bluuebunny/crossref_metadata_2025 huggingface dataset:
Accumulation of 5-Hydroxytryptamine by Aging Platelets: Studies in a Model of Suppressed Thrombopoiesis in Dogs
Authors: Aranda Eduardo , Pizarro Myriam , Pereira Jaime , Mezzano Diego
Published: July 2018

Thrombocytopenia was induced in healthy, male mongrel dogs by intramuscular injection of a single dose of estradiol valerate (1 mg/kg). A steady, almost linear decay of the blood platelet count starting about day 6 post-estradiol and attaining a mean value of 14 × 103 platelets/pi one week later was observed. Thrombocytopenia is explained mainly by suppression- of thrombocytopoiesis, as established by two independent ways: 1. Megakaryocytes in the bone marrow were markedly reduced. 2. Kinetic studies with 11‘In labeled autologous platelets revealed a nearly linear decay of the radioactivity and mean survival times within the expected range. The progressive reduction in the platelet count is associated with an increase in the mean age of the platelets still circulating. Following estradiol injection, platelet 5-hydroxytryptamine (5-HT) increased from a basal value of 130 ± 30 ng/108 platelets (platelet count of 351 ± 53 × 103 platelets/p.1) to 343 ± 100 ng/108platelets eleven days latter, when the platelet count dropped to 32 ± 18 × 103 platelets/pi No significant changes in the number or affinity of the 5-HT uptake receptors could be demonstrated in platelets exposed in vitro and in vivo to estradiol. Our results indicate that aging platelets accumulate 5-HT, probably by a sustained exposure to the monoamine in plasma, confirming previous observations based on models in which thrombopenia was induced by immune and mechanical means.
Platelet Deposition Induced by Severely Damaged Vessel Wall Is Inhibited by a Boroarginine Synthetic Peptide with Antithrombin Activity
Authors: Badimon J J , Weng D , Chesebro J H , Fuster V , Badimon L
Published: July 2018

Thrombin plays a key role in platelet activation and thrombosis. Specific inhibition of thrombin appears to be one of the best approaches to prevent thrombus formation. We have studied the effects of a synthetic a-aminoboronic acid derivative - [Ac, (D) Phe-Pro-Boro-Arg-Hydrocloric acid] - on platelet deposition on severely damaged arterial wall. Platelet deposition was evaluated under well characterized rheological conditions in an original perfusion chamber and detected by autologous mIn-labeled platelets. The study was performed “in vivo” in a porcine model of arterial thrombosis triggered by severely damaged vessel wall at blood flow conditions mimicking mild stenosis (1690 s−1) and patent (212 s−1) vessels. In addition, ex-vivo platelet aggregation activity was evaluated by whole blood impedance aggregometry using collagen, ADP and thrombin as agonists. The synthetic a-aminoboronic peptide was intravenously administered as a bolus followed by continuous infusion. Ex vivo thrombin-induced whole blood platelet aggregation was totally abolished, while ADP- and Collagen-induced whole blood platelet aggregation was not modified. The effects of the synthetic antithrombin on platelet deposition were evaluated in native blood (non-anticoagulated) conditions and in combination with heparin. Under both experimental conditions, the synthetic peptide significantly inhibited platelet deposition at local flow conditions of both high (1690 s−1) and low (212s−1) shear rates. Our results suggest that specific inhibition of locally generated thrombin might be a good strategy to prevent platelet dependent arterial thrombus formation independently of the local flow shear rate of the area at risk.
Evaluation of Recombinant Platelet Factor 4 and Protamine Sulfate for Heparin Neutralization: Clotting and Clearance Studies in Rat
Authors: Korutla Laxminarayana N , Stewart Gwendolyn J , Lasz Elizabeth C , Maione Theodore E , Niewiarowski Stefan
Published: July 2018

