bluuebunny/crossref_metadata_2025 huggingface dataset:
Modal analysis of railway current collectors using Autodesk Inventor
Authors: Wilk Andrzej , Judek Slawomir , Karwowski Krzysztof , Mizan Mirosław , Kaczmarek Paweł
Published: July 2018

The paper presents the results of modal analysis of railway current collector type 160EC. In the first place, the analysis was carried out analytically for a simplified two lumped mass pantograph model. Then numerical analysis was conducted in the Autodesk Inventor (AI) on the prepared multibody model using the AI modal analysis algorithm, which is based on the finite element method (FEM). Model elements which are most relevant for attaining a correct representation of vibration properties when using AI modal analysis were indicated. The influence of selected parameters of modal analysis algorithm on results accuracy was investigated, e.g. the FEM mesh density. The natural frequencies and shapes of the first few vibration modes are shown. The results indicate that the frequencies of natural vibrations of the moving pantograph components are within the range of up to tens of hertzs. The possible use of results of pantograph modal analysis at the design stage and in the operation phase was also discussed.
Traction induction motor
Authors: Bernatt Jakub , Gawron Stanisław , Glinka Tadeusz , Polak Artur
Published: July 2018

The paper presents a traction induction motor with an innovative rotor winding design. The winding of the rotor is almost identical to the armature winding in the dc traction motors, with the exception of commutator. Winding is double layered. The bars are insulated. Along the iron core bars are secured with wedges and in the winding outhang with bandages. The bars of the bottom layer in the winding outhang part near the iron core are bent radially in the direction of the shaft axis. On the winding outhang of the bottom layer an inner bandage is applied. On the winding outhang of the top layer an outer bandage is applied. All the ends of the bottom and top layers bars, on both sides of the rotor’s core, are connected together by ferrule. There is a ring placed on the shaft or on the coil support on one side of the rotor’s core. It is best if this ring is made of copper. The ring is characterized by mp tongues, which are distributed evenly along its circumference (p is number of winding pole pairs and m is number of rotor winding phases). Tongues are connected to equally uniformly placed ferrules. Bandages are made of carbon fibre or glass fibre tape.
The use of the PN-EN 62305-2 standard to the risk assessment of losses in the equipped object in station- devices of the railway traffic controlling
Authors: Wróbel Zofia
Published: July 2018

The valuation of the risk of losses makes easy the correct estimation of resulted threats as a result of atmospheric discharges and harms connected to them. Qualifying the need of lightning protection use for the object, we ought to take into account the risk R for the object and for the public services devices. In every case of examining risks we ought to fulfill: the identification of components RX forming the risk, counting the identified components of the risk RX, the entire risk R, identify the tolerated risk RT and compare the risk R with the tolerated value RT. As a result of such analysis we can come to a decision about the use of protection resources. In the report was realized the risk analysis of devices damages for a chosen object - the signal box with installed station - relaying devices of the railway traffic controlling with a computer adjustable control panel. From the realized analysis results that DEHN Risk Tool is a useful tool for the risk analysis of lightning losses in buildings, making possible the improvement of the calculations process, especially in the range of the choice of proper protection resources.
Operational criteria in the justification of electrification of railway lines
Authors: Massel Andrzej
Published: July 2018

The process of electrification of the Polish railways took place from 1936 till early 1990s. Despite the political constraints of the post-war times, the decisions on electrification of particular sections of the railway network were usually based on economic factors. In 1970s and 1980s so called electrification thresholds were used to justify the need for electrification of railway line in question. They took into the number of tracks (single-track lines, double-track lines), terrain conditions (flat terrain, upland terrain) and the traffic structure (the share of passenger traffic) into account. In the framework of National Railway Program till 2023 (KPK) the realization of electrification projects have been undertaken again. The present paper deals with importance of the operational criteria in the decision-making concerning justification of electrification of railway lines. These criteria include the shortening of the journey times on particular sections, shortening of stops on the stations with the change of the type of traction, the savings of train operating companies resulting from the traction unification (change of demand for rolling stock and for workshops for its servicing), improvement of reliability and punctuality of services.
Ruptured Abdominal Aortic Aneurysm in a Patient with Congenital Fused Pelvic Kidney: A Case Report of Emergency Endovascular Treatment
Authors: Bianchini Massoni Claudio , Azzarone Matteo , Barbarisi Danilo , Perini Paolo , Freyrie Antonio
Published: July 2018

A 90-year-old male developed acute onset of abdominal and lumbar pain due to the rupture of an 11-cm abdominal aortic aneurysm. A congenital fused pelvic kidney perfused by three renal arteries arising from iliac axes was detected. In an emergent setting, an aorto-uni-iliac endograft was deployed through right femoral surgical access with occlusion of the upper right renal artery. An occluder device was placed in the common iliac artery above the renal artery through left femoral access. A femorofemoral crossover bypass completed the procedure. The patient developed acute renal failure, with no dialysis necessity. One-month computed tomography angiography showed procedure success.
Successful Repair of Concomitant Acute Type A Aortic Dissection and Saddle Pulmonary Embolism
Authors: Ramponi Fabio , Papps Theone , Edwards James
Published: July 2018

Patients presenting with acute onset of chest pain require prompt diagnosis and rapid establishment of a management plan. Acute aortic dissection and acute pulmonary embolism are life-threatening emergencies that can mimic each other at presentation. Correct identification of this uncommon scenario is crucial to initiate the appropriate interventions. The authors present a unique case of concomitant acute type A aortic dissection and acute saddle pulmonary embolism; the patient underwent successful aortic repair and pulmonary embolectomy.
Haemostatic Effects of Supraphysiological Levels of Testosterone in Normal Men
Authors: Anderson R A , Ludlam C A , Wu F C W
Published: July 2018

The effects of exogenous testosterone on the haemostatic system were studied in a group of 32 healthy men undergoing a clinical trial of hormonal male contraception. The men received 200 mg testosterone oenanthate (TE) weekly i.m., and plasma samples were taken pretreatment, at defined time points up to 52 weeks of treatment, and 4 and 8 weeks after discontinuing TE. This dose of TE caused a 2-fold increase in trough plasma testosterone levels.

TE caused a fall in plasma fibrinogen concentration after 16 weeks of treatment. This was sustained for the duration of TE treatment and recovered to pretreatment levels during the recovery phase. There was also a sustained fall in the level of C4b binding protein which showed a rebound to levels above pretreatment during recovery. Levels of antithrombin III and prothrombin fragment F1.2 rose initially during TE treatment, and levels of protein C, protein S (free) and plasminogen activator inhibitor fell, but the concentrations of these factors all returned to pretreatment levels during continued treatment. There was no change in the plasma concentrations of β-thromboglobulin, tissue plasminogen activator, protein S (total), or D-dimer. There was a sustained increase in haemoglobin concentration and haematocrit, without any change in platelet count.

The observed changes were consistent with mild activation of the haemostatic system during initial treatment with testosterone. After several months the raised activation markers had returned to pretreatment levels indicating that a new equilibrium had been established which did not appear to be prothrombotic. The increase in prothrombin fragment F1.2 for the first 32 weeks, and at four weeks after discontinuation of treatment, is consistent with prolonged mildly increased prothrombinase activity. The observed substantial fall in fibrinogen is likely to have reduced, whereas the small rise in haemoglobin will have increased, the tendency to arterial thrombosis. We conclude that supraphysiological doses of testosterone do not result in a sustained marked prothrombotic state, but these results do not exclude a small change in thrombotic risk.
A Comparative Study of the Anticoagulant and Antithrombotic Effects of Unfractionated Heparin and a Low Molecular Weight Heparin (Fraxiparine®) in an Experimental Model of Human Venous Thrombosis
Authors: Diquélou Armelle , Dupouy Dominique , Cariou Roger , Sakariassen Kjell S , Boneu Bernard , Cadroy Yves
Published: July 2018

summary

We have compared the anticoagulant and the antithrombotic effects of unfractionated heparin(Calciparine®)and low molecular weight heparin(Fraxiparine®)in an experimental human venous thrombosis model.One single subcutaneous injection of Calciparine® or Fraxiparine® was administered to healthy male volunteers at one month intervalin a randomised and cross-over design.Ten subjects received doses used in man for preventing venous thrombosis(5,000 IU and 3,075 IU,respectively),and seven other subjects received curative doses (12,500 IU and 6,150 IU, respectively).Thrombus formation was measured 3 h and 8 h after drug administration.Non-anticoagulated humanblood was drawn for 5 min directly from an antecubital vein over confluent cultured endothelial cells positioned in a parallel-plate perfusion chamber.The cells were previously stimulated for 4 h with lipopolysaccharides(10 µg/ml) and interleukin 1β(50 U/ml),resulting in optimal expression of biological active tissue factor.The wall shear rate at the cell surface was 50 s-1 and mimicked venous blood flow conditions.

Immunologically quantified fibrin deposition on the stimulated cells was reduced only by curative doses of Calciparine® and Fraxiparine® at 3 h(3.4 ± 0.8 versus 1.0 ± 0.2 µg/cm2 and 2.6 ± 0.8 versus 1.0 ± 0.1 µg/cm2, respectively,p ≤0.05).The influence of Calciparine® and Fraxiparine® on the formation of thrombin and fibrin was determined by measuring the plasma levels of thrombin-antithrombin III complexes and fibrinopeptide A (FPA) in blood samples collected distally to the perfusion chamber.The generation of these markers was significantly inhibited (50-83%) by both prophylactic and curative doses of Calciparine® and Fraxiparine®(p ≤0.05).However, Fraxiparine® still significantly inhibited the thrombin and fibrin generation at 8 h (p ≤0.05), whereas Calciparine® did not.The antithrombotic effects of both heparins were correlated with their plasma activities as measured by the antifactor Xa or the antithrombin assays.Thus,it appears in this model that Calciparine® and Fraxiparine® produce comparable antithrombotic effects at clinically comparable doses. However Fraxiparine® has a longer-lasting anticoagulant activity than Calciparine®. These results are ingood agreement with clinical observations in man,and thus in favour of our model of human venous thrombogenesis for further studies of antithrombotic molecules.
Immunohistochemical Localization of a Novel Peptide, Prostacyclin-Stimulating Factor (PSF), in Human Tissues
Authors: Masakado Mitsunorl , Umeda Fumio , Takei Akira , Hashimoto Toshihiko , Suelshi Katsuo , Nawata Hajime
Published: July 2018

In a recent study, we purified and cloned a newly identified bioactive factor that stimulates prostacyclin (PGI2) production by vascular endothelial cells (ECs) using conditioned medium (CM) from cultured human diploid fibroblast cells. The present study was undertaken to clarify whether PSF is expressed in ECs and vascular smooth muscle cells (SMCs) of human tissues at a protein level. In an immunohistochemical study of seven human autopsy cases, all arteries in all lungs (n = 4) and kidneys (n = 6) examined stained positive to variable extents for PGI2-stimulating factor (PSF). PSF was predominantly expressed by SMCs in the media of small arteries. Staining for PSF was weaker in SMCs of aortic media (n = 3) and strong in SMCs of vaso vasorum (n = 3). PSF staining was also found in the SMCs of human bronchi (n = 4). Immunoblot analysis confirmed that PSF is present in CM from cultured bovine aortic SMCs.
Collagen-Mediated Platelet Aggregation: The Role of Multiple Interactions between the Platelet Surface and Collagen
Authors: Santoro Samuel A , Cunningham Leon W
Published: July 2018

Although the requirement for collagen fibrils to initiate platelet aggregation is well established, there has been no satisfactory explanation for this requirement. One possibility is that multiple simultaneous and linked interactions between collagen and the platelet surface must occur to initiate the release reaction and subsequent aggregation.

Direct evidence in support of this proposal was obtained by examination of the ability of collagen crosslinked in a random manner with glutaraldehyde to initiate platelet aggregation. Collagen crosslinked with 0.25 % glutaraldehyde is only a slightly less effective aggregating agent than native fibrillar collagen. Further studies revealed that whereas native triple helical cross-linked collagen is an effective aggregating agent, denatured crosslinked collagen is ineffective.

It thus appears that crosslinking of platelet receptor sites by multiple simultaneous and linked interactions with a rigid collagen matrix is required to initiate platelet aggregation. The precise steric relationship of the collagen sites does not appear to be of great importance.
Fat Emulsion Infusion Potentiates Coagulation Activation during Human Endotoxemia
Authors: van der Poll Tom , Coyle Susette M , Levi Marcel , Boermeester Marja A , Braxton Carla C , Jansen Patty M , Hack C Erik , Lowry Stephen F
Published: July 2018

Intravenous fat emulsions are frequently given to malnourished patients who are prone to suffer from infectious complications. As injection of low dose endotoxin represents a model to study the human response to acute infection, we sought to determine the effect of lipid emulsion infusion on endotoxin-induced activation of the hemostatic mechanism in man. Ten healthy men received a bolus intravenous injection of endotoxin (lot EC-5; 20 U/kg) midway through a 4-h infusion (125 ml/h) of either dextrose 5% (n = 5) or Intralipid 20% (n = 5). Lipid infusion potentiated endotoxin-induced coagulation activation, as indicated by higher plasma levels of the prothrombin fragment FI + 2 and of thrombin-antithrombin III complexes (both p <0.05 for the difference between groups). However, lipid infusion did not influence the fibrinolytic response to intravenous endotoxin, as reflected by similar increases in the levels of tissue-type plasminogen activator and plas-min-α2-antiplasmin complexes in both groups. Endotoxin-induced appearance of plasminogen activator inhibitor type I was enhanced by lipid infusion (p <0.05). These data suggest that fat emulsion infusion may enhance the tendency towards thrombotic complications in patients with infections.
Effects of Chronic Factor VIII Substitution on Immune Parameters in HIV Seronegative Haemophiliacs: a Comparison between Cryoprecipitate and Factor VIII Concentrate
Authors: Allersmaa D P , Smld W M , van der Does J A , van der Meer J , Briët E
Published: July 2018

Chronic substitution therapy of HIV-negative haemophiliacs with factor VIII products can result in abnormalities of ex-vivo measured immune parameters. To assess a possible relation between these abnormalities and product purity, we analyzed two groups of HIV-negative HCV-positive haemophiliacs, one treated with cryoprecipitate exclusively, the other with more purified factor VIII concentrates. Compared to age matched non-transfused male controls, increased numbers of white cells, granulocytes, IgG and IgM levels and decreased CD4+/CD8+ ratios were found in both patient groups. In the concentrate receivers, the numbers of mononuclear cells, CD4+, CD8+ and CD3+/HLA-DR+ cells indicating activated T-cells, were higher than in the cryoprecipitate group. In conclusion, both cryoprecipitate and intermediate/high purity concentrate recipients showed immune parameter abnormalities. These abnormalities tended to be somewhat more pronounced in patients treated with concentrates. By now there is no indication of the clinical relevance of the abnormalities in previously treated HIV seronegative haemophiliacs.
Platelet Reactivity In Vitro in Relation to Thromboxane in Healthy Pregnancy
Authors: Horn E H , Hardy E , Cooper J , Heptinstall S , Rubin P C
Published: July 2018

There is substantial evidence of increased platelet reactivity in vivo and in vitro during pregnancy. Previous in vitro studies suggest that platelets from pregnant women show increased sensitivity to agonists, the response to which has a thromboxane dependent component. The aim of this study was to determine whether this is due to increased activity of the thromboxane biosynthetic pathway or to increased platelet sensitivity to the effects of thromboxane. During pregnancy, platelets were more sensitive to the pro-aggregatory effects in vitro of the thromboxane mimetic U46619, in whole blood and in platelet rich plasma, compared to those from non-pregnant controls. The difference in extent of U46619-induced platelet aggregation between groups was abolished in the presence of a high concentration of the specific thromboxane antagonist ICI 192605, but not by prior incubation of blood with aspirin. Platelets from pregnant women were significantly less sensitive to inhibition of arachidonic acid induced activation by the thromboxane synthetase inhibitor dazmegrel, but there was no change in platelet cyclic AMP accumulation under these conditions. Arachidonic acid induced platelet thromboxane B2 production was similar in pregnant and non-pregnant subjects. In conclusion, platelets are more sensitive to the activating effects of thromboxane during pregnancy, but there is no change in the intrinsic reactivity of the thromboxane biosynthetic pathway.
A Novel Platelet Activating Factor Antagonist, SM-12502, Attenuates Endotoxin-induced Disseminated Intravascular Coagulation and Acute Pulmonary Vascular Injury by Inhibiting TNF Production in Rats
Authors: Murakami Kazunori , Okajima Kenji , Uchiba Mitsuhiro , Johno Masayoshi , Okabe Hiroaki , Takatsuki Kiyoshi
Published: July 2018

Adult respiratory distress syndrome and disseminated intravascular coagulation are important pathologic conditions affecting the outcome of patients with sepsis. To elucidate the possible therapeutic efficacy of SM-12502, a novel platelet activating factor antagonist, on acute lung injury and disseminated intravascular coagulation in sepsis, we investigated the effect of SM-12502 on an endotoxin (ET)-induced septic model in rats. SM-12502 prevented ET-induced increases in pulmonary vascular permeability and ET-induced histologic changes, such as leukocyte infiltration and pulmonary interstitial edema, 6 h following the administration of ET (5 mg/kg). SM-12502 also inhibited the decrease in fibrinogen and the increase in fibrin and fibrinogen degradation products observed following ET administration. SM-12502 prevented increases in the serum concentration of tumor necrosis factor (TNF) 90 min following ET administration in vivo, and significantly inhibited the production of TNF-α by ET-stimulated monocytes in vitro.

These findings suggest that SM-12502 attenuates the actions of endotoxin by the inhibition of TNF production
Decreased Potency Of Factor VIII Concentrates
Authors: Kasper C K
Published: July 2018

Plasma factor VIII recoveries after infusions of factor VIII concentrates into patients with classic hemophilia have been measured in this laboratory for 14 years. Recently, we observed a decline in the in vivo recovery of factor VIII per factor VIII unit infused. In 1980, plasma factor VIII levels were measured by a one-stage APTT-based assay before and 10 min after 150 infusions of 46 lots of 3 brands of factor VIII concentrate produced in the U.S.A. Our pooled normal plasma reference was calibrated against WHO International Standard 2 and results expressed in International factor VIII units. Observed in vivo factor VIII recovery was compared to the value expected from calculations based on the unitage stated on the label. The ratio of observed/expected recovery averaged 56% per lot for brand A, 60% per lot for brand B, and 103% per lot for brand C. In vitro assays were performed on 22 lots on 36 occasions, and the ratio of observed/labelled units average 46% per lot for brand A, 53% for brand B and 75% for brand C. The two-stage factor VIII assay method of Pool and Robinson was also used to assay plasma samples from 18 infusions, and results averaged 135% of the one-stage values for infusions of brand A, 160% for brand B, and 109% for brand C. (Brand A is assayed by the manufacturer by a two-stage method, brands B and C by one-stage methods.)

Decreased clinical efficacy was observed when postinfusion plasma factor VIII levels were lower than customary. The decline in potency of brands A and B has necessitated more frequent assay of patients and use of larger amounts of concentrate, with greatly-increased expense. Investigation of the effect of different assay methods and different factor VIII standards and references on the apparent factor VIII content of concentrates has begun.
Interaction Of Factor VIII/Von Willebrand Factor With Phospholipid Vesicles
Authors: Brown J E , Andersson L O
Published: July 2018

The interaction of factor VIII/von Willebrand factor with phospholipid vesicles was studied using sucrose density gradient ultracentrifugation. Purified VIII/vWf (Kabi) sediments as a complex in the lower third of a 5-30% sucrose gradient centrifuged for 18 hours at 160,000 g. Addition of sonicated phosphatidylserine-phosphatidylethanolamine vesicles at concentrations above 250 μg/ml results in complete separation of VIII:C from vWf, the former appearing with the phospholipid in the top of the gradient and the latter sedimenting as before. At lower levels of phospholipid, vWf competes for binding of VIII:C. The separation at higher levels of phospholipid is obtained in the presence of DFP and Trasylol, does not require calcium and occurs with plasma as well as purified preparations. Activation (7-10-fold) of purified VUI/vWf by thrombin (10-3 units/ml) results in the formation of a slowly sedimenting component containing essentially all of the VIII:C activity with little or no associated vWf. The thrombin-activated VIII:C is strongly bound to phospholipid vesicles and is more stabile than uncomplexed VIII:C (thrombin-activated). By varying the concentration of thrombin activated VIII:C with a constant (5 μg/ml) concentration of phospholipid, a Scatchard binding plot was obtained and a dissociation constant of 2.5 x 10-9 M estimated (assuming a molecular weight for VIII:C of 90,000) for the thrombin-activated VIII:C-phospholipid complex. These studies suggest that thrombin activated VIII:C binds to exposed phospholipid on released platelets concentrating the factor X activator complex.
LDL-Induced Cell Injury. An Effect Of LDL Independent Of Specific Binding And Uptake Of LDL
Authors: Børsum T , Henriksen T , Carlander B
Published: July 2018

LDL can injure endothelial cells in culture. HDL can inhibit this injurious effect of DDL. This effect of LDL seems to be independent of the LDL-receptor pathway since LDL-receptor negative cells were also injured. Ehdocytotic uptake of LDL appear not to be necessary for the DDL- induced cell injury to occur because LDL can injure both endothelial cells and erythrocytes at 4°C. By using radioactive 125I-DDL an increasing amount of 125I-LDL was shown to be associated with the cell with increasing concentrations of 125I-LDL in the incubation medium. A corresponding increase in cell injury as measured by 51Cr-release was observed. Presence of HDL in the incubation medium reduced both the cell associated radioactivity and the 51Cr-release. Thus, a relationship between the amount of 125I-DDL associated with the cell and the degree of cell injury was present.

In conclusion, association of DDL to the cell surface seems to be closely related to the mechanism by which DDL can induce cell injury. Any kind of endocytotic uptake of DDL is not a prerequisite for the occurrence of DDL-mediated cell injury.
Enhancement Of The Effect Of Bradykinin On Microvascular Permeability By A Peptide Derived From Fibrinogen
Authors: Eriksson M , Gerdin B , Saldeen T
Published: July 2018

Some low molecular weight fibrin degradation products (LMW-FDP) cause increased microvascular leakage in the dorsal skin of the rat. Two peptides earlier termed 6A and 6D seem to cause most of this effect. As unfractioned LMW-FDP potentiate bradykinin we have investigated how the leakage due to bradykinin is affected by the peptides 6A and 6D

Methods. Different concentrations of peptide 6A (Ala-Arg- Pro-Ala-Lys), 6D (Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys), inhibitors of kininase I and II (arginine and SQ14,225) were tested alone as well as together with different concentrations of bradykinin. The substances were injected in the previously shaved dorsal skin of 125I-albumin treated rats. The radioactivity content in the skin was measured in each injection site and the effect on microvascular permeability was calculated.

Results. Thirty minutes after an injection of 6A or SQ14,225 together with bradykinin the leakage due to each mixture was greater than the sum of each substance per se. The response was dose-dependant. Simultaneous application of 6A, bradykinin and SQ14,225 caused a further increase in microvascular permeability. 6A and arginine had only marginal action upon the leakage due to bradykinin. 6A did not potentiate the effect of bradykinin after 5 min, while SQ14,225 showed a slight potentiation, however less than after 30 min. SQ14,225 itself was without effect.

Discussion. As peptide 6A did not potentiate bradykinin after 5 min in contradiction to SQ14,225 it seems that their effects are not completely identical. The dramatical effect of SQ14,225 and the limited effect of arginine indicate that kininase II is the principle enzyme degrading bradykinin in rat skin. The effect of peptide 6A, even at low concentrations, indicate that this peptide, apart from its intrinsic effect on microvascular permeability, also can be of pathophysiologic significance in inflammatory states as potentiator of bradykinin.
Models Of Granulocyte-Mediated Endothelial Injury In Vitro
Authors: Vercellotti G , Flynn P , Weisdorf D , Lammi-Keefe C J , Jacob H , Moldow C F
Published: July 2018

To determine the role of neutrophil (PMN) induced vascular injury during inflammation an in vitro model of endothelial damage was investigated. Injury to human umbilical vein endothelial cells (EC) labeled with 51Cr or 14c sodium arachidonate was monitored by specific release of these labels or their products. Several agents were capable of triggering PMN to induce significant EC injury: these include activated serum complement (C') opsonized particles, serotonin , phorbol myristate acetate, and the lipid A moiety of endotoxin. PMN must adhere closely to the EC for effective cytotoxicity, since agents which retard PMN adherence (cytochalasin B, methyl prednisolone) inhibit 51Cr release.

Lyscsorcal proteases did not mediate PMN induced endothelial injury since there was no correlation between release and injury, and soluble stimuli which did not release lysosomal contents induced injury. Free radical scavengers such as SOD/catalase, and a-tocopherol significantly reduced PMN mediated endothelial injury implying that PMN generated reactive oxygen species were responsible for this damage.

To further study PMN mediated endothelial injury, other inflammatory agents were also utilized. C' activated PMN’s exposed to Ibuprofen (I) (50 μg/ml) but not Aspirin (ASA) (200 μg/ml) induced no EC injury (51cr releasey Furthermore, it was shown that I inhibits O-
2 production, blocks release of PMN lysozyme and glucuronidase, and inhibits aggregation of C' stimulated PMN’s. ASA at doses of 500 μg/ml (clinically toxic), failed to inhibit these in vitro activities. This data suggests that I’s anti-inflammatory affect may be expressed through inhibition of PMN functions. Since I and ASA both inhibit cyclooxygenase, but only I modulated PMN induced endothelial injury, these agents may provide useful probes to elucidate PMN-endothelial interactions in vivo.
Does ADP-Induced Platelet Aggregation Mediate Lung Vascular Injury?
Authors: Malik A B , Minnear F L , Tahamont M V , Moon D G , Kaplan J E
Published: July 2018

We determined the effects of ADP-induced platelet aggregation on lung fluid and protein exchange to examine whether platelet aggregation mediates lung vascular injury. The studies were made in intact sheep in which pulmonary lymph was obtained, and the protein concentration of lymph was compared to that of plasma. Two groups were studied: Control sheep receiving i.v. infusion of 10 mg/kg of ADP and experimental sheep in which platelets were depleted with anti-platelet serum prior to ADP infusion. In the control group, ADP decreased the platelet count from 178,554 ± 62,750 to 103,500 ± 47,828 cells/mm3, suggesting the entrapment of platelet in the pulmonary circulation.
The pulmonary arterial pressure (Ppa) increased from 13.1 ± 1.8 to 15.9 ± 1.2 mmHg. Lung lymph flow (Qlym) increased from 8.4 ± 1.8 to 11.4 ± 2.3ml/hr (p < 0.05) and transvascular protein clearance (Qlym x lymph/plasma protein concentration), a measure of protein exchange, increased from 6.7 ± 1.3 to 9.4 ± 3.0 ml/hr (p < 0.05). These increases could be explained by an increase in microvascular pressure (Pmv) and ultrafiltration since mechanically elevation of Pmv produced the same changes in Qlym and clearance. Platelet depletion prevented the ADP-induced increases in platelet aggregation does not mediate lung vascular injury, but increases fluid filtration by increasing the microvascular pressure. This effect may be mediated by release of pulmonary vasoconstrictor substances such as thromboxane A2 and serotonin after platelet aggregation.
Measurement Of Bradykinin-Induced Venous Dilation By Ultrasound And Correlation With Heart Rate, Arterial And Venous Pressure And Endothelial Damage
Authors: Stewart G J , Schaub R G , Cartee R E
Published: July 2018

This study was done to correlate known cardiovascular responses to bradykinin (increased heart rate, lowered arterial blood pressure) with recently demonstrated endothelial damage and proposed venous dilation. Healthy dogs of mixed breed were used. Blood pressures and heart rate were monitored and recorded on a Narco physiograph. The diameter of a jugular vein was monitored with an ADR ultrasound machine using a 10 MHz probe with linear array of crystals and recorded on polaroid prints. Jugular veins and carotid arteries were removed and prepared for scanning electron microscopy after removal of blood and partial in situ fixation by whole body perfusion. The response of arterial pressure was dose dependent with no change at 6 ug/min, variable drop at 12 ug/min and 22-40% drop at 60 ug/min and above. Venous pressure increased in 1 dog but was unchanged in 4 others. The increase of heart rate paralled the drop in arterial blood pressure. The diameter of a jugular vein increased in 3 of 3 monitored dogs by 25, 33, 50% of baseline diameter (average increase 36%) with high (300 ug/min) bradykinin. Endothelial damage (microtears) occurred around 70-80% of branches, at some valves and on the main vessel occassionally. The tears were infiltrated with leukocytes and some red cells and platelets indicating that tearing occurred while blood was still circulating, i.e. before dissection for removal of vessels. Carotid arteries showed no tears. Dilation of arteries would be limited by their elastic layers (missing in veins). These observations show that venous dilation and endothelial tearing around side branches are part of the cardiovascular response to blood born bradykinin. They also show that venous dilation can be measured by ultrasound.
The Influence Of Red Cell Size On Platelet-Vessel Wall Interaction
Authors: Aarts P A M M , Sixma J J , Sakariassen K S , Bolhuis P A , Heethaar R M
Published: July 2018

The hematocrit is one of the main factors influencing platelet adherence to the vessel wall. Raising the hematocrit causes an increase on platelet accumulation of about one order of magnitude.

These studies disregard the influence of the red cell size. We have studied this effect using an annular perfusion chamber according to Baumgartner, with human umbilical arteries and a steady flow system. Perfusions were performed with reconstituted blood consisting of the appropriate washed red cells, aspirin treated and 51Cr labelled human platelets and human plasma. Perfusions were at a calculated vessel wall shear rate of 800 sec-1 for 5 min at 37°C. Platelet adherence was measured by 51Cr counting and controlled by morphometry. Human, goat and rabbit red blood cells were utilized. Human red blood cells (mean cell volume 100 f1) increase platelet adherence sevenfold, as the hematocrit increases from 0 to 60%. Human erythrocyte ghosts had a similar effect. Goat erythrocytes (m.c.v. 25 f1) caused no increment in adherence in the same hematocrit range. Rabbit erythrocytes (m.c.v. 70 f1) caused an intermediate increase in adherence.

These data indicate that the red cell size is of major importance for platelet adherence. They may be explained by postulating that red cell rotation is responsible for diffusivity.
Depressed Responsiveness To Adrenaline In Platelets From Apparently Normal Human Donors – A Familial Trait
Authors: Scrutton M C , Bruckdorfer K R , Hutton R A
Published: July 2018

Decreased responsiveness to adrenaline has been observed in 5 out of approximately 150 apparently normal unrelated human donors. In 4 donors, familial studies have shown that this trait is inherited. Three of the donors, as well as their affected relatives, exhibit depressed responsiveness to collagen and vasopressin but normal responsiveness to ADP and thrombin in association with the decreased responsiveness to adrenaline. The other two affected donors exhibit normal responsiveness to most other agonists although in one instance depression of responsiveness to vasopressin and absence of a secretory response to ADP may be associated with the decreased adrenaline response.

Normal responsiveness can be restored in all instances either by incubating the platelet-rich plasma at 20°C or by addition at 37°C of a low concentration of the divalent cation ionophore, A-23187. No such effect results from addition of an adenylate cyclase inhibitor. All affected platelets have normal ATP and ADP contents, cholesterol to phospholipid ratios, and composition of the phospholipid classes. Mixing experiments demonstrate the absence of a circulating inhibitor of platelet function and suggest that the defect resides in the platelets. We conclude that depressed responsiveness of human platelets to adrenaline may result from a defect in Ca2+ mobilisation to the cytosol. The observed selectivity in the agonists affected may indicate that the stimulus-response coupling pathways converge at the level of an increase in cytosolic Ca2+ concentration.
Thrombocytopathy In Chronic Myelocytic Leukemia: A Possible Defect In The Response To Thromboxane A2
Authors: Okuma M , Takayama H , Uchino H
Published: July 2018

Platelet functions, adenine nucleotide contents and ara- chidonic acid (AA) metabolism have been studied in a chronic myelocytic leukemia patient with slight thrombocytosis and a mild bleeding tendency. Platelet aggregation with 5 μM ADP was completely reversible. Platelet aggregation as well as ATP release induced with AA and collagen was defective. Only high concentrations of AA (≥2 mM) induced slight aggregation with its complete reversal. Normal platelets suspended in patient’s plasma were aggregated by AA but patient’s platelets in normal plasma were not, showing the abnormality to be in patient’s platelets per se. 14C-Serotonin uptake by the platelet and adenine nucleotide (ADP and ATP) contents in the platelet were normal, excluding a possibility of storage pool deficiency. Normal activities of cyclo-oxygenase and lipoxygenase pathways in patient’s platelets were demonstrated both by thin-layer radiochromatographic analysis of lipid products obtained by incubating [l-14C]AA with the platelet (Blood 1979;54:1258) and by the determination of thiobarbituric acid-reactive substances produced by the incubation of AA with the platelet (Thromb. Haemost. 1979;42:245). Normal biological activity of AA metabolites produced by patient’s platelets was shown by strong irreversible platelet aggregation produced by the addition of normal citrated platelet rich plasma (PRP) to a reaction mixture in which patient’s washed platelets had been incubated with AA at 37°C for 30 sec. Only slight aggregation with its reversal was observed when patient’s PRP was added to a reaction mixture in which thromboxane A2 (TXA2) had been generated by the incubation of AA with the microsomal fraction prepared from normal platelets, while irreversible aggregation was produced when normal PRP was added in similar experiments. These results suggest that abnormal platelet functions in this patient are due to a defective platelet response to TXA2.
Megakaryocytic Colony Stimulating Activity A Potential Regulator Of Human Megakaryocytopoiesis
Authors: Hoffman R , Mazur E , Bruno E , Floyd V
Published: July 2018

The regulation of megakaryocytopoiesis is presently poorly understood. Utilizing an in vitro clonal assay system for the human megakaryocytic progenitor cell (CFU-M) we have attempted to define factors which are important in the control of megakaryocytopoiesis at the stem cell level. Sera were obtained from individuals with clinical disorders associated with quantitative platelet abnormalities and were added to plasma clot cultures of bone marrow mononuclear cells obtained from nine normal individuals. When serum samples from nine patients with aplastic anemia comprised 10% of the growth media, each significantly increased CFU-M derived colony formation (400-1250%) when compared to cultures containing normal human AB serum. Under similar conditions, neither sera from eight individuals with thrombocytosis associated with myeloproliferative disorders nor sera from eight patients with severe thrombocytopenia but with normal or increased numbers of bone marrow megakaryocytes (ITP, hypersplenism, TTP, DIC, megakaryocytic leukemia) altered colony formation. When aplastic anemia sera was added in increasing amounts (0, 5, 10, 20, 30%) to bone marrow cultures, CFU-M derived colonies per 5x10$ cells plated increased in a linear fashion (14, 42, 89, 123 and 238, respectively). Preliminary characterization of this megakaryocytic colony stimulating activity (M-CSA) reveals that it is dialyzable and its effect is not neutralized by pretreatment with rabbit anti-erythropoietin antisera. These studies have defined a newly recognized serum factor M-CSA that regulates in vitro megakaryocytic colony formation. M-CSA levels in various disease states suggest that it has physiological significance and that its production might be inversely related to bone marrow megakaryocyte numbers.
Dextran Sulfate Induced Activation Of Prekallikrein In Normal Plasma And Inactivation Of Kallikrein
Authors: Graaf F V D , Keus J F A , Rietveld A , Vlooswijk R A A , Bouma B N
Published: July 2018

Addition of dextran sulfate (DXS; Mr 500.000) to normal human plasma (n.h.p.) at 4° C results in the generation of kallikrein amidolytic activity. Maximum kallikrein activity is generated after 7 minutes in n.h.p., while no kallikrein activity is generated in Factor XII and Prekallikrein (PK) deficient plasma and only small amounts (8%) in High Mr Kininogen (HMWK) deficient plasma. Anti Factor XII, anti PK or anti HMWK added to n.h.p. blocked the formation of kallikrein activity. This shows that Factor XII, PK and HMWK are necessary for optimal activation of PK.

By adding 125I-PK to n.h.p. followed by activation with DXS it was shown that the appearance of kallikrein activity is paralled by limited proteolysis of 125I-PK, as judged on reduced SDS gels. The same cleavage fragments were observed as obtained by activation of purified PK by ²-Factor XIIa (28.000 Mr form). Addition of 131I-HMWK and 125I-PK or 131I-HMWK rand I-Factor XII to normal plasma followed by activation with DXS indicated on SDS gels a similar rate of cleavage for HMWK and PK whereas Factor XII was cleaved less extensive.

Inactivation of kallikrein in plasma was studied at 37°C after activation with DXS at 4°C. Kallikrein was rapidly inactivated, reaching a plateau after 4 minutes of 10% of its maximum activity. In Cj inhibitor deficient plasma kallikrein was less rapid inactivated and a plateau of 30% was reached after 9 minutes. 125I-PK was added to n.h.p. prior to activation at 4°C and inactivation at 37°C. This plasma was analyzed by crossed immunoelectrophoresis. Radioactivity was detected in the precipitin peak using anti C1 inhibitor and anti α2-macroglobulin (β2M) but not with anti antithrombin III. Using purified proteins it was shown that C1 inhibitor inhibited kallikrein amidolytic activity completely, whereas α2M inhibited this activity only to 25% of its original activity. This remaining amidolytic activity is that of the α2M-kallikrein complex. Complexes of kallikrein and inhibitor and kallikrein and α2M were observed on SDS gels in the presence and absence of reducing agents.
Thrombin And Factor Xa Inhibition By Hog Mucosal Heparins Fractionated According To Charge Density
Authors: Poon M-C , Hurst R E
Published: July 2018

Since heparin inhibition of thrombin (ThI) and factor Xa (XaI) have been shown to depend differently upon the molecular size of heparin, this study was undertaken to determine their dependence upon charge density (Z). Fractions varying systematically in charge density were isolated from 3 hog mucosal heparin preparations (2 decolorized and 1 undecolorized) using a 2 phase sequential extraction system. Xal assay was performed by the plasma clotting method of Yin using a commercial kit. ThI assay involved inhibition of plasma clotting by partially purified bovine thrombin.

When heparin potencies were plotted against Z2, all 3 preparations determined by both assays showed a linear relationship with the exception of one fraction with the highest charge density. For each of the 2 assays, the curves for the 2 decolorized preparations were essentially parallel. Although the initial slope of the undecolorized preparation was parallel to those of the decolorized heparins for each assay, the potency of the fraction with highest charge density was different. Thus, all 3 preparations appeared similar for a given anticoagulant function except for the highest charged fractions. When the activity of each preparation was compared to each other, the XaI and ThI curves did not necessarily parallel each other or to the APPT potency curve. No clear cut systematic relationship or differential effects could be established between the heparin anticoagulant functions in relationship to charge density differences. The data suggested also heterogeneity of activities within each fraction with apparent charge density homogeneity.
Effect Of Some Experimental Conditions On The Activity Of A Low Molecular Weight (LMW) Heparin Fraction Compared To A Hight Molecular Weight (HMW) Fraction
Authors: Aiach M , Nussas C , Mardiguian J
Published: July 2018

In this work, we aimed to demonstrate that different methods can give different results when the same pair of heparin samples are compared, even when specific antiprotease assays are performed. For this purpose, the effect of heparin on factor Xa (Xa) or thrombin (IIa) inhibition by antithrombin III (AT III) was examined in the presence of varying amounts of AT III, during different incubation times.

The molecular weight of the two heparins were 5,200 (LMW) and 42,000 (HMW). Solutions containing 2 y.g per ml of heparin and a 1.4 to 15 μM freshly purified human AT III were incubated with either bovine Xa or human Ila. After a 20, 30, 60 or 90 secondes incubation at 30° C, the remaining protease activity was measured by the initial velocity of a chromogenic substrate. The method was entirely automated using a reaction rate analyser and an adapted program.

The antiprotease activity of the LMW heparin (related to the HMW heparin activity) varied from 0.23 to 0.89 in the anti Xa system, from 0.30 to 0.77 in the anti Ila system. The ratio of LMW to HMW activity was a parabolic function of either AT III concentration or incubation time. No meaning differences were observed between anti Xa and anti Ila activity when the inhibiting capacity was assayed in the same experimental conditions. These results suggest that the relative activities of HMW and LMW fractions depend upon the assay procedure. AT III concentration as well as incubation time are of particular importance.
Anti Factor Xa Activity In Plasma Following Oral, Pulmonary, Subcutaneous And Intravenous Administration Of Cd5000 Low Molecular Weight Heparin And Commercial Heparin To Rats, Rabbits And Dogs
Authors: Harrison L I , Kehe C R , Ober R E
Published: July 2018

CD5000 heparin (LMWH) is a low molecular weight heparin fraction, ave. mol wt. ∼ 5100. Plasma levels of antiFactor Xa activity (XaA) after iv, pulmonary, sc and oral administration of LMWH and commercial heparin (CH) were examined in rats, rabbits and dogs. Overall, LMWH maintained higher levels of XaA in plasma than did a similar mg dose of CH. When the heparins were given iv, plasma XaA after LMWH had a t1/2 ∼ 2X as long as that after CH. When similar mg doses were given sc, the average plasma XaA following LMWH was significantly higher than that following CH during 0-6 hrs postdose. When equal USP unit doses (four times as much LMWH on a mg basis) were administered into the lungs of dogs, LMWH showed plasma XaA significantly higher than after CH. LMWH also showed higher plasma XaA on oral administration of equal USP unit doses in rats, but the fraction of the dose absorbed and the plasma levels were low. About 4X as much LMWH on a mg basis as CH had to be given to achieve similar APTT values in dog plasma. LMWH may have significant therapeutic advantages in man if pharmacokinetic differences and different blood coagulation effects of the various mol wt. heparins described here in animals also occur in man. Studies in humans are planned.