Biomedical subjects
Publications and source records attributed to M Nikolova.
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The levels of CD98 antigen expression were studied in 62 consecutive cases of adult acute leukemia including 24 acute lymphoblastic leukemia (ALL) and 38 acute myeloid leukemia (AML) using the monoclonal antibody CAF7 and flow cytometry. The mean follow-up was 13.5 months. The mean relative fluorescence intensity (MIF) of CAF7 varied between 6 and 83 channels (256 channels resolution). No correlation was established between CAF7 cell surface density and most of the predictive parameters such as age, sex, blood counts, immunophenotype, proliferative index (PI) or DNA index. Nevertheless expression of CAF7 correlated positively with survival duration (mean 210 vs 391 days, P = 0.048) and complete remission (CR) duration (mean 132 vs 361, days P = 0.032). The levels of CAF7 differed significantly between ALL and AML (P < 0.001), the ALL cases being all CAF7intermediate or CAF7high. In the AML group the low levels of CAF7 expression correlated with shorter CR duration (mean 132 vs 414 days, P = 0.017). The lack of correlation with other clinical and biological parameters suggested that CAF7 might have an independent prognostic significance in adult AML. Although PI was also positively related to survival duration (P = 0.02), it did not correlate with CR duration or the expression of CAF7. We suppose that the prognostic impact of CD98 is related to the control of cell growth and survival in which the molecule normally participates.
The Nkx2.6 gene belongs to the NK superfamily of homeobox genes (Harvey, 1996). We report here the expression pattern of the murine Nkx2.6 gene during early mouse development, which is unique among the NK family of homeobox genes in that its expression is restricted to the very narrow development period between stages E8.5 and E10.5 of embryogenesis. The distribution of Nkx2.6 transcripts is also quite restricted spatially, with expression detected uniquely within the caudal branchial arches. Nkx2.6 is expressed in all three layers comprising the caudal branchial arches (ectoderm, mesectoderm and endoderm) with the strongest expression being detected in the surface ectoderm.
A study has been made of 36 body and 11 craniofacial measurements in a selected sample of 251 Bulgarian families, comprising parents and their children over 15 years. The mid parent-offspring and correlation coefficients indicate that the extent of genetic determination varies considerably from one measurement to another. There is an evidence of directional dominance for three body traits and for two craniofacial traits. None of the different parent-offspring correlations is compatible with X-linked inheritance. A greater maternal than paternal influence is evident for biacromial diameter but a greater paternal influence is seen for head height, nose height and for ear height and breadth.
The expression of a novel B-cell-associated carbohydrate epitope (1D8) was studied by means of flow cytometry in 153 well defined cases of leukemias and lymphomas and 19 cases of lymphadenopathy used as controls. The 1D8 epitope was detected preferentially in proliferations of mature B-lymphocytes (11/15 CD20+ acute lymphoblastic leukemia (ALL), 14/16 chronic lymphocytic leukemia (CLL), 4/7 mantle cell non-Hodgkins lymphoma (NHL), 3/8 follicle cell NHL. However its expression did not appear lineage- or differentiation stage-restricted. Intensive expression on in vivo and in vitro-activated lymphocytes as well as in some high grade malignancies indicated a relationship to the functional state of cells. Bearing in mind the enhanced detection of 1D8 upon desialylation, the epitope might be involved in the regulation of adhesion/migration potential of normal leukocytes and their malignant counterparts.
A novel murine monoclonal antibody (MAb) 1D8 was produced after immunization with the nylon wool-adherent fraction of human peripheral blood mononuclear cells (PBMNC). Its reactivity pattern was studied on a panel of hemopoetic normal cells, cell lines and malignancies. Mab 1D8 detects a lymphocyte-specific surface antigen expressed on a major subpopulation of mature B lymphocytes as well as on a minor T-cell subset. Activation-related changes in the expression of 1D8 molecule were observed on both B and T lymphocytes. As compared with the pattern of known activation-associated antigens, 1D8 seems to play a role in the early stages of lymphocyte activation. The antigen could not be immunoprecipitated by the conventional methods for glycoproteins.