Recombinant platelet factor 4 (rPF4) efficiently neutralized heparin anticoagulant activity in rats without the adverse effect of protamine sulfate (PS) (Circulation 1992; 85: 1102). This study confirmed that rPF4 and PS neutralized heparin in rats. In vitro addition of excess PS but not rPF4 to plasma prolonged the activated partial thromboplastin time. Injection of rPF4 or PS 2 min following injection of 3H-heparin augmented loss of radioactivity from the circulation over the first 2 min but did not affect the half life of 3H-heparin for the next 58 min. PS was coupled to 4-(p-Azidosalicylamido)butylamine (ASBA), radioiodina- ted and purified by means of heparin-agarose chromatography. Heparin prevented the rapid loss of 125I-rPF4 from the circulation within the first 2 min but modestly increased loss of radioiodinated derivatized PS. Heparin extended the half-life of derivitized radioiodinated PS (measured between 2 and 60 min after injection) while modestly shortening that of 125I-rPF4. Both radioiodinated heparin binding proteins accumulated predominantly in liver and kidney. A greater percentage of radioactivity was found in these organs with rPF4 than with PS but more PS was found in urine. A larger percentage of radioiodinated derivatized PS than 125I-rPF4 was undetected. These results indicate that rPF4 and PS affect the kinetics of heparin clearance similarly but that organ deposition of the two agents may differ and offer an explanation of different physiological effects seen previously.
Effects on Thrombin Generation of Single Injections of Hirulog™ in Patients with Calf Vein Thrombosis
Authors: Ginsberg J S , Nurmohamed M T , Gent M , MacKinnon B , Stevens P , Weitz J , Maraganore J , Hirsh J
Published: July 2018

1. Study objective: To determine whether single injections of Hirulog, a direct thrombin inhibitor, can inhibit thrombin generation in patients with calf vein thrombosis and, if so, if the inhibition is sustained.

2. Design: Phase II open label cohort study.

3. Setting: Tertiary-care referral centres, university affiliated hospitals.

4. Patients: 10 patients with venographically-demonstrated calf vein thrombosis.

5. Intervention: Patients received a single injection of Hirulog, either 1.0 mg/kg subcutaneously or 0.6 mg/kg as a 15 min intravenous infusion. Prothrombin fragment (F1+2) levels, as an index of thrombin generation, were measured before as well as 6 h post- and 24 h post-Hirulog administration. Patients were followed with non-invasive tests to detect thrombus extension into the proximal veins.

6. Results: There was a significant reduction in the levels of F1+2 with both regimens, 6 h after Hirulog. The Fl+2 levels 24 h post-Hirulog showed a significant increase relative to the 6 h post-Hirulog results. One patient developed thrombus extension into the popliteal vein and was treated with conventional anticoagulants.

7. Conclusion: The single injections of Hirulog used in the study produced incomplete and temporary suppression of F1+2. Complete and permanent inhibition of thrombin generation with Hirulog in patients with calf vein thrombosis may require higher doses, multiple subcutaneous injections and/or prolonged intravenous infusion.
Effects of Acetylsalicylic Acid on Inhibition of Ex Vivo Platelet Aggregation and Secretion by SKF 107260, a Novel GPIIb/IIIa Receptor Antagonist
Authors: Freed Martin I , Boike Steven , Zariffa Nevine , Jorkasky Diane K
Published: July 2018

SKF 107260 is a potent pentapeptide antagonist of the platelet membrane glycoprotein receptor GP IIb/IIIa. The in vitro platelet inhibitory effects of SKF 107260, acetylsalicylic acid (ASA), and their combination, on collagen-induced platelet aggregation and secretion (ATP release) were assessed in human whole blood. Additionally, the con-centration-response relationships for these inhibitors were compared for males and females in order to explore gender differences in platelet responsiveness. SKF 107260 caused a concentration-dependent inhibition of platelet aggregation which was significant at concentrations ≥30 nM. ASA also caused a concentration-dependent inhibition of platelet aggregation which was significant at concentrations ≥ 1 mg/dl. The addition of ASA 1 mg/dl to increasing concentrations of SKF 107260 resulted in a more pronounced inhibition of platelet aggregation than when either agent was used alone. These data suggest a pharmacologic interaction, especially at SKF 107260 concentrations ≤30 nM. Since ATP release was significantly inhibited at concentrations ≥ 1 nM, platelet secretion appears to be more sensitive than aggregation to inhibition by SKF 107260. These data suggest that platelet secretion in response to collagen is dependent on the aggregation response mediated by GP IIb/IIIa. In conclusion, SKF 107260 is a potent inhibitor of both whole blood platelet aggregation and secretion and these anti-aggregatory effects may be augmented by concomitant ASA administration.
Study of the Interaction of Dextran and Enoxaparin on Haemostasis in Humans
Authors: Matthiasson Stefan E , Lindblad Bengt , Mätzsch Thomas , Molin Jarl , Qvarfordt Peter , Bergqvist David
Published: July 2018

