bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECT OF PIRACETAM IN ISCHEMIC FLAP VASCULARISATION
Authors: Rossillon O , Bayet B , Huymans M , Englebert P , Stren Ides , Calteux N , Vanwyck R 
Published: August 2018

Piracetam. a drug traditionally used for stimulating the telencephalon has a strong anti-aggregant, anti spasmodic and rheological action, due to its antisludge effect and the increase of the red cell deformability capacity. The authors show the interest of this substance in reconstructive surgery : Piracetam significantly increases the circulation in the flaps, reduces the zones prone to necrosis and allows for a faster skin expansion. The first three experiments have been performed on rats - on an epigastric flap with thoracic pedicle-. In the first one. we operated on 150 rats divided into 5 groups: a control series, and 4 series which received the following doses of Piracetam per os : 20.40.80 and 100 mg/100 g/day. The necrotic area, as measured daily, represents 13.8%+−2.6 (+− SEM) in the control series. 6% +− 0.8 in the series with 20 mg/100 g. 2.53% +− 0.66 in that with 40 mg/100 g. 1.67% +− 0.4 in thatwith 80 mg/100 g and 2.77% +− 1.96 in that with 100 mg/100 g. (all these percentages are expressed versus the overall surface). A thorough statistical study including the AN0VA table.“t” and regression tests shows that these differences are significant at 0.0001 for the 40 mg/100 g dosis and 0.0000 for the 80 mg/100 g dosis. A second experiment measured the local blood flow in 4 areas of the flap from its thoracic basis towards its epigastric point thanks to the radio-active microsphere technique described 1n rats by He Oevitt and Mallck. Measures were carried out on 60 rats divided into 3 groups : control series without flap, series with a flap at the second post-operative day without Piracetam. series with a flap at thesecond post-operative day with Piracetam.With Piracetam. the increase of the bloodflow in the thoracic part proximal to th flap (zone 1) is of 60% +− 13 (p < 0.0000). that of zone 2 of 72% +< 20 (p < 0.0008). that of zone 3 of 92% +< 23 (p < 0.0003), and finally that of the epigastric zone 4 of 117% +− 40 (p <0.004) (vs the overall surface). A thirdexperiment measured the temperature difference of these 4 zones by means of a, thermocouple according to the method described by Jones in 1983 and it compared the results obtained with the flow measured by microspheres. Finally, in a last experiment, the blood flow in expanded tissueswith- and without- piracetam 40 mg/100 gwas measured with a laser-doppler.Therefore it was concluded that piracetam is a useful drug to prevent necrosis in flaps. It can also be used to expand tissues more quickly.
TREATMENT OF RAYNAUD SYNDROMES WITH PIRACETAM(NOOTROPIL R),NOOTROPIC AND ANIPLATELET AGENT
Authors: Moriau M , Lavenne-Pardonge E , Col-De Beys C H 
Published: August 2018

Three prospective studies have been performed with piracetam (Nootropil ®-) in the treatment of Raynaud disease and syndromes.The first one, realized in 20 cases of Raynaud disease established that 8 g piracetam daily was the optimal dosage necessary to obtain a significant clinical, ultrasonic and biologic improvement.In the second one, 58 cases of Raynaud syndromes (47 idiopathic and 11 associated with systemic disease) were treated with 8 g daily piracetam during 6 to 12 months. A clinical and ultrasonic improvement was observed in 75 and 80 % of the cases and a normalisation of the disturbed platelet functions (36/58) in 88 %. Moreover a benefic rheologic effect was noted and related to the membrane deformability, the antiplatelet and the Von Willebranc factor synthese or release inhibiting activity of piracetamThe third one realized in cross over in 30 cases of Raynaud syndromes compare the effects of piracetam alone (dosage 8 g daily) with the combination piracetam (4 g daily) - aspirin (100 mg daily) or with other drugs like buflomedil, calcium antagonists and ketanserine.A synergic effect was obtained with the combination piracetam -aspirine and piracetam alone seems to be more efficient than the other drugs.A fourth double blind study is actually performed
INHIBITION OF HUMAN PLATELET FUNCTION BY PCA-4230
Authors: Ortega M P , Sunkel C , Priego J G 
Published: August 2018

