Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.
The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.
Venoms from snakes of the subfamily Crotalinae or pit vipers, found mostly in the Americas. They include the rattlesnake, cottonmouth, fer-de-lance, bushmaster, and American copperhead. Their venoms contain nontoxic proteins, cardio-, hemo-, cyto-, and neurotoxins, and many enzymes, especially phospholipases A. Many of the toxins have been characterized.
Proteins and peptides found in SALIVA and the SALIVARY GLANDS. Some salivary proteins such as ALPHA-AMYLASES are enzymes, but their composition varies in different individuals.
A family of polypeptides purified from snake venoms, which contain the arginine-glycine-aspartic acid (RGD) sequence. The RGD tripeptide binds to integrin receptors and thus competitively inhibits normal integrin-ligand interactions. Disintegrins thus block adhesive functions and act as platelet aggregation inhibitors.
Glands that secrete SALIVA in the MOUTH. There are three pairs of salivary glands (PAROTID GLAND; SUBLINGUAL GLAND; SUBMANDIBULAR GLAND).
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.
The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.
The number of PLATELETS per unit volume in a sample of venous BLOOD.
Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.
Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Laboratory examination used to monitor and evaluate platelet function in a patient's blood.
Platelet membrane glycoprotein complex important for platelet adhesion and aggregation. It is an integrin complex containing INTEGRIN ALPHAIIB and INTEGRIN BETA3 which recognizes the arginine-glycine-aspartic acid (RGD) sequence present on several adhesive proteins. As such, it is a receptor for FIBRINOGEN; VON WILLEBRAND FACTOR; FIBRONECTIN; VITRONECTIN; and THROMBOSPONDINS. A deficiency of GPIIb-IIIa results in GLANZMANN THROMBASTHENIA.
Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function.
An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.
The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).
A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.
A CXC chemokine that is found in the alpha granules of PLATELETS. The protein has a molecular size of 7800 kDa and can occur as a monomer, a dimer or a tetramer depending upon its concentration in solution. Platelet factor 4 has a high affinity for HEPARIN and is often found complexed with GLYCOPROTEINS such as PROTEIN C.
A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.
Platelet membrane glycoprotein complex essential for normal platelet adhesion and clot formation at sites of vascular injury. It is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX. Glycoprotein Ib functions as a receptor for von Willebrand factor and for thrombin. Congenital deficiency of the GPIb-IX complex results in Bernard-Soulier syndrome. The platelet glycoprotein GPV associates with GPIb-IX and is also absent in Bernard-Soulier syndrome.
The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).
Formation and development of a thrombus or blood clot in the blood vessel.
A subclass of purinergic P2Y receptors that have a preference for ADP binding and are coupled to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI. The P2Y12 purinergic receptors are found in PLATELETS where they play an important role regulating PLATELET ACTIVATION.
A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).
The transfer of blood platelets from a donor to a recipient or reinfusion to the donor.
An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro.
A calcium-activated enzyme that catalyzes the hydrolysis of ATP to yield AMP and orthophosphate. It can also act on ADP and other nucleoside triphosphates and diphosphates. EC 3.6.1.5.
A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor.
Cell adhesion molecule and CD antigen that mediates the adhesion of neutrophils and monocytes to activated platelets and endothelial cells.
A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.
The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).
Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase.
Disorders caused by abnormalities in platelet count or function.
A subnormal level of BLOOD PLATELETS.
Human alloantigens expressed only on platelets, specifically on platelet membrane glycoproteins. These platelet-specific antigens are immunogenic and can result in pathological reactions to transfusion therapy.
A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)
The formation of clumps of RED BLOOD CELLS under low or non-flow conditions, resulting from the attraction forces between the red blood cells. The cells adhere to each other in rouleaux aggregates. Slight mechanical force, such as occurs in the circulation, is enough to disperse these aggregates. Stronger or weaker than normal aggregation may result from a variety of effects in the ERYTHROCYTE MEMBRANE or in BLOOD PLASMA. The degree of aggregation is affected by ERYTHROCYTE DEFORMABILITY, erythrocyte membrane sialylation, masking of negative surface charge by plasma proteins, etc. BLOOD VISCOSITY and the ERYTHROCYTE SEDIMENTATION RATE are affected by the amount of erythrocyte aggregation and are parameters used to measure the aggregation.
The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION.
Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.
The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.
An effective inhibitor of platelet aggregation commonly used in the placement of STENTS in CORONARY ARTERIES.
A congenital bleeding disorder with prolonged bleeding time, absence of aggregation of platelets in response to most agents, especially ADP, and impaired or absent clot retraction. Platelet membranes are deficient in or have a defect in the glycoprotein IIb-IIIa complex (PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX).
A phospholipid from the platelet membrane that contributes to the blood clotting cascade by forming a phospholipid-protein complex (THROMBOPLASTIN) which serves as a cofactor with FACTOR VIIA to activate FACTOR X in the extrinsic pathway of BLOOD COAGULATION.
Platelet membrane glycoprotein IIb is an integrin alpha subunit that heterodimerizes with INTEGRIN BETA3 to form PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX. It is synthesized as a single polypeptide chain which is then postranslationally cleaved and processed into two disulfide-linked subunits of approximately 18 and 110 kDa in size.
Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.
Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.
An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Antibodies produced by a single clone of cells.
Endogenous substances, usually proteins, that are involved in the blood coagulation process.
A subclass of eicosanoid receptors that have specificity for THROMBOXANE A2 and PROSTAGLANDIN H2.
The deformation and flow behavior of BLOOD and its elements i.e., PLASMA; ERYTHROCYTES; WHITE BLOOD CELLS; and BLOOD PLATELETS.
A subclass of purinergic P2Y receptors that have a preference for ATP and ADP. The activated P2Y1 receptor signals through the G-PROTEIN-coupled activation of PHOSPHOLIPASE C and mobilization of intracellular CALCIUM.
The rate dynamics in chemical or physical systems.
Laboratory tests for evaluating the individual's clotting mechanism.
Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes.
Peptides composed of between two and twelve amino acids.
A dual specificity phosphatase subtype that plays a role in intracellular signal transduction by inactivating MITOGEN-ACTIVATED PROTEIN KINASES. It has specificity for EXTRACELLULAR SIGNAL-REGULATED MAP KINASES and is primarily localized to the CELL NUCLEUS.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
An enzyme found predominantly in platelet microsomes. It catalyzes the conversion of PGG(2) and PGH(2) (prostaglandin endoperoxides) to thromboxane A2. EC 5.3.99.5.
A preparation consisting of PLATELETS concentrated in a limited volume of PLASMA. This is used in various surgical tissue regeneration procedures where the GROWTH FACTORS in the platelets enhance wound healing and regeneration.
Blood clot formation in any part of the CAROTID ARTERIES. This may produce CAROTID STENOSIS or occlusion of the vessel, leading to TRANSIENT ISCHEMIC ATTACK; CEREBRAL INFARCTION; or AMAUROSIS FUGAX.

