Biomedical subjects

S Maśliński

Publications and source records attributed to S Maśliński.

At least 19 recordsLinked to original sources

PubMed2001

Accumulation, distribution and phenotype heterogeneity of mast cells (MC) in human brains with neurocysticercosis.

Neurocysticercosis (NCC) is one of the most common parasitic brain infections in the world NCC can cause widely varied clinical manifestations, mainly due to the host immune-inflammatory response. The immunological hallmark of the infection with helminth parasites is infiltration into the inflamed mucosa of the gastrointestinal tract of numerous mast cells. It has been postulated that mediators released by activated mast cells might contribute to the local inflammatory response. Since data concerning the association of mast cells with neurocysticercosis are not available, the aim of our study is to determine the distribution and phenotypes of mast cells in human brain infested by cysticerci. The study was performed on 20 human autopsy brains. Mast cells (MC) were identified by means of immunohistochemical method using specific MC tryptase and chymase monoclonal antibodies. In the control brains, mast cells were very few and showed a very sparse distribution. They had been occasionally found in meninges and in perivascular areas of some brain blood vessels. Those cells were mainly tryptase-chymase phenotype (MCTTC). In contrast, in the brain sections with neurocysticercosis, mast cells were numerous. A striking feature of identified mast cells was their phenotype heterogeneity. The tryptase mast cells (MCT) phenotype dominated over the tryptase-chymase (MCTC) phenotype. MCT infiltrated mainly meninges and brain parenchyma around cysts with viable and necrotic parasites. MCTC infiltrated perivascular area of the blood vessels penetrating to the depth of the brain. Summarising, this is the first report which documents the accumulation and phenotype heterogeneity of mast cells in human brains with neurocysticercosis. Our findings suggest that the effector mechanism responsible for the host responses to the parasitic infection that involves numerous mast cells in the human brain may be very important for pathomechanism of this disease.

Adolescent↗

PubMed1998

Ligation of selectin L and integrin CD11b/CD18 (Mac-1) induces release of gelatinase B (MMP-9) from human neutrophils.

OBJECTIVE AND DESIGN: To examine whether ligation of the adhesive receptors - selectin L and Mac-1 on the neutrophil surface could induce gelatinase B exocytosis. MATERIALS: Neutrophils were isolated from fresh heparinized blood of human donors by Gradisol G centrifugation and hypotonic lysis of erythrocytes. METHODS: Integrin CD1 1b/CD18 and selectin L mediated adhesive interaction of human neutrophils were mimicked by binding antibodies to these receptors on the surface of isolated leukocytes. Neutrophils (5 x 10(6)/ml) were incubated with antibodies against selectin L (40/microg/ml) and CD18 or CDI 1b (10microg/ml). The secretion of gelatinase was examined by determination of enzyme activity and gelatin substrate zymography of cell supernatants. RESULTS: Ligation of selectin L, CD18 and CD11b integrin subunits by monoclonal antibodies induced a rapid release of 24.6+/-1.8% (p<0.005), 24.0+/-2.9% (p<0.001) and 22.7+/-2.0% (p < 0.005) of total neutrophil gelatinase, respectively as compared with 11.1+/-1.6% in the control. These values were equivalent to N-formyl-methionylleucyl-phenylalanine (fMLP)-stimulated secretion of gelatinase. Under these experimental conditions there was no significant beta-glucuronidase release from azurophilic granules. Gelatinase exocytosis elicited by selectin L and CD18 ligation was inhibited by 82.7+/-10.1% and 49.3+/-5.9%, respectively after preincubation of the neutrophils with 10 microM herbimycin A. CONCLUSIONS: Ligation of selectin L and integrin CD11b/ CD18 provides stimulatory signals to neutrophils which induce secretion of gelatinase B that may facilitate their transmigration into sites of inflammation.

Antigens, Surface↗

PubMed1995

Neutrophil gelatinase levels in plasma and synovial fluid of patients with rheumatic diseases.