PCA-4230 (3-{2-(N-l,2-benzisothiazolyl-3(2H)one-1,1-dioxide) ethoxycarbonyl}-2,6-dimethyl-5-ethoxycarbonyl-4-methyl-l,4-dihy-dropyridine) is a new synthetic compound which has been selected after evaluation of .several series of molecules included in an ex tensive program of synthesis and biological screening.The purpose of this study was to investigate the In vUjiO effects of PCA-4230 on human platelet function.Platelet aggregation (PA) was measured, in platelet rich plasma (PRP) or washed platelets, according to Born’s technique. Release reaction (RR) was measured by the luminiscence method as adenosine triphosphate (ATP) release in response to stimulation. Aggregating agents were adenosine diphosphate (ADP), epinephrine (Epi), collagen (Col), thrombin (Thr), calcium ionophore (A23187) arachidonic acid (AA), thromboxane agonist (U46619) or platelet activating factor (PAF). Incubation with PCA-4230 (1 to 10 μM) we re carried out at 37°C for 15 minutes. PCA-4230 potentiation of Prostacyclin (PGI2) anti-aggregatory activity was also studied by addition to PRP of PGI2, PCA-4230 or both, and PA by ADP.PCA-4230 inhibited PA and RR in PRP in a concentration-dependent fashion when Col, Epi, U46619 or PAF were used as agonists. AA-and Thr-induced aggregation were only slightly impaired and no in hibition was shown on ADP or A23187-triggered activation. A23187-induced aggregation and RR were inhibited only in the absence of extracellular Ca++ in washed platelets. This effect was overcome by addition of Ca++ 1 mM. Additionally, the inhibitory effect of PGI2 on ADP-induced PA, was synergistically potentiated by PCA-4230, suggesting inhibitory activity of the compound on cjy clic nucleotide phosphodiesterase.Since PCA-4230 inhibited PA and RR induced by Epi, U46619 and PAF, mediated viareceptor-agonist binding, and Col-inducedactivation, it is reasonable to suspect that common process(es) may be involved. Recently, it has been suggested that intraplatelet Ca++ levels, actingas a second messenger, are directly linked to the d<2 gree of platelet activation.Therefore, the ability of PCA-4230 to modulate platelet function appears, at leastin part, to be due to regulation of cytosolic Ca++ levels. This hypothesis is confii: med by the results with A23187-induced aggregation in absence of extracellular Ca++.
CORRELATION BETWEEN INHIBITION OF PLATELET PHOSPHODIESTERASES (PDEs) AND PLATELET FUNCTION TESTS.
Authors: Weisenberger H , Haarmann W 
Published: August 2018

A systematic investigation of over 100 PDE inhibiting pyrimidopyrimidines was performed regarding a possible correlation between influence on platelet function tests and inhibition of platelet PDEs. Basically, the compounds tested were congeners of Dipyridamole but lack substitution in position 6. The concentration necessary for a 50% inhibition of PDE activity in platelet homogenates ranged between 0.000045 and 35 μmoles/L.The inhibition of platelet PDEs was measured in freeze-thaw homogenates of human platelets using 3H-cAMP as substrate. Intraplatelet cAMP changes were measured by prelabelling the ATP pool with 3H-adenine and isolation of 3H-cAMP. Inhibition of platelet retention was determined using Morris' method (rotating citrated whole blood with glass beads) and the aggregation tests were performed according to Born and Cross in citrated platelet rich plasma.The rather large number of compounds allowed the application of correlation analysis. The results of linear regression tests (IC50 and EC200 values) are shown in the table.It appears that increased intracellular cAMP caused by PDE inhibition shows a strong correlation to the inhibition of the above mentioned platelet function tests. A weaker relation exists between inhibition of isolated PDEs and platelet function. Thus, determination of intrinsic PDE inhibitory potency is not sufficient to predict the influence of a given compound on platelet function tests.
ADDITIVE EFFECT OF DILTIAZEM (DIL) ON THE INHIBITION OF PLATELET AGGREGATION PRODUCED BY ASPIRIN (ASA).
Authors: Altman R , Scazziota A , Windor S , Dujovne C A 
Published: August 2018