Interleukin-12 is synthesized by mesangial cells and stimulates platelet-activating factor synthesis, cytoskeletal reorganization, and cell shape change. (1/4442)

Preliminary studies indicate the involvement of interleukin (IL)-12 in experimental renal pathology. In the present study, we evaluated whether cultured glomerular mesangial cells are able to produce IL-12 and whether IL-12 may regulate some of their functions, including the cytoskeletal reorganization, the change in cell shape, and the production of platelet-activating factor (PAF). The results obtained indicate that pro-inflammatory stimuli, such as tumor necrosis factor-alpha and bacterial polysaccharides, induce the expression of IL-12 mRNA and the synthesis of the protein by cultured mesangial cells. Moreover, cultured mesangial cells were shown to bind IL-12 and to express the human low-affinity IL-12 beta1-chain receptor. When challenged with IL-12, mesangial cells produced PAF in a dose- and time-dependent manner and superoxide anions. No production of tumor necrosis factor-alpha and IL-8 was observed. Moreover, we demonstrate that IL-12 induced a delayed and sustained shape change of mesangial cells that reached its maximum between 90 and 120 minutes of incubation. The changes in cell shape occurred concomitantly with cytoskeletal rearrangements and may be consistent with cell contraction. As IL-12-dependent shape change of mesangial cells was concomitant with the synthesis of PAF, which is known to promote mesangial cell contraction, we investigated the role of PAF using two chemically different PAF receptor antagonists. Both antagonists inhibited almost completely the cell shape change induced by IL-12, whereas they were ineffective on angiotensin-II-induced cell shape change. In conclusion, our results suggest that mesangial cells can either produce IL-12 or be stimulated by this cytokine to synthesize PAF and to undergo shape changes compatible with cell contraction.  (+info)

The mechanism of the increasing action of TA-993, a new 1,5- benzothiazepine derivative, on limb blood flow in anesthetized dogs: selective suppression of sympathetic nerve activity. (2/4442)

TA-993, (-)-cis-3-acetoxy-5-(2-(dimethylamino)ethyl)-2, 3-di-hydro-8-methyl-2-(4-methylphenyl)-1,5-benzothiazepin-4(5H)one maleate, a new 1,5-benzothiazepine derivative with l-cis configuration, has a unique and selective increasing action on limb blood flow with little influence on arterial pressure besides an antiplatelet action. We studied the mechanism of increasing action of TA-993 on limb blood flow in anesthetized dogs. In a canine blood-perfused hindlimb preparation with a donor dog, TA-993 (100 microg/kg i.v.) did not increase femoral blood flow when administered to the donor dog, but did when administered to a recipient dog. TA-993 did not show the increasing action on femoral blood flow in the presence of hexamethonium or phentolamine, whereas it did in the presence of propranolol or atropine. TA-993 also showed a weak increasing effect on heart rate, which was inhibited by any one of these blockers. TA-993 (300 microg/kg i.v.) did not alter the phenylephrine (1-100 ng/kg i.a.)- or the talipexole (3-100 ng/kg i.a.)-induced increase in perfusion pressure in an autoperfused hindlimb. These results suggest that the increasing action of TA-993 on limb blood flow is mediated by the sympathetic nervous system but that the adrenergic receptors are not likely to be the central point of action of this new agent. There is a possibility that the mechanism of the increasing action on heart rate is different from that of its increasing action on limb blood flow.  (+info)

Labeling of the internal pool of GP IIb-IIIa in platelets by c7E3 Fab fragments (abciximab): flow and endocytic mechanisms contribute to the transport. (3/4442)

Abciximab is a new antiplatelet therapeutic in ischemic cardiovascular disease. The drug, chimeric Fab fragments of a murine monoclonal antibody (MoAb) (c7E3), blocks GP IIb-IIIa function. However, its capacity to reach all receptor pools in platelets is unknown. Electron microscopy and immunogold labeling were used to localize abciximab in platelets of patients receiving the drug for up to 24 hours. Studies on frozen-thin sections showed that c7E3 Fab, in addition to the surface pool, also labeled the surface-connected canalicular system (SCCS) and alpha-granules. Analysis of gold particle distribution showed that intraplatelet labeling was not accumulative and in equilibrium with the surface pool. After short-term incubations of platelets with c7E3 Fab in vitro, gold particles were often seen in lines within thin elements of the SCCS, some of which appeared in contact with alpha-granules. Little labeling was associated with Glanzmann's thrombasthenia platelets, confirming that the channels contained bound and not free c7E3 Fab. Endocytosis of abciximab in clathrin-containing vesicles was visualized by double staining and constitutes an alternative mechanism of transport. The remaining free pool of GP IIb-IIIa was evaluated with the MoAb AP-2; flow cytometry showed it to be about 9% on the surface of nonstimulated platelets but 33% on thrombin-activated platelets. The ability of drugs to block all pools of GP IIb-IIIa and then to be associated with secretion-dependent residual aggregation must be considered when evaluating their efficiency in a clinical context.  (+info)

Glutamate receptor signaling interplay modulates stress-sensitive mitogen-activated protein kinases and neuronal cell death. (4/4442)

Glutamate receptors modulate multiple signaling pathways, several of which involve mitogen-activated protein (MAP) kinases, with subsequent physiological or pathological consequences. Here we report that stimulation of the N-methyl-D-aspartate (NMDA) receptor, using platelet-activating factor (PAF) as a messenger, activates MAP kinases, including c-Jun NH2-terminal kinase, p38, and extracellular signal-regulated kinase, in primary cultures of hippocampal neurons. Activation of the metabotropic glutamate receptor (mGluR) blocks this NMDA-signaling through PAF and MAP kinases, and the resultant cell death. Recombinant PAF-acetylhydrolase degrades PAF generated by NMDA-receptor activation; the hetrazepine BN50730 (an intracellular PAF receptor antagonist) also inhibits both NMDA-stimulated MAP kinases and neuronal cell death. The finding that the NMDA receptor-PAF-MAP kinase signaling pathway is attenuated by mGluR activation highlights the exquisite interplay between glutamate receptors in the decision making process between neuronal survival and death.  (+info)

Effects of docosahexaenoic and eicosapentaenoic acid on lipid metabolism, eicosanoid production, platelet aggregation and atherosclerosis in hypercholesterolemic rats. (5/4442)

Exogenously hypercholesterolemic (ExHC) rats were fed on an atherogenic diet supplemented with 1% each of either ethyl ester docosahexaenoic acid [EE-DHA, 22:6(n-3)], ethyl ester eicosapentaenoic acid [EE-EPA, 20:5(n-3)] or safflower oil (SO) for 6 months. The rats fed on the diets containing EE-EPA or EE-DHA, compared with those fed on SO, had lower serum cholesterol and triacylglycerol levels, less aggregation of platelets and slower progress of intimal thickening in the ascending aorta. Relative to the SO-fed rats, both of the (n-3) fatty acid-fed rats had a significantly reduced proportion of arachidonic acid in the platelet and aortic phospholipids, and lower production of thromboxane A2 by platelets and of prostacyclin by the aorta. These results suggest that EPA and DHA are similarly involved in preventing atherosclerosis development by reducing hypercholesterolemia and modifying the platelet functions.  (+info)

Predominant inhibition of ganodermic acid S on the thromboxane A2-dependent pathway in human platelets response to collagen. (6/4442)

Ganodermic acid S (GAS), a membrane acting agent, exerts multiple effects on human platelet function (C.N. Wang et al. (1991) Biochem. J. 277, 189-197). The study reported how GAS affected the response of human gel-filtered platelets (GFP) to collagen. The agent inhibited cell aggregation by prolonging lag and shape change periods and decreasing the initial cell aggregation rate. However, the inhibitory efficiency was less than its inhibition on GFP response to U46619, a thromboxane (TX) A2 mimetic. In the agent-effect on biochemical events, GAS effectively inhibited Ca2+ mobilization, phosphorylation of myosin light chain, dense granule secretion and TXB2 generation. The inhibitions might originate from blocking Ca2+ mobilization of the TXA2-dependent pathway. GAS partially decreased the phosphorylation of most phosphotyrosine proteins from early activation to the integrin alphaIIbbeta3-regulated steps. The agent did not affect the phosphorylation of three proteins at the steps regulated by integrin alphaIIbbeta3. The results suggest that GAS inhibits the collagen response predominantly on the TXA2-dependent signaling, and the tyrosine kinase-dependent pathway in collagen response plays a major role in aggregation.  (+info)

PAF binding to a single receptor in corneal epithelium plasma membrane. (7/4442)

