ASSESSMENT OF THE EFFECT OF CARBON MONOXIDE DONOR (CORM-2) ON BLOOD CLOTTING RATE UNDER CONDITIONS OF IMMUNE RESPONSE

The balance between the liquid state support of the blood and the thrombus formation process depends on the activity of plasma factors and thrombocytes. In a vascular injury condition, thrombocytes form a thrombocyte plug, vasoconstriction and, further, take part in the restoration of the tissues. Reducing the clotting function of thrombocytes is a current problem. The search for agents - modulators of thrombocyte activity - is a promising area of research. Compounds - gas-transmitters can be used to model the activity of thrombocytes hemostasis. Carbon monoxide (CO) gas belongs to this group as well. CO in very low concentrations affects in a different way the process of apoptosis, stimulates calcium-dependent potassium channels, and changes the activity of mitochondria. To investigate the effect of CO on blood clotting rate, laboratory mice were injected with the compound CO donor (CORM-2). This substance was administered separately during the inductive and productive phases of the immune response. The dynamics of the immune response were measured by IgA, IgM and IgG immunoglobulin levels. It was found that blood clotting was intensified under the influence of CORM-2 (20 mg/kg). Especially, the increase was during the productive phase. At the end of the experiment, the percentage of megakaryoblasts in the total population of thrombocyte precursors decreased in the bone marrow of animals (to which CORM-2 was administered). Against this background, an increased content of megakaryocytes was found in the group that received CORM-2 during the productive phase. In the group that received CORM-2 during the inductive phase, in addition to an increase in megakaryocyte levels, there was an increase in thrombocyte levels. The group that received CORM-2 during the productive phase also had a predominance of metamegakaryocytes and reducing of thrombocyte amount. Key words: thrombocytes, carbon monoxide donor, CORM-2, immune response phases.

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Study of nickel-molybdenum catalysts for methanation of carbon monoxide

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19800783 ◽

1980 ◽

Vol 45 (3) ◽

pp. 783-790 ◽

Cited By ~ 1

Author(s):

Petr Taras ◽

Milan Pospíšil

Keyword(s):

Carbon Monoxide ◽

Catalytic Activity ◽

Mixed Oxides ◽

Minor Component ◽

Fast Neutrons ◽

Scanning Calorimetry ◽

Low Concentrations ◽

Γ Rays ◽

Molybdenum Catalysts ◽

Kinetics Of

Catalytic activity of nickel-molybdenum catalysts for methanation of carbon monoxide and hydrogen was studied by means of differential scanning calorimetry. The activity of NiMoOx systems exceeds that of carrier-free nickel if x < 2, and is conditioned by the oxidation degree of molybdenum, changing in dependence on the composition in the region Mo-MoO2. The activity of the catalysts is adversely affected by irradiation by fast neutrons, dose 28.1 Gy, or by γ rays using doses in the region 0.8-52 kGy. The system is most susceptible to irradiation in the region of low concentrations of the minor component (about 1 mol.%). The dependence of changes in catalytic activity of γ-irradiated samples on the dose exhibits a maximum in the range of 2-5 kGy. The changes in catalytic activity are stimulated by the change of reactivity of the starting mixed oxides, leading to different kinetics of their reduction and modification of their adsorption properties. The irradiation of the catalysts results in lowered concentration of the active centres for the methanation reaction.

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Abstract 489: Mechanisms of Carbon Monoxide Attenuation of Tubuloglomerular Feedback

Hypertension ◽

10.1161/hyp.60.suppl_1.a489 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

YiLin Ren ◽

Martin A D'Ambrosio ◽

Hong Wang ◽

Jeffrey L Garvin ◽

Oscar A Carretero

Keyword(s):