Platelet activation in vivo occurs by the action of several stimuli. It is generally agreed that actives products of arachidonic acid derived via the cyclooxy-genase pathway can stimulate platelet aggregation. ASA decrease thromboxane A2 generation and thereby inhibit platelet aggregation produced by AA and, partially, by others agonists. Nevertheless, the antiaggregating effect of ASA can be overcome by the conjointly activity of arachidonic acid(AA) and platelet activating factor (PAF). The inhibition of this cooperative aggregating effect can be important in platelet function suppressive therapy. The effect of DIL was tested in this sys tern. DIL was added in vitro to platelet rich plasma oS talned from volunteers before and after ASA(100mg/dayT intake for 7 days. DIL (2ug/ml) inhibited 50% platelet aggregation induced by AA (0.75mM) in non aspiri-nated volunteers. At even lower concentrations of DIL (0.4-lug/ml) an inhibition of aggregation induced by 300nM of PAF was also observed. After ASA, no aggregation by AA, only a first wave followed by disaggregation when PAF (30nM) was used and a full response when this pair of agonists were added together was obtained. DIL (0.lug/ml) added in vitro, produced significant inhibition of the synergism.The effect in vivo of DIL plus low dose of ASA was also explored. In vivo administration of therapeutic dose of DIL (60mg T.I.D.) and low dose of ASA (75-100 mg/day), prevented the synergistic activity of AA plus PAF on platelet aggregation. In conclusion, DIL may enhance the effectiveness of low dose of ASA in the prevention of arterial thromboembolism.
EFFECTS OF DILAZEP ON CYTOPLASMIC CALCIUM ION CONCENTRATION AND ARACHIDONIC ACID METABOLISM IN HUMAN PLATELETS AND NEUTROPHILS.
Authors: Okuma M , Kanaji K , Sensaki S , Uchino H 
Published: August 2018

We studied effects of dilazep(DZ), an antiplatelet drug, on the cytoplasmic Ca2+ concentration ([Ca2+]-i) and arachidonic acid (AA) metabolism in human platelets and neutrophils. [Ca2+]i of aequor-in-loaded platelets was estimated by using the platelet ionized calcium aggregometer. AA metabolism was studied by the determination of AA metabolites including hydroxyheptadecatrienoic acid (HHT), hydroxyeicosatetraenoic acid (HETE) and leukotriene B4 (LTB4) by reversed-phase high-performance liquid chromatography. When aequorin-loaded platelets were preincubated with DZ (0−0.5 mM) for 1 min at 37°C, both platelet aggregation and [Ca2+]i elevation induced by thrombin, AA and collagen were inhibited by DZ in a concentration dependent manner, while only aggregation was inhibited after stimulation by the calcium ionophore A23187 (1 yM). Both influx and release of Ca2+ into platelet cytoplasm induced by thrombin or AA were inhibited by DZ, while neither of them was affected when induced by A23187. The production of HHT and 12-HETE by the reaction of 100 yM AA with platelets preincubated with DZ (0−1 mM) was not inhibited, whereas their production by throirfbin (10 u/ml) was remarkably inhibited by DZ in a concentration dependent manner. When DZ (0−0.3 mM)-treated neutrophils were incubated with 5 μM A23187 in the presence or absence of 20 μM AA, the production of LTB4 and 5-HETE was increased by DZ in the presence of AA, whereas their production was inhibited by DZ in its absence. When platelet/neutrophil mixtures preincubated with DZ (0−0.3 mM) and cytochalasin B were stimulated by thrombin (5 u/ml) in the presence of FMLP, DZ inhibited LTB4 production in a concentration dependent manner, while 5S,12S-diHETE synthesis was enhanced by lower concentrations of DZ and inhibited by its higher concentrations (> 0.1 mM).Thus, DZ inhibits platelet aggregation induced by any agonist including A23183, while [Ca2+]i elevation is inhibited by the drug only when it is induced by the receptor-mediated agonist. Furthermore, it was suggested that AA liberation from phospholipids in platelets and neutrophils was inhibited by DZ, leading to reduced production of all endogenous AA metabolites by these cells after appropriate stimulation, although lipoxygenase metabolites of liberated or exogenous AA could be increased.
INFLUENCE OF L0MUSTIN ON SOME PLATELET FUNCTIONS IN VITRO
Authors: Kubisz P , Brahimi S , Cronberg S 
Published: August 2018