The effect on haemostatic variables by dextran 70, enoxaparin and their combinations, given in doses of 500 ml i.v. and 40 mg s.c. respectively, was studied in a randomised cross-over fashion in twelve healthy male volunteers. Antifactor-IIa activity, antifactor-Xa activity, APTT, factor VIII, vWF, bleeding time and blood counts were analysed over a 24-h period. Dextran alone did not affect antifactor-IIa activity and antifactor-Xa activity. No difference in antifactor-IIa and antifactor-Xa activity was found for Amax, tmax, AUC0-8 h and AUC0-24 h in the groups treated with enoxaparin or the combination of enoxaparin and dextran. Only minor changes in APTT were observed without statistical significance between the treatment groups. Factor VIII did not change significantly in the three treatment groups. However, vWF was significantly reduced in the dextran and the dextran/enoxaparin group (p = 0.046 and 0.01 respectively) but no difference was found between the two groups. Bleeding time was not significantly increased four hours after administration of the test substances and no difference was found between the individual treatment groups. Our findings indicate that dextran can be combined with enoxaparin, when used in thromboprophylactic doses, without increased risk for bleeding.
Evaluation of Recently Described Tests for Detection of the Lupus Anticoagulant
Authors: Forastiero Ricardo R , Cerrato Graciela S , Carreras Luis O
Published: July 2018

It is known that lupus anticoagulants (LA) are antibodies which interfere with phospholipid-dependent coagulation tests, but due to the heterogeneity of LA and the differences in sensitivity of reagents and tests, the diagnosis of LA remains difficult.

Recently, Triplett et al. (26) have proposed a new test based on two venoms, Textarin (T) and Ecarin (E), that activate prothrombin but differ in their phospholipid requirements. By testing this new assay we have evaluated 36 patient plasmas containing LA according to standard tests (activated partial thromboplastin time, dilute Russell viper venom time and platelet neutralization procedure) and our results confirm a high sensitivity for LA of the T/E test.

In addition, we observed a greater sensitivity of the tissue thromboplastin inhibition test using a recombinant thromboplastin instead of a human placenta thromboplastin.

Our study also showed that the T/E test seems to be a useful assay in confirming the diagnosis of LA in patients with an unexplained prolonged APTT.
A Dose Ranging Study to Evaluate Dermatan Sulphate in Preventing Deep Vein Thrombosis following Total Hip Arthroplasty
Authors: Cohen A T , Phillips M J , Edmondson R A , Skinner J A , Das S K , Cooper D J , Thomas E M , Melissari E , Kakkar V V
Published: July 2018

Dermatan sulphate catalyses thrombin inhibition by heparin cofactor II; it has a lower haemorrhagic to antithrombotic ratio than that of heparin in animal models. Consecutive patients aged forty years or more, electively undergoing total hip replacement under general anaesthesia, were randomly allocated to one of three dosage regimens of dermatan sulphate (MF701, Mediolanum Farmaceutici) given intramuscularly. These were 200 mg once daily (n = 50), 200 mg twice daily (n = 52) and 300 mg twice daily (n = 51), administered from twenty-four hours pre-operatively until the tenth postoperative day. The overall incidence of DVT assessed by bilateral venography was 53%, 51% and 34% respectively (Chi-square test for trend p = 0.06). The incidence of major proximal DVT was 10.6%, 8.5% and 2.1% respectively. Pulmonary embolism (PE) and bleeding were assessed in all 153 patients. There was one case of PE in each dose group. The incidence of bleeding episodes, volume of blood lost and blood transfusion requirements were low and showed no increase with increasing dose. The patients were followed up 4-8 weeks after discharge.

We conclude that the two lower doses were subtherapeutic in this population, however dermatan sulphate given 300 mg twice daily, proved to be efficacious with an incidence of proximal major DVT of 2.1% and a low incidence of bleeding complications. A trial of dermatan sulphate 300 mg twice daily compared to standard prophylactic agents is needed.
Compound Heterozygous Protein C Deficiency Caused by Two Mutations, Arg-178 to Gin and Cys-331 to Arg, Leading to Impaired Secretion of Mutant Protein C
Authors: Sugahara Yuichi , Miura Osamu , Hirosawa Shinsaku , Aoki Nobuo
Published: July 2018

