scholarly journals Effects of a microtubule stabilizing agent on the response of platelets to vincristine

Blood ◽  
1982 ◽  
Vol 60 (2) ◽  
pp. 474-483 ◽  
Author(s):  
JG White ◽  
GH Rao
Keyword(s):  
Platelet Function ◽  
Shape Change ◽  
Blood Platelets ◽  
Secretory Activity ◽  
Prostaglandin Synthesis ◽  
Stabilizing Agent ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Antimitotic Drug ◽  
Tubulin Paracrystals ◽  
Microtubule Stabilizing Agent

Abstract The discoid shape of blood platelets is supported by a circumferential bundle of microtubules. Removal of the microtubules by an antimitotic drug, vincristine, is associated with loss of lentiform appearance, formation of tubulin paracrystals, a depressed response to aggregating agents, and impaired secretory activity. Recent studies have suggested that the action of vincristine on platelet secretion and aggregation is directly related to its action on microtubules, while other work had indicated that the antimitotic drug prevents the release reaction by inhibiting prostaglandin synthesis. The present study has examined the influence of taxol, a microtubule stabilizing agent, on the response of platelets to vincristine. Taxol completely prevented vincristine- induced shape change, microtubule disassembly, and tubulin paracrystal formation, even at concentrations one-tenth that of the antimitotic drug. Pretreatment with vincristine to dissociate microtubules and convert tubulin to crystals before exposure to taxol did not affect altered shape or tubulin paracrystals, but did cause assembly of free pools of tubulin into tubular polymers. Studies of physiology confirmed that vincristine, in amounts that remove microtubules, depresses platelet aggregation and secretion, effects that could be overcome by increasing agonist concentration. Although completely preventing microtubule dissociation, taxol had no corrective influence on vincristine-induced inhibition of platelet function. Biochemical studies revealed that vincristine concentrations that disassembled microtubules and blocked secretion did not inhibit conversion of 14C- arachidonic acid to thromboxane B2. The findings suggest that vincristine inhibits platelet function through some mechanism other than disassembling microtubules, but the other mechanism does not involve inhibition of prostaglandin synthesis.

scholarly journals Effects of a microtubule stabilizing agent on the response of platelets to vincristine

Blood ◽  
1982 ◽  
Vol 60 (2) ◽  
pp. 474-483 ◽  
Author(s):  
JG White ◽  
GH Rao
Keyword(s):  
Platelet Function ◽  
Shape Change ◽  
Blood Platelets ◽  
Secretory Activity ◽  
Prostaglandin Synthesis ◽  
Stabilizing Agent ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Antimitotic Drug ◽  
Tubulin Paracrystals ◽  
Microtubule Stabilizing Agent

The discoid shape of blood platelets is supported by a circumferential bundle of microtubules. Removal of the microtubules by an antimitotic drug, vincristine, is associated with loss of lentiform appearance, formation of tubulin paracrystals, a depressed response to aggregating agents, and impaired secretory activity. Recent studies have suggested that the action of vincristine on platelet secretion and aggregation is directly related to its action on microtubules, while other work had indicated that the antimitotic drug prevents the release reaction by inhibiting prostaglandin synthesis. The present study has examined the influence of taxol, a microtubule stabilizing agent, on the response of platelets to vincristine. Taxol completely prevented vincristine- induced shape change, microtubule disassembly, and tubulin paracrystal formation, even at concentrations one-tenth that of the antimitotic drug. Pretreatment with vincristine to dissociate microtubules and convert tubulin to crystals before exposure to taxol did not affect altered shape or tubulin paracrystals, but did cause assembly of free pools of tubulin into tubular polymers. Studies of physiology confirmed that vincristine, in amounts that remove microtubules, depresses platelet aggregation and secretion, effects that could be overcome by increasing agonist concentration. Although completely preventing microtubule dissociation, taxol had no corrective influence on vincristine-induced inhibition of platelet function. Biochemical studies revealed that vincristine concentrations that disassembled microtubules and blocked secretion did not inhibit conversion of 14C- arachidonic acid to thromboxane B2. The findings suggest that vincristine inhibits platelet function through some mechanism other than disassembling microtubules, but the other mechanism does not involve inhibition of prostaglandin synthesis.

Platelet Aggregation Caused by Dithiothreitol

1984 ◽  
Vol 51 (01) ◽  
pp. 119-124 ◽  
Author(s):  
M B Zucker ◽  
N C Masiello
Keyword(s):  
Shape Change ◽  
Blood Platelets ◽  
Dense Granule ◽  
Metabolic Inhibitors ◽  
Electrophoretic Patterns ◽  
Discernible Effect ◽  
Variable Extent ◽  
Triton X ◽  
Induced Aggregation ◽  
Platelet Shape

SummaryMacIntyre et al. showed that over 1 mM dithiothreitol (DTT) aggregates blood platelets in the presence of fibrinogen; aggregation is not inhibited by prostaglandin E1. We confirmed their data and found that 70 mM 2-mercaptoethanol was also active. DTT- induced aggregation was not associated with platelet shape change or secretion of dense granule contents, was not inhibited by tetracaine or metabolic inhibitors, was prevented at pH 6.5, and prevented, reversed, or arrested by EDTA, depending on when the EDTA was added. DTT did not cause aggregation of thrombasthenic, EDTA-treated, or cold (0° C) platelets, which also failed to aggregate with ADP. Platelets stimulated with DTT bound 125I-labeled fibrinogen. Thus DTT appears to “expose” the fibrinogen receptors. SDS gel electrophoresis of platelet fractions prepared by use of Triton X-114 showed that aggregating concentrations of DTT reduced proteins of apparent Mr 69,000 and 52,000 (probably platelet albumin) and, to a variable extent, glycoproteins Ib, IIb and III. Exposure of unlabeled or 125I- labeled platelets to ADP had no discernible effect on the electrophoretic patterns.

Antipyretic Activity of the Root Extracts of Xylocarpus

2019 ◽  
Vol 9 (3) ◽  
pp. 35-38
Author(s):  
Ganesh Kumar Y ◽  
Pranitha D ◽  
Phaneendra D ◽  
Madhava Reddy Ch
Keyword(s):  
Mechanisms Of Action ◽  
Prostaglandin Synthesis ◽  
The Body ◽  
Human Race ◽  
Pharmacological Activities ◽  
Standard Drug ◽  
Root Extracts ◽  
Antipyretic Activity ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Elevated Body Temperature

Various types of conditions exist in the body that causes fever and pain. Drugs that are used to treat fever are called antipyretics, and those are usually prescribed to treat elevated body temperature. But those drugs result in many other side effects like ulcers, perforations, bleedings and obstructions, which make their use questionable and limiting. Medicinal plants are used in the treatment of diseases from the starting of the human race and the process; they had been subjected to rigorous investigations and tests to establish a scientific proof and validation of the various pharmacological activities and their respective mechanisms of action in treating the herbs. Considering the anti-inflammatory properties of the plant, Xylocarpus mekongesis was investigated for its antipyretic activity in yeast method and 3doses out of which 00mg/kg body weight showed a better activity compared to the standard drug and other extracts too. The mechanism of action was similar to the paracetamol action that is inhibition of prostaglandin synthesis.

scholarly journals Transformation and motility of human platelets: details of the shape change and release reaction observed by optical and electron microscopy.

1979 ◽  
Vol 83 (1) ◽  
pp. 126-142 ◽  
Author(s):  
R D Allen ◽  
L R Zacharski ◽  
S T Widirstky ◽  
R Rosenstein ◽  
L M Zaitlin ◽  
...  
Keyword(s):  
Shape Change ◽  
Human Subjects ◽  
Blood Platelets ◽  
Time Lapse ◽  
Human Platelets ◽  
Transformation Process ◽  
Epifluorescence Microscopy ◽  
Scanning Electron Micrographs ◽  
Dense Bodies ◽  
Short Wavelength Light

Blood platelets from 10 normal human subjects have been examined with a sensitive differential interference contrast (DIC) microscope. The entire transformation process during adhesion to glass is clearly visible and has been recorded cinematographically, including the disk to sphere change of shape, the formation of sessile protuberances, the extension and retraction of pseudopodia, and the spreading, ruffling, and occasional regression of the hyalomere. The exocytosis of intact dense bodies can be observed either by DIC microscopy, or by epifluorescence microscopy in platelets stained with mepacrine. Details of fluorescent flashes indicate that the dense bodies usually release their contents extracellularly, may do so intracytoplasmically under the influence of strong, short wavelength light on some preparations of mepacrine-stained platelets. The release of one or more dense bodies leaves a crater of variable size on the upper surface of the granulomere. Such craters represent the surface component of the open canalicular system and their formation and disappearance can be directly observed. Because these techniques permit quantitation of several parameters of motility which are not readily observable by other techniques, it is suggested that high extinction DIC microscope examination may become a rapid and useful method of studying congenital and acquired platelet disorders. Many features of platelet transformation have been confirmed and extended by scanning electron micrographs. These can in turn be interpreted by reference to time-lapse films of living platelets.

scholarly journals Influence of γ-Secretase Inhibitor 24-Diamino-5-Phenylthiazole DAPT on Platelet Activation

2016 ◽  
Vol 38 (2) ◽  
pp. 726-736 ◽  
Author(s):  
Guoxing Liu ◽  
Guilai Liu ◽  
Madhumita Chatterjee ◽  
Anja T. Umbach ◽  
Hong Chen ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Platelet Function ◽  
Blood Platelets ◽  
Annexin V ◽  
Negative Regulator ◽  
Ros Generation ◽  
Integrin Activation ◽  
Forward Scatter ◽  
Secretase Inhibitor ◽  
Αiibβ3 Integrin

Background/Aims: DAPT (24-diamino-5-phenylthiazole) inhibits γ-secretase, which cleaves the signaling molecule CD44, a negative regulator of platelet activation and apoptosis. CD44 is a co-receptor for macrophage migration inhibitory factor (MIF) an anti-apoptotic pro-inflammatory cytokine expressed and released from blood platelets. Whether DAPT influences platelet function, remained, however, elusive. Activators of platelets include collagen related peptide (CRP). The present study thus explored whether DAPT modifies the stimulating effect of CRP on platelet function. Methods: Platelets isolated from wild-type mice were exposed for 30 minutes to DAPT (10 µM). Flow cytometry was employed to estimate Orai1 abundance with specific antibodies, cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, platelet degranulation from P-selectin abundance, integrin activation from αIIbβ3 integrin abundance, generation of reactive oxygen species (ROS) from DCFDA fluorescence, mitochondrial transmembrane potential from TMRE fluorescence, phospholipid scrambling of the cell membrane from annexin-V-binding, relative platelet volume from forward scatter and aggregation utilizing staining with CD9-APC and CD9-PE. Results: Exposure of platelets to 2-5 µg/ml CRP was followed by significant increase of Orai1 abundance, [Ca2+]i, and P-selectin abundance, as well as by αIIbβ3 integrin activation, ROS generation, mitochondrial depolarization, enhanced annexin-V-binding, decreased cell volume, and aggregation. All CRP induced effects were significantly blunted in the presence of DAPT. Conclusions: The γ-secretase inhibitor DAPT counteracts agonist induced platelet activation, apoptosis and aggregation.

scholarly journals THE EFFECT OF INHIBITION OF PROSTAGLANDIN SYNTHESIS ON OVARIAN HYPERTROPHY IN THE RAT

Reproduction ◽  
1975 ◽  
Vol 44 (3) ◽  
pp. 473-479 ◽  
Author(s):  
V. D. CASTRACANE ◽  
L. F. TANKENOW ◽  
A. A. SHAIKH
Keyword(s):  
Prostaglandin Synthesis ◽  
Inhibition Of Prostaglandin Synthesis

Platelet PI3K Modulates Innate Leukocyte Extravasation during Acid-Induced Acute Lung Inflammation

2019 ◽  
Vol 119 (10) ◽  
pp. 1642-1654 ◽  
Author(s):  
Julia Barbara Kral-Pointner ◽  
Waltraud Cornelia Schrottmaier ◽  
Manuel Salzmann ◽  
Marion Mussbacher ◽  
Georg Johannes Schmidt ◽  
...  
Keyword(s):  
Platelet Function ◽  
Lung Inflammation ◽  
Blood Platelets ◽  
Regulatory Subunit ◽  
Interleukin 12 ◽  
Pi3k Signaling ◽  
Acute Lung Inflammation ◽  
Activation Markers ◽  
Leukocyte Extravasation ◽  
The Impact

Introduction Blood platelets are increasingly recognized as modulators of leukocyte effector functions in various pathologies including acute lung injury (ALI). ALI is a life-threatening disease, caused by damage to the alveolar epi- and endothelium. Excessive accumulation of leukocytes leads to severe lung inflammation, resulting in impaired lung function and hypoxemia. Objective Since leukocyte migration is modulated by activated platelets and phosphatidylinositol 3-kinase (PI3K) signaling is involved in platelet function, we aimed to elucidate the effect of PI3K on platelet-mediated immune responses. Materials and Methods We generated a mouse model with a platelet-specific deletion of p85α, the most important regulatory subunit of the class IA PI3K, and evaluated platelet function and platelet–leukocyte interactions. Moreover, we analyzed the impact of platelet-specific p85α gene deficiency during sterile peritonitis and acid-induced ALI. Results In vitro analyses of platelets revealed that lack of p85α led to decreased downstream signaling and diminished expression of surface activation markers, for example, CD62P and CD63, as well as reduced platelet aggregation. Moreover, platelet PI3K essentially mediated direct interactions of platelets with monocytes and neutrophils. In mice, platelet-specific p85α deficiency prevented leukocyte infiltration into the peritoneum and the bronchoalveolar compartment during sterile peritonitis and ALI, respectively. Additionally, the release of the inflammatory cytokine interleukin-12/23 was diminished in platelet p85α-deficient mice during ALI. In contrast to PI3K, neither overexpression nor depletion of platelet phosphatase and tensin homolog, the endogenous antagonist of PI3K, significantly modulated platelet function. Conclusion Our data indicate a crucial role of platelet PI3K signaling for leukocyte extravasation upon inflammatory stimuli in various diseases models.

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