Lomustin (CCNU) is a cytostatic drug that is used in the trea-tement of some forms of solid tumors and hemoblastosis. The most important form of toxicity associated with its use consists of thrombocytopenia often associated with hemorrhagic syndrome. Lomustin may exert its action on the formation of platelets, but it may also interfere with platelets themselves.In the present study its influence on the platelet function was investigated using a wide battery of tests.Platelet-rich plasma was incubated with lomustin (1,5 to 15 jjg/ml and 30 minutes at 37°C) in vitro.This inhibited strongly aggregation by ADP (2 × 10-6 M), adrenaline (2×10−6 M) and collagen (15 ¼g/ml). Platelet factor 4 release was almost completly inhibited independently of the inducer used. 14C-serotonin release was decreased by approximately 70% when incubation proceeded in the presence of 15 ¼g/ml of lomustin, and completly at higher concentration. Platelet factor 3 availability was also significantly impaired. Reptilase clot retraction was diminished, regardless of inducer used. In the presence of N-ethyl maleimide (1 mmol) significantLy lower malondialdehyde was produced in platelets incubated with lomustin, than in that from normal controls. After addition of arachidonic acid (1 mmol), the platelet synthesized Less thromboxane B2. Lomustin did not interfere with coagulation factors and did not induce overt fibrinolysis.Its is concluded that lomustin acts as an inhibitor of platelet functions and can induce an acquired thrombocytopathy.Thus impairement of platelet functions might play a part in hemorrhagic complications accompanying in some cases lomustin therapy.
SURPRISING EFFECTS OF THE CONSECUTIVE ADMINISTRATION OF PENTOXIFYLLINE AND LOW DOSE ACETYLSALICYLIC ACID ON THROMBUS FORMATION.
Authors: SEIFFGE D , Weithmann U 
Published: August 2018

The effect of the combined oral administration of pentoxifylline (pof) and low dose acetylsalicylic acid (ASA) was evaluated with the help of the laser-induced thrombosis model in rat mesenteric arterioles. Laser-induced thrombosis is inhibited in a dose-dependent way by both drugs. The administration of ASA, either simultaneously with or 1 hour prior to pof, does not show any effects in the laser model. On the contrary, the administration of pof followed 1 h later by ASA not onyl exhibited a significant effect but also produced a supraadditive inhibition of the laser-induced thrombus formation. Specific investigations concerning the time interval between the administration of both drugs determined that a significant effect can be achieved only after an interval of 30 to 90 minutes (principle of HWA 5112).The striking results could also be shown in diseased animals after consecutive chronic administration of pof 1 h prior to ASA. HWA 5112 exhibits significant effects on laser-induced thrombus formation in the following chronic animal models: 1. adjuvant arthritic rats, 10 → 1 mg/kg for 21 days; 2. spontaneously hypertensive stroke-prone rats, 10→ 1 mg/kg three times within 24 h; 3. cholesterol-induced atherosclerosis in rabbits, 10→ 1 mg/kg for 14 days. The reported data clearly demonstrate that the sequential drug administration of first pentoxifylline followed 30 to 90 min later by ASA exhibits a supraadditive antithrombotic effect.
EFFECT OF A SYNTHETIC ANTICOAGULANT (MD 805) ON PLATELETS IN HUMAN VOLUNTEERS AND HEMODIALYSIS PATIENTS.
Authors: Matsuo T , Yamada T , Nakao K 
Published: August 2018