Carbon Monoxide ◽

Physiological Role ◽

Inhibitory Effect ◽

Tubuloglomerular Feedback ◽

Renal Microcirculation ◽

Low Concentrations ◽

Cgmp Analog ◽

Cell Depolarization ◽

Toxic Concentrations

Tubuloglomerular feedback (TGF) is an autoregulatory mechanism of the renal microcirculation in which the macula densa (MD) senses NaCl concentration in the lumen of the nephron and sends a signal that controls glomerular filtration rate by constricting the afferent arteriole (Af-Art). We have shown that MD depolarization is sufficient for inducing TGF. Carbon monoxide (CO), either endogenous or exogenous, is known to inhibit TGF, at least in part via cGMP. However, whether cGMP-independent mechanisms are involved, and where in the TGF cascade CO exerts its inhibitory effect, remain unknown. Thus we hypothesize that CO, acting via both cGMP-dependent and -independent mechanisms, attenuates TGF by acting downstream from MD cell depolarization. In vitro , microdissected rabbit Af-Arts and their attached MD were simultaneously perfused and TGF was measured as the decrease in Af-Art diameter. Depolarization of the MD was induced by switching luminal KCl from 4 to 50 mM in the presence of the potassium ionophore valinomycin, while adding the CO-releasing molecule CORM-3 to the MD perfusate at non-toxic concentrations. CORM-3 blunted depolarization-induced TGF at a concentration of 50 μM, from 3.6±0.4 to 2.5±0.4 μm (P<0.01), and completely abolished it at a concentration of 100 μM, to 0.1±0.1 μm (P<0.001, n=6). Similar results were found with 100 μM CORM-3 when depolarization was induced by nystatin (3.0±0.2 vs. 0.4±0.2 μm, P <0.001, n=6). This indicates that CO inhibits TGF acting downstream from depolarization. When cGMP generation was blocked with the guanylate cyclase inhibitor LY-83583 (1 μM) added to the MD, CORM-3 no longer had an effect on depolarization-induced TGF at 50 μM (2.9±0.4 vs. 3.0±0.4 μm), but retained partial inhibitory effect on TGF at 100 μM (1.3±0.2 μm, P =0.02, n=9). This suggests that CO acts via cGMP at low concentrations, but additional mechanisms of action may be involved at higher concentrations. Finally, we confirmed that cGMP inhibits TGF downstream from MD depolarization by adding the degradation-resistant cGMP analog dibutyryl-cGMP (500 μM), which attenuated depolarization-induced TGF (from 3.9±0.5 to 0.6±0.2 μm, P <0.01, n=6). Our results could help explain the physiological role of CO in controlling the renal microcirculation.

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Rituximab treatment results in impaired secondary humoral immune responsiveness

Blood ◽

10.1182/blood.v100.6.2257 ◽

2002 ◽

Vol 100 (6) ◽

pp. 2257-2259 ◽

Cited By ~ 156

Author(s):

Lizet E. van der Kolk ◽

Joke W. Baars ◽

Martin H. Prins ◽

Marinus H. J. van Oers

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Infectious Complications ◽

Low Grade ◽

Immune Responsiveness ◽

B Cell Depletion ◽

Treatment Results ◽

Humoral Immune ◽

Immunoglobulin Levels ◽

Humoral Immune Responsiveness

Abstract In lymphoma patients, treatment with chimeric CD20 monoclonal antibodies (rituximab) results in a depletion of normal and malignant B cells, persisting for 6 to 9 months. This B-cell depletion leads neither to a decrease in immunoglobulin levels nor an increase in the number of infectious complications. However, the effect of rituximab treatment on the immune responsiveness is unknown. In 11 patients with relapsed, low-grade lymphoma, we investigated the effect of rituximab treatment on the humoral immune response to 2 primary antigens and 2 recall antigens. After rituximab treatment, the humoral immune response to the recall antigens was significantly decreased when compared with the response before treatment. Already before rituximab treatment, none of these patients was able to mount a response to the primary antigens. These findings are relevant regarding the feasibility of rituximab in maintenance treatment and may also offer a rationale for the treatment of antibody-mediated autoimmune diseases with rituximab.

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Ventilatory response of intact cats to carbon monoxide hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.1983.55.4.1064 ◽

1983 ◽

Vol 55 (4) ◽

pp. 1064-1071 ◽

Cited By ~ 17

Author(s):

H. Gautier ◽

M. Bonora

Keyword(s):

Carbon Monoxide ◽

Brain Stem ◽

Ventilatory Response ◽

Hypoxic Hypoxia ◽

Small Decrease ◽

Low Concentrations ◽

Initial Decrease ◽

Respiratory Centers ◽

Ventilatory Response To Co2

Adult intact conscious or anesthetized cats have been exposed to either hypoxia or low concentrations of CO in air. In addition, the ventilatory response to CO2 was studied in air, hypoxic hypoxia, and CO hypoxia. The results show that 1) in conscious cats, low concentrations of CO (0.15%) induce a slight decrease in ventilation and higher concentrations of CO (0.20%) induce first a small decrease in ventilation and then a characteristic tachypnea similar to the hypoxic tachypnea described in carotid-denervated cats; 2) in anesthetized cats, CO hypoxia induces only mild changes in ventilation; and 3) the ventilatory response to CO2 is increased in CO hypoxia in both conscious and anesthetized animals but differs from the increase observed during hypoxia. It is concluded that the initial decrease in ventilation may be caused by some brain stem depression of the respiratory centers with CO hypoxia, whereas the tachypnea originates probably at some suprapontine level. Conversely, the possible central acidosis may account for the potentiation of the ventilatory response to CO2 observed in either conscious or anesthetized animals.

