bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change In TXB2, MDA And AMP Levels During Artificial Pancreas Treatment On Diabetic Patients
Authors: Braun G , Guimont C , Voisin Ph , Rousselle D , Drouin P , Stoltz J F 
Published: July 2018

A study carried out on 9 insulin-dependent diabetic patients undergoing continuous blood glucose control by means of ex-vivo insulin injection (artificial pancreas - Biostator) has revealed : a relationship between the synthetic capacity of TXA2 (proaggregating molecule) by the platelet and the blood glucose level prior to feed back control. Concurrently, an identical relationship is observed in the case of platelet AMPc levels.After 24 hours of artificial pancreas treatment, it is noted that the greater the effectiveness of the treatment, the greater the increase in the synthetic capacity of TXA2. This observation is confirmed after 48 hours of treatment.Further, the relationship between MDA and Thromboxane B2 synthetized from the same precursory molecules is reversed during treatment.On the basis of these results we may assume that there is a disturbance in the regulation mechanisms of platelet synthesis during diabetes, but that these mechanisms are parthy reversible after artificial pancreas treatment.
Effect Of A Fish Oil On Blood Lipids And Coagulation
Authors: Saynor R , Verel D 
Published: July 2018

Considerable evidence lias accumulated on the association between abnormal lipoprotein patterns and ischaemic heart disease. There is suggestive evidence that prolonged byper- lipidaemia may cause an increased tendency to thrombosis as a result of a number of factors. The Eskimo diet of marine animals is high in elcosapentaenoio acid (EPA) and it is possible that the low incidence of nyocardial infarction in this race is due to diet. The high intake of SPA by Eskimos is probably the reason for their increased tendency to bleed.The present study was designed to observe the effectiveness of a fish oil high in EPA as a lipid-lowering agent, and its effect on coagulation. Of the 18 subjects in the study 6 were volunteers with no evidence of heart disease- the remaining 12 were attending hospital with angina or post-myocardial infarction. One of this group had undergone a coronary artery by-pass graft operation.Venous blood was taken after a 12-14 hour fast and the subjects instructed to take 10ml of fish oil twice daily with meals. No modification of their normal diet was attempted. A further blood sample was taken 6 weeks later and at 3 months in 5 subjects. Laboratory investigations included blood cholesterol, triglyceride, high density lipoprotein cholesterol (CHDL;, bleeding time, platelet count and agpegation, antithrombin III, fibrinogen, thrombin time partial thromboplastin time and prothrombin ratio.At six weeks the cholesterol fell lqy an average of 6.3% and triglyceride 36.8% but CHDL was raised 12.4%. The 3 month levels (5 subjects) were cholesterol - 9.2%, triglyceride - 52.1% and CHDL + 16.9%. There were no significant changes observed in the coagulation parameters measured.From the foregoing it would appear that supplementing the diet with fish oil has a desirable effect on blood lipids but at this dose does not influence coagulation.
Antiplatelet Actions Of Low Molecular Weight Peptides And Their Derivatives
Authors: Fareed Jawed , Messmore Harry L , Walz Daniel A 
Published: July 2018

We have reported on the antiserine protease actions of low molecular weight peptides with arginine and lysine at the carboxyl terminus and their derivatives. In order to investigate the action of these peptides and their analogues on other components of hemostasis we studied their effects on platelet function; aggregation and release reactions, clot retraction and serotonin uptake by platelets. D-Phe-Pro-Arg-NH-heptyl, D-Phe-Pro-Arg-O-heptyl, D-Phe-Pro-Arg-thiobenzyl, D-Phe-Pro-Arg-COOH, D-Phe-Pro-Arg-NH2, D-Phe-Pro-Arginal and similar derivatives of D-Pro-Phe-Arg, D-Phe-Phe-Arg and Val-leu-lys- were screened None of these peptides produced aggregation and release reactions in concentration >10 mM. D-Phe-Pro-Arg-thiobenzyl and D-Phe-Pro-Arginal produced a strong inhibition of thrombin induced aggregation and release reactions at sub ymolar levels. Both of these peptides also inhibited thrombin’s action in amidolytic and coagulant assays. D-Phe-Pro-Arg-thiobenzyl ester also produced a complete inhibition of arachidonic acid induced aggregation of platelets and showed varying inhibitory actions against ADP, epinephrine, collagen, and serotonin induced aggregation and release reactions. Although ristocetin induced aggregation was only slightly effected, a complete block of the release reaction was seen. ADP induced β-thrombo- globulin release was also inhibited by this peptide.Heptyl amide and esters of H-D-Phe-Pro-Arg-and free acid, amide and arginal forms of various other peptides exhibited relatively weaker antiplatelet actions. Our studies suggest that peptides with amino acid resembling serine protease sensitive sites can be molecularly manipulated to design potent antiplatelet agents. Furthermore these peptides may provide a useful probe to study the molecular mechanisms involved in the pathophysiology of thrombotic disorders and to design new antiplatelet drugs.
Recovery Of Platelet And Endothelial Cyclooxygenase After Aspirin Measured By Radioimmunoassay For Thromboxane B2 And 6-Keto-Pg-F1α
Authors: Greaves M , Bull Helen , Castaldi P A 
Published: July 2018