PURPOSE: To study the binding characteristics and the expression of platelet-activating factor receptors (PAF-R) in corneal epithelium to elucidate the site of action of PAF. METHODS: Binding of [3H]PAF was investigated in subcellular fractions of the epithelia of bovine corneas and in membranes from cultured rabbit corneal epithelial cells. Dose-response inhibition curves of [3H]PAF-specific binding were generated using increasing concentrations of several PAF-R antagonists. RNA from rabbit corneal epithelial cells was probed for PAF-R expression by reverse transcription-polymerase chain reaction (RT-PCR) with specifically designed degenerated primers. RESULTS: Scatchard analysis showed a high-affinity binding site in bovine and rabbit corneal epithelium. The dissociation constant (Kd) and the maximum binding sites (Bmax) in a bovine membrane preparation and similar rabbit fraction were 0.77+/-0.03 nM and 180+/-21 femtomoles/mg protein and 4.3 nM and 1.3 picomoles/mg protein, respectively. Specific PAF-binding sites were found in bovine preparations enriched in plasma membranes with a Kd = 69.6 pM and Bmax = 80 femtomoles/mg protein; no specific binding was found in nuclei or microsomal fractions. RT-PCR of rabbit corneal epithelium generated a single product of the predicted size (478 bp). The deduced amino acid sequence of the purified PCR product was 87% homologous to human PAF-R. The hetrazepines BN 50727 and BN 50730 and the PAF structural analogues CV 3988 and CV 6209 competitively inhibited [3H]PAF binding to corneal epithelium with similar potency. WEB 2086 BS was two orders of magnitude less active in antagonizing PAF binding. CONCLUSIONS: Corneal epithelium contains a single population of receptors localized in the plasma membrane. PAF antagonists exert their actions by blocking this PAF-R. The partial sequence deduced in rabbit corneal PAF-R show a higher homology to the human PAF-R.  (+info)

Conformational changes in the A3 domain of von Willebrand factor modulate the interaction of the A1 domain with platelet glycoprotein Ib. (8/4442)

Bitiscetin has recently been shown to induce von Willebrand factor (vWF)-dependent aggregation of fixed platelets (Hamako J, et al, Biochem Biophys Res Commun 226:273, 1996). We have purified bitiscetin from Bitis arietans venom and investigated the mechanism whereby it promotes a form of vWF that is reactive with platelets. In the presence of bitiscetin, vWF binds to platelets in a dose-dependent and saturable manner. The binding of vWF to platelets involves glycoprotein (GP) Ib because it was totally blocked by monoclonal antibody (MoAb) 6D1 directed towards the vWF-binding site of GPIb. The binding also involves the GPIb-binding site of vWF located on the A1 domain because it was inhibited by MoAb to vWF whose epitopes are within this domain and that block binding of vWF to platelets induced by ristocetin or botrocetin. However, in contrast to ristocetin or botrocetin, the binding site of bitiscetin does not reside within the A1 domain but within the A3 domain of vWF. Thus, among a series of vWF fragments, 125I-bitiscetin only binds to those that overlap the A3 domain, ie, SpIII (amino acid [aa] 1-1365), SpI (aa 911-1365), and rvWF-A3 domain (aa 920-1111). It does not bind to SpII corresponding to the C-terminal part of vWF subunit (aa 1366-2050) nor to the 39/34/kD dispase species (aa 480-718) or T116 (aa 449-728) overlapping the A1 domain. In addition, bitiscetin that does not bind to DeltaA3-rvWF (deleted between aa 910-1113) has no binding site ouside the A3 domain. The localization of the binding site of bitiscetin within the A3 domain was further supported by showing that MoAb to vWF, which are specific for this domain and block the interaction between vWF and collagen, are potent inhibitors of the binding of bitiscetin to vWF and consequently of the bitiscetin-induced binding of vWF to platelets. Thus, our data support the hypothesis that an interaction between the A1 and A3 domains exists that may play a role in the function of vWF by regulating the ability of the A1 domain to bind to platelet GPIb.  (+info)

There are several types of thrombosis, including:

1. Deep vein thrombosis (DVT): A clot forms in the deep veins of the legs, which can cause swelling, pain, and skin discoloration.
2. Pulmonary embolism (PE): A clot breaks loose from another location in the body and travels to the lungs, where it can cause shortness of breath, chest pain, and coughing up blood.
3. Cerebral thrombosis: A clot forms in the brain, which can cause stroke or mini-stroke symptoms such as weakness, numbness, or difficulty speaking.
4. Coronary thrombosis: A clot forms in the coronary arteries, which supply blood to the heart muscle, leading to a heart attack.
5. Renal thrombosis: A clot forms in the kidneys, which can cause kidney damage or failure.

The symptoms of thrombosis can vary depending on the location and size of the clot. Some common symptoms include:

1. Swelling or redness in the affected limb
2. Pain or tenderness in the affected area
3. Warmth or discoloration of the skin
4. Shortness of breath or chest pain if the clot has traveled to the lungs
5. Weakness, numbness, or difficulty speaking if the clot has formed in the brain
6. Rapid heart rate or irregular heartbeat
7. Feeling of anxiety or panic

Treatment for thrombosis usually involves medications to dissolve the clot and prevent new ones from forming. In some cases, surgery may be necessary to remove the clot or repair the damaged blood vessel. Prevention measures include maintaining a healthy weight, exercising regularly, avoiding long periods of immobility, and managing chronic conditions such as high blood pressure and diabetes.

Some common types of blood platelet disorders include:

1. Thrombocytopenia: This is a condition in which there are too few platelets in the blood. It can be caused by a variety of factors, including autoimmune disorders, bone marrow disorders, and certain medications.
2. Bernard-Soulier syndrome: This is a rare inherited disorder that affects the function of platelets and causes easy bruising and prolonged bleeding.
3. Glanzmann's thrombasthenia: This is a rare inherited disorder that affects the platelets' ability to clot properly, leading to excessive bleeding.
4. Platelet dysfunction: This can be caused by a variety of factors, including certain medications, infections, and autoimmune disorders. It can lead to excessive bleeding or prolonged bleeding after injury or surgery.
5. Congenital amegakaryocytic thrombocytopenia: This is a rare inherited disorder that affects the development of platelets in the bone marrow, leading to a lack of platelets in the blood.
6. Grey platelet syndrome: This is a rare inherited disorder that affects the structure of platelets, making them more prone to rupture and lead to easy bruising and prolonged bleeding.
7. Platelet-type von Willebrand disease: This is a mild bleeding disorder caused by a deficiency of von Willebrand factor, a protein that helps platelets stick together to form clots.
8. acquired platelet dysfunction: This can be caused by various conditions such as infections, medications, and autoimmune disorders.

These disorders can be diagnosed through blood tests, including a complete blood count (CBC) and a platelet function test. Treatment options vary depending on the specific disorder and may include medication, surgery, or lifestyle changes.

There are several possible causes of thrombocytopenia, including:

1. Immune-mediated disorders such as idiopathic thrombocytopenic purpura (ITP) or systemic lupus erythematosus (SLE).
2. Bone marrow disorders such as aplastic anemia or leukemia.
3. Viral infections such as HIV or hepatitis C.
4. Medications such as chemotherapy or non-steroidal anti-inflammatory drugs (NSAIDs).
5. Vitamin deficiencies, especially vitamin B12 and folate.
6. Genetic disorders such as Bernard-Soulier syndrome.
7. Sepsis or other severe infections.
8. Disseminated intravascular coagulation (DIC), a condition where blood clots form throughout the body.
9. Postpartum thrombocytopenia, which can occur in some women after childbirth.

Symptoms of thrombocytopenia may include easy bruising, petechiae (small red or purple spots on the skin), and prolonged bleeding from injuries or surgical sites. Treatment options depend on the underlying cause but may include platelet transfusions, steroids, immunosuppressive drugs, and in severe cases, surgery.

In summary, thrombocytopenia is a condition characterized by low platelet counts that can increase the risk of bleeding and bruising. It can be caused by various factors, and treatment options vary depending on the underlying cause.

The term "thrombasthenia" comes from the Greek words "thrombos," meaning clot, and "basis," meaning foundation. It was first used by the British physician Sir William Osler in the late 19th century to describe a group of rare bleeding disorders characterized by abnormal platelet function.

