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Biomedical subjects

M Neagu

Publications and source records attributed to M Neagu.

At least 19 recordsLinked to original sources

On the Na+,K+ pump in fluctuating membrane potentials.

The present work investigates the usefulness of noise in the activity of the Na+,K+ pump. Random gating activity of the neighboring ion channels causes local fluctuations of the electric potential. They are modeled by a Markovian symmetric dichotomic noise, added to the membrane potential. The noise-averaged pump current is calculated for a general rectangular voltage signal and the model parameters of the effective two-state enzyme cycle are tuned to fit experimental results. Then, using these parameters, the amount of transported charge is calculated, and studied as a function of noise intensity. Signal and noise characteristics are identified at which fluctuations enhance pump activity. The biological impact of this phenomenon seems to be absent in physiological conditions for it occurs at noise amplitudes over 50 mV, which are unlikely to appear due to ion channels. However, under some conditions, externally applied dichotomic noise of intensity about 150 mV may sensibly increase the quantity of transported charge.

Biophysical Phenomena↗

Fluctuations and the Hofmeister effect.

The Hofmeister effect consists in changes of protein solubility triggered by neutral electrolyte cosolutes. Based on the assumption that salts cause stochastic fluctuations of the free energy barrier profiles, a kinetic theory of this phenomenon is proposed. An exponentially correlated noise, of amplitude proportional to the salt concentration, is added to each energy level, and the time-dependence of the mean protein concentration is calculated. It is found that the theory yields the well-known Setschenow equation if the noise correlation time is low in comparison to the aggregation time constant. Experimental data on salting-in agents are well fitted, whereas, in the case of salting-out cosolutes, two independent dichotomic fluctuations are needed to fit the data. This may result from the fact that, in both cases, the low-concentration regime is dominated by salting-in electrostatic contributions, whereas, at high salt concentrations, electron donor/acceptor interactions become important; these have opposite effects. The theory offers a novel way to metricate Hofmeister effects and also leads to thermodynamic quantities, which account for the influence of salts. The formalism may also be applied to describe kinetic phenomena in the presence of cosolutes.

Electrolytes↗

The in vitro effect of a low molecular weight heparin, nadroparin (Fraxiparine), on leukocytes obtained from patients with vascular diseases.

BACKGROUND: Both lymphocytes and granulocytes may play a role in the immune system-mediated inflammatory response associated with non-Q wave infarction and aortic aneurysms. METHODS: The purpose of this study was to establish the in vitro effects of a low molecular weight heparin (LMWH), nadroparin (Fraxiparine), on some functional parameters of peripheral granulocytes and lymphocytes isolated from control subjects and patients with aortic aneurysm or non-Q wave infarction. RESULTS: Nadroparin (0.06-600 AXaU/ml) exerted different in vitro effects on granulocytes and lymphocytes isolated from normal subjects and the patient groups. The following indices were assessed: superoxide anion release, lymphocyte proliferation, phagocytic activity and the cellular respiratory burst. The effects of nadroparin varied according to the patient group and the index of lymphocyte/granulocyte assessed. CONCLUSIONS: Since peripheral granulocytes isolated from these patients are activated, the observed inhibition exerted by nadroparin on superoxide anion release may be beneficial. LMWHs have additional effects that are independent of their anticoagulant activity. These effects may influence the "inflammatory component" of the atherosclerotic process.

Aged↗

Selective immunosuppression by administration of major histocompatibility complex class II-binding peptides. II. Preventive inhibition of primary and secondary in vivo antibody responses.