Twelve normal subjects were injected with 5000 U of commercial mucous heparin with or without preloading of 1.0 g aspirin, and 0.2 mg/kg MD 805, an arginine derivative, which is a new synthetic compound with an extremely strong affinity for thrombin, at an interval of 4 weeks after each injection. Heparin injection with or without aspirin significantly increased platelet factor 4 release. In contrast, the preloading of aspirin significantly inhibited the decrease of platelet count and the elevation of /8 thromboglobulin induced by heparin. However, MD 805 had no effect on platelet release proteins, and adequate anticoagulation by APTT was still present 60 min after the injection. MD 805 shows no stimulative effects on platelets such as with heparin.In the case of the patient's study, three patients complicated with heparin induced thrombocytopenia plus thrombus formation in the extracorporeal circulation during hemodialysis, and were treated with MD 805 instead of heparin. The platelet counts in those patients quickly returned to within the normal range, and adequate anticoagulation was obtained in the following hemodialysis sessions and no further bleeding or clot formation was noted.In conclusion, MD 805 may represent a useful alternative anticoagulant in patients with heparin induced thrombocytopenia.
BLOOD PLATELET FUNCTION OF HYPERLIPIDEMIC PATIENTS TREATED WITH BEZAFIBRATE
Authors: Borowska A 
Published: August 2018

Platelets from patients with hyperlipoproteinemia (HLP) are more sensitive to some aggregating agents than platelets from normal persons.On the other hand, it is known that from 15% to 20% of patients with coronary heart disease have primary or secondary HLP.The progress of the knowledge in this field has been expressed in production of the new drugs diminishing HLP.Be-zafibrate is a new derivative of clofibric acid,which has been used in the treatment of HLP.The purpose of our study was and assessment of the effect of bezafi-brate on platelet aggregation and thromboxane (TXB2) generation.The experiments were carried out in 18 patients (7 women and 11 men),aged 32-60 (mean 46 years) with type Ila HLP.The control group of consisted of 10 healthy volunteers.For 6 weeks the patients with HLP were given bezafibrate (Bezalip-Boehringer Mannheim) 600mg daily in divided doses and were taking the same diet as before the treatment.Blood platelet aggregation and 14C arachidonic acid (AA) conversion to thromboxane in washed platelets (using thin-layer-chromatography) were determined before and after bezafibrate administration. The obtained results are presented in the table (mean±S.E.).It is concluded that the main arteriosclerosis-protecting bezafibrate action lies not only in decreasing of lipid levels in serum, but also in normalization of platelet function.
SYNVINOLIN (SYN) IN TYPE Ha HYPERLIPOPROTEINAEMIA : NORMALIZED PLATELET HYPERREACTIVITY ASSOCIATED WITH AN IMPROVED RESPONSIVENESS AGAINST PGI2 AND ENHANCED PGI2 RECEPTORS
Authors: Schrör K , Löbel P , Steinhagen-Thiessen E 
Published: August 2018