Fifteen original piperazine derivatives were synthesized: 11 esters of 1-substituted-4-(3'-phenyl-3'-hydroxypropyl)-piperazines with acetic, propionic, benzoic and phenylacetic acids and 4 symmetrical esters of 1,4-bis-(3'-phenyl-3'-hydroxypropyl)-piperazine with acetic, propionic, benzoic and phenylacetic acids. The compounds were tested with respect to their analgesic and behavioural activity, as well as toxicity. Three nociceptive tests were used: chemical intraperitoneal irritation with acetic acid, thermal contact irritation and thermal radiation irritation. The tests were performed on albino mice breed H. All tested compounds were biologically active and showed analgesic effect. The "therapeutic index" was determined on the basis of the mean effective doses (ED50) and the mean lethal doses (LD50). Most favorable "therapeutical" indices were distinguished in 1,4-bis[3'-phenyl-3'-acetoxypropyl]-piperazine (12), 1-benzhydryl-4[3'-benzyloxypropyl]-piperazine (10) and 1-benzhydryl-4[3'-phenyl-3'-phenylacetyloxypropyl]-piperazine (11).
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.
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).
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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.
A beneficial stabilizing effect of nicergoline on EEG recorded from cortex and some subcortical structures was established in cats under acute normal and anoxic conditions.
The effects of flunarizine and fezam on the local cerebral blood flow (LCBT) were examined by the hydrogen clearance with inhalation of hydrogen. The experiments were carried out on male nonbred cats under cetamine narcosis. The results showed that flunarizine (1 mg/kg i.v.) induced apparent enhancement of LCBF with 58% in comparison with the control values. The effect was read up to 60 min. The combined preparation fezam (100 mg/kg i.v.) caused considerable improvement of LCBF 30 min after inhalation with 63% in comparison with the control values. It is suggested that the observed effects are due to Ca-blocking action on cerebral vessels after flunarizine treatment as well as a reduction of cerebral-vascular resistance and influence on the metabolism after the combination fezam.
The effects of a new benzamide derivative LIS-630 and the well-known neuroleptic, tiapride, were studied on stress-induced hyper- and hypoactive emotional behavioral reaction of animals depending on the individual ability for perceptive-cognitive activity in stress situations, and their affinity to striatal DA receptors. A modified variant of forced swimming method was used. The affinity of the substances to striatal DA receptors was studied by the radioligand binding method using 3H-spiroperidol. The results show that the psychopharmacological profile of LIS-630 differs significantly from the neuroleptic, tiapride. LIS-630 restored escape behavior from stress situation after preliminary exposure of rats to forced swimming and did not disturb escape behavior in animals more resistant to emotional hypoactivity. LIS-630 reduced immobility time at forced swimming. However, it is not effective in preventing hyperemotional reactions induced by L-dopa and stress. The radioligand binding study shows that LIS-630 did not displace 3H-spiroperidol from the binding sites of striatum membranes. The parameters of displacement with tiapride were satisfactory.
The anti-amnestic action of nicergoline was studied using the following experimental methods for learning and memory impairment, based on passive avoidance response: amnesia induced by maximal electroshock in mice, scopolamine-induced amnesia in mice and amnesia by paradoxical sleep deprivation in rats. Piracetam, meclofenoxate, pyritinol, deanol and phenazepam were used as reference drugs. The results show that nicergoline demonstrates well-expressed anti-amnestic effect manifested by reducing the amnestic effect of maximal electroshock, scopolamine or paradoxical sleep deprivation, its effect being equal to or more pronounced than piracetam, meclofenoxate, pyritinol, deanol and phenazepam.
The cerebroprotective effect of nicergoline was studied using the following experimental methods: hypobaric and anoxic hypoxia in mice, complete ischemia by decapitation in mice, incomplete ischemia by bilateral carotid ligation in rats, hemic hypoxia in rats and asphyxic anoxia in cats. Xanthinol nicotinate, vincamine, vinpocetine and cinnarizine were used as reference drugs. In hypobaric hypoxia and complete ischemia by decapitation the interaction of nicergoline with the effect of prostacyclin (PGI2) was investigated. Nicergoline showed cerebroprotective effect of varying potency in all the methods used except asphyxic anoxia. Nicergoline manifested a synergic effect with PGI2 shifting its anti-hypoxic dose-response curve to the left.
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The antagonistic action of aligeron as compared to that of papaverine against different smooth muscle stimuli was studied in experiments in vitro. Three series of experiments were conducted: study of the antagonistic action against experimental spasms of isolated organs caused by different spasmogens; determination of the type of antagonism to adrenaline in isolated vas deferens preparation; and study of the antagonistic action against vasoconstrictor effects of noradrenaline and adrenaline in isolated perfused rabbit renal artery. Aligeron showed a broad spectrum of antagonistic action against different spasmogens in different isolated organs. Its effect was more pronounced than that of papaverine. The antagonism was of the non-competitive type. The experiments on isolated perfused rabbit artery showed the antagonistic action of aligeron against the vasoconstrictor effects of noradrenaline and adrenaline. The results suggest the clinical use of aligeron in conditions associated with increased release of these vasoactive substances.