The self-mouse lysozyme peptide corresponding to residues 46-62 (ML46-62) binds to the major histocompatibility complex (MHC) class II molecules I-A(k) and it selectively inhibits, when coinjected with antigen, priming of I-A(k)-restricted, antigen-specific T cells. We demonstrate that administration of ML46-62 also inhibits in vivo antibody responses induced by I-A(k)-restricted T helper cells. ML46-62 is able to prevent the primary anti-hen egg white lysozyme (HEL) antibody response induced by the entire HEL molecule in B10.A(4R) mice, expressing only I-A(k) molecules, but not in mice of H-2d haplotype. ML46-62 also strongly decreases, in B10.A(4R) mice, the antibody response to ribonuclease A, a protein antigen unrelated to the MHC blocker, indicating that MHC blockade is the mechanism leading to inhibition of antibody response. This is further supported by the concomitant decrease, in vivo, of complex formation between immunodominant HEL peptides and I-A(k) molecules, preventing I-A(k)-restricted T cell induction. Administration of ML46-62 after antigen priming does not affect ongoing antibody responses, as expected from MHC blockade. A single injection of ML46-62 at the time of protein antigen priming precludes not only the primary, but also the secondary antibody response to a subsequent challenge with soluble protein, even when the challenge is performed several months after priming. Coinjection of antigen and MHC antagonist inhibits production of all antibody isotypes equally well, suggesting that MHC class II blockade affects both Th1- and Th2-type T helper cells. Therefore, these results indicate that administration of MHC class II-binding peptides can efficiently and selectively prevent the induction of T cell-dependent primary and secondary in vivo antibody responses by blocking antigen presentation to class II-restricted T helper cells.

Animals↗

In vivo and in vitro effect of Cantastim, an immunomodulatory agent extracted from a highly pathogenic Pseudomonas aeruginosa strain.

Cantastim is a biological product consisting of distinct molecules of phospholipids obtained from a peculiar Pseudomonas aeruginosa strain. It enhanced the IgM and especially the IgG responses of mice pretreated with Cantastim and then intraperitoneally inoculated with T-dependent antigens such as sheep erythrocytes; restored cellular immunocompetence as evidenced by an increase in the in vitro proliferative responses to T-cell mitogens and allogeneic stimuli of murine splenocytes from in vivo pretreated mice activated NK cytotoxicity, and inhibited in vivo growth of the Ehrlich ascites tumor. In vitro it stimulated the mitogenesis of mouse lymphocytes but did not exert such stimulatory effect on guinea pig or human lymphocytes. All these findings allow to define Cantastim as an immunomodulating agent influencing mainly the cell-mediated immune response.

Adjuvants, Immunologic↗

Effects of synovial fluid on the respiratory burst of granulocytes in rheumatoid arthritis.

Neutrophil infiltration in the synovia is an important feature of the local inflammatory process associated with rheumatoid arthritis. The present study is focused on the effects exerted in vitro by the synovial fluid versus serum on the respiratory burst of granulocytes isolated either from blood or synovial fluid of rheumatoid arthritis patients. The respiratory burst was evaluated as superoxide anion release, by lucigenin-amplified chemiluminescence. Our data show that the respiratory burst of granulocytes isolated from rheumatoid arthritis patients might trigger a significant oxidative stress both in periphery and the inflamed joint. These cells show no pathological pattern when activated in vitro by the chemotactic peptide fMLP, heterologous synovial fluid or serum. Acellular synovial fluid amplifies the superoxide anion release induced by fMLP more than the corresponding serum, indicating that a bacterial infection in the joint might enhance the oxidative damage in the inflamed synovium.

Arthritis, Rheumatoid↗

[Parinaud's dermoepithelioma].

The paper presents the clinical and histopathological findings in 18 cases with Parinaud dermoepithelioma an uncommon tumor of the conjunctiva, in a retrospective study made on patients who were investigated in our clinic, during January 1975-January 1995.

Carcinoma↗

Peripheral leukocytes activation in aortic aneurysmal disease.

The pathogenesis of aneurysmal disease involves factors acting over time. A sustained chronic inflammatory reaction is observed in association with initiations, maintenance, rapid growth and rupture of aortic aneurysms. This study was designed to identify the possible pathogenic role of the inflammatory cells in the outcome of aneurysmal disease, testing the activation state of peripheral lymphocytes and neutrophils. Circulating activated lymphocytes and repeated peaks of neutrophils activation in sequential follow-up is associated with larger aneurysms, mural thrombosis, tendency to aneurysm extension and rupture.

