[Primary Generalized Glucocorticoid Resistance: a case report].

Primary glucocorticoid resistance (OMIM 615962) is a rare endocrinologic condition caused by resistance of the human glucocorticoid receptor (hGR) to glucocorticoids (GR) and characterised by general or partial insensitivity of target organs to GK. Compensatory activation of hypothalamic-pituitary-andrenal axis results in development of a various pathological conditions caused by overstimulation of adrenal glands. Clinical spectrum may range from asymptomatic cases to severe cases of mineralocorticoid and/or androgen excess. At present time, primary generalized glucocorticoid resistance has been exclusively associated with defects in the NR3C1 gene. Here, we present a case report of an adolescent patient with clinical presentation of glucocorticoid resistance confirmed by detailed endocrinologic evaluation but no confirmed mutations in the NR3C1 gene.

[The mechanisms of anti-inflammatory action of enisamium iodide].

AIM: The role of cyclooxygenases (COX-1 and/or COX-2), transcription nuclear factor NF-κB, anti-inflammatory cytokines - TGF1b, IL-4, IL-10 and pro-inflammatory cytokines IL-1, IL-6 were studied to substantiate the expediency of antiviral agent enisamium iodide (Nobazit) using to regulate key inflammatory components in acute respiratory infections, IL-8, TNF-alpha in the realization of the pharmacological activity of this drug. MATERIALS AND METHODS: Gene expression was determined by real-time RT-PCR, the concentration of interleukins was determined by ELISA, and the viability of peripheral blood mononuclear cells (PBMC) was assessed by the MTT spectrophotometric method. The chemiluminescence method was used to assess PBMC oxidant activity. RESULTS: Enisamium iodide (10 µM) reduced mRNA levels of COX-1, COX-2, NF-κB, TGF1b, IL-1, IL-6 in stimulated PBMC of healthy donors by an average of 48% (p≤0.05). At 5 times higher concentration, 50 µM, enisamium iodide suppressed the expression of these genes by an average of 43% (p≤0.05). At a concentration of 100 µM, enisamium iodide reduced the expression of COX-2, TGF1b, IL-1, IL-6 by an average of 47% (p≤0.05). At a concentration of 10 µM, enisamium iodide stimulated the secretion of IL-10 by mononuclear cells by 1.2 times, p≤0.05. The tested drug at a concentration of 50 µM did not affected on the concentration of IL-1, IL-4, IL-8 and TNF-alpha, but significantly stimulated the production of IL-10 by 1.5 times, p≤0.05. The chemiluminescence method revealed that enisamium iodide in the entire concentration range (10-100 µM) does not reduce the viability of macrophages, but inhibits their oxidative activity (maximum value of CL intensity) by an average of 55% (p≤0.05). CONCLUSION: The anti-inflammatory effect of enisamium iodide at a concentration of 10 µM may be associated with inhibition of the expression of COX-1, 2, NF-κB, IL-1, IL-6, TGF1b and an increase in the expression and production of IL-10. An additional contribution to the anti-inflammatory activity of enisamium iodide is made by its antioxidant and antiradical activity. The absence of the effect of enisamium iodide (10-100 µM) on the viability of PBMC indicates its safety for the cells of the immune system and the expediency of using it to suppress inflammatory reactions in acute respiratory infections, restore the quality of life of patients and the possibility of using Nobazit as an effective agent for treatment of these infections of various etiologies.

Magnetic Resonance Imaging of Brain Involvement in Dogs Using Paramagnetic Contrast Enhancement with Mn(II)-DCTA P.

Experimental study of a new paramagnetic complex Mn-DCTA is carried out. The complex (0.5 M manganese(II) solution with trans-1,2-diamine cyclohexane-N,N,N',N'-tetraacetic acid; Cyclomang) was used for contrast magnetic resonance imaging visualization of CNS involvement in dogs with severe forms of Babesia canis infection. CNS injuries were visualized in all cases, with highly intense contrasting at the expense of Mn-DCTA accumulation at the periphery of the damaged zone. Quantitative evaluation of the paramagnetic accumulation in the focus showed that the amplification index wa s 1.19±0.11 for the central areas and 1.47±0.17 for the peripheral ones. The pituitary (1.18±0.05) and vascular plexuses of the lateral ventricles (1.12±0.09) were also contrasted. Injection of the paramagnetic to dogs was not associated with any kinds of pathological or physiological reactions. Mn-DCTA complex allowed contrast visualization of the focal injuries to the CNS and could be regarded as a paramagnetic contrast agent for magnetic resonance imaging of brain injuries in dogs.

[INFLUENCE OF PROGESTERONE DERIVATIVES ON THE VIABILITY AND EXPRESSION OF ESTROGEN RECEPTOR-ALPHA MRNA IN HELA CELLS.]

We have studied the effect of new ligands of progesterone receptors, including pregna-D'-pentaran 6-methoxyimino-16a,17a-cyclohexanopregn-4-en-3,20-dio-ne (K1047), 17a-acetoxy-3b-butanoyloxy-6-methylpregna-4,6-dien-20-one (buterol), progesterone (P4), and medroxyprogesterone acetate on the viability of HeLa cells and expression of estrogen receptor-alpha (Era) mRNA gene in these cells. K1I047 and buterol exhibited high cytostatic activity, which exceeded the activity of reference compounds on the average by 15% (p < 0.05). Both buterol and K-1047 (at 10(-6)M) effectively suppressed ERa mRNA gene expression in HeLa cell culture by 83.4 - 9 8.6%.

[ANTIOXIDANT AND CYTOPROTECTOR PROPERTIES OF GENISTEIN - ISOFLAVONE WITH ESTROGENIC ACTIVITY.]

Phytoestrogen genistein can exhibit cytoprotective and antioxidant properties, providing chemopreventive action, and produce cytotoxic effects on some tu- mors. In this work, the cytotoxic, cytoprotective, and antioxidant properties of genistein have been studied on model tumor cells (human cervical cancer HeLa cells) and normal cells (rat dermal fibroblasts, RDF). For assessing the cytotoxic effect of genistein (spectrophotometric MTT assay), the reference drug was cis-diaminodichloroplatinum (cisplatin); for evaluating antioxidant action, beta-estradiol was the reference drug. It is established that genistein produces a cyto- toxic effect only at high concentrations, IC50 = 20 mM and 14 mM for RDF and HeLa cells, respectively, which is 30 and 10 times higher than IC50 for cisplatin on these cells. Genistein like estradiol, but unlike cisplatin, had no effect on the mitochondrial pore induction from rat liver mitochondria. Thus, genistein at physiological concentrations (up to 200 n) acts as a cytoprotective agent. High antioxidant activity of genistein also suggests the possibility of its use as a chemopreventive drug.

[Cytoprotective Effects of Phytoestrogen Genistein against Cancer Cells].

In this paper we study the effect of synthetic isoflavonoid genistein against cancer HeLa cells, which contain estrogen receptors alpha but not beta, with the aim to determine the cytotoxic or cytoprotective effect of genistein. It is shown that the half maximal inhibitory concentration (IC50) value of genistein (0.2 mM) for the growth inhibition of HeLa cells is at least ten times higher than that one of tamoxifen and cisplatin--drugs, used in cervical cancer treatment. In micromolar concentrations (0.1-10 µM) genistein decreased the cytotoxic effects of cisplatin and tamoxifen. The decreased Bax mRNA expression and increased Bcl-2 mRNA expression after incubation .of the cells with genistein also demonstrate the cytoprotective, anti-apoptotic effect of genistein. Genistein, even in high concentrations, had no effect on membrane potential and calcium capacity of isolated mitochondria, without activating the opening of Ca(2+)-induced mitochondrial pore. Thus, these data demonstrate a cytoprotective effect of isoflavonoid genistein against this type of cancer cells.

[Antitumor and antiproliferative action of the steroidal cytostatic antiestrogen cytestrol acetate on hormone-dependent tumor models].

Cytestrole acetate (CA), in the structure of which the steroidal antiestrogen component is associated with bis-ß-cloroethylamino group, exhibits a strong cytotoxic activity against hormone-dependent cancer cell lines (CaOV, HeLa, MCF-7). In doxorubicin-resistant MCF-7 cells, CA potentiates the cytotoxic effect of etoposide and doxorubicin, and the IC50 for CA in these cells is 40 times lower than that for tamoxifen (TAM). In transplantable mice breast adenocarcinoma Ca-755, the therapeutic CA dose is 25 mg/kg when administered subcutaneously in oil solution for 5 days. On the DMBA-induced mammary tumors in rats, CA injected subcutaneously led to partial regressions 4 weeks after treatment in 75% of test rats, whereas TAM produced this effect in 43% of rats. Among various drug forms of CA, the most active were oil solution of CA in gelatin capsules for oral use and liposomal emulsion for intravenous administration, since these forms exhibited the highest values of Ca-755 tumor growth inhibition index (TGI = 97 - 98%).

[Redox-dependent ferric oxide nanoparticles loaded with doxorubicin and their influence on the functions of mitochondria].

The spectral, fluorescent and functional properties of ferric oxide and ferric hydroxide nanoparticles loaded with doxorubicin and stabilized with citric acid or lysine were studied in comparison with free doxorubicin. Their effect on the opening of calcium-induced mitochondrial pore and the possibility of the controlled release of doxorubicin under the influence of redox stimuli were investigated. The data show that the effect of nanoparticles on mitochondria depends on the type of a stabilizer. The spectral and fluorescence methods used allow us to estimate the presence or absence of free doxorubicin in solution of nanoparticles and the:concentration of bound doxorubicin. It is shown that the dithiotreitol and glutathione increase the amplitude of absorption and fluorescence of doxorubicin during incubation with nanoparticles. It is assumed that this effect may be associated with the reduction of the oxidized iron by thiols with subsequent release of doxorubicin.

[Relative binding activity of dydrogesterone with blood mononuclear cells progesterone receptors of women included in the IVF program].

It has been shown that specific binding of dydrogesterone with progesterone receptors in blood mononuclear cells of the patients included in the programs of in vitro fertilization, varies from 0 to 298%, thus at 38% of women dydrogesterone concedes to a progesterone in the competition for receptors of a progesterone, and 62%--exceed. The revealed variations of specific binding dydrogesterone with receptors of a progesterone are a reserve of increase of efficiency of auxiliary reproductive technology at the expense of individual selection of hormonal agents.

[Bolus contrast-enhanced multislice spiral computed tomography of the chest: new possibilities in the diagnosis of lung diseases].

OBJECTIVE: To elaborate optimal programs for bolus contrast-enhanced multislice spiral computed tomography (MSCT) of the chest for different types of tomographic scanners and in some lung diseases. MATERIAL AND METHODS: Contrast-enhanced MSCT findings were analyzed in 637 patients, 536 of whom presented with a focal pathological process in the lung and 101 had pulmonary emphysema. RESULTS: There is evidence proving the expedience of using the contrast medium iopromide that has an optimal balance between the high concentration of iodine and its excellent tolerance due to low osmolarity and low viscosity. CONCLUSION: Intravenous bolus contrast-enhancement using an automated injector can visualize chest organs in different phases of contrast enhancement, by significantly improving the quality of diagnosis and achieving 100% disease diagnosis comparable with its morphological diagnosis.

[Estimating ability of dihydroquercetin to inhibit oxidation of fibrinogen by ozone].

The ability of dihydroquercetin to inhibit the oxidation of fibrinogen has been evaluated. It is established that dihydroquercetin inhibits oxidation of fibrinogen by ozone, thus preventing oxidative modification of fibrinogen and preserving its functional activity.

[Prevention of contrast-induced nephropathy in the context of evidence-based medicine].

The paper considers the mechanisms of development of contrast-induced nephropathy in the use of iodinated radiopaque contrast agents (RCAs), as well as the criteria of their assessment. It gives different existing recommendations for prevention of the nephrotoxic effects of RCAs.

[Antihypertensive and neuroprotective activity of quercetin and its derivatives].

Data available in the literature on the pharmacological activity of quercetin and its derivatives, which possess various biological properties including antihypertensive and neurotropic activity, are reviewed. The mechanisms of these effects and results of clinical trials are considered and prospects for the clinical use of quercetin and its derivatives are discussed.

[Estrogens and brain].

Recent data upon molecular mechanisms of pleiotropic action of estrogens in human brain is presented in the article. Given detailed descriptions of properties of classical and membrane bound estradiol receptors, that maintain gene expression regulation, modulation of neurotransmittent systems and signal cascade activation in neuronal cells. Data upon regional distribution of estradiol receptor subtypes in the brain, their participation in main cell population function control (including progenitor cells) is given. Special attention is paid to estrogen participation in neurogenesis, inflammation and apoptosis regulation in central nervous system; in the control of formation and functioning of cerebral vessels.

[Effect of steroid hormones on production of reactive oxygen species in mitochondria].

Among the targets of the steroid hormones are mitochondria, which as the main source of reactive oxygen species (ROS) in the cell play a central role in the development of various pathologies. We studied the effect of progesterone and its synthetic analogues on mitochondrial ROS production. It was found that progesterone activates the formation of superoxide anion and hydrogen peroxide in mitochondria during oxidation of complex I substrates of the respiratory chain and exerts no influence on production of ROS during oxidation of succinate, complex II substrate of the respiratory chain. Synthetic analogues of progesterone - medroxyprogesterone acetate, buterol, acetomepregenol, megestrol acetate, have different effects on ROS production, depending on their chemical structure. By the effectiveness of impact on ROS production in mitochondria all the steroids tested can be classified in the descending order as follows: progesterone > buterol > or = atsetomepregenol > medroxyprogesterone acetate > megestrol acetate. Activation of ROS production by progesterone and buterol has different mechanisms: progesterone acts as an inhibitor of NAD-dependent respiration, while buterol and acetomepregenol form noncovalently associated complexes by hydrogen bonds between the ester carbonyl at C3 and SH-groups of the respective targets.

[Experimental study of indium-111 labeled octreotide application for radionuclide diagnostics of tumors with high expression of somatostatin receptors].

We have studied the possibility of using octreoitid labeled by indium-111 for radionuclide diagnostics of neoplasms with high expression of somatostatin receptors. It has been established that, using experiments with cell cultures, it is possible to predict the application of 111In-labeled octreotid and determine time intervals for the best visualization of tumors. Indium-111-labeled octreotid accumulation in animals with transferred B16 tumor (pigment melanoma) shows evidence for the opportunity of using this substance as radiopharmaceutical medium for tumor diagnostics.

[Empiric treatment of pyelonephritis].

The article analyses the most typical clinical situations in empirical treatment of pyelonephritis including situations with comorbid severe diseases: decompensated diabetes mellitus, chronic renal failure, HIV-infection. Choice of antibacterial medicines for empiric treatment of pyelonephritis is based on the results of the latest studies of antibioticoresistance of pyelonephritis pathogens as well as on specific features of pharmacokinetics and pharmacodynamics of antibacterial drugs.

[Antiproliferative and antioxidant activity of new dihydroquercetin derivatives].

Effect of nine new derivatives of dihydroquercetin (taxifolin) on the viability of cultivated normal and tumor cells, their antioxidant activity, and interconnection of the antioxidant activity with the chemical structure have been studied. Among these dihydroquercetin derivatives, the maximum antiproliferative activity on the model of rat fibroblast culture exhibited KN-2, KN-4, KN-7, and KN-8 compounds, while KN-7 and KN-8 compounds also showed maximum activity on the model of MCF-7 tumor cell culture (human breast cancer). The maximum general antioxidant activity was observed for the native dihydroquercetin and KN-8 compound. There is a strong correlation (with a correlation coefficient of 0.93) between the antiproliferative effects of dihydroquercetin derivatives on murine skin fibroblasts and MCF-7 cells (human breast cancer).