There are three main types of thrombasthenia:

1. Bernard-Soulier syndrome: This is the most common type of thrombasthenia and is caused by a defect in the gene that codes for the protein known as platelet membrane glycoprotein (PMG) IIb. People with this condition have large, fragile platelets that are prone to bleeding.
2. Glanzmann's thrombasthenia: This is a rare type of thrombasthenia caused by a defect in the gene that codes for the protein known as platelet membrane glycoprotein (PMG) IIIa. People with this condition have small, irregular platelets that are unable to form proper blood clots.
3. Gray platelet syndrome: This is a rare type of thrombasthenia caused by a defect in the gene that codes for the protein known as alpha-granule membrane protein (AGM). People with this condition have small, gray-colored platelets that are prone to bleeding.

Thrombasthenia can be diagnosed through blood tests that evaluate platelet function and genetic testing to identify the specific defect responsible for the disorder. Treatment typically involves avoiding medications that can exacerbate bleeding, using platelet transfusions to increase platelet numbers, and in some cases, undergoing surgery to repair or remove affected blood vessels.

Carotid artery thrombosis is often caused by atherosclerosis, which is the buildup of plaque in the arteries that can lead to the formation of blood clots. Other risk factors for carotid artery thrombosis include high blood pressure, smoking, high cholesterol, diabetes, and obesity.

Diagnosis of carotid artery thrombosis typically involves imaging tests such as ultrasound, CT or MRI scans, and Doppler studies to visualize the blood flow in the neck and brain. Treatment options for carotid artery thrombosis include anticoagulation medications to prevent further clotting, medications to dissolve the clot, and surgery to remove the clot or repair the affected artery.

In severe cases, carotid artery thrombosis can lead to stroke or brain damage if not treated promptly. Therefore, it is important to seek medical attention immediately if symptoms persist or worsen over time.