To examine the clinical significance of neutrophil gelatinase in rheumatic diseases, plasma and synovial fluid (SF) gelatinase levels were determined in 62 patients with rheumatoid arthritis (RA), 12 patients with ankylosing spondylitis (AS), 18 patients with osteoarthritis (OA) and 17 healthy controls. The gelatinase level was measured by enzyme-linked immunoassay (ELISA). The assay had a sensitivity of 1 ng/ml and a working range of 5-25 ng/ml. Gelatinase levels were significantly higher in the plasma of patients with RA and of patients with RA complicated by amyloidosis or vasculitis as compared to those of healthy controls. Moreover, the mean value of gelatinase in the plasma of patients with RA complicated by vasculitis was found to be significantly higher than that of RA patients without vasculitis. A significant increase in gelatinase concentration was also observed in the plasma of AS patients but not in the plasma of patients with OA. The concentration of gelatinase in the RA SF samples was much higher (18-fold) than the level of the enzyme in the plasma of RA patients. There was also a higher concentration of gelatinase (four-fold) in OA SF compared with OA plasma. The results suggested that circulating gelatinase may reflect some degree of neutrophil activation in patients with inflammatory arthritis, especially in those with RA complicated by vasculitis. However, the results did not allow a differentiation between chronic and acute inflammation.

Adult↗

PubMed1995

The neuromodulation aspects of ischaemic myocardium: the importance of cholinergic system.

The ability of the heart to increase contractility and heart rate is facilitated by postganglionic sympathetic nerve endings that terminate within myocardium. In fact, the heart is often regarded as an "adrenergic" organ because beta-adrenergic agonists are powerful stimulants of cardiac contractility. Muscarinic cholinergic receptors mediate parasympathetic control of heart function. A primary effects of the muscarinic stimulation are opposite to those of beta-adrenergic stimulation. The modulation of an adrenergic receptors stimulation in the heart by cholinergic agonists may be the major means by which the muscarinic agonists alter heart function. When the hypoxic myocytes were exposed to adrenaline, the responsiveness of the cardiac cells to muscarinic stimuli had significantly increased, and a simultaneous potent increase in the expression of muscarinic receptors was observed. These result support the hypothesis that in ischaemic/hypoxic myocardium the role of cholinergic system may be more important than previously assumed. In this review an attempt was made to summarize the physiological and biochemical interactions in an autonomic nervous system in an ischaemic myocardium. The evidences of a relationship between ischaemia and inflammation are discussed. The better knowledge of feasible interactions of neuromodulators of an autonomic nervous system with myocardial and inflammatory cells, should lead to the development of successful pharmacological strategies for the prevention of ischaemic injury.

Animals↗

PubMed1994

Gastric cytoprotective activity of endogenous 5-HT.

The role of endogenous serotinin in the formation of gastric damage was studied in rats. Stress ulcers were induced by ultrasounds, immobilization and immobilization plus cold. The damage of gastric mucosa was estimated (arbitrary scale) and serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in this tissue measured. In all examined groups of animals with gastric mucosal damages the lower levels of 5-HT and 5-HIAA in gastric mucosa were observed. In some experimental groups animals were treated with serotonergic receptor antagonists 30 min. before stress. The administration of ICS 205-930 (80 micrograms/kg), 5-HT3 receptor antagonist, and DAU-62855 (80 micrograms/kg), 5-HT4/5-HT3 receptors antagonist, reduced the intensity of stress gastric injuries. In contrast the administration of methysergide (8 mg/kg), 5-HT1/5-HT2 receptors antagonist, enhanced the stress gastric mucosa damage. 16, 16 dimethyl PGE2 (10 micrograms/kg) protected stomach against stress stimuli and accompanied increase of serotonin and 5-HIAA concentration in gastric mucosa was observed. Both 5-HT3/5-HT4 receptor antagonist had an additive cytoprotective effect when given in combination with PGE2 analog. In the presence of methysergide gastroprotective effect of PGE2 was abolished. The present studies demonstrate that cytoprotective effect of endogenous serotonin depends on 5-HT1 and 5-HT2 receptors stimulation in the gastric mucosa and the protective effect of prostaglandins depends partly on the regulation of serotonin metabolism.

Acoustic Stimulation↗

PubMed1993

Comparison of Delmée and Polish serogroup-specific Clostridium difficile strains.

