scholarly journals Sex related differences in platelet function: the effect of aspirin

Blood ◽  
1982 ◽  
Vol 59 (3) ◽  
pp. 625-627 ◽  
Author(s):  
JG Kelton ◽  
CJ Carter ◽  
A Santos ◽  
J Hirsh
Keyword(s):  
Platelet Function ◽  
Animal Experiments ◽  
Inhibitory Effect ◽  
Thromboxane B2 ◽  
Equal Dose ◽  
Before And After ◽  
Male Patients ◽  
Induced Aggregation

Abstract There is evidence from clinical studies and animal experiments that aspirin has a greater antithrombotic activity in males compared to females. We investigated platelet function in vitro and in vivo in rabbits before and after the administration of a dose of aspirin (5 mg/kg) which inhibited collagen stimulated thromboxane B2 generation. Infusion of collagen into untreated animals resulted in a 38 +/- 4% (m +/- SE, n = 13) decrease in platelet count (assessed by whole blood radioactivity) in the male animals, and a 27 +/- 3% (m +/- SE, n = 13) in the female animals. Pretreatment with aspirin resulted in a significant inhibitory effect in the male but not the female animals (p less than 0.05). The male animals had significantly greater thromboxane B2 generation in vivo than did the female animals following an equal dose of collagen (males, 2.64 +/- 0.7 ng/ml thromboxane B2, n = 14; females, 1.67 +/- 0.4 ng/ml thromboxane B2, n = 15, p less than 0.05). In contrast no sex related difference in the inhibitory effect of aspirin on maximal collagen induced aggregation was found when platelets were studied in vitro. The greater reactivity of male patients in vivo may be accounted for by the observed increase in thromboxane B2 generation. This might also explain the greater thrombotic tendency of males, and the observed difference in the antithrombotic effect of aspirin in males and females.

scholarly journals Sex related differences in platelet function: the effect of aspirin

Blood ◽  
1982 ◽  
Vol 59 (3) ◽  
pp. 625-627
Author(s):  
JG Kelton ◽  
CJ Carter ◽  
A Santos ◽  
J Hirsh
Keyword(s):  
Platelet Function ◽  
Animal Experiments ◽  
Inhibitory Effect ◽  
Thromboxane B2 ◽  
Equal Dose ◽  
Before And After ◽  
Male Patients ◽  
Induced Aggregation

There is evidence from clinical studies and animal experiments that aspirin has a greater antithrombotic activity in males compared to females. We investigated platelet function in vitro and in vivo in rabbits before and after the administration of a dose of aspirin (5 mg/kg) which inhibited collagen stimulated thromboxane B2 generation. Infusion of collagen into untreated animals resulted in a 38 +/- 4% (m +/- SE, n = 13) decrease in platelet count (assessed by whole blood radioactivity) in the male animals, and a 27 +/- 3% (m +/- SE, n = 13) in the female animals. Pretreatment with aspirin resulted in a significant inhibitory effect in the male but not the female animals (p less than 0.05). The male animals had significantly greater thromboxane B2 generation in vivo than did the female animals following an equal dose of collagen (males, 2.64 +/- 0.7 ng/ml thromboxane B2, n = 14; females, 1.67 +/- 0.4 ng/ml thromboxane B2, n = 15, p less than 0.05). In contrast no sex related difference in the inhibitory effect of aspirin on maximal collagen induced aggregation was found when platelets were studied in vitro. The greater reactivity of male patients in vivo may be accounted for by the observed increase in thromboxane B2 generation. This might also explain the greater thrombotic tendency of males, and the observed difference in the antithrombotic effect of aspirin in males and females.