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Biomechanical thrombosis: the dark side of force and dawn of mechano-medicine

Stroke and Vascular Neurology ◽

10.1136/svn-2019-000302 ◽

2019 ◽

Vol 5 (2) ◽

pp. 185-197 ◽

Cited By ~ 1

Author(s):

Yunfeng Chen ◽

Lining Arnold Ju

Keyword(s):

Platelet Aggregation ◽

Blood Clotting ◽

Thrombus Formation ◽

Dark Side ◽

Atherosclerotic Plaques ◽

Excessive Bleeding ◽

Glycoprotein Vi ◽

Device Implantation ◽

Platelet Binding ◽

Platelet Thrombus

Arterial thrombosis is in part contributed by excessive platelet aggregation, which can lead to blood clotting and subsequent heart attack and stroke. Platelets are sensitive to the haemodynamic environment. Rapid haemodynamcis and disturbed blood flow, which occur in vessels with growing thrombi and atherosclerotic plaques or is caused by medical device implantation and intervention, promotes platelet aggregation and thrombus formation. In such situations, conventional antiplatelet drugs often have suboptimal efficacy and a serious side effect of excessive bleeding. Investigating the mechanisms of platelet biomechanical activation provides insights distinct from the classic views of agonist-stimulated platelet thrombus formation. In this work, we review the recent discoveries underlying haemodynamic force-reinforced platelet binding and mechanosensing primarily mediated by three platelet receptors: glycoprotein Ib (GPIb), glycoprotein IIb/IIIa (GPIIb/IIIa) and glycoprotein VI (GPVI), and their implications for development of antithrombotic ‘mechano-medicine’ .

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Calcium-dependent proapoptotic effect of Taenia solium metacestodes annexin B1 on human eosinophils: A novel strategy to prevent host immune response

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2008.02.018 ◽

2008 ◽

Vol 40 (10) ◽

pp. 2151-2163 ◽

Cited By ~ 18

Author(s):

Hong-li Yan ◽

Geng Xue ◽

Qian Mei ◽

Fei-xiang Ding ◽

Yu-zhao Wang ◽

...

Keyword(s):

Immune Response ◽

Taenia Solium ◽

Host Immune Response ◽

Calcium Dependent ◽

Novel Strategy ◽

Annexin B1

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Control of Platelet Adhesion by Rigidity Sensing at the Surface of Fibrin Clot.

Blood ◽

10.1182/blood.v110.11.3906.3906 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3906-3906

Author(s):

Nataly P. Podolnikova ◽

Benjamin Bowen ◽

Valeryi K. Lishko ◽

Andriy V. Podolnikov ◽

Tatiana Ugarova

Keyword(s):

Platelet Adhesion ◽

Leukocyte Adhesion ◽

Thrombus Formation ◽

Focal Adhesions ◽

Fibrin Clot ◽

Fibrin Gel ◽

Vessel Occlusion ◽

Leukocyte Integrins ◽

Low Concentrations ◽

Platelet Spreading

Abstract Thrombus formation at sites of vascular injury must occur quickly to reduce blood loss, but is carefully controlled to limit vessel occlusion. Arrest of bleeding is mediated by adhesion and aggregation of platelets and the formation of the fibrin clot. While the interactions responsible for platelet adhesion and thrombus growth have been extensively researched, the mechanisms that limit platelet adhesion are not clear. We have previously demonstrated that plasma fibrinogen is a potent inhibitor of integrin-mediated leukocyte adhesion to fibrin clots and surface-bound fibrinogen, and have provided evidence that fibrinogen reduces cell adhesion by binding to the surface of fibrin rather than blocking leukocyte integrins. Accordingly, cells that engage fibrinogen molecules loosely bound to fibrin (soft substrate) are not able to consolidate their grip on the surface; subsequently, cells detach. Conversely, cells that adhere to the naked fibrin clot (rigid substrate) adhere firmly. Since fibrin and immobilized fibrinogen support platelet adhesion, we examined the effect of soluble fibrinogen on integrin αIIbβ3-mediated adhesion. We show that the anti-adhesive fibrinogen layer formed on the surface of fibrin inhibits platelet adhesion. We also demonstrate that fibrinogen immobilized on plastic at high densities (>20 μg/ml) supports weak platelet adhesion whereas at low concentrations (∼2 μg/ml) it is highly adhesive. An investigation of the mechanism underlying differential platelet adhesion indicates that platelet adhesion to rigid substrates (low-density fibrinogen and naked fibrin gel) induces much stronger phosphorylation of FAK and Syk kinases than that to soft substrates (high-density fibrinogen and fibrin exposed to soluble fibrinogen). Furthermore, the rigid, but not the soft substrates induce recruitment of signaling molecules talin and skelemin to αIIbβ3-containing focal adhesions. Consistent with their limited ability to induce sufficient signaling, soft substrates do not support platelet spreading. These data suggest that circulating fibrinogen prevents stable platelet adhesion by modifying the mechanical properties of the fibrin clot’s surface which results in reduced force generation and insufficient signaling.