Patients with familial hyperlipoproteinaemia (HLP) are at high risk for the premature development of atherosclerosis. This study was designed to investigate the effect of long-term treatment (8 months) with the HMG-CoA-reductase inhibitor SYN (20-40 mg/day) on platelet reactivity and PGIo receptors in 12 HLP patients (B) as compared with 11 untreated HLP patients (A) and 11 healthy subjects (C). Treatment with SYN reduced the plasma cholesterol to 234 ± 12 mg/dl as compared to 307 ± 21 (A) and 195 ± 14 mg/dl (C), respectively. Collagen (0.6 pg/ml) induced platelet thromboxane (TXB2) formation was 50±6 ng/ml in group A and significantly reduced to 32 ± 3 (B) which was not different from the 28±3 ng/ml in group C. Similar results were obtained by measuring pTatelet ATP secretion and aggregation. SYN treatment significantly improved the reduced number of PGI2 receptors (determined according to Schillinger & Prior, 1980) and normalized the iloprost (ILO, 30 nM) induced cAMP stimulation in platelet-rich plasma while the kg remained unchanged:These data demonstrate that SYN-treatment of HLP patients at doses that reduce plasma cholesterol by about 25% results in sig-ficant improvement of platelet function. This includes both normalization of platelet hyperreactivity against proaggregatory agents as well as platelet hyporeactivity aganist PGI2. The last effect might involve an increase of the (reduced) number of PGI2 receptors in HLP type IIa.
R 68 070, A COMBINED TXA2-SYNTHETASE/TXA2-PROSTAGLANDIN ENDOPEROXIDE RECEPTOR INHIBITOR. REDUCES CEREBRAL INFARCT SIZE AFTER PHOTOCHEMICALLY INITIATED THROMBOSIS IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Van Reempts J , Van Deuren B , Borqers M , De Clerck F 
Published: August 2018

The effects of R 68 070, an oxime-alkane carboxylic acid derivative combining specific thromboxane A2 (TXA2) synthetase inhibition with TXA2/prostaglandin endoperoxide receptor blockade in one molecule, were investigated in a model of photochemically induced stroke in spontaneously hypertensive rats.Each experimental group was compared with an untreated control group. All animals were anesthetized with halothane in N20/02 and artificially ventilated. After incision of the scalp and stereotaxic positioning of a fibre optic light source, halothane was discontinued. When physiological variables reached normal values, a focal cortical infarction was produced by injection of 10 mg.kg-1 rose bengal and 20 min irradiation of the brain through the intact skull. Four hours later the brains were perfusion fixed and damaged areas measured on consecutive histologic sections. Infarct size was calculated by numerical integration.R 68 070 (40 mg.kg-1 p.o.,-3 h) significantly reduced the cerebral infarct size to 2.32 mm3 compared with 5.78 mm3 in controls (median values; n = 5; p < 0.05). At 2.5 mg.kg-1 the lesion was reduced from 11.75 mm3 in the control group to 7.82 mm3 in the treated group (n = 5; p = 0.095). Serum TXB2 levels were reduced by > 80 %.Production of damage in this model is based upon photodynamic generation of singlet molecular oxygen, resulting in peroxidative endothelial cell injury and subsequent platelet thrombus formation. Protection with R 68 070 can be explained by the anti-thrombotic effect of the compound. The relative contribution to this protective effect of synthetase and receptor blockade by R 68 070 are being investigated.
CHANGES IN PLATELET ACTIVITY, FIBRONECTIN AND TISSUE PLASMINOGEN ACTIVATOR DURING ARTERIOGRAPHY IN PATIENTS WITH ISCHAEMIA EXTREMITIES INFERIES
Authors: Augustyniak W , Cierniewski C S , Slawincki V , GOCH J H , Polanowaka R 
Published: August 2018

Platelets and endothelial cells may be activated to release their contents during arteriography, which is one of the most frequently used examinations of patients with peripheral vascular diseases. This technique involves lumbar aortic puncture and catheterization with administration of contrast medium in arteriosclerosis obliterans (AO) extremities inferies. In this report we have studied 26 patients aged 37 to 73 years with AO who were subjected to arteriography performed according to the Seldinger method. Concentrations of β-thromboglobulin (β-TG), platelet factor 4 (PF4) and plasma fibronectin (Fn) were determined by radioimmunoassay and tissue plasminogen activator (t-PA) activity was measured by a solid-phase fibrinolytic assay using polystyrene test tubes coated with 125I-fibrin. The levels of these parameters were analysed in samples of both the arterial and vein blood which had been taken before and after the injection of contrast medium and obtained results are given in the Table.Our results suggest that after the injection of contrast medium there is a significant increase in the t-PA activity in the arterial blood and the β-TG concentration in the vein blood.