In this study we compared Delmée and Polish serogroup-specific Clostridium difficile strains by slide agglutination, observation of flagella and SDS-PAGE protein patterns. Among Delmée serogroup specific strains we observed flagella in groups A, D and K. Among Polish serogroup-specific Clostridium difficile strains we did not observe flagella. The Polish serogroup-specific strains gave different protein patterns compared to Delmée strains. SDS-PAGE protein pattern analyses of Polish serogroup-specific strains divide these strains into 3 groups: 71, 88 and third embracing 18, 27, 70, 72, and 89.

Adult↗

PubMed1993

Enhanced responsiveness of rat cardiac myocytes to muscarinic cholinergic stimulation during chemically-induced hypoxia.

In contrast to adrenaline, exogenously administered cholinergic agonist, carbachol have very little effect on the contractility of rat cardiac myocytes, unless its contractile has been increased by adrenergic agonist. This interaction between the muscarinic and adrenergic pathways has been suggested to be the major means by which muscarinic agonist alters adrenergic function. When the cardiac myocytes were incubated in the medium contained the mitochondrial respiratory inhibitor potassium cyanide (chemically-induced hypoxia) the spontaneous contractility was ceased. The contractility partly recovered when the cells were exposed to adrenergicstimulation. We showed that during chemical hypoxia, in which cellular ATP is decreased (37% of control), the responsiveness of myocytes to muscarinic cholinergic stimulation significantly increase. Contraction of myocytes, stimulated by adrenaline was totally inhibited by 10(-4)M of carbachol in control cells and 5 x 10(-6)M of carbachol in cells with chemically-induced hypoxia. This increase in physiological response to muscarinic stimulation was associated with an increase of muscarinic receptors (630%). The results support the hypothesis that in ischaemic/hypoxic myocardium the role of cholinergic system may be more important than previously assumed.

Animals↗

PubMed1992

Fibronectin and fibrinogen degradation products stimulate PMN-leukocyte and mast cell degranulation.

The ability of various peptides cleaved by plasmin from human fibrinogen and fibronectin or fibrinogen- and fibronectin- related synthetic peptides to induce histamine release from mast cells and collagenase and elastase from PMN-leukocytes was examined. Low molecular weight fibrinogen degradation products showed dose dependent secretion of collagenase. These peptides (mol. wt. 1.4 kD) at the concentration of 10(-5) M released about 47% of collagenase and 13% of elastase. Synthetic fibrinopeptides A and B had a similar strong collagenase releasing potency and also released histamine from mast cells. Peptides from plasmin digestion of fibronectin containing cell attachment site with sequence Arg-Gly-Asp-Ser and also synthetic peptide reproducing this amino-acid sequence at the concentration of 1000 micrograms/ml released about 50% of collagenase and 55% of elastase from PMN-leukocytes. Moreover peptides containing cell attachment and gelatin binding site induced histamine release from mast cells. The association of fibrinogen and fibronectin degradation with activation of mast cells may motivate the treatment with antihistaminic drugs of all pathological conditions where the intensive protein degradation takes place.

Animals↗

PubMed1991

Activation of the latent human neutrophil gelatinase by urea.

The mechanism of activation of the latent human neutrophil gelatinase by urea has been studied in greater detail. After dialysis of the latent gelatinase against increasing concentrations of urea a considerable increase of its activity was observed. Moreover, the results indicate a progressive conversion of the latent 94,000 Da gelatinase into a proteolytically active fragment of 80,000 Da, which was subsequently processed to a few species of lower molecular mass inactive against gelatin. This conversion was completely inhibited by EDTA, suggesting an autocatalytic reaction. The inhibition was reversed by Zn2+ or Co2+. Thus, urea alters both the enzymatic and physical characteristics of the latent gelatinase which suggests that conformational changes may induce autoactivation of the latent enzyme.

Electrophoresis, Polyacrylamide Gel↗

PubMed1991

Increase in the expression of muscarinic cholinergic receptors in isolated, neonatal rat cardiac myocytes treated with potassium cyanide.

On treatment of rat cardiac myocytes with potassium cyanide, ATP content significantly and rapidly decreased in all experimental groups as compared to untreated cells. Contrary to that, the level of muscarinic cholinergic receptors increased significantly, depending on the cyanide concentration. Twenty four hours after removal of cyanide, myocytes exhibited normal levels of both the receptor expression and ATP content.

