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Kireev R.A.,Research Institute of General Pathology and Pathophysiology | Tresguerres A.C.F.,Complutense University of Madrid | Garcia C.,Complutense University of Madrid | Borras C.,University of Valencia | And 4 more authors.
Biogerontology | Year: 2010

There is now a large body of evidence suggesting that the decline in ovarian function with menopause is associated with spontaneous increases in pro-inflammatory cytokines. On the other hand, oxidative stress has been implicated in the pathogenesis of several alterations due to menopause, and can arise through the increased production of lipid peroxides (LPO) and/or a deficiency of antioxidant defense. The aim of the present study was to investigate the effect of aging and ovariectomy on various physiological parameters related to inflammation and oxidative stress in livers obtained from old female rats and the influence of chronic exogenous administration of estrogens, phytoestrogens and growth hormone on these. Thirty-six female Wistar rats of 22 months of age were used in the present study. Twelve of them remained intact, and the other 24 had been ovariectomized at 12 months of age. Intact animals were divided into two groups and treated for 10 weeks with GH or saline, and ovariectomized animals were divided into four groups and treated for the same time with GH, estrogens, phytoestrogens or saline. A group of 2 month old intact female rats was used as young control. Protein expression of iNOS, HO-1, IL-6, TNFa, and IL-1b were determined by Western blot analysis. The levels of NOx, LPO, TNFα, IL-1β, IL-6 and IL-10 were determined in different fractions of the liver. Levels of LPO in the liver homogenates as well as iNOS protein expression and NOx levels were increased in old rats as compared to young animals; this effect was more evident in ovariectomized animals. Pro-inflammatory cytokines TNF-α, IL-1β and IL-6 were significantly increased and anti-inflammatory IL-10 decreased during ageing and after ovariectomy. Aging also significantly increased expression of HO-1 protein and ovariectomized rats showed an additional increase. Hormonal administration to the ovariectomized groups decreased NOx, LPO levels and pro-inflammatory cytokines as compared with untreated rats. Significant rise in IL-10 and reductions in the iNOS, IL-6, TNFα and IL-1β, proteins expression were also found. Oxidative stress and inflammation induced during aging in the liver are more marked in cas trated than in intact old females. Administration of the different hormonal replacement therapies was able to inhibit the induction of proinflammatory cytokines and iNOS, decreased the levels of oxidative stress markers and had therapeutic potential in the prevention of liver injury. . Source

Galatenko V.V.,Moscow State University | Lebedev A.E.,BioKlinikum Scientific and Technical Center | Nechaev I.N.,Research Institute of General Pathology and Pathophysiology | Shkurnikov M.Yu.,Research Institute of General Pathology and Pathophysiology | And 2 more authors.
Bulletin of Experimental Biology and Medicine | Year: 2014

The paper presents a formalized statement of the problem of selecting parameters and construction of a genomic classifier for medical test systems with mathematical methods of machine learning without the use of biological and medical knowledge. A method is proposed to solve this problem. The results of testing the method using microarray datasets containing information on genome-wide transcriptome of the samples of estrogen positive breast tumors are discussed. Testing showed that the quality of classification provided by the constructed test system and implemented on the basis of assessments of expression of 12 genes is not inferior to the quality of classification carried out by such test systems as OncotypeDX and MammaPrint. © 2014 Springer Science+Business Media New York. Source

Saakyan S.V.,Helmholtz Moscow Research Institute of Eye Diseases | Amiryan A.G.,Helmholtz Moscow Research Institute of Eye Diseases | Tsygankov A.Yu.,Helmholtz Moscow Research Institute of Eye Diseases | Loginov V.I.,Research Institute of General Pathology and Pathophysiology | Burdennyi A.M.,Research Institute of General Pathology and Pathophysiology
Arkhiv Patologii | Year: 2014

The study investigated the association of the ABCB1 C3435T polymorphism gene with the risk for uveal melanoma (UM). Genotyping was carried out using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. All the tumors under study were histologically verified. The patients with UM were found to have a high frequency of predisposing alleles and genotypes of this polymorphism in the patients with UM. The CC genotype of the ABCB1 C3435T polymorphism was shown to be associated with the increased risk of UM (OR=8.5;p=7·10-4). A significant correlation was first found between the frequency of the CC genotype of the ABCB1 C3435T polymorphism and the height of a tumor and degree of its pigmentation (p=0.0391 and p=0.0381, respectively, Fisher's test). A marginal association was first shown between the CC genotype of the ABCB1 C3435T polymorphism and the vascular state and histological type. Source

Karpova M.N.,Research Institute of General Pathology and Pathophysiology | Kuznetsova L.V.,Research Institute of General Pathology and Pathophysiology | Zin'kovskii K.A.,Tver State Medical Academy | Klishina N.V.,Research Institute of General Pathology and Pathophysiology
Bulletin of Experimental Biology and Medicine | Year: 2016

We studied anticonvulsant effects of combined treatment with citicoline, a nootropic substance with neuroregenerative and neuroprotective activities, and valproate, an antiepileptic agent widely used in the treatment of epilepsy, on the model of pentylenetetrazole-induced (75 mg/kg, intraperitoneally) acute generalized convulsions in male Wistar rats. Combined treatment with citicoline and valproate in minimum effective doses (70 and 300 mg/kg, respectively) potentiated the anticonvulsant properties of both agents. © 2016 Springer Science+Business Media New York Source

Alchinova I.B.,Research Institute of General Pathology and Pathophysiology | Khlebnikova N.N.,Research Institute of General Pathology and Pathophysiology | Karganov M.Y.,Research Institute of General Pathology and Pathophysiology
Human Physiology | Year: 2015

Information value of the radioadaptive response test was assessed during functional evaluation of pilots in the course of adaptation to flight factors. The functional evaluation was performed at the system level using cardiorespiratory parameters (spirometry and arterial cardiography), at the cellular level using individual sensitivity to ionizing radiation (a radioadaptive response (RAR) test on lymphocytes of peripheral blood), and at the molecular level using the direction of metabolic shifts (laser correlation spectroscopy of biological liquids). Changes in molecular composition of the blood serum and cardiorespiratory functions were compared depending on individual radiosensitivity of pilots with different flight hours. The incidence and strength of RAR in lymphocytes decreased with an increase in flight hours. In light scattering spectra, the input of particles with small hydrodynamic radii (smaller than 11 nm) decreased and that of large particles (larger than 200 nm) increased. The total power of the heart rate variability (HRV) spectrum decreased, whereas the value of stress index increased. Breathing test through a mask raised peripheral systolic and diastolic blood pressure in pilots without RAR. Moreover, it reduced the total spectrum of variability of systolic pressure and input of very low frequencies. In the group of pilots with RAR, the relative input of low frequencies into HRV increased and that of high frequencies decreased, the blood pressure not being altered. Decreased input of small particles and increased input of large particles in light scattering, when compared to the baseline values, were found only in pilots with RAR, which suggests shifts in the metabolism and humoral immunity. It could be hypothesized that the level of individual radiosensitivity reflects the general resistance of the body to negative factors of the environment. © 2015, Pleiades Publishing, Inc. Source

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