The protein C gene in a patient apparently homozygous for protein C deficiency was analyzed. Two different point mutations, each located in a different allele, were detected to reveal that the patient is a compound heterozygote. Mutation of Arg-178 (CGG) to Gin (CAG) [mutation I] was detected in exon VII, in the vicinity of activation peptide cleavage site by thrombin. Mutation of Cys-331 (TGC) to Arg (CGC) [mutation II] was found in exon IX, at one of the sites involved in disulfide bond formation in the catalytic domain of the heavy chain. The alteration of Cys-331 to Arg disables the formation of the disulfide bond and would alter the protein conformation. Transient expression assays using COS-7 cells transfected with protein C expression vectors containing each one of these two mutations suggested that each of the two mutations would lead to the protein C deficiency by an impairment of secretion of the respective mutant proteins.
Homozygosity for a Novel Missense Mutation in the Prothrombin Gene Causing a Severe Bleeding Disorder
Authors: Poort S R , Michiels J J , Reitsma P H , Bertina R M
Published: July 2018

A patient with a severe bleeding tendency and hypoprothrombin-emia (Factor II activity 2%, Factor II antigen 5%) was screened for the presence of alterations in his prothrombin gene. Direct sequencing of PCR fragments derived from the coding and flanking regions of the prothrombin gene, revealed that the patient was homozygous for an A ⟶ G substitution in exon 3. This substitution predicts the replacement of Tyr 44 (TAC) by Cys (TGC) in the prothrombin molecule. Both parents were found to be heterozygous for the same mutation. Further family studies revealed complete cosegregation of the mutation with the prothrombin deficiency. Only the five homozygous brothers and sisters of the propositus were clinically affected (severe hemorrhages including epistaxis, soft tissue, muscle and joint bleedings in all, and severe hemorrhages in the two women). The bleeding tendency therefore seems to inherit as an autosomal recessive trait.
Heparin and Low Molecular Weight Heparins Inhibit Prothrombinase Formation but not its Activity in Plasma
Authors: Ofosu Frederick A , Lormeau J C , Craven Sharon , Dewar Lori , Anvari Noorildan
Published: July 2018

Factor V activation is a critical step preceding prothrombinase formation. This study determined the contributions of factor Xa and thrombin, which activate purified factor V with similar catalytic efficiency, to plasma factor V activation during coagulation. Prothrombin activation began without a lag phase after a suspension of coagulant phospholipids, CaCl2, and factor Xa was added to factor X-depleted plasma. Hirudin, a potent thrombin inhibitor, abrogated prothrombin activation initiated with 0.5 and 1.0 nM factor Xa, but not with 5 nM factor Xa. In contrast, hirudin did not abrogate prothrombin activation in plasmas pre-incubated with 0.5,1.0 or 5 nM α-thrombin for 10 s followed by the coagulant suspension containing 0.5 nM factor Xa. Thus, thrombin activates plasma factor V more efficiently than factor Xa. At concentrations which doubled the clotting time of contact-activated normal plasma, heparin and three low Mr heparins also abrogated prothrombin activation initiated with 0.5 nM factor Xa, but not with 5 nM factor Xa. If factor V in the factor X-depleted plasma was activated (by pre-incubation with 10 nM a-thrombin for 60 s) before adding 0.5,1.0, or 5 nM factor Xa, neither hirudin nor the heparins altered the rates of prothrombin activation. Thus, none of the five anticoagulants inactivates prothrombinase. When 5 or 10 pM relipidated r-human tissue factor and CaCl2 were added to normal plasma, heparin and the three low Mr heparins delayed the onset of prothrombin activation until the concentration of factor Xa generated exceeded 1 nM, and they subsequently inhibited prothrombin activation to the same extent. Thus, hirudin, heparin and low Mr heparins suppress prothrombin activation solely by inhibiting prothrombinase formation.
Effects of Magnesium on Platelet Aggregation and Adhesion
Authors: Gawaz M , Ott I , Reininger A J , Neumann F-J
Published: July 2018