Adenosine Triphosphate↗

PubMed1991

Neutrophils-induced increase of adenosine triphosphate depletion in rat neonatal cardiac myocytes with impaired energy metabolism.

Isolated, cultured rat neonatal cardiac myocytes were placed in medium supplemented with mitochondrial respiratory inhibitor potassium cyanide which caused a rapid adenosine triphosphate (ATP) depletion. These myocytes with the impaired energy metabolism ("hypoxia-like state") were exposed to unstimulated human neutrophils. Effect of human neutrophils on the myocytes in the "hypoxia-like state" was quantified as a total change in the amount of ATP in cardiac cells. After 5 hours of incubation of neutrophils with the myocytes in the "hypoxia-like state" an additional decrease (of 50 per cent) in ATP content was observed. Since catalase (which destroys hydrogen peroxide) prevented the further decline in ATP level in the myocytes with impaired energy metabolism, it seem that hydrogen peroxide and possibly their products are responsible for this effect. These results suggest that unstimulated human neutrophils after activation by the contact with injured cardiac cells caused further decrease of ATP level in target cells.

Adenosine Triphosphate↗

PubMed1989

Neutrophil enzyme activities in carrageenan-induced inflammation in rats.

During the course of carrageenan-induced inflammation in rats major changes were observed in the activities of neutrophil granule enzymes. The activities of three enzymes--gelatinase, collagenase and beta-glucuronidase, the markers of three different types of granules, have been measured and compared to those of a control group of animals. Total collagenase and gelatinase activities of control rats were 59.4 +/- 3.6 (mean +/- SD) and 23.0 +/- 2.9 units/mg protein, respectively. Significantly reduced levels of both collagenase (35.6 +/- 2.5 units) (p less than 0.05) and gelatinase (7.1 +/- 0.7 units) (p less than 0.001) were measured in the blood neutrophils of inflamed rats; and the collagenase activity of neutrophils derived from inflamed pleural exudate was also significantly decreased to a level of 19.7 +/- 1.8 units/mg protein (p less than 0.01). However, the gelatinase activity of exudate neutrophils did not differ from that of blood cells of inflamed rats. In contrast, no change was found for the beta-glucuronidase activity in blood neutrophils of control and inflamed rats. These observations support the concept that during the inflammatory response in rats, neutrophils in the circulation may become activated as judged by the extracellular secretion of collagenase and gelatinase. Therefore, neutrophils accumulating in acute inflammatory lesions contain decreased levels of collagenolytic enzymes and the significance of this observation is discussed.

Animals↗

PubMed1988

Is histamine involved in ethanol-induced inflammation?

The participation of histamine in ethanol-induced inflammation has been estimated in rats. Administration of ethanol caused an increase in the total number of blood leukocytes and changed the composition of the leukocyte population. The histamine receptor antagonists mepyramine and cimetidine did not affect the changes in cellular composition. Pretreatment with the anti-allergic drug Tritoqualine had no effect on the total number of leukocytes and PMN-leukocytes. PMN-leukocytes from ethanol treated rats had a greater capacity to activate latent collagenase. This ability was partially inhibited by the histamine receptor antagonists mepyramine and cimetidine, particularly in combination. Pretreatment with Tritoqualine apparently protected the latent collagenase against ethanol activation. Thus we conclude that histamine is possibly implicated in the process of generating activity for latent collagenase.

Animals↗

PubMed1988

Anti-inflammatory drugs modulate histamine release from mast cells induced by fibrinogen degradation products.

The products resulting from proteolytic degradation of human fibrinogen (FDP) were found to induce the release of histamine from rat peritoneal mast cells. Low molecular weight, dialysable peptides (FDP) showed the highest dose dependent, histamine releasing activity. Histamine release induced by FDP was effectively inhibited by the gold compound auranofin at a concentration of 10(-5)-10(-7) mol/l and also by the non-steroidal anti-inflammatory drugs BW 755c, timegadine, medosan, naproxen, and aspirin at the higher concentration range of 10(-4)-10(-6) mol/l. It is concluded that the release of histamine from mast cells may be modulated to some extent by anti-inflammatory drugs, especially auranofin, BW 755c and timegadine, a functional property which may be beneficial in the management of joint disease.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1988

Influence of lipid peroxidation and hydrogen peroxide on muscarinic cholinergic receptors and ATP level in rat myocytes and lymphocytes.