Recovery of platelet and endothelial prostaglandin synthetic activity by membrane cyclooxygenase after aspirin suppression of the enzyme is relevant to attempts to influence these pathways in platelet and microvascular disorders. Recovery from platelet inhibition has previously been measured by a colorimetric technique and proposed as a method for measurement of platelet turnover. Indirect methods have been used to determine prostacyclin production after similar inhibition and have not clarified the precise recovery rates. In the present study recovery in human and rat platelets was measured using a radioimmunoassay (RIA) for thromboxane B2 (TXB2) and in rat aortic endothelium with a RIA for 6-keto-prostaglandin- F1α (6KPGF1α).TXB2 was measured in human platelet rich plasma stimulated with collagen and arachidonic acid before and after ingestion of 900 mg of aspirin. TXB2 returned to preaspirin levels in 8.5 ± 0.6 (S.D.) and 8.25 ± 0.5 days respectively with collagen and arachidonic acid, the recovery corresponding with platelet survival time of 51Cr autologous platelets. The recovery curve was linear with collagen but not with arachidonic acid where a late rise occurred.Rats were treated with a single dose of aspirin 20 or 100 mg/kg and sacrificed at intervals for measurement of collagen stimulated platelet TXB2 aortic endothelial 6KPGF1α- Recovery of both of these products was linear and reached pretreatment levels after 120 hrs in platelets and 48 hrs in endothelium after 20 mgAg but 100 mg/kg delayed endothelial recovery to 96 hrs.These results indicate that the endothelial and platelet enzyme are equally susceptible to aspirin but endothelial recovery is more rapid at low doses. Collagen stimulated platelet recovery may prove a useful method for measuring platelet production.
Effects Of Altered pH And Sodium Concentration On The Response Of Megakaryocytes And Platelets To ADP
Authors: Leven R M , Nachmias V T 
Published: July 2018

By using both megakaryocytes and platelets to study effects of adenosine diphosphate (ADP), we hope to understand the ionic events underlying the shape changes induced by this nucleotide. Guinea pig bone marrow megakaryocytes were isolated to 50-90% purity by modifications of published procedures, and cultured for 12-48 hours. In response to ADP (l-10μM) megakaryocytes develop a ruffled border and spread in 15-30 minutes to 2-3 times their original diameter and adhere strongly to the substrate. Several other diphosphonuc1eotides or adenosine monophosphate have no effect. Spreading occurs in calciummagnesium free Hank’s salt solution, but is blocked when extracellular sodium was replaced by potassium, choline, or lithium. Amiloride, an inhibitor of sodium uptake, inhibits the extent of spreading 90% at 10-4M, but allows partial spreading in 60% of the cells. Spreading can be mimicked by incubating the cells with 2μM A-23187 combined with either 5mM methylamine or 1μM monensin, but not by A-23187 alone.The rate of platelet shape change was measured spectro- photometrical1y at 37°C with 5mM EGTA both in platelet rich plasma (PRP) or after gel filtration in phosphate buffered saline. Amiloride inhibits shape change completely at 1mM and 50-60% at 0.1mM, but only if present during gel filtration. A rapid drop in buffer pH from 7.4 to 6.9 causes a 50% inhibition of rate of shape change in PRP or after gel filtration, but the inhibition spontaneously reverses within three minutes incubation at the lower pH.These results are compatible with a model in which ADP causes a sodium influx which is linked to a change in intracellular pH. This may be a necessary but not necessarily sufficient step in ADP induced shape change.
Cerebrovascular Injuries Caused By Intravascular Platelet Aggregation Induced By Arachidonic Acid (AA) Or ADP
Authors: Yamazaki H , Fugimoto T , Kobayashi M , Matsubara O , Tanoue K , Isohisa I , Inaba Y 
Published: July 2018

