieved by 54.3% of mice in control female group and 30% of metformin-treated females (P < 0.03). Thus, neonatal metformin exposure slows down aging and prolongs lifespan in male but not in female mice.

Potentilla erecta, the tormentil, and its rhizome extracts have been known for a long time in traditional medicine as a remedy for the treatment of inflammations, wounds, and gastrointestinal disorders. Tormentil rhizomes have also been used as part of alcoholic beverages in Germany, the Ukraine, and Russia. Acute toxicity of an aqueous P. erecta rhizome extract was evaluated with a single dose administered by the intragastric route to rats and mice in dosages of 2.5 g/kg and 6.8 g/kg of body weight, respectively. Further, a single dose of this extract was applied intraperitoneally to rats and mice in dosages of 3.8 and 14.5 g/kg of body weight, respectively. After an observation period of 2 weeks after intragastric administration and 3 days following intraperitoneal administration, no mortality or any changes in appearance, behavior, or body weight occurred for both rats and mice in the high dosages mentioned. Macroscopic and microscopic studies of the internal organs of these rodents revealed no pathological changes. The data are in line with the long-time traditional use of P. erecta rhizome extracts and results from recent clinical trials in which no signs of any toxic effects have been known after the administration of a P. erecta rhizome extract for the treatment of ulcerative colitis in adults and rotavirus-induced diarrhea in children. Thus P. erecta rhizome extracts should be considered safe with respect to acute toxicity when applied to humans.

FVB/N wild type and transgenic HER-2/neu FVB/N female mice breed at N.N. Petrov Research Institute of Oncology were under observation until natural death without any special treatment. Age-related dynamics of body weight, food consumption and parameters of carbohydrate and lipid metabolism, level of nitric oxide, malonic dialdehyde, catalase, Cu, Zn-superoxide dismutase, vascular endothelial growth factor were studied in both mice strains. The parameters of life span and tumor pathology were studied as well. Cancer-prone transgenic HER-2/neu mice developed in 100 % multiple mammary adenocarcinomas and died before the age of 1 year. Forty tree percent of long-lived wild type mice survived the age of 2 years and 19 %-800 days. The total tumor incidence in wild type mice was 34 %. The age-associated changes in the level of serum IGF-1, glucose and insulin started much earlier in transgene HER-2/neu mice as compared with wild type FVB/N mice. It was suggested that transgenic HER-2/neu involves in initiation of malignization of mammary epithelial cells but also in acceleration of age-related hormonal and metabolic changes in turn promoting mammary carcinogenesis.

Tuberculosis remains a common and dangerous chronic bacterial infection worldwide. It is long-established that pathogenesis of many autoimmune diseases is mainly promoted by inadequate immune responses to bacterial agents, among them Mycobacterium tuberculosis. Tuberculosis is a multifaceted process having many different outcomes and complications. Autoimmunity is one of the processes characteristic of tuberculosis; the presence of autoantibodies was documented by a large amount of evidence. The role of autoantibodies in pathogenesis of tuberculosis is not quite clear and widely disputed. They are regarded as: (1) a result of imbalanced immune response being reactive in nature, (2) a critical part of TB pathogenicity, (3) a beginning of autoimmune disease, (4) a protective mechanism helping to eliminate microbes and infected cells, and (5) playing dual role, pathogenic and protective. There is no single autoimmunity-mechanism development in tuberculosis; different pathways may be suggested. It may be excessive cell death and insufficient clearance of dead cells, impaired autophagy, enhanced activation of macrophages and dendritic cells, environmental influences such as vitamin D insufficiency, and genetic polymorphism, both of Mycobacterium tuberculosis and host.

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