Comparison of in Vivo and in Vitro Effects of Platelet Function Suppressing Drugs

1975 ◽  
Author(s):  
M. Buchanan ◽  
J. Hirsh
Keyword(s):  
Platelet Function ◽  
Prosthetic Heart Valve ◽  
Inhibitory Effect ◽  
Potent Effect ◽  
Platelet Survival ◽  
In Vitro Effects ◽  
Antithrombotic Efficacy ◽  
Induced Aggregation

Comparison of in vivo and in vitro platelet function tests to assess the antithrombotic efficacy of drugs which suppress platelet function have been contradictory. For example, aspirin (ASA) has a potent effect in vitro but little effect when tested on platelet survival in prosthetic heart valve replacements whereas dipyridamole (DIP) has little or no effect in vitro but a marked effect on platelet survival. We have compared in parallel the in vivo and in vitro effects of a number of drugs which suppress platelet function in an animal model. Rabbits were infused with homologous 51Cr-labelled platelets and then given either ASA (10-200 mg/kg), DIP (1-20 mg/kg) or sulfinpyrazone (SUF) (30-200 mg/kg) intravenously. One hour later PRP from each rabbit was tested by ADP and collagen-induced aggregation. Then each rabbit was infused with an identical final concentration of collagen and the subsequent recovery of 51Cr platelet radioactivity was monitored. In untreated rabbits collagen infusion produced 30% reduction of 51Cr platelets which returned to within 85% of a procollagen level by 5 min. ASA (⪖ 10 mg/kg) inhibited in vitro collagen-induced aggregation while a dose of 100 mg/kg of ASA was necessary to achieve the same inhibitory effect in vivo. On the other hand, DIP (1-20 mg/kg) had no inhibitory effect on in vitro platelet aggregation whereas it inhibited aggregation in vivo. The results of SUF were similar in vitro and in vivo. These results suggest that the effectiveness of drugs on platelet function may be affected by centrifugation, addition of anticoagulant or removal of red cells. This may explain the discrepancies reported between the in vivo and in vitro effectiveness of such drugs.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

Effect Of Solvents On Indium-111 Oxine Transport In Human Platelets And On Platelet Function In Vitro

1981 ◽  
Author(s):  
T Tsukada
Keyword(s):  
Platelet Function ◽  
Kinetic Constant ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Polysorbate 80 ◽  
Autologous Plasma ◽  
Indium 111 ◽  
Induced Aggregation ◽  
Water Space

Mechanism of Indium-111 oxine(In) transport in human platelets in buffered saline and the effect of In-labeling on platelet function were studied using In dissolved in 25% of ethanol in saline (In-ES) or 0.01% of polysorbate 80 in HEPES buffer(In-PH). Increase in temperature up to 37° C progressively enhanced the transport of In-ES, while transport of In-PH reached to plateau at 15°C. A states of equilibrium was not reached during 2 hr incubation at 22°C in In-ES. Uptake of In-PH reached to plateau after only 15 min of incubation. Distribution of In taken up by platelets in InES was 57% in cytosol and 27% in stroma, while in In-PH 69% in stroma and 22% in cytosol. 88% of In in cytosol was bound to lipids(46% in cholesterol and 27% in PS+PI). 82% of In in stroma was found in PS+PI fraction.The fact that the ratio of free In between the platelet water space and the outside medium after 30 min of incubation at up to 0.1 uM of In exceeded unity, suggests satura- , ble component of In transport prevails at this concentration in In-ES and In-PH. Kinetic constant could be calculated, Kt= 2nM, Vmax= 2.5 pmol/min/ml in In-ES, and Kt= InM, Vmax=0.7 pmol/min/ml in In-PH.Elution of In from radiolableled platelets in autologous plasma incubated at 37°C for 5 hr was less than 10% in the case of In-ES and 56% in the case of In-PH. Less than 3% of labeled-In was eluated from platelets in collagen-induced aggregation and 4-7% of In was eluated in thrombin-induced aggregation.Although 0.3% of ethanol and/or 6nM of oxine have no inhibitory effect of platelet aggregation, collagen-induced aggregation and release reaction of In-labeled platelet was impaired. 0.003% of polysorbate 80 itself abolished completely the aggregability of platelets by collagen or thrombin.It is concluded In-PH is unsuitable for platelet labeling. In-111 oxine also seems to have problems which Cr-51 has, i.e. inhomogenous distribution of In in a platelet population, elution of In from labeled platelets in circulation.