Magnesium deficiency and its association with platelet hyperreactivity has been well recognised in a variety of diseases including myocardial infarction, preeclampsia, and diabetes. In order to investigate potential effects of intravenous Mg2+ supplementation, platelet function was studied by measurements of in vitro bleeding time (BT) and of fibrinogen (Fg)-mediated aggregation of washed platelets. In addition, the effect of Mg2+ on platelet adhesion onto immobilised Fg, on Fg binding to activated platelets, and on surface expression of GMP-140 or GP53 was evaluated. Mg2+(4 mM) prolonged in vitro BT by 30% and inhibited Fg-mediated aggregation significantly, independent of the agonist used to initiate platelet aggregation (ADP, collagen, epinephrine, thrombin, phorbol ester). Adhesion of resting platelets to immobilised Fg was reduced by 50% in the presence of 2 mM Mg2+. Moreover, Mg2+ reduced Fg binding to ADP- or collagen-stimulated platelets as well as surface expression of GMP-140 with an IC50 of approximately 3 mM. Intravenous administration of Mg2+ to healthy volunteers inhibited both ADP-induced platelet aggregation (p <0.05) by 40% and binding of Fg or surface expression of GMP-140 by 30% (p <0.05). Thus, pharmacological concentrations of Mg2+ effectively inhibit platelet function in vitro and ex vivo.
Protein-tyrosine Kinase p72
syk
Is Activated by Platelet Activating Factor in Platelets
Authors: Rezaul Karim , Yanagi Shigeru , Sada Kiyonao , Taniguchi Takanobu , Yamamura Hirohei
Published: July 2018

It has been demonstrated that activation of platelets by platelet-activating factor (PAF) results in a dramatic increase in tyrosine phosphorylation of several cellular proteins. We report here that p72
syk
is a potential candidate for the protein-tyrosine phosphorylation following PAF stimulation in porcine platelets. Immunoprecipitation kinase assay revealed that PAF stimulation resulted in a rapid activation of p72
syk
which peaked at 10 s. The level of activation was found to be dose dependent and could be completely inhibited by the PAF receptor antagonist, CV3988. Phosphorylation at the tyrosine residues of p72
syk
coincided with activation of yllsyk. Pretreatment of platelets with aspirin and apyrase did not affect PAF induced activation of p72
syk
.Furthermore, genistein, a potent protein-tyrosine-kinase inhibitor, diminished PAF-induced p72
syk
activation and Ca2+ mobilization as well as platelet aggregation. These results suggest that p72
syk
may play a critical role in PAF-induced aggregation, possibly through regulation of Ca2+ mobilization.
Lipopolysaccharide Induced Monocyte Thromboplastin Synthesis and Coagulation Responses in Patients Undergoing Coronary Bypass Surgery after Preoperative Supplementation with n-3 Fatty Acids
Authors: Nilsen D W T , Almdahl S M , Svensson B , Vaage J , Rasmussen K , Østerud B
Published: July 2018

Twenty patients with coronary heart disease (CHD) and elevated serum lipids were randomized into 2 groups of 10 to receive encapsulated preparations of either a concentrated ethylester form of eicosapentaenoic acid (EPA) and docosa-hexaenoic acid (DHA) or corn oil in doses of 6 g per day, given double blindly for approximately two months prior to coronary bypass surgery. Lipopolysaccharide (LPS) induced monocyte thromboplastin synthesis was studied during the preoperative period and one week following surgery. The ability of n-3 fatty acids to modify tissue factor pathway inhibitor (TFPI) and tissue plasminogen activator inhibitor (PAI-1) was also evaluated along with fibrinogen and thrombin-antithrombin III (TAT) complexes.

No significant changes were noted preoperatively. Monocyte reactivity, PAI-1, fibrinogen and TAT increased significantly after surgery. These changes were not modified by preoperative loading with n-3 fatty acids.
Markers of Hemostatic System Activation in Acute Deep Venous Thrombosis-Evolution during the First Days of Heparin Treatment
Authors:   The DVTENOX Study Group
Published: July 2018

Fibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly allocated into two treatment groups: 44 patients received adapted doses of continuous intravenous unfractionated heparin (UH) whereas 47 received 1 mg/kg every twelve hours of a low molecular weight heparin (enoxaparin) subcutaneously. A phlebography and a perfusion lung scan were performed before inclusion and on day 10. Failure of therapy (n = 9) was defined by venogram worsening or confirmed pulmonary embolism. Improvement (n = 44) or stationary state (n = 38) were defined by venogram evolution in the absence of new leg scan defects.