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THE RAPID DETERMINATION OF LOW CONCENTRATIONS OF CARBON MONOXIDE IN AIR

Canadian Journal of Research ◽

10.1139/cjr48f-033 ◽

1948 ◽

Vol 26f (8) ◽

pp. 318-330 ◽

Cited By ~ 6

Author(s):

Morris Katz ◽

John Katzman

Keyword(s):

Carbon Monoxide ◽

Flow Rate ◽

Rapid Determination ◽

Major Change ◽

Space Velocity ◽

Optimum Flow Rate ◽

Low Concentrations ◽

High Space ◽

Optimum Flow

A granular form of silver permanganate on a zinc oxide carrier has been found to oxidize carbon monoxide in air at ordinary temperatures and at high space velocities. There is no noticeable change in activity over the range of 30 to 100% relative humidity of the air, although a small amount of water vapor is essential to initiate the combustion of carbon monoxide. The above properties have been utilized in the rapid determination of low concentrations by measuring the heat of oxidation in a thermocouple cell. The relation between the potential of the thermocouple junctions and the concentration of carbon monoxide is linear over the range of 0 to 600 p.p.m. at a definite space velocity. With increasing flow rate at a constant concentration the potential rises rapidly to a maximum, but in the range of optimum flow the flow rate may be varied considerably without producing a major change in e.m.f. The thermal efficiency is about 81% at the optimum flow rate. Hydrogen, unless it is present in amounts considerably in excess of the carbon monoxide concentration, does not introduce an appreciable error in the determination. The method is applicable to the field determination of considerably less than 0.005% carbon monoxide in air and the degree of precision is about equal to that of most laboratory methods. Twenty to twenty-five cubic centimeters of the material will give a useful life of over eight hours in continuous tests on concentrations below 0.1% carbon monoxide.

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Opposing actions of the enantiomers of BAY-K-8644 on calcium currents and ACTH secretion in clonal pituitary corticotrophs

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y87-382 ◽

1987 ◽

Vol 65 (12) ◽

pp. 2409-2414 ◽

Cited By ~ 7

Author(s):

J. F. MacDonald ◽

Z. Miljkovic ◽

S. Heisler

Keyword(s):

Bay K 8644 ◽

Calcium Currents ◽

Similar Relationship ◽

Acth Secretion ◽

Calcium Dependent ◽

Low Concentrations ◽

Voltage Dependent ◽

High Concentrations ◽

Opposing Effects ◽

Stimulation Of

BAY-K-8644 in low concentrations is known to stimulate, and in higher concentrations, to depress calcium-dependent ACTH secretion from mouse clonal (tumor) pituitary corticotrophs, AtT-20/D16-16 (AtT-20). In the present study, voltage-dependent inward calcium currents in these cells were potentiated by low concentrations of this compound and depressed by higher concentrations consistent with its actions on ACTH secretion. A similar relationship was demonstrated for a different but related compound, CGP 28 392. Each of BAY-K-8644's enantiomers, BAY-R(−)5417 and BAY-R(+)4407, had opposing effects upon these inward calcium currents and ACTH secretion. The (+)isomer antagonized both inward calcium currents and ACTH secretion. In contrast, the (−)enantiomer was responsible for the stimulatory effects of BAY-K-8644. Nevertheless, some antagonistic properties were noted with high concentrations of this latter enantiomer. The stimulation of ACTH secretion in AtT-20 cells by low concentrations of BAY-K-8644 can be attributed to a potentiation of voltage-activated calcium currents by one of its enantiomers, BAY-R-(−)5417. In contrast, the depression of secretion that occurs at higher concentrations is likely to be the result of the reduction of these currents by the other enantiomer (BAY-R(+)4407).

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