scholarly journals In vivo hypotensive effect and in vitro inhibitory activity of some Cyperaceae species

2013 ◽  
Vol 49 (4) ◽  
pp. 803-809
Author(s):  
Monica Lacerda Lopes Martins ◽  
Henrique Poltronieri Pacheco ◽  
Iara Giuberti Perini ◽  
Dominik Lenz ◽  
Tadeu Uggere de Andrade ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Colorimetric Assay ◽  
Hypotensive Effect ◽  
Ace Inhibition ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Total Phenolic ◽  
Before And After

In 1820, French naturalist August Saint Hillaire, during a visit in Espírito Santo (ES), a state in southeastern Brazil, reported a popular use of Cyperaceae species as antidote to snake bites. The plant may even have a hypotensive effect, though it was never properly researched. The in vitro inhibitory of the angiotensin converting enzyme (ACE) activity of eigth ethanolic extracts of Cyperaceae was evaluated by colorimetric assay. Total phenolic and flavonoids were determined using colorimetric assay. The hypotensive effect of the active specie (Rhychonospora exaltata, ERE) and the in vivo ACE assay was measured in vivo using male Wistar Kyoto (ERE, 0.01-100mg/kg), with acetylcholine (ACh) as positive control (5 µg/kg, i.v.). The evaluation of ACE in vivo inhibitory effect was performed comparing the mean arterial pressure before and after ERE (10 mg/kg) in animals which received injection of angiotensin I (ANG I; 0,03, 03 and 300 µg/kg, i.v.). Captopril (30 mg/kg) was used as positive control. Bulbostylis capillaris (86.89 ± 15.20%) and ERE (74.89 ± 11.95%, ERE) were considered active in the in vitro ACE inhibition assay, at 100 µg/mL concentration. ACh lead to a hypotensive effect before and after ERE's curve (-40±5% and -41±3%). ERE showed a dose-dependent hypotensive effect and a in vivo ACE inhibitory effect. Cyperaceae species showed an inhibitory activity of ACE, in vitro, as well as high content of total phenolic and flavonoids. ERE exhibited an inhibitory effect on both in vitro and in vivo ACE. The selection of species used in popular medicine as antidotes, along with the in vitro assay of ACE inhibition, might be a biomonitoring method for the screening of new medicinal plants with hypotensive properties.

Inhibition of Human Platelet Aggregation by the Proteolytic Effect of Streptokinase (SK). Role of the Factor VIII Related Antigen

1975 ◽  
Author(s):  
R. Castillo ◽  
S. Maragall ◽  
J. A. Guisasola ◽  
F. Casals ◽  
C. Ruiz ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Platelet Rich Plasma ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Factor Viii Related Antigen ◽  
Human Factor Viii ◽  
Induced Aggregation

Defective ADP-induced platelet aggregation has been observed in patients treated with streptokinase. This same effect appears “in vitro” when adding SK to platelet rich plasma (PRP). Classic hemophilia and normal platelet poor plasmas (PPP) treated with SK inhibit the aggregation of washed platelets; plasmin-treated normal human serum also shows an inhibitory effect on platelet aggregation. However, von Willebrand SK-treated plasmas do not inhibit the aggregation of washed platelets. The same results appear when plasmas are previously treated with a rabbit antibody to human factor VIII.This confirms that the antiaggregating effect is mainly linked to the digested factor VIII related antigen.The inhibition of ADP-induced platelet aggregation has been proved in gel filtration-isolated and washed platelets from SK-treated PRP.Defective ristocetin-induced platelet aggregation has also been observed- This action does not appear in washed platelets from SK-treated PRP in presence of normal PPP, but it does in presence of SK-treated PPP, which suggests that the inhibition of the ristocetin-induced aggregation is due to the lack of factor VIII and not to the factor VIII-related products.Heparin, either “in vivo” or “in vitro”, has corrected the antiaggregating effect of SK.