Effects of acutely induced intravascular aggregation of platelets on cerebral arteries were examined. A polyethylene catheter was inserted into the right lingual artery through the right carotid artery. A group of 30 rabbits (22 with no pretreatment , 8 thrombocytopenic) were given 0.7 mg/kg of AA as a bolus within 5 sec through the catheter. Thirty min. later, Evans blue was injected as marker for extravasation. Another group of 20 rabbits (12 no pretreatment, 8 thrombocytopenic) were given 20 mg/kg of ADP within 1 min. One hour after injection, brains were observed histologically after perfusion of fixatives. Brains of 77%(17/22) of AA-injected rabbits showed irregular blue staining in the right hemisphere. Extravasation of plasmal substance was histologically observed in medium or larger-sized cerebral arteries. Frequent platelet adhesion on the luminal wall was seen. Scanning electron micrograms revealed almost all adherent platelets were spherical and aggregated. Fibrin formation was rarely seen. Derangement of endothelial lining was apparent around the area to where platelets adhered.Some places showed irregular concaves and others a flattened luminal lining. Endothelial cells were lacking in some places. The changes were not observed in the opposite hemisphere or in the thrombocytopenic group. Sixty-seven percent (8/12) of ADP injected rabbits showed marked blue staining and edematous changes in the right cortex. Ipsilateral hemispheres were stained in 2 cases and 2 cases showed no changes. The ADP-injected group showed similar, but less pronounced histological changes. Platelet count was more marked and longer duration in the AA group as compared to the ADP group. Prominent decreases were seen in the cases which showed remarkable vascular changes. These vascular injuries may be related to the consumption of intravascular platelet aggregates. Activated platelets might play an important role in the genesis of vascular injuries.
Localization Of Antithrombin III On The Vascular Endothelium And Its Function
Authors: Nakagawa M , Okajima Y , Kitani T , Watada M , Yoshikawa H , Hino R , Ijichi H 
Published: July 2018

Vessel wall is known to be rich in sulfated glycosamino glycans (GAGs) including heparin and they may serve as the natural catalysts of antithrombin III (AT III). This paper reports the possible role of AT III on the development of anticoagulant activity of activated AT m on the vessel wall. The freshly prepared rat aortic ring was washed in 0.05M Tris HC1 0.15M NaCl buffer (ph 7.5) with or without protamine, and was fixed for histochemical and immunofluo- rescent examinations. Anti-rat AT III serum was obtained from rabbit immunized with the purified AT III. Mucopolysaccharide stainings including Alcian Blue revealed the sulfated GAGs on the endothelium and the media. The GAGs on the endothelium corresponded with the specific AT III fluorescence localization. Protamine treatment disclosed the disappearance of the AT III fluorescence on the surface of endothelium. AT III-heparin complex was observed to be dissociated by protamine treatment through the investigations with affinity chromatography and sephadex G75 column chromatography, and the separated AT III was proved to recover the original progressive antithrombin activity.Based on these experimental results it is concluded that the localized AT III on the surface of endothelium may be present in complexed with the exposed heparin or other GAGs and be present in activated, and that the complexed AT III is considered to inhibit proteases in situ in the circulating blood to prevent the activation of coagulation process. This phenomenon may have a clinical significance on the pathogenesis and treatment of thromboembolic vascular diseases.
Endothelial Permeability And C-14- And I-131-Cholesterol Uptake On Aortocoronary Femoral Vein Bypass Grafts In Dogs
Authors: Dewanjee M K , Shapira N , Tago M , Fuster V , Kaye M P 
Published: July 2018