Isolated rat neonatal cardiac myocytes and rat lymph-node lymphocytes were treated with Fe2+ cumene hydroperoxide or hydrogen peroxide. The intensity of lipid peroxidation was estimated by measuring production of malondialdehyde (MDA). The level of muscarinic cholinergic receptors was determined by [3H]-QNB binding. Cumene hydroperoxide treatment was found to induce lipid peroxidation in both myocytes and lymphocytes, the process being more pronounced in myocytes. An important decrease of muscarinic cholinergic receptor level and a significant drop of intracellular ATP level in these cells were simultaneously observed. In both cell types, hydrogen peroxide treatment decreased the ATP level while lipid peroxidation and muscarinic cholinergic receptors were unaffected. The different effect of hydrogen peroxide on lipid peroxidation and the level of muscarinic cholinergic receptors on the one hand and the ATP level on the other suggests that this substance acts mainly in the intracellular space.

Adenosine Triphosphate↗

PubMed1987

Inhibitory effect of tritoqualine on activation of latent polymorphonuclear leukocyte collagenase.

Treatment of rats with histamine releaser compound 48/80 caused changes in blood leukocyte populations. An increased number of PMN-leukocytes was observed. Tritoqualine only modestly reduced the number of granulocytes. In animals treated with compound 48/80 an activation of PMN-leukocyte latent collagenase of up to 80% was observed. This activation was partially inhibited (about 40%) in animals pretreated with tritoqualine. The results presented suggest that the beneficial effect of tritoqualine in allergic diseases may be in part connected with an indirect inhibition of collagenase activity.

Animals↗

PubMed1987

Auranofin modulates gelatinase release from rat neutrophils.

We have examined the effects of auranofin and some nonsteroidal anti-inflammatory drugs (NSAID) on the release of gelatinase from rat neutrophils. Two preparations of neutrophils were used, one derived from normal blood and the other from the inflamed pleural fluids of carrageenin-elicited pleurisy. Both neutrophil preparations released gelatinase in response to stimulation by serum-treated zymosan (STZ) or concanavalin A (Con A). Control, blood-derived neutrophils exposed to STZ produced more than a four-fold increase in the release of gelatinase, a response significantly inhibited by the presence of auranofin at 10(-5) and 10(-4) M. Inflamed, pleural neutrophils exposed to STZ produced a doubling in gelatinase release and this was also inhibited by auranofin at 10(-5) and 10(-4) M. The release of gelatinase by control neutrophils (no stimulation) or by neutrophils exposed to Con A was enhanced by 10(-6) M auranofin. In contrast, the NSAIDs aspirin, piroxicam, sulindac, indomethacin and naproxen had no inhibitory action on neutrophil gelatinase release. We conclude that auranofin is an effective inhibitor of gelatinase release from neutrophils and this property may represent a contributory factor assigned to the beneficial therapeutic action of gold salts.

Animals↗

PubMed1986

Auranofin modulates mast cell histamine and polymorphonuclear leukocyte collagenase release.

Auranofin, an orally gold preparation, effective in the treatment of rheumatoid arthritis, was found to be a potent noncytotoxic inhibitor of histamine and collagenase release from mast cells and polymorphonuclear (PMN) leukocytes respectively. Histamine release has been inhibited by auranofin in dose-dependent fashion. Auranofin at concentration of 10(-5) M inhibited 100% of the release, lower concentration 10(-6) M and 10(-7) M produced 80 and 40% decrease. The exposure of PMN-leukocytes to auranofin caused also dose-dependent inhibition of collagenase release. Auranofin at a concentration of 10(-4) M produced a marked reduction (75-100%) of enzyme release from human and rat blood PMN-leukocytes. The modest inhibition 40 and 15-20% at a concentration of 10(-5) M and 10(-6) M respectively was obtained. Auranofin more significantly suppressed collagenase release from leukocytes isolated from inflammatory exudate. Decrease of 100, 80 and 60% were observed upon addition of 10(-4) M, 10(-5) M and 10(-6) M of auranofin. These results suggest that therapeutic action of auranofin may be caused, at least in part, by the inhibition of cellular release of histamine and collagenase in the course of inflammation.

Animals↗