... is a platelet aggregation inhibitor. It acts as a reversible cyclooxygenase inhibitor. The Merck Index (12th ed.). p ...
Potent Inhibitors of the Aggregation of Human Platelets". Planta Medica. 51 (4): 300-3. doi:10.1055/s-2007-969496. PMID ...
... is an antispasmodic, vasodilator, and platelet aggregation inhibitor. Grignard addition of benzylmagnesiumbromide to ...
... is a platelet aggregation inhibitor. It works as a thromboxane synthase inhibitor and a thromboxane receptor ... inhibitor, the latter by modifying cellular responses to activation of the thromboxane receptor. Picotamide is licensed in ...
... is a platelet aggregation inhibitor. Orefice G, Grasso A, Fazio N, Del Vecchio G, Volpe G, Coppola M, D'Alessio A, ...
Fabian, K; Anke, T; Sterner, O (2001). "Mariannaepyrone--a new inhibitor of thrombroxane A2 induced platelet aggregation". ... elegans induces the aggregation of human platelet cells. M. elegans may also be consumed by amoebae. Bisette, John (1979). " ...
Cinnamtannin B-1 as an antioxidant and platelet aggregation inhibitor. Life sciences, 82(19), 977-982. doi:10.1016/j.lfs. ... and anti-platelet aggregation that may protect damaged tissues in wounds Anderson; Broadhurst, CL; Polansky, MM; Schmidt, WF; ...
... platelet aggregation inhibitors, which prevent the formation of blood clots; and other anticoagulants. These compounds in their ...
"Design and Synthesis of Piperidine-3-carboxamides as Human Platelet Aggregation Inhibitors". Journal of Medicinal Chemistry. 38 ...
... constitutes an antithrombotic, specifically an inhibitor of platelet aggregation. Tirofiban is a modified version of ... Tirofiban is a small molecule inhibitor of the protein-protein interaction between fibrinogen and the platelet integrin ... non-peptide inhibitor of the interaction of fibrinogen with the integrin glycoprotein IIb/IIIa on human platelets. The Merck ... Lazarovici P, Marcinkiewicz C, Lelkes PI (May 2019). "From snake venom's disintegrins and C-type lectins to anti-platelet drugs ...
In molecular biology, ornatin is a potent glycoprotein IIb-IIIa (GP IIb-IIIa) antagonist and platelet aggregation inhibitor ... potent glycoprotein IIb-IIIa antagonists and platelet aggregation inhibitors from the leech Placobdella ornata". Eur. J. ...
... the most potent inhibitor of platelet aggregation. More importantly, PGI2 (and not nitrous oxide) is also associated with an ... "Modulation of human platelet aggregation by the phosphodiesterase type 5 inhibitor sildenafil". Journal of Cardiovascular ... though it prolongs bleeding time by inhibiting collagen-induced platelet aggregation. Another drug, Milrinone, a Type 3 PDE-i ... Phosphodiesterase inhibitors (PDE-i) have been employed with excellent results. It has been shown to reduce mean PAP by as much ...
It acts as a platelet aggregation inhibitor by antagonising the P2Y12 receptor. The drug is produced by AstraZeneca. The most ... Inhibitors of the liver enzyme CYP3A4, such as ketoconazole and possibly grapefruit juice, increase blood plasma levels of ... Ticagrelor is a weak CYP3A4 inhibitor and is known to increase the concentrations of CYP3A4 metabolised medications; however, ... inhibitors and moderate or severe hepatic impairment due to the risk of increased exposure to ticagrelor. The common adverse ...
Hawkey C (November 1967). "Inhibitor of platelet aggregation present in saliva of the vampire bat Desmodus rotundus". British ...
... a new platelet aggregation inhibitor produced by Penicillium herquei Fg-372". The Journal of Antibiotics. 49 (1): 50-3. doi: ... a New Platelet Aggregation Inhibitor Produced by Penicillium herquei Fg-372". ChemInform. 27 (27): no. doi:10.1002/chin. ...
... is an analgesic, antipyretic, and anti-inflammatory drug, as well as a platelet aggregation inhibitor. It ...
PGD2 is also involved in smooth muscle contraction/relaxation and is a potent inhibitor of platelet aggregation. This gene is ...
This diverse range of compounds may include: inhibitors of platelet aggregation, ADP, arachidonic acid, thrombin, and PAF. ... Additionally, Ixolaris, a tissue factor inhibitor has been shown to block primary tumor growth and angiogenesis in a ... Ixolaris, a tissue factor inhibitor, blocks primary tumor growth and angiogenesis in a glioblastoma model. J. Thromb. Haemost. ... Tick saliva is a potent inhibitor of endothelial cell proliferation and angiogenesis. Thromb. Haemost. 94, 167e174. Maritz- ...
... is a phosphodiesterase 3 inhibitor which works by inhibiting platelet aggregation and dilating arteries. Cilostazol ... The proton pump inhibitor omeprazole, an inhibitor of CYP2C19, increases exposure to the active metabolite of cilostazol. A ... which is directly related with an inhibition in platelet aggregation. PKA also prevents the activation of an enzyme (myosin ... Serious side effects may include decreased survival in those with heart failure, low platelets, and low white blood cells. ...
Kistrin is a protein inhibitor of platelet aggregation. It belongs to the homologous family of glycoprotein IIb-IIa antagonists ... but platelet aggregation must grow exponentially to form a platelet thrombus and prevent blood loss. Platelet aggregation ... Some thromboregulators enhance platelet aggregation and some others inhibit the process. Platelet aggregation plays a critical ... These inhibitors are substances that prevent the clot formation by preventing platelet adhesion. Platelet inhibition is ...
... common origins for blood coagulation and platelet aggregation inhibitors from soft ticks of the genus Ornithodoros". Molecular ... it inserts its hypostome and prevents the blood from clotting by excreting an anticoagulant or platelet aggregation inhibitor. ...
... inhibitors are used clinically as effective inhibitors of adenosine diphosphate-mediated platelet activation and aggregation. ... Angiolillo DJ, Capranzano P (August 2008). "Pharmacology of emerging novel platelet inhibitors". American Heart Journal. 156 (2 ... reversible inhibitor of P2Y12 receptors that causes almost complete inhibition of ADP-induced platelet aggregate. It is a ... impaired platelet turnover, and lung sequestration or apoptosis of overloaded destructive platelets. The dyspnea risks ...
It is also a platelet aggregation inhibitor which is marketed in Spain and Portugal under the trade name Ageroplas. "Ditazole ...
... a potent vasodilator and inhibitor of platelet aggregation. An imbalance of prostacyclin and its physiological antagonist ...
What had been shown was that they were potent inhibitors of ADP-induced platelet aggregation, but the P2Y12 receptor had not ... Ticagrelor is a much more potent inhibitor of platelet aggregation than clopidogrel, however, it is associated with increase of ... Activation of platelets and the subsequent aggregation of platelets has a crucial role maintaining normal haemostasis. ... When a vessel is damaged ADP is released from damaged cells and activated platelets, inducing further platelet aggregation. The ...
... a potent inhibitor of platelet aggregation from Echis carinatus: synthesis and biological activity of selected analogs". Proc. ...
Aggregation of platelets is highly regulated by cyclic nucleotides. PDE3A is a regulator of this process, and PDE3 inhibitors ... vascular smooth muscle and platelet aggregation. PDE3 inhibitors have been developed as pharmaceuticals, but their use is ... Cilostazol is approved for treatment of intermittent claudication and is thought to involve inhibition of platelet aggregation ... Electronic charges conserve the net charge overall and across the transition state PDE3 inhibitors: antagonize platelet ...
... platelet aggregation inhibitors (most notably apyrase, collagenase, and calin), vasodilators, and proteinase inhibitors. It is ... inhibition of platelet aggregation and of leukocyte activity and examination of reputed anaesthetic effects". Comparative ...
... is a platelet aggregation inhibitor that was discovered and developed in the Uriach Laboratories, and commercialised ... which in turn regulates the expression of the mRNA of the vascular cell adhesion molecule-1 needed for platelet aggregation. ... which regulates the expression of the mRNA of vascular cell adhesion molecule-1 needed for platelet aggregation blocks ... It is a COX-1 inhibitor. It also inhibits the activation of nuclear factor k-B, ...
... is a cyclooxygenase inhibitor that was under development for its anti-platelet-aggregation effects. Light P ( ... "Pamicogrel inhibits platelet aggregation". Inpharma Weekly. 1272 (1): 11. January 2001. doi:10.2165/00128413-200112720-00021. ... COX-2 inhibitors, Phenol ethers, Thiazoles, Pyrroles, Ethyl esters, All stub articles, Cardiovascular system drug stubs). ...
... platelet aggregation inhibitor)-like and C-type lectin-like domains". The Journal of Biological Chemistry. 267 (20): 14109-17. ...
Because thromboxanes play a role in vasoconstriction and platelet aggregation, their dominance can disrupt vascular homeostasis ... Thromboxane synthase inhibitors are used as antiplatelet drugs. Ifetroban is a potent and selective thromboxane receptor ... a potent vasoconstrictor and inducer of platelet aggregation, and also to 12-Hydroxyheptadecatrienoic acid (i.e. 12-(S)-hydroxy ... Thromboxane A synthase 1 (EC 5.3.99.5, platelet, cytochrome P450, family 5, subfamily A), also known as TBXAS1, is a cytochrome ...
Platelet aggregation studies are optional. Serum protein electrophoresis results indicate evidence of a monoclonal spike but ... Mensah-Osman, E.; Al-Katib, A.; Dandashi, M.; Mohammad, R. (2003). "XK469, a topo IIbeta inhibitor, induces apoptosis in ... A low white blood cell count, and low platelet count in the blood may be observed. A low level of neutrophils (a specific type ... According to the model, factors predicting reduced survival are: Age > 65 years Hemoglobin ≤ 11.5 g/dL Platelet count ≤ 100×109 ...
In circulating platelets there is no neutral SMase activity, but they do have S-SMase enzymatic activity. It has been shown ... Acid SMase has been shown to accelerate atherosclerotic lesion progression through promoting aggregation of lipoproteins to ... "Identification of novel functional inhibitors of acid sphingomyelinase". PLOS ONE. 6 (8): e23852. doi:10.1371/journal.pone. ... and have been implicated in the metabolism of lipoprotein-bound SM to Ceramide and the aggregation of LDL particles. ...
Kerr WG (January 2011). "Inhibitor and activator: dual functions for SHIP in immunity and cancer". Annals of the New York ... phosphatase SHIP binds to immunoreceptor signaling motifs and responds to high affinity IgE receptor aggregation". The Journal ... "Tyrosine phosphorylation and relocation of SHIP are integrin-mediated in thrombin-stimulated human blood platelets". The ...
1991). "Use of d-erythro-sphingosine as a pharmacologic inhibitor of protein kinase C in human platelets". Biochem. J. 278 (2 ... PAF is a potent activator of platelet aggregation, inflammation, and anaphylaxis. It is similar to the ubiquitous membrane ... Certain growth-inducing proteins such as platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) and vascular ... histone deacetylase inhibitors and paclitaxel. In some studies, SMase activation results to its transport to the plasma ...
Coxon CH, Geer MJ, Senis YA (June 2017). "ITIM receptors: more than just inhibitors of platelet activation". Blood. 129 (26): ... If the kinase is associated with an NTR, aggregation brings two or more SFK into close proximity, which allows them to ... Whether a receptor acts as an inhibitor or activator depends on the conserved tyrosine-containing motifs present in its ... The induced proximity or aggregation model suggests that upon receptor-ligand binding multiple receptors aggregate. SFKs have ...
The plants are also effective against blood platelet aggregation and murine tumors. "Giant Diospyros - Diospyros abyssinica - ... The extraction of the root bark is attractive to scavengers and some 15 lipoxygenase inhibitors have been found. The attraction ...
... an inhibitor of human platelet aggregation (see Dihydroxy-E,Z,E-PUFA). 5(S),15(S)-dihydroxy-6Z,8E,llE,13Z-eicosatetraenoic acid ... it is also has activities on THP1 cell line cells suggesting that it might act as an inhibitor of inflammatory and oxidative ... have been made and tested as inflammation inhibitors in animal models. These synthetic analogs may prove to be clinically ...
... supplements due to sertraline's inhibitory effects on platelet aggregation via blocking serotonin transporters on platelets. ... Dopamine reuptake inhibitors, Pfizer brands, Selective serotonin reuptake inhibitors, Sigma antagonists, Wikipedia medicine ... "Effect of proton pump inhibitors on the serum concentrations of the selective serotonin reuptake inhibitors citalopram, ... "Comparative efficacy and safety of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in ...
... the general population and treatment of bleeding diathesis is guided by the specific factor deficiency or platelet aggregation ... and an imbalance of plasminogen activator inhibitor type-1 (PAI-1) and tissue plasminogen activator (t-PA) activity. It has ... A number of bleeding disorders have been associated with Noonan syndrome, these include platelet dysfunction, Blood clotting ... been associated with Von Willebrand disease, Amegakaryocytic thrombocytopenia (low platelet count), prolonged activated partial ...
... decreased cell proliferation and inhibition of platelet aggregation, all beneficial in the treatment of pulmonary arterial ... In Europe, use of selexipag together with strong inhibitors of the liver enzyme CYP2C8, such as gemfibrozil, is contraindicated ...
The P-selectin then promotes platelet aggregation through platelet-fibrin and platelet-platelet binding. P-selectin attaches to ... plasma P-selectin concentration was reported to be highly correlated to plasminogen activator inhibitor-1 activity and tissue ... P-selectin is also very important in the recruitment and aggregation of platelets at areas of vascular injury. In a quiescent ... In unactivated platelets P-selectin is stored in α-granules. Other names for P-selectin include CD62P, Granule Membrane Protein ...
Also there is not as much inhibition of aggregation of platelets. In this case, the greater aggregation of platelets produce ... asthma attacks Organic nitrates should not be taken with PDE5 inhibitors (i.e. sildenafil) since both NO and PDE5 inhibitors ... and reduce aggregation of platelets. Aggregating platelets stimulate ADP to act on endothelial cells and help them induce ... However, aggregating platelets also stimulate thromboxane A2 and serotonin which can induce contraction of the smooth muscle ...
... and platelet aggregation. All these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is ... and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients". BMJ. 349: g4379. doi:10.1136/ ...
cAMP inhibits platelet aggregation, and decreased amounts of cAMP in platelets lead to platelet aggregation. The PGE1 reagent ... Prostaglandin E1 (PGE1) is a platelet inhibitor that causes an increase in cyclic adenosine monophosphate (cAMP) in platelets ... Binding of fibrinogen to GPIIb/IIIa receptors leads to platelet-to-platelet bridges and results in platelet aggregation. ... TXA2 increases platelet aggregation, promotes degranulation and stimulates platelet activation. Inhibition of COX1, as with ...
As an MAO inhibitor, it has potential to serve as a treatment for individuals with psychological disorders similar to ... More severe side effects include deafness, low blood platelets, and an irregular heartbeat. Use can make one more prone to ... which facilitates the aggregation of cytotoxic heme.[medical citation needed] Free cytotoxic heme accumulates in the parasites ... Quinine can also act as a competitive inhibitor of monoamine oxidase (MAO), an enzyme that removes neurotransmitters from the ...
The mechanism of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation ... The activation of FX (to form FXa) by TF-FVIIa is almost immediately inhibited by tissue factor pathway inhibitor (TFPI). FXa ... thrombin is generated by activated platelets at the initiation of the platelet plug, which in turn promotes more platelet ... This process adheres platelets to the site of injury. Activated platelets release the contents of stored granules into the ...
Symptoms that develop, like other forms of ALL, relate to deficiency of platelets, resulting in bruising or bleeding; ... Concentric, nest-like bodies called Hassall's corpuscles (also called thymic corpuscles) are formed by aggregations of the ... This is done by acetylcholinesterase inhibitors such as pyridostigmine. Tumours originating from the thymic epithelial cells ... such as low platelets or anaemia. Immunophenotyping will reveal cells that are CD3, a protein found on T cells, and help ...
... platelet aggregation inhibitors MeSH D27.505.954.613 - renal agents MeSH D27.505.954.613.056 - anti-infective agents, urinary ... enzyme inhibitors MeSH D27.505.519.389.099 - aromatase inhibitors MeSH D27.505.519.389.200 - carbonic anhydrase inhibitors MeSH ... trypsin inhibitors MeSH D27.505.519.389.755 - protein kinase inhibitors MeSH D27.505.519.389.760 - protein synthesis inhibitors ... integrase inhibitors MeSH D27.505.519.389.375.400 - hiv integrase inhibitors MeSH D27.505.519.389.480 - lipoxygenase inhibitors ...
Platelet numbers and morphology are normal. Platelet aggregation is normal with ristocetin, but impaired with other agonists ... Understanding of the role of GpIIb/IIIa in Glanzmann's thrombasthenia led to the development of GpIIb/IIIa inhibitors, a class ... which is an integrin aggregation receptor on platelets. This receptor is activated when the platelet is stimulated by ADP, ... which is required for fibrinogen-dependent platelet-platelet interaction (aggregation).[citation needed] ...
Erythromelalgia is caused by an increased platelet count or increased platelet "stickiness" (aggregation), resulting in the ... Ruxolitinib, a Janus kinase 2 (JAK2) inhibitor, is also used to treat polycythemia. Ropeginterferon alfa-2b (Besremi) was ... It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with ... Fjellner B, Hägermark O (1979). "Pruritus in polycythemia vera: treatment with aspirin and possibility of platelet involvement ...
44 compared prasugrel versus higher loading and maintenance doses of clopidogrel for inhibiting platelet aggregation in ... TIMI 12 evaluated the safety and efficacy of the oral GP IIb/IIa inhibitor sibrafiban for the treatment of patients with a ... SEPIA-ACS-TIMI 42 evaluated the efficacy and safety of otamixaban, a direct factor Xa inhibitor, in patients with non-ST- ... ATLAS ACS-TIMI 46 compared the safety and efficacy of rivaroxaban, an oral direct factor Xa inhibitor, to placebo in patients ...
Gresele P, Momi S, Falcinelli E (October 2011). "Anti-platelet therapy: phosphodiesterase inhibitors". British Journal of ... inhibiting platelet aggregation. Zaprinast inhibits the growth of asexual blood-stage malaria parasites (P. falciparum) in ... sildenafil as a PDE5 inhibitor and Rolipram as a PDE4 inhibitor). The PDE nomenclature signifies the PDE family with an Arabic ... Inhibitors of PDE can prolong or enhance the effects of physiological processes mediated by cAMP or cGMP by inhibition of their ...
Stabilization of the platelet aggregation by fibrin mesh ultimately leads to clot formation. Darexaban and darexaban ... Darexaban (YM150) is a direct inhibitor of factor Xa created by Astellas Pharma. It is an experimental drug that acts as an ... an oral factor Xa inhibitor, in human liver and intestine". Drug Metabolism and Disposition: The Biological Fate of Chemicals. ... an oral direct factor Xa inhibitor". European Journal of Pharmacology. 673 (1-3): 49-55. doi:10.1016/j.ejphar.2011.10.009. PMID ...
F. necrophorum produces hemagglutinin which causes platelet aggregation that can lead to diffuse intravascular coagulation and ... Penicillin and penicillin-derived antibiotics can thus be combined with a beta-lactamase inhibitor such as clavulanic acid or ... Platelet count can be low or high. Liver and kidney function tests are often abnormal.[citation needed] Thrombosis of the ...
... reduces blood viscosity and decreases the potential for platelet aggregation and blood clot formation. Pentoxifylline is also ... Adenosine reuptake inhibitors, Ketones, PDE4 inhibitors, Vasodilators, Xanthines, Sanofi). ... Like other methylated xanthine derivatives, pentoxifylline is a competitive nonselective phosphodiesterase inhibitor which ... a PDE-3 inhibitor with better evidence for intermittent claudication on the Cochrane review cited above. Drugs.com drugs.com ...
The possible exceptions may be aspirin and naproxen due to their anti-platelet aggregation properties. Analyses in 2011 and ... COX-2 selective inhibitor Discovery and development of cyclooxygenase 2 inhibitors David Graham (epidemiologist) "Vioxx PI" ( ... Traditional NSAIDs are avoided in this population due to their effects on platelet aggregation and risk of gastrointestinal ... Traditional NSAIDs are avoided in this population due to their effects on platelet aggregation and risk of gastrointestinal ...
Pyridines are known to have an inhibiting effect on the synthesis of TxA2 Thromboxane - known for platelet aggregation and ... Multiple cyclooxygenase inhibitors are already used as drugs against thrombotic diseases. These drugs inhibit both the ... Thromboxane A2, the compound synthesized by this enzyme, promotes the aggregation of platelets and is a vasoconstrictor. The ... In platelets this fatty acid is metabolized to an endoperoxide called prostaglandin H2 by the enzyme cyclooxygenase 1. This ...
... which promote platelet aggregation and adhesion to the subendothelium, and thus the formation of potentially fatal thrombi. ... junctional molecules and endogenous inhibitors. Angiopoietin-2 works with VEGF to facilitate cell proliferation and migration ... Platelet activation Susac's syndrome Tunica intima VE-cadherin Weibel-Palade body Angiocrine growth factors Endothelial Cell ... and the subsequent recruitment of white blood cells and platelets, as well as proliferation of smooth muscle cells, leading to ...
Platelet Aggregation Inhibitors. Class Summary. Platelet aggregate inhibitors may have a positive influence on several ... Aspirin may be used in low doses to inhibit platelet aggregation and to improve complications of venous stases and thrombosis. ... Binds to receptor with high affinity and reduces platelet aggregation by 80% for up to 48 h following infusion. Prevents acute ... It binds to receptors with high affinity and reduces platelet aggregation by 80% for up to 48 hours following infusion. ...
Enhanced platelet aggregation by oral contraceptives: effect of PG synthetase inhibitors.. Authors: Sudhir, S. Gupta, L C. ... Enhanced platelet aggregation by oral contraceptives: effect of PG synthetase inhibitors. Indian Journal of Physiology and ... Platelet aggregation time was significantly (P less than 0.01) decreased in female rabbits treated with oral contraceptive (a ... PG synthetase inhibitors) along with oral contraceptives or diethylstilbestrol there was no significant alteration in platelet ...
Platelet Aggregation Inhibitors / therapeutic use * Prospective Studies * Stents * Treatment Outcome * United States ...
Blood Platelet Disorders. Blood Coagulation Disorders. Hemorrhagic Disorders. Aspirin. Anticoagulants. Anti-Inflammatory Agents ... Concomitant use of a strong inhibitor or inducer of CYP3A4 (like ruxolitinib). ... platelet abnormalities, clonality, specific cytokines…) and they are exposed to a lower risk of digestive hemorrhages. It is ...
Acute chest pain diagnostic accuracy and pre-hospital use of anticoagulants and platelet aggregation inhibitors. Dtsch Arztebl ... Acute chest pain diagnostic accuracy and pre-hospital use of anticoagulants and platelet aggregation inhibitors. Dtsch Arztebl ...
Figure 1.Btk inhibitors completely block CLEC-2-mediated platelet aggregation in vitro and ex vivo. Washed platelets at 4x108/ ... CLEC-2-mediated human platelet aggregation is inhibited by low concentrations of Btk inhibitors. To examine the role of Btk ... Btk inhibitors block platelet activation by CLEC-2. However, based on studies using ibrutinib-treated human platelets, Manne et ... Btk inhibitors selectively block platelet activation by CLEC-2 relatively to GPVI. This suggests that Btk inhibitors can be ...
Pharmacological Actions : Platelet Aggregation Inhibitors. [+] Red wine extract disrupts Th17 lymphocyte differentiation in a ... Pharmacological Actions : Antioxidants, NF-kappaB Inhibitor, Vascular Cell Adhesion Molecule-1 Inhibitor ... Evaluation of anti-Inflammatory, anti-platelet and anti-oxidant activity of wine extracts.Jan 29, 2020. ...
ClinicalTrials.gov: Platelet Aggregation Inhibitors (National Institutes of Health) * ClinicalTrials.gov: Warfarin (National ... Antiplatelet drugs - P2Y12 inhibitors (Medical Encyclopedia) Also in Spanish * Aspirin and heart disease (Medical Encyclopedia) ... Antiplatelets, such as aspirin and clopidogrel, prevent blood cells called platelets from clumping together to form a clot. ... Article: Daidzein Inhibits Human Platelet Activation by Downregulating Thromboxane A(2) Production and... ...
He also took a platelet aggregation inhibitor as prophylaxis against heart attack and stroke. In 1999, a carotid ultrasound ...
... are defined by specific alterations in hemostasis and platelet function. ... Platelet Dysfunction An inhibitor of platelet aggregation has been observed in the plasma of patients with severe LF and ... Cummins D, Fisher-Hoch SP, Walshe KJ, Mackie IJ, McCormick JB, Bennett D, et al. A plasma inhibitor of platelet aggregation in ... platelets exposed to the aggregation inhibitor begin to aggregate normally (32; Figure 8, panel A), indicating platelet ...
Categories: Platelet Aggregation Inhibitors Image Types: Photo, Illustrations, Video, Color, Black&White, PublicDomain, ...
Clopidogrel belongs to the class of medications called platelet aggregation inhibitors or antiplatelets. Clopidogrel is used to ... Clopidogrel belongs to the class of medications called platelet aggregation inhibitors or antiplatelets. Clopidogrel is used to ... Proton pump inhibitors: Proton pump inhibitors (PPIs) are medications such as omeprazole and lansoprazole that are taken to ... certain protein kinase inhibitors (e.g., dabrafenib, dasatinib, pazopanib). *proton pump inhibitors (PPIs; e.g., esomeprazole, ...
Raghavendra, R. H. and Naidu, K. A. Spice active principles as the inhibitors of human platelet aggregation and thromboxane ... Saraswat, M., Muthenna, P., Suryanarayana, P., Petrash, J. M., and Reddy, G. B. Dietary sources of aldose reductase inhibitors ...
... clopidogrel or platelet aggregation inhibitor -Concurrent malignancy requiring cytotoxic chemotherapy or radiation therapy - ... Adequate blood counts (hemoglobin greater than or equal to 9.0 g/dL, platelets greater than or equal to 50,000 cells/mm(3)) - ...
3. Effects of gliclazide on platelet aggregation and the plasminogen activator inhibitor type 1 level in patients with type 2 ... Effects of gliclazide on platelet aggregation and the plasminogen activator inhibitor type 1 level in patients with type 2 ... A: Glim 500 not only has a hypoglycemic action but also possesses antiplatelet activity by inhibiting platelet aggregation via ...
Platelet aggregation inhibitors. • Accumulation of LMWH, FXa inhibitors, thrombin inhibitors. ADP, adenosine diphosphate; APC, ... Inhibition platelet aggregation by vasoactive substances: ↑NO production by platelets. • ↓ in anemia (less scavenging of NO by ... Competitive binding of FDP bind to αIIbβ3→ ↓adhesion, ↓ aggregation. • Reduced collagen-induced platelet aggregation 20. • ... resulting in platelet adhesion, activation, and aggregation (Figure 1).9 Activated platelets exocytose α-granules (containing, ...
Keywords: Stroke, Myocardial Infarction, Platelet Aggregation Inhibitors, Heparin, Fibrinolytic Agents, Hirudins, Tyrosine, ... and heparin plus a glycoprotein IIb/IIIa inhibitor. ... bivalirudin versus the heparin/heparin plus tirofiban-inhibitor ...
Selective serotonergic reuptake inhibitors (SSRIs) may decrease platelet aggregation. We hypothesized that Cardiovascular ...
Platelet Aggregation Inhibitors 9% * Oxide ceramics for biomedical applications. Piconi, C. & Tampieri, A., May 24 2021, ... Roles of the tumor suppressor inhibitor of growth family member 4 (ING4) in cancer. Shatnawi, A., Abu Rabe, D. I. & Frigo, D. E ...
See Platelet Aggregation Inhibitors Drugs or agents which antagonize or impair any mechanism leading to blood platelet ... See Platelet Aggregation Inhibitors Drugs or agents which antagonize or impair any mechanism leading to blood platelet ... aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and ... aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and ...
... interference with platelet aggregation, and renal and cardiovascular risks.. FDA label warnings for NSAIDs note that risks for ... And tricyclics are predominately norepinephrinereuptake inhibitors. SNRIs are less so.. And evidence strongly supports that ... Tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors or SNRIs are effective and recommended in multiple ... Risks of NSAIDs and COX-2 inhibitors include gastritis, gastrointestinal bleeding, or perforation, fluid retention, ...
Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet ... Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet ... Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet ... Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet ...
Disintegrins are a family of small proteins from viper venoms that function as potent inhibitors of both platelet aggregation ... serving as the final common pathway leading to aggregation via formation of platelet-platelet bridges, which are essential in ... Disintegrins act as receptor antagonists, inhibiting aggregation induced by ADP, thrombin, platelet-activating factor and ... Crystal structure of vascular apoptosis-inducing protein-1(inhibitor-bound form). 2erq. Crystal structure of vascular apoptosis ...
Inhibitor, Platelet Aggregation Inhibitors, Platelet Aggregation Platelet Aggregation Inhibitor Platelet Antiaggregant Platelet ... Inhibitor, Platelet. Inhibitor, Platelet Aggregation. Inhibitors, Platelet. Inhibitors, Platelet Aggregation. Platelet ... Platelet Aggregation Inhibitors Entry term(s). Aggregation Inhibitor, Platelet Aggregation Inhibitors, Platelet Antiaggregant, ... Blood Platelet Aggregation Inhibitor Blood Platelet Aggregation Inhibitors Blood Platelet Antiaggregant Blood Platelet ...
Platelet Aggregation Inhibitors 22% * Mortality 19% 12 Scopus citations * 2003 Newly Emerging Concepts in Blood Vessel Growth: ...
Platelet Aggregation Inhibitors 11% * Endothelin-1 11% * Wounds and Injuries 11% * Metabolic Syndrome 11% ...
  • When anticoagulants or platelet aggregation inhibitors are indicated, they are resumed early. (bvsalud.org)
  • At 30 days, net adverse cardiovascular results were significantly reduced in the bivalirudin versus the heparin/heparin plus tirofiban-inhibitor groups. (acc.org)
  • Further, with the use of a routine post-PCI bivalirudin infusion, the rates of stent thrombosis were similar with bivalirudin, heparin, and heparin plus a glycoprotein IIb/IIIa inhibitor. (acc.org)
  • Antiplatelets, such as aspirin and clopidogrel, prevent blood cells called platelets from clumping together to form a clot. (medlineplus.gov)
  • Clopidogrel reduces the chances of these events by preventing platelets from forming into clumps. (medbroadcast.com)
  • Whole blood dynamic platelet aggregation counting and 1-year clinical outcomes in patients with coronary heart diseases treated with clopidogrel. (cdc.gov)
  • Evidence shows that antiplatelet agents, antioxidant therapies, amino acid supplementation, angiotensin converting enzyme (ACE) inhibitors, and angiotensin-receptor blockers may be able to prevent or slow the progression of atherosclerosis. (medscape.com)
  • Inhibitors of the tyrosine kinase Btk have been proposed as novel antiplatelet agents. (haematologica.org)
  • Potential cellular targets include vascular smooth muscle cells, monocyte/macrophage cell lines, platelets, and endothelial cells. (medscape.com)
  • If MPN patients are also considered to be cancer patients in many countries, the pathophysiology of thrombosis is quite specific (hyperviscosity, platelet abnormalities, clonality, specific cytokines…) and they are exposed to a lower risk of digestive hemorrhages. (clinicaltrials.gov)
  • Integrin receptors are involved in cell-cell and cell-extracellular matrix interactions, serving as the final common pathway leading to aggregation via formation of platelet-platelet bridges, which are essential in thrombosis and haemostasis. (embl.de)
  • Increased intake of linoleic acid is known to interfere with the incorporation of EPA and DHA (which have the most potent inflammatory effects) in cell membrane lipids, and causes platelet aggregation and oxidation of low-density lipoprotein. (researchgate.net)
  • A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A . It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II , a vasoconstrictor and important regulator of arterial blood pressure . (lookformedical.com)
  • Ticagrelor, a purinergic P2Y12 receptor blocker, is a potent platelet antagonist and an important component in the treatment for acute coronary syndromes identified to have a potential risk to cause bradyarrhythmias. (manipal.edu)
  • Effects of aging on clinical outcomes in patients receiving genotype-guided P2Y12 inhibitor selection after percutaneous coronary intervention. (cdc.gov)
  • Aspirin and HMG-CoA reductase inhibitors may reduce plaque inflammation. (medscape.com)
  • P-selectin, soluble endothelial protein C receptor, soluble thrombomodulin, plasminogen activator inhibitor 1, ADAMTS-13, von Willebrand factor, tissue factor, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 were more elevated in LF patients than in controls. (cdc.gov)
  • Endothelial protein C receptor, thrombomodulin, intercellular adhesion molecule 1, plasminogen activator inhibitor 1, D-dimer, and hepatocyte growth factor were higher in fatal than nonfatal LF cases. (cdc.gov)
  • The C-type lectin receptor CLEC-2 is expressed at high levels on platelets and at low levels on a subpopulation of hematopoietic cells. (haematologica.org)
  • 7-9 This hemITAM signaling pathway is similar to that used by the YxxL-containing platelet ITAM receptors such as the collagen receptor GPVI-FcRγ complex and the low affinity immune receptor FcγRIIA 10 . (haematologica.org)
  • Disintegrins contain an RGD (Arg-Gly-Asp) or KGD (Lys-Gly-Asp) sequence motif that binds specifically to integrin IIb-IIIa receptors on the platelet surface, thereby blocking the binding of fibrinogen to the receptor-glycoprotein complex of activated platelets. (embl.de)
  • To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II , patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS . (lookformedical.com)
  • Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction. (medscape.com)
  • Effect of CYP2C19 Genotype on Ischemic Outcomes During Oral P2Y Inhibitor Therapy: A Meta-Analysis. (cdc.gov)
  • In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCγ2 in human platelets. (haematologica.org)
  • An angiotensin-converting enzyme inhibitor that is used to treat HYPERTENSION and HEART FAILURE . (lookformedical.com)
  • Thrombocytopenia is a common feature of hemorrhagic fevers and vascular permeability disorders ( 8 ), but the decrease in platelet counts in acute LF is not low enough to cause spontaneous hemorrhage. (cdc.gov)
  • Selective serotonergic reuptake inhibitors (SSRIs) may decrease platelet aggregation. (duke.edu)
  • The American Heart Association (AHA) has promulgated its Get With the Guidelines program, which involves an Internet-based checklist of discharge medications to ensure that coronary artery disease (CAD) patients are started on aspirin, beta-blockers, ACE inhibitors, and statins (if needed) in the hospital. (medscape.com)
  • Platelet aggregation time was significantly (P less than 0.01) decreased in female rabbits treated with oral contraceptive (a preparation containing low dose of estrogen) as also by injection of diethylstilbestrol (10 mg/kg), while in animals that received indomethacin (10 mg/kg) or aspirin (30 mg/kg) (PG synthetase inhibitors) along with oral contraceptives or diethylstilbestrol there was no significant alteration in platelet aggregation time. (who.int)
  • Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. (bvsalud.org)
  • The collagen-induced platelet aggregation of platelet-rich plasma samples from 14 healthy rabbits was measured turbidometrically using a platelet aggregometer, before and 1 hour after intravenous injection of alum. (who.int)
  • Collagen-induced platelet aggregation was significantly reduced after alum injection. (who.int)
  • contradiction in the mechanism of action of alum, we evaluated the in vivo effect of Alum (aluminium potassium sulfate) is a alum in terms of collagen-induced platelet food additive and traditional remedy used to aggregation and bleeding time. (who.int)
  • The impaired homeostasis and platelet dysfunction implicate alterations in the protein C pathway, which might contribute to the loss of endothelial barrier function in fatal infections. (cdc.gov)
  • Normally, platelets help the blood to clot when needed, such as after an injury. (medbroadcast.com)
  • In Sierra Leone during 2015-2018, we assessed LF patients' day-of-admission plasma samples for levels of proteins necessary for coagulation, fibrinolysis, and platelet function. (cdc.gov)
  • Platelet aggregation study on the blood. (who.int)
  • IMSEAR at SEARO: Enhanced platelet aggregation by oral contraceptives: effect of PG synthetase inhibitors. (who.int)
  • This study investigated the in vivo effect of alum on platelet aggregation and bleeding time in rabbits. (who.int)
  • Ces résultats semblent indiquer que l'utilisation de l'alun en tant qu'antiplaquettaire oral pourrait faire l'objet d'études complémentaires, en tenant compte des effets secondaires éventuels notamment chez les patients dont la fonction rénale est altérée. (who.int)
  • These results show that Btk inhibitors selectively block activation of human platelets by CLEC-2 relative to GPVI suggesting that they can be used at 'low dose' in patients to target CLEC-2 in thrombo-inflammatory disease. (haematologica.org)
  • This feedback role is not seen in mouse platelets and, consistent with this, CLEC-2-mediated activation is blocked by high but not by low concentrations of ibrutinib. (haematologica.org)
  • Platelet disaggregation occurred only in samples from fatal LF cases. (cdc.gov)
  • 11 Another difference between CLEC-2 and GPVI signaling in human platelets is the critical dependence of CLEC- 2 on positive feedback signaling through ADP and thromboxane A2 (TxA2), actin polymerization, and the small GTPase Rac. (haematologica.org)
  • adults and adolescents weighing at least 35 kg who have previously been treated with a protease inhibitor (`protease inhibitor-experienced') or in children and adolescents from the age of 3 years with a body weight of at least 14 kg. (who.int)