Background. The aim was to investigate the influence of propionic acid (PA) on the endoplasmic reticulum (ER), unfolded protein response (UPR) state, and astrocyte/microglia markers in rat ventromedial hypothalamus (VMH) after type 2 diabetes mellitus (T2DM). Methods. Male Wistar rats were divided: (1) control, (2) T2DM, and groups that received the following (14 days, orally): (3) metformin (60 mg/kg), (4) PA (60 mg/kg), and (5) PA+metformin. Western blotting, RT-PCR, transmission electron microscopy, and immunohistochemical staining were performed. Results. We found T2DM-associated enlargement of ER cisterns, while drug administration slightly improved VMH ultrastructural signs of damage. GRP78 level was 2.1-fold lower in T2DM vs. control. Metformin restored GRP78 to control, while PA increased it by 2.56-fold and metformin+PA—by 3.28-fold vs. T2DM. PERK was elevated by 3.61-fold in T2DM, after metformin—by 4.98-fold, PA—5.64-fold, and metformin+PA—3.01-fold vs. control. A 2.45-fold increase in ATF6 was observed in T2DM. Metformin decreased ATF6 content vs. T2DM. Interestingly, PA exerted a more pronounced lowering effect on ATF6, while combined treatment restored ATF6 to control. IRE1 increased in T2DM (2.4-fold), metformin (1.99-fold), and PA (1.45-fold) groups vs. control, while metformin+PA fully normalized its content. The Iba1 level was upregulated in T2DM (5.44-fold) and metformin groups (6.88-fold). Despite PA treatment leading to a further 8.9-fold Iba1 elevation, PA+metformin caused the Iba1 decline vs. metformin and PA treatment. GFAP level did not change in T2DM but rose in metformin and PA groups vs. control. PA+metformin administration diminished GFAP vs. PA. T2DM-induced changes were associated with dramatically decreased ZO-1 levels, while PA treatment increased it almost to control values. Conclusions. T2DM-induced UPR imbalance, activation of microglia, and impairments in cell integrity may trigger VMH dysfunction. Drug administration slightly improved ultrastructural changes in VMH, normalized UPR, and caused an astrocyte activation. PA and metformin exerted beneficial effects for counteracting diabetes-induced ER stress in VMH.

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To define the development of herpes virus infection and morphological changes in the brain a upon a cerebrovascular accident. Methods. The experiments were performed on white mice weighing 18-20g. The animals were infected with type I HSV. Stroke was simulated after recovery and the rate of virus reactivation was determined. The rate of HSV production was evaluated by determination of viral antigens in Vero cell culture, PCR and dot-ELISA methods. The neurodegenerative process was confirmed by histological examination. Results. Reactivation of HSV-I was detected after the stroke. Histological study confirmed anincreased degree of neurodystrophic process around the hemorrhage, including hippocampus. A diagnostic value of the molecular methods has been proven in the detection of herpes infection in the biological samples (plasma, homogenates of animal organs). Conclusions. This study provided new data on the pathogenesis of herpes virus infection after acute stroke and its place in the development of complications. We have shown that the ischemic brain damage was a factor of type I HSV reactivation and it was characterized by a higher rate of neurodegenerative changes in hippocampus as compared to the isolated development of neuroinfection or impairment of cerebral circulation.

Lead as any heavy metals may be found in soil, water, air, and is used in everyday life. Once in the body, it causes toxic effect, making the liver, which is one of the main organs of detoxification, suffer. Recently, the study of the action of not only ionic forms of lead, but also its nanoparticles, has become topical. The study aims at determining changes in the liver of rats and biochemical changes in their blood both at late term of exposure to nanoparticles of lead compounds and in the post-exposure period. The study was performed on 120 male rats of Wistar line, which were divided into two series, each series containing four groups. The first and the second groups of animals were intraperitoneally injected with colloidal solution of nanoparticles of lead sulfide of 10 and 30 nm in size, and the third group were intraperitoneally injected with a solution of lead nitrate. The fourth group of animals served as control. In the first series, the investigated substances were administered 60 times within 12 weeks. In the second series, after 60-fold administration of the investigated substances, the exposure was discontibued and animals were observed for 6 weeks-overall duration of 18 weeks. Histological, morphometrical and biochemical methods were used. The body weight was reduced in the rats exposed to PbS at week 12 of experiment and in rats exposed to both PbS and Pb(NO ) in the second series. Absolute liver weight increased at week 12 of experiment in all experimental groups. In the second series this value almost reached that of the control level. Relative liver weight in the animals of all experimental groups was higher than that in the control at week 12 of experiment. In the second series this value remained higher in rats exposed to PbS . After 12 weeks of exposure dystrophic changes in the liver were found in all experimental groups. At week 6 after the exposure (the second series) destructive changes in the liver decreased. Total protein, albumin, glucose, total lipids, cholesterol, triglycerides content in blood serum corresponded with morphological data. The experiment has demonstrated that the 12 weeks long exposure to lead nanoparticles had harmful effect on the liver. Within the postexposure 6-weeks period structural changes in the liver and biochemical changes in blood serum decreased. Biochemical changes in blood serum corresponded to the morphological data. By many parameters PbS had more pronounced harmful effect. Toxicity of PbS and Pb(NO ) were comparable.

Background: Herpes simplex virus (HSV) is prevalent in today’s world population, and there is evidence of potential HSV reactivation in patients with immune deficiency induced by acute stroke. However, the data on the use of antivirals in the setting of stroke are scarce. The aim of this study was to evaluate the reactivation of HSV-1 in patients with stroke, using several methods, and to assess the efficacy of acyclovir in the treatment of experimental stroke. In the employed methodology, PCR and dot-ELISA were used to detect the occurrence of HSV-1 in patients with acute stroke. White mice were infected with HSV-1 and experimental stroke was simulated. The infected mice with stroke were subdivided into two groups: one of them received no treatment, while the other one was treated with acyclovir. The level of HSV-1 reactivation was determined by the methods used in human patients. The brain tissue of experimental animals was also subjected to morphological and morphometrical study. The results of such work reveal that, by the applied serological method, HSV-1 was found in all patients with stroke. Herein, the increased level of HSV-1 was seen in the brain tissue and blood in 100% of the experimental infected animals. However, the use of acyclovir suppressed reproduction of HSV-1. Hence, it can be concluded that clinical and laboratory studies have demonstrated the different sensitivity of Dot-Elisa and PCR, with the former being more sensitive. Moreover, the use of acyclovir in the experiment inhibited viral reproduction and further development of viral infection. Still, chemic lesions in the brain persisted.