The Effects Of Prostacyclin (PGI2) On Intravascular Platelet Aggregation

1981 ◽  
Author(s):  
G G Duncan ◽  
G Mallarkey ◽  
G M Smith
Keyword(s):  
Platelet Count ◽  
Guinea Pigs ◽  
Adenosine Diphosphate ◽  
Before And After ◽  
Dependent Inhibition ◽  
Induced Aggregation ◽  
Dose Dependent ◽  
Anaesthetised Rats

Intravascular aggregation can be measured by counting the number of circulating platelets before and after the injection of aggregation agents. The Technicon Autocounter was modified to count platelets continuously and connected via a double cannula in a carotid artery to an anaesthetised animal.Adenosine diphosphate (ADP) and collagen gave dose- dependent falls in the circulating platelet count when injected into rats, guinea pigs and rabbits. This enabled aggregation to be accurately quantitated in vivo.The infusion of PGI2 (0.25-1 ug/kg/min) in anaesthetised rats and rabbits produced a dose-dependent inhibition of the fall in platelet count produced by ADP and collagen. The formation of PGI2 can be inhibited in vitro by 15- hydroperoxyarachidonic acid (15HPAA). When 20 ug/kg/min of 15HPAA was infused into rats, aggregation produced by collagen was significantly increased suggesting that PGI2 is continuously formed by the rat vascular endothelium. This observation was confirmed by infusing 6-keto PGF1α antiserum. This antibody also prevented the inhibitory activity of PGI2 on collagen-induced aggregation. The study of continuous platelet counting in guinea pigs has been hampered by the occurrence of thrombocytopenia in certain animals. When 2 ug/kg/min of PGI2 was infused for 10 mins, a rise in the circulating platelet count to a steady plateau 4-5 × 105 platelets occurredThese experiments have shown that PGI2 will prevent aggregation by ADP and collagen and will reverse spontaneous thrombocytopenia and that PGI2 is continuously released from the vessels of anaesthetised rats.

scholarly journals ‘In Vivo’ and ‘In Vitro’ Effects of Some Vasoactive Drugs on Platelet Function and on Coagulation/Fibrinolysis System

1977 ◽  
Author(s):  
A.G. Dettori ◽  
O. Ponari ◽  
C. Manotti ◽  
A. Megha ◽  
M. Pini
Keyword(s):  
Platelet Function ◽  
Vasoactive Drugs ◽  
Platelet Function Tests ◽  
Lysis Time ◽  
Low Concentrations ◽  
Euglobulin Lysis Time ◽  
In Vitro Effects ◽  
Induced Aggregation

Three substances widely used as vasoactive drugs are known to have an inhibiting effect on platelet aggregation ‘in vitro’. We investigated the changes induced on thrombelastogram, routine clotting tests, euglobulin lysis time (ELT), platelet count, aggregation, and adhesiveness by i, v. administration of these drugs to man. The same indices were also studied ‘in vitro’ by adding comparable concentrations of the substances to human blood or plasma.Aminophilline did not produce any significant variation in ADP-or collagen-induced aggregation either ‘in vitro’ (50 to 200 μg/ml) or ‘in vivo’ (240 mg). A trend to disaggregation was seen only in a few cases. Shorter ELT were found 30 and 120 minutes after injection.A papaverine derivative (Metaverinum, 150 mg) showed a similar ‘in vivo’ pattern: minor changes in platelet function tests and a moderate activation of fibrinolysis were seen. The drug acted ‘in vitro’ as a powerful inhibitor of aggregation (from 30 µg/ml)while fibrinolysis was only activated at the highest concentration (120 µg/ml).Bencyclan, capable of inhibiting platelet function ‘in vitro’ at very low concentrations (0.25µM) did not show similar effects ‘in vivo’ (50 mg) apart from a reduced platelet adhesiveness to glass.

Is Beta-thromboglobulin a useful indicator of thrombosis in nephrotic syndrome?