Eighteen dogs underwent aortocoronary femoral vein bypass graft surgery. All dogs were injected with 300 μCi of I-131-iodocholesterol and 100 μCi of C-14-cholesterol and sacrificed 24 hours postoperatively: group I dogs, 1 day; group II dogs, 3 days; group III dogs, 7 days; and group IV dogs, 1 year after surgery respectively. Radioactivity in blood, grafted femoral vein (GFV), control femoral vein (CFV), femoral artery, aorta and vena cava were determined with Beckman gamma and beta counters. Results indicate a sixfold increase in permeability as assessed by uptake of cholesterol in grafted vein with respect to control vein in the 1-day period postsurgery.The cholesterol uptake in GFV (p<.01) decreases to half of this value seven days after surgery. Scanning electron microscopy demonstrates patchy endothelial cell loss from GFV and slow re-endothelialization which decreases cholesterol uptake.Vein graft permeability as assessed by cholesterol uptake thus provides a sensitive marker of graft de- endothelialization. This information is now permitting us to better understand the platelet-arterial wall interaction and of the role of platelet inhibiting drugs at different stages after aortocoronary bypass surgery.
Antigenic Properties And Structure Of Membrane Glycoprotein Receptors
Authors: Kunicki T J 
Published: July 2018

Membrane glycoproteins (GP) IIb and IIIa are not detectable on the platelets of a majority (Type 1) of patients with Glanzmann’s thrombasthenia, a hereditary disorder of platelet function characterized by an absence of platelet-platelet adhesion. These platelets also do not express the human platelet alloantigen, PlA1, a finding which led to the demonstration that the PlA1 alloantigen is associated with GPIIIa, but not with GPIIb. Alloantibodies directed against the PlA1 determinant or certain other determinants associated with GPIIb and/or GPIIIa appear to be capable of inhibiting normal platelet- platelet adhesion, suggesting that these glycoproteins function as key mediators of this process, an obligate step in normal hemostasis. Subsequent studies have supported this hypothesis by demonstrating that fibrinogen, which is known to be a key cofactor in normal platelet aggregation, does not bind to thrombasthenic platelets.We have used crossed immunoelectrophoresis of Triton X-100 soluble membrane glycoproteins against a multispecific rabbit antibody to quantitate levels of GPIIb and GPIIIa on normal and thrombasthenic platelets and to study the interaction of these two glycoproteins in a soluble nondenatured state. These studies have provided information on 1) the inheritance of PlA1 and the glycoprotein IIb/IIIa defect in Glanzmann’s thrombasthenia, and 2) reversible Ca++-dependent changes in the orientation of GPIIb and GPIIIa, which may contribute to understanding of the function of these glycoproteins in normal platelet aggregation. In the presence of sufficient Ca++, glycoproteins IIb and IIIa were found to exist only in heterogenous complexes, whether within isolated membranes, or in solution. Chelation of Ca++ by EDTA or EGTA resulted in the dissociation of these glycoproteins; reassociation could be induced by readdition of excess Ca++.
The Vascular Smooth Muscle Cell In Culture
Authors: Campbell G R , Chamley-Campbell J H 
Published: July 2018

When smooth muscle from the aortic media of adult pigs, monkeys and rabbits are dispersed into single cells and seeded into primary culture they are in the contractile phenotype and do not undergo cell division when challenged with 5 or 10% whole blood serum. However, after 6-8 days the isolated cells undergo a spontaneous change in phenotype to a synthetic state whereby their contractility is lost and they become responsive to serum mitogens. This change in function is accompanied by distinct morphological changes and is reversible if the cells are seeded sufficiently dense (5 × 104 -1 × 105/ml) that a confluent monolayer of cells is achieved within 5-7 days of the original change in phenotype. If however the cells are seeded so sparsely (1 × 103 - 5 × 103/ml) that 2-3 weeks of proliferation is necessary for confluence to be achieved then the cells remain permanently in the synthetic phenotype and immediately responsive to serum mitogens upon subculture. While the cells are in the synthetic phenotype, whether proliferating or quiescent, they have a considerably decreased production of prostaglandins E2, F2α and I2. They also have a decreased ability to metabolize low density lipoprotein, a decrease in the specific activity of cholesteryl esterase and an increase in cholesterol ester deposits.The spontaneous change in phenotype from the contractile to synthetic state in culture can be prevented by seeding the contractile smooth muscle sufficiently dense (1 × 106/ ml) that a confluent monolayer is present from day 1. It can also be inhibited by a confluent monolayer of contractile smooth muscle or endothelial cells in co-culture with the sparsely-seeded smooth muscle such that the two cell layers are not in contact but bathed by the same nutrient medium. A factor which inhibits smooth muscle phenotypic change can also be extracted from pig and rabbit aortic tissue and its effect mimicked by sodium heparin at 50 units/ml.It is suggested that smooth muscle phenotype and its control are important but unrecognized factors in atherogenesis.
Growth Regulation Of Endocytosis In Cultured Vascular Cells
Authors: Davies Peter F 
Published: July 2018

Endocytosis is involved in the metabolism of blood-borne macromolecules by both vascular endothelium and smooth muscle cells (SMC). Intimal SMC proliferation is a prominent feature of atherogenesis and therefore the interactions between the cell cycle, growth factors and endocytosis are relevant to this disease process. Manipulation of the growth of smooth muscle cells in culture by platelet- derived growth factor (PDGF), fibroblast growth factor (FGF) and epidermal growth factor (EGF) has demonstrated a coupling between endocytic volume (fluid endocytosis), endocytosis of low density lipoproteins (LDL) and growth regulation. Fluid endocytosis rate increased up to 10 fold per responding cell early in the cell cycle and continued elevated through S phase before declining. The magnitude of the effect was proportional to the fraction of cells entering the cycle, and when density-dependent inhibition of growth occurred, it was accompanied by density-dependent inhibition of fluid endocytosis rate. In addition to these changes in rate of fluid endocytosis, we also studied the high affinity binding, endocytosis and degradation of LDL. PDGF and FGF stimulated LDL binding by up to 300% and this also resulted in enhanced LDL degradation. Removal of growth factor after initiation of the cell cycle, however, abolished the response, suggesting that the continued presence of growth factor was required for enhanced LDL binding.A direct relationship between fluid endocytosis and cell growth was also measured in cultured endothelium, but exposure of confluent endothelium to PDGF or FGF resulted in increased binding of LDL without a growth response.These results, together with the failure to enhance binding of LDL to cycling SMC after removal of mitogen, suggest that growth factor stimulation of LDL binding and its consequences may be uncoupled from cell growth even though the common carrier for internalisation (endocytic vesicle volume) is closely related to the cell cycle.
Arterial Injury Alters Metabolism Of The Arterial Wall
Authors: Minick C R , Hajjar D P , Falcone D J , Fowler S , Eldor A , Weksler B B 
Published: July 2018

Results of our previous experiments indicate that following de-endothelialization aortic intima was thicker and contained more lipid in re-endothelialized (RA) and not de-en- dothelialized areas (DA) as we anticipated. Chemical analysis revealed that, in rabbits fed lipid-poor diets, there was 2 to 3 times as much cholesteryl ester (CE) in RA as compared to DA or uninjured aortas. In hypercholesterole- mic rabbits, aortic total cholesterol content correlated with serum cholesterol concentration in RA but not DA.Taken together, these findings suggest that aortic cholesterol (CH) and CE accumulation are not simply a result of increased filtration of lipoproteins into the de-endo- thelialized aorta but may result from altered metabolism of the arterial wall. Previous findings showing increased glycosaminoglycan (GAG) accumulation in RA supported this concept of altered metabolism and suggest that these GAGs may sequester lipoproteins. Recent experiments indicate that: 1) CE synthetic and hydrolytic activity as well as activities of several marker enzymes were increased in injured aortas, 2) CE hydrolytic activity was relatively greater in DA as compared to RA, 3) Neointimal smooth muscle cells (SMC) in DA synthesized increased quantities of PGI2 and that PGI2 increased CE hydrolase activity of SMC and 4) RA accumulate more 125I-apo-B-lipoproteins than adjacent DA. In conclusion, results indicate that RA accumulate more CE rich apo-B-lipoproteins and have decreased ability to degrade CE. This may, at least in part, account for the increased CH and CE accumulation in RA. Further, the findings suggest that arterial injury alters arterial wall metabolism and that interactions between neointimal smooth muscle cells and endothelial cells may modify these metabolic changes.