At presentation, D-Di, F 1 + 2 and TAT were above cut-off values in 97, 66 and 89% of patients respectively. D-Di levels correlated with the extent of venous thrombosis whereas TAT and F 1 + 2 did not. Mean levels of D-Di decreased sharply during the first days of treatment but were still abnormal on day 10. A secondary increase of D-Di on days 6 or 10 by more than 3 μg/ml occurred in 4 of the 9 patients who developed a thromboembolic recurrence but in none of the 72 patients who had a more favorable outcome. F 1 + 2 and TAT time-courses were not related to clinical evolution. In the Enoxaparin group, there was no relationship between antifactor Xa activities and any biological markers. TAT and F 1 + 2 levels fell on day 2 and remained stable until day 10. In contrast, in the UH group, TAT and F 1 + 2 did not significantly decrease on day 2, probably due to a delay in dose adaptation, but they declined slowly until day 10.

In conclusion, D-Di displays a higher sensitivity than F 1 + 2 or TAT for the diagnosis of D\T. D-Di, but not TAT or F 1 + 2, follow-up seems to be of potential value for early detection of recurrency. Hemostatic activation is controlled earlier by fixed doses of a low molecular weight heparin, irrespective of the plasma anti-factor Xa activities, than by unfractionated heparin at adapted doses.
Are Capillary Whole Blood Coagulation Monitors Suitable for the Control of Oral Anticoagulant Treatment by the International Normalized Ratio?
Authors: Tripodi Armando , Arbini Arnaldo A , Chantarangkul Veena , Bettega Donato , Mannucci Pier Mannuccio
Published: July 2018

The 512 Coagulation Monitor is a portable coagulation photometer that uses disposable cartridges containing a lyophilized rabbit brain thromboplastin to measure the PT for capillary whole blood. It has been proposed as a suitable system for patient self monitoring at home, but its performance has never been thoroughly assessed for results expressed as International Normalized Ratio (INR). In particular, there is no available information about the adequacy of the WHO calibration model with the Monitor. The aims of the study were to determine the International Sensitivity Index (ISI) against the secondary International Reference Preparation for rabbit thromboplastin and to assess the precision of the INR. The study demonstrates that the Monitor can be calibrated with the WHO model, because log-transformed PTs for patients stabilized on oral anticoagulants and normal individuals are linearly related and because the same orthogonal regression line describes patient and normal data points adequately. However, the ISI calculated in this study (2.715) is higher than that adopted by the manufacturer (2.036). The between-assay reproducibility of the Monitor is acceptable (CV = 9.7%) with results expressed in seconds, but become unacceptably poor when the results are converted into INR (CV = 18.8%) because of the high ISI value of the thromboplastin used. We think that the Monitor might be suitable for monitoring oral anticoagulant therapy if the manufacturer would provide a more sensitive thromboplastin in the cartridges.
Expression and Localization of Tissue Factor-Based Procoagulant Activity (PCA) in Pigeon Monocyte-Derived Macrophages
Authors: Gupta Madhu , Doellgas George J , Cheng Therese , Lewis Jon C
Published: July 2018

Monocyte-derived macrophages, focal to initiation and progression of atherosclerosis, have been implicated in thrombotic complication of this disease. In the present study we demonstrated tissue factor based procoagulant activity in cultured macrophages from the White Carneau pigeon following endotoxin (1-2 μg/ml) stimulation. This macrophage procoagulant activity paralleled activity obtained with pigeon brain homogenate. We used Enzyme-Linked Coagulation Assay (ELCA), an ultrasensitive microtiter plate assay, to measure procoagulant activity in these cells. Through the use of clotting factors purified from pigeon plasma, procoagulant activity could be detected with as few as 1-3 cells. Tissue factor antigen, detected through the use of immunogold labelling in conjunction with a polyclonal antibody which was highly specific to human tissue factor, was distributed uniformly over the plasma membrane of the endotoxin-stimulated cells. These studies suggest that this procoagulant activity might play an important role in the pathobiology of atherosclerosis in White Carneau pigeons by initiating fibrin polymerization and thus leading to thrombotic complications of the disease.
Frangulin B, an Antagonist of Collagen-Induced Platelet Aggregation and Adhesion, Isolated from Rhamnus formosana
Authors: Teng Che-Ming , Lin Chien-Huang , Lin Chun-Nan , Chung Mei-lng , Huang Tur-Fu
Published: July 2018