1979 ◽  
Author(s):  
K. Andrassy ◽  
D. Deppermann ◽  
E. Walter ◽  
J. Koderisch ◽  
E. Ritz ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Disease ◽  
Serum Albumin ◽  
Platelet Function ◽  
Before And After

In nephrotic Syndrome (NS), thrombotic episodes are common and this is thought to result from altered platelet function. In the present study we tried to correlate beta-thromboglobulin (TG) cone, with parameters of platelet function, - Patients and methods - In 26 pt. with NS platelet aggregat. test (PA) and TG were analysed before and after 2 weeks treatm. with ASA/Dipyridamole. None of the pat. had diseases with known platelet consumption or medication which interferes with platelets. - Results - Although, none of the pat. had clinically overt thrombosis (Doppler, phlebo-gr.) PA was increased in all pat.(PAT I and III, collagen/ADP ind. aggregate,, PF 4). There was an inverse correlat. between platelet abnormality and serum albumin cone, and a pos. correlat. with the elevation of cholesterol, TG cone, in NS did not differ signif. from control individ. without renal disease and from pat. with chron. glomerulonephr.(33.4±11.1 vs 33.9±9.7 vs 31.«±13.2 ng/ml). ASA/Dipyrid. did not change TG cone. - Conclusions - TC cone, in vivo do not reflect the degree of platelet abnorm, in vitro in pat. with NS. This finding may indicate that TG is not sensitive enough to monitor plat, abnorm, short of overt thromb. or else may indicate the fact, that TG is lost in the urine in NS.

Abstract 17537: Stably Expressed APEX2 Identifies the Integration of iPSC-derived Cardiomyocytes in a Mouse Model of Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Takeshi Hatani ◽  
Shunsuke Funakoshi ◽  
Thomas J Deerinck ◽  
Eric A Bushong ◽  
Takeshi Kimura ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Animal Experiments ◽  
Induced Pluripotent Stem Cell ◽  
Physical Interaction ◽  
Histone H2b ◽  
Before And After ◽  
Induced Pluripotent

Background: Although studies have feasibility of in vivo cardiac transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) in animal experiments, nano-structural confirmation of the successful incorporation of the engrafted iPSC-CMs including electron microscopy (EM) has not been accomplished, partly because identification of graft cells in EM has proven to be difficult. However, with a new genetically encoded probe, the monomeric 28-kDa peroxidase reporter 2 (APEX2), which withstands strong EM fixation, this problem can now be done. We have now been able to test whether APEX2 can identify iPSC-CMs in host heart after long-term engrafting, and evaluate the engrafted iPSC-CMs in post-myocardial infarction using EM. Methods: We established human iPSC lines which stably expressed histone H2B-APEX2 (APEX2 iPSCs). After differentiating APEX2 iPSCs into CM in vitro, purified cells were transplanted into NOG mouse hearts with myocardial infarction by direct injections into the myocardium. One and 3 months after transplantation, we mapped engraft iPS-CMs using high resolution micro-CT and evaluated their ultrastructure by EM. Results: APEX2 was stably expressed and labeled histone H2B in iPSCs before and after in vitro differentiation into CM. Graft efficiency of APEX2 iPSC-CMs in NOG heart was excellent and APEX2 expression sustained over 3 months in vivo . APEX2 reaction observed in EM clearly identified engrafted APEX2 iPSC-CMs in niches surrounded by host CMs and their physical interaction was visualized. EM also revealed a progression in the maturation of sarcomeric structure and mitochondria in engrafted iPSC-CMs, by comparing data at 1 and 3 months after transplantation. Conclusion: We demonstrate that APEX2 is a versatile genetic reporter to trace cell fates in living animals over many months. Using APEX2-based staining, we were able to identify and characterize the maturation process of iPSC-CMs, and determine how they distribute within myocardial niches, as well as their interaction with host CMs. This method should be useful to many studies of stem cell-based cell replacement therapy, as it allows both tracking of cells and the ultrastructural characterization of engrafted cell and graft-host interactions.

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