Aged↗

The in vitro action of a succussed substance on the proliferative response of human lymphocytes stimulated with phytohemagglutinin.

Human peripheral blood lymphocytes from healthy controls, immunodepressed patients presenting chronic bacterial infections or neoplasias and from allergic patients were stimulated in vitro with phytohemagglutinin (PHA) in culture medium supplemented or not with 1 x 10(-7), 1 x 10(-15) or 1 x 10(-30) succussed dilutions or bee venom or phosphorus in tridistilled water. The most significant inhibition due to DNA incorporation was noted in lymphocytes from allergic patients cultivated in media supplemented with 1 x 10(-30) succussed substance dilution in the presence of PHA. The cells from immunodepressed patients did not show a significant inhibition at 1 x 10(-30) dilution. Hypothetically, we try to explain these findings as the expression of the changes induced by the succussed solution on the water molecule which in turn, influences the chemical structure of the cellular membrane and implicitly, its functions.

Bee Venoms↗

Flow cytometry measurements of intracellular Ca2+ in K 562 cells.

The aim of this study is to show the intracellular Ca2+ changes induced by methotrexate, a cell cycle inhibitor, in order to prove the intracellular Ca2+ implication in cell proliferation processes. The fluorescent dye used to measure this parameter is Fluo-3, a fluorescein derivative useful for measuring the kinetics of Ca2+ transitions, waves and oscillations. The alterations of Ca2+ concentration proper to K562 cells have been studied, using methotrexate as a cell activation factor, both as direct effects on the cell response (1-15 minutes), and effects in time (24h.), using methotrexate in the culture medium. The K562 response at Ca2+ level in time remained constant for the cells grown in methotrexate medium, showing a slight increase in the control medium. We proved that methotrexate, a cell cycle inhibitor decreased the cytoplasmatic Ca2+ concentration in K562 cells, soon after adding methotrexate both to T0 and T1.

Aniline Compounds↗

[Inframicrobiological research on cases of insulin-dependent diabetes mellitus].

A group of 55 patients with insulin-dependent diabetes mellitus, aged from 8 to 40 years, was followed and compared to a group of controls, in view of detecting a possible relation between the presence of inframicrobial agents and diabetes pathogenesis. The investigations revealed, in patients, significantly higher positivity rate of antibodies against mumps (27% versus 16.3% in controls), parainfluenza type 1 (45.4% versus 29.1%) and Epstein-Barr (54.5% versus 10.9%) viruses, and Mycoplasma pneumoniae (43.6 versus 18.2%).

Adolescent↗

[A nonspecific immunostimulant effect with Cantastim on the cellular and humoral immune responses in mice evaluated by in vivo and in vitro tests].

The stimulatory effect was evaluated, of an ethanol extraction obtained from a pathogenic strain of Pseudomonas aeruginosa type XV. It was noted that this extract, commercially known as "Cantastim" has mitogenic effects in vitro for mouse lymphocytes, but not for those of humans or of guinea pigs. It activates the cytostatic functions of macrophages. It is thermoresistant, nonimmunogenic and it is not allergic. A low amount of proteins and carbohydrates are contained in this extract, but it contains over 80% phospholipids. It has a transient stimulating effect of the cytotoxic effects of NK cells, and it also activates the synthesis of antibodies from the IgM and the IgG classes. It probably stimulates the expression of receptors for PHA in the membrane of T lymphocytes, and retards the development of the Ehrlich ascites tumour, protecting at the same time the animals from severe infections with conditionally pathogenic germs. These data suggests that "Cantastim" is a potent immunomodulating agent that could be used successfully in the fight against certain chronic diseases with a bacterial or neoplastic etiology of humans.

Adjuvants, Immunologic↗