Emodin and its glycoside frangulin B were isolated from the plant Rhamnus formosana. Emodin inhibited the aggregation of rabbit platelets induced by arachidonic acid and collagen, without affecting that by ADP or PAF, while emodin acetate had no any antiplatelet effect. Frangulin B inhibited selectively and concentration-dependently collagen-induced aggregation and ATP release in rabbit platelets, without affecting those induced by arachidonic acid, ADP, PAF and thrombin. Frangulin B also inhibited the platelet aggregation induced by trimucytin which was reported to be a collagen receptor agonist isolated from Trimeresurus muscrosquamatus snake venom. The aggregability of platelets inhibited by frangulin B could be recovered after washing the platelets. Frangulin B also selectively suppressed the thromboxane B2 formation caused by collagen, but not those by arachidonic acid and thrombin. Similarly, the formation of inositol phosphate caused by collagen was also suppressed by frangulin B, while that of PAF or thrombin was not affected. In the presence of PGE1, frangulin B also decreased Mg2+-dependent platelet adhesion to collagen. It is concluded that frangulin B may be an antagonist of collagen receptor in platelet membrane.
Hemophilic Bledding Evaluated by Blood Pool Scanning
Authors: Green D , Spies S M , Rana N A , Milgram J W , Mintzer R
Published: July 2018

The technique of blood pool scanning was used to examine 15 hemophilic subjects. Employing an in vivo method for erythrocyte labeling with Technetium-99 m, a dynamic perfusion sequence is obtained using a scintillation camera positioned over the area to be examined. This demonstrates the vascularity of the tissue. Subsequently, equilibrium blood pool images of the area are obtained and analyzed with a densitometer to assess relative regional blood volume. In patients who were not bleeding but had chronic arthropathy, vascularity was not increased, and the blood volume of comparable joints was similar. By contrast, marked increases in vascularity and image density were observed in studies of acutely bleeding joints. Chronic hemarthroses were associated with persistent, but less marked increases in joint perfusion. Transient increases in joint vascularity were demonstrated after insertion of knee prostheses. In a patient with a thigh hematoma, the dimensions of the hemorrhage were clearly delineated. Since only a tracer dose of nuclide is infused intravenously, there are no allergic reactions or other side effects of the procedure. Blood pool scanning is a safe, non-invasive technique that augments clinical and radiographic evaluations, and provides a new dimension in the assessment of the hemophilic patient.
Effect of Local Urokinase on Arterial Occlusion of Lower Limbs
Authors: Fiessinger J-N , Aiach M , Capron L , Devanlay M , Vayssairat M , Juillet Y
Published: July 2018

Sixty nine patients were treated with local intra-arterial urokinase (37,500 U/CTA. hr-1) for recent severe ischemia of lower limbs: 27 (40%) ultimately required amputation. The difference of amputation rate between the groups with and without thrombolysis was not significant (33% v. 42%). A biological study in 6 patients showed that local arterial plasminemia occurred in only 1 patient. Local urokinase does not strongly stimulate “endogenous” thrombolysis and enhances “exogenous” thrombolysis only very inconstantly. A better adaptation of urokinase dosage or the use of an agent with a higher affinity for fibrin might improve the efficiency of local thrombolytic therapy.
Measurement of Fibrinopeptide A in Patients Treated with Phenoprocoumon
Authors: Harenberg J , Haas R , Zimmermann R
Published: July 2018

Fibrinopeptide A (FPA), which is considered to be a quantitative indicator for the thrombin activity in vivo, was measured in 136 patients treated with phenprocoumon in order to obtain information on the effectiveness of the inhibition of the coagulation system. The results show a decrease of the FPA concentration in relation to the efficacy of the anticoagulant therapy as measured by the thrombotest coagulation method (p<0.01). However, elevated FPA was observed even under an effective oral anticoagulation.

These data indicate that an increased thrombin activity cannot be completely prevented by oral anticoagulants in every patient. Combined measurement of FPA and the thrombotest coagulation method might be used to detect patients with an elevated risk of recurrent thromboembolism despite treatment with phenprocoumon.
Abnormal Aggregation Accompanies Abnormal Platelet Ca2+ Handling in Arterial Thrombosis
Authors: Shanbaky Nabila M , Ahn Yeon , Jy Wenche , Harrington William , Fernandez Luis , Haynes Duncan H
Published: July 2018

The resting levels of cytoplasmic Ca2+ (measured by Quin 2 fluorescence) and dense tubular Ca2+ (measured by chlorotetracycline, CTC, fluorescence) are shown to be higher in platelets from patients with arterial thrombosis than from normal donors. Turbidmetric studies of aggregation of diluted platelet-rich plasma (PRