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R Nikolov

Publications and source records attributed to R Nikolov.

At least 19 recordsLinked to original sources
PubMed2001

Enhanced sensitivity of insulin-resistant adipocytes to vanadate is associated with oxidative stress and decreased reduction of vanadate (+5) to vanadyl (+4).

Vanadate (sodium orthovanadate), an inhibitor of phosphotyrosine phosphatases (PTPs), mimics many of the metabolic actions of insulin in vitro and in vivo. The potential of vanadate to stimulate glucose transport independent of the early steps in insulin signaling prompted us to test its effectiveness in an in vitro model of insulin resistance. In primary rat adipocytes cultured for 18 h in the presence of high glucose (15 mm) and insulin (10(-7) m), sensitivity to insulin-stimulated glucose transport was decreased. In contrast, there was a paradoxical enhanced sensitivity to vanadate of the insulin-resistant cells (EC(50) for control, 325 +/- 7.5 microm; EC(50) for insulin-resistant, 171 +/- 32 microm; p < 0.002). Enhanced sensitivity was also present for vanadate stimulation of insulin receptor kinase activity and autophosphorylation and Akt/protein kinase B Ser-473 phosphorylation consistent with more effective PTP inhibition in the resistant cells. Investigation of this phenomenon revealed that 1) depletion of GSH with buthionine sulfoximine reproduced the enhanced sensitivity to vanadate while preincubation of resistant cells with N-acetylcysteine (NAC) prevented it, 2) intracellular GSH was decreased in resistant cells and normalized by NAC, 3) exposure to high glucose and insulin induced an increase in reactive oxygen species, which was prevented by NAC, 4) EPR (electron paramagnetic resonance) spectroscopy showed a decreased amount of vanadyl (+4) in resistant and buthionine sulfoximine-treated cells, which correlated with decreased GSH and increased vanadate sensitivity, while total vanadium uptake was not altered, and 5) inhibition of recombinant PTP1B in vitro was more sensitive to vanadate (+5) than vanadyl (+4). In conclusion, the paradoxical increased sensitivity to vanadate in hyperglycemia-induced insulin resistant adipocytes is due to oxidative stress and decreased reduction of vanadate (+5) to vanadyl (+4). Thus, sensitivity of PTP inhibition and glucose transport to vanadate is regulated by cellular redox state.

Acetylcysteine↗
PubMed2001

[Adult respiratory distress syndrome--etiology and pathogenesis].

Adult respiratory distress syndrome (ARDS) is not a specific lung disease. It represents an acute respiratory insufficiency syndrome in patients with non-injured lung as a result of severe multiple lung lesions of different etiology and pathogenesis. ARDS is provoked by a great number of etiologic factors of two main groups: 1) etiologic factors directly injuring the alveolo-capillary wall and 2) etiologic factors indirectly injuring the alveolo-capillary wall. ARDS develops in three phases: phase of exudation, phase of injury of the alveolocapillary wall and phase of proliferation (chronic phase).

Adult↗
PubMed2001

[Interleukins and endocrine function].

Views and experimental data on the role of interleukins in the regulation of the endocrine functions of hypothalamus, pituitary gland, thyroid gland, suprarenal gland and pancreas are presented. The role of interleukin-1 and interleukin-6 in the regulation of normal and pathological processes is examined. Data on cellular and molecular operation mechanisms of some interleukins on functions of the endocrine glands are included in the survey. The clarification of these mechanisms leads to new pharmacotherapeutical approaches to endocrine diseases treatment.

Adrenal Glands↗
PubMed2000

[Macrolides: pharmacology and clinical use].

Members of macrolides are Erythromycin, Oleandomycin, Spiramycin, Roxithromycin, Josamycin, Midecamycin, Clarithromycin, Azithromycin and Dirithromycin. This review present mechanism of action, pharmacokinetic, adverse drug reactions and main clinical uses of the macrolides.

Anti-Bacterial Agents↗
PubMed1997

Evaluation of an ion-selective electrolyte analyzer: Microlyte 6.

Microlyte 6 (Kone, Finland) is an ion-selective analyzer designed to measure simultaneously the concentration of six important electrolyte parameters--potassium, sodium, chloride, ionized calcium, ionized magnesium and pH in whole blood, serum and plasma. Two values are obtained in analyzing the ionized fractions of magnesium and calcium--one at the actual pH and another at a recalculated measurement for pH = 7.4. Direct determination of ionized calcium and ionized magnesium simultaneously with that of the other electrolytes is of great clinical significance. It is only recently that ion-selective analysis of ionized magnesium has been proposed. The analytical reliability of the results and the operational characteristics of the Microlyte 6 ion-selective analyzer were evaluated for approximately one year. The coefficient of variation of the results in the reference and pathological range was 0.49%-2.23%, and 0.68%-4.42% for the within-run and between-run series, respectively. The inaccuracy of the results expressed by d% was from -4.23% to +4.06%. The comparative evaluation of the results for potassium, sodium, chloride, and ionized calcium between Microlyte-6 and the clinical chemistry analyzer Dynamic (Kone) showed a high correlation (correlation coefficient in the range 0.9868-0.9970). The correlation between the results for the ionized fraction and those obtained for total magnesium was consistent with that generally given in the literature.

Chemistry, Clinical↗
PubMed1995

Central effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) in mice.

The central effects of endothelin-1 (ET-1, 0.5, 1, 2.5 and 10 pmol/mouse) and endothelin-3 (ET-3, 2.5, 5, 10, 20 and 25 pmol/mouse) have been studied after intracerebroventricular (i.c.v.) administration in mice. The following methods were used: behavioral observations, rotarod, spontaneous and amphetamine-stimulated motor activity, and hexobarbital-induced narcosis. ET-1 and ET-3 evoked a dose-dependent behavioral syndrome with a short excitatory period in the higher doses lasting for 5-10 min, followed by a prolonged depressive phase (about 90 min). ET-1 and ET-3 produced central depressive effects demonstrated by depressive behavior signs, decrease of the spontaneous and amphetamine-stimulated motor activity, and prolongation of the hexobarbital-induced narcosis.

Amphetamine↗
PubMed1993

Endothelin-1 exacerbates focal cerebral ischemia without exerting neurotoxic action in vitro.

In a model of focal cerebral ischemia in mice, intracisternal injection of 5 and 10 pmol/mouse endothelin-1 significantly increased the infarcted surface area by 15.5% and by 23.5%, respectively. Endothelin-1 (0.01, 1, and 100 nmol/l) added to the primary neuronal cultures of chick embryo cerebral hemispheres for 1 h and 24 h did not influence the viability of the neurons or the protein content of the cultures. When applied simultaneously with 1 mmol/l sodium cyanide for 30 min, endothelin-1 (0.01, 1, and 100 nM) did not modify the hypoxia-induced changes. The results show that exogenously applied endothelin-1 could exacerbate cerebral ischemia, probably due to its vasoconstrictive properties and not to a direct neurotoxic effect.

Animals↗
PubMed1993

Antinociceptive effect of centrally administered endothelin-1 and endothelin-3 in the mouse.

The antinociceptive effects of centrally administered (i.c.v.) endothelin-1 (ET-1) and endothelin-3 (ET-3) were studied in mice by the use of 3 experimental procedures: hot plate, tail flick and acetic acid writhing tests. ET-1 (0.625-5 pmol/mouse) and ET-3 (2.5-25 pmol/mouse) produced statistically significant increase of the hot plate and tail flick latencies with duration of about 120 min. ET-3 showed weaker antinociceptive effect. ET-1 inhibited acetic acid-induced writhings with ED50 = 1.9 (1.1-2.7) pmol/mouse. With ET-3 a maximum effect of 45.2% suppression of the writhing response was achieved at 5 pmol/mouse. The antinociception due to ET-1 and ET-3 was not antagonized by naloxone and is thus independent of endogenous opioid release.

Analgesics↗
PubMed1992

Clinical meaning of GGT activity in follow-up of patients with alcohol-related liver injury and cholestasis.

The dynamics of GGT was investigated in three groups of patients after removing some primary causes of GGT increase. Group A included 34 patients with alcohol-related liver disease, group B included 16 patients with alcoholic liver injury and cholestasis, caused by concomitant alcoholic pancreatitis and group C included 17 patients with extrahepatic cholestasis, caused by choledocholithiasis. Follow-up assays of GGT were performed on the 7th, 14th and 30th days. Our results showed that the dynamics of GGT was more rapid after removing the cause for cholestasis than in stopping alcohol consumption in patients with chronic liver diseases. On the 14th day more than a 50% decrease in GGT activity was noted in 20% of the patients from groups A and B and in almost all cases from group C. On the 30th day, the reference range of GGT was not attained by any of the patients with liver disease nor in five patients from group C. No significant correlation was found between the severity of liver damage and the extent of GGT increase at the beginning and at the end of the follow-up period.

Cholestasis↗
PubMed1992

Effects of intracerebroventricular endothelin-1 on CNS and cerebral hypoxia/ischemia and their modification by cinnarizine.

The central effects of endothelin-1 (ET-1) and their modification by the calcium entry blocker cinnarizine have been investigated using CNS and hypoxia/ischemia tests. CNS tests comprised behavior, horizontal and vertical motor activity and hot plate test. Hypoxia/ischemia tests used were hypobaric hypoxia and complete ischemia by decapitation. ET-1 was injected intracerebroventricularly (i.c.v.) in a volume of 0.01 ml at doses of 1.25, 2.5 and 5 pmol/mouse 15 min before the tests. Cinnarizine (10 mg/kg, i.p.) was administered 60 min prior to ET-1. The i.c.v. ET-1 at all the doses used decreased horizontal and vertical motor activity and produced barrel-rolling. Survival/gasping time of mice subjected to hypoxia/ischemia increased dose-dependently. ET-1 showed an antinociceptive effect. Cinnarizine attenuated the appearance of barrel-rolling, did not antagonize disturbances in motor activity and reversed the antinociceptive effect of ET-1. In hypobaric hypoxia and decapitation cinnarizine antagonized the effects of 5 pmol/mouse ET-1 and potentiated that of 1.25 pmol/mouse. The pharmacological modification of the ET-1 effects by cinnarizine strongly suggests that the CNS actions of ET-1 might be due to multiple mechanisms triggered by an increased influx of extracellular Ca2+ into the brain cells.

Air Pressure↗
PubMed1992

Intracerebroventricular endothelin-1 (ET-1) produces Ca(2+)-mediated antinociception in mice.

Intracerebroventricular (i.c.v.) administration of endothelin-1 (ET-1) at doses of 0.313, 0.625, 1.25, 2.5 and 5 pmol/mouse produced a strong antinociceptive effect as evaluated by hot plate method in mice. The effect was dose-dependent and lasted for more than 120 min. The opioid receptor antagonist naloxone did not antagonize, and the cyclooxygenase inhibitors indomethacin and diclofenac slightly inhibited the ET-1 effect. The calcium overload blocker cinnarizine antagonized the antinociceptive effect of ET-1, suggesting that the ET-1 effect might be Ca(2+)-mediated.

Analgesia↗
PubMed1990

Eicosanoids in rat brain during ischemia and reperfusion--correlation to DC depolarization.

The effects of complete ischemia on cerebral arachidonic acid (AA) metabolism were investigated in the isolated perfused rat brain. During 12.5 min of ischemia, AA, 5-hydroxy-6,8,11,14-eicosatetraenoic acid, and 15-hydroxy-5,8,11,13-eicosatetraenoic acid increased 129-, 4-, and 10-fold, respectively, while subsequent reperfusion for 30 min resulted in normalized levels independently of the duration of preceding ischemia. Prostaglandin (PG) F2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha, and thromboxane (Tx) B2 remained at preischemic levels during 12.5 min of complete ischemia. However, at the end of subsequent reperfusion for 30 min, the levels of the prostanoids PGF2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha, and TxB2 increased according to the preceding ischemic time. The levels reached a maximum after 7.5 min of ischemia and were elevated by 7-, 14-, 48-, 3-, and 30-fold, respectively. A prolongation of ischemia of up to 12.5 min was not associated with further increases of prostanoids at the end of reperfusion. The mechanisms underlying the metabolism of eicosanoids are discussed in relation to the changes of cortical direct current potential.

Animals↗
PubMed1990

Rheoencephalographic and electroencephalographic studies on flunarizine.

The effect of flunarizine on the rheoncephalogram (REG) and on spontaneous electroencephalographic activity (EEG) was studied in acute experiments in cats. The following REG parameters were assayed: amplitude, anacrotic section of the curve and its relative part, and dicrotic index. EEG spectra were derived from 10-sec samples of EEG and the relative amplitudes were estimated at 2 Hz-intervals from 0-40 Hz. The REG study showed that flunarizine (2.5 and 5 mg/kg i.v.) caused an increase of the amplitude and a decrease of the anacrote, of its relative part, and the dicrotic index, changes indicating a lowering of the cerebrovascular resistance. EEG study showed a decrease of the amplitudes of the alpha-frequency band, and an increase of the fast-waves amplitudes, most pronounced at 5 mg/kg, changes showing enhancement of the activation processes in the brain cortex.

Animals↗
PubMed1990

Rheoencephalographic and electroencephalographic studies on nicergoline.

The effect of nicergoline on the rheoencephalogram (REG) and on spontaneous electroencephalographic activity (EEG) was studied in acute experiments in cats. The following REG parameters were assayed: amplitude, anacrotic section of the curve and its relative part and dicrotic index. EEG spectra were derived from 10-sec samples of ECoG and the relative amplitude was estimated at 2 Hz-intervals from 0-44 Hz. The REG study showed that nicergoline (0.05 mg/kg i.v.) caused an increase of the amplitude, and a decrease of the anacrote, of the relative part of the anacrote and the dicrotic index - changes indicating a lowering of cerebrovascular resistance. EEG study showed a decrease of the slow activities (theta and delta), and an increase of the fast activities (alpha and beta-1).

Animals↗
PubMed1989

Streptozotocin-induced diabetes in rat. III. Antioxidant protection of vascular complications by flunarizine and aligeron.

In rats with streptozotocin-induced diabetes antioxidant protection of diabetic angiopathy was performed by flunarizine (10 mg/kg/day) and aligeron (10 mg/kg/day), applied intraperitoneally during 2.5 months of diabetes. Diabetic vascular complications were assessed by morphologic determination of PAS-positive mucopolysaccharides and measurement of vascular wall thickness in addition to quantitative estimation of lipid hydroperoxides, thromboxane A2/prostacyclin disbalance and plasma beta-thromboglobulin changes. Both drugs prevented development of diabetic angiopathy in rats by inhibition of lipid peroxidation, prostanoid synthesis and platelet activity, but the effect of flunarizine was more pronounced, which could be explained by its additional blocking effect of abnormal calcium flux into vascular cells. The free radical scavenging action of flunarizine and aligeron was investigated.

Animals↗
PubMed1989

Effects of nicergoline in experimental models related to pathogenesis of migraine.

The effect of nicergoline on cerebral blood flow (CBF), cerebrovascular resistance, the constriction of cerebral vessels caused reflectorily or by 5-hydroxytryptamine (5-HT) and on the transport of 5-HT in rat brain synaptosomes was studied using different experimental models. Nicergoline reduced cerebrovascular resistance in the carotid and vertebrobasilar system. The drug decreased carotid blood flow and local cortical CBF, preceded in some experiments by short-lasting CBF increase. Nicergoline almost completely inhibited brain vessels responses in the carotid and vertebrobasilar systems after tibial nerve stimulation. Simultaneously, inhibition of reflectory discharges of the sympathetic nerves was observed. Nicergoline showed an antiserotonin action by antagonizing the 5-HT effect on the cerebral circulation and inhibiting 5-HT-induced constriction of isolated rabbit basilar artery. The inhibition of uptake and enhancement of the release of 5-HT from brain synaptosomes indicates its ability to affect neuronal transmission in serotoninergic neurons. The effects of nicergoline are probably involved in the realization of its antimigraine action.

Animals↗
PubMed1989

Prostacyclin as a cerebroprotective agent against brain hypoxia.

The cerebroprotective effect of prostacyclin (PGI2) was studied using the following methods: hypobaric hypoxia in mice, anoxic hypoxia in mice, complete ischemia by decapitation in mice, hypoventilation hypoxia in cats, and hypovolemic hypoxia in cats. PGI2 induced a dose-dependent prolongation of the survival time of mice, when administered either I.C.V. (0.001-10/micrograms/mice), I.V. (0.5-500/micrograms/kg), or I.P. (50-500/micrograms/kg). In the experiments on cats PGI2 (250 ng/kg/min I.V.) led to a significant improvement of the hypoxic ECoG. In another series of experiments, an interaction of some cerebroprotective agents with the anti-hypoxic effect of PGI2 was investigated. Piracetam, meclofenoxate, nicergoline, naftidrofuryl, cinnarizine, and nifedipine shifted the anti-hypoxic dose-response curve of PGI2 to the left indicating synergistic interaction. The results obtained suggest the function of PGI2 as a cerebroprotective prostanoid in brain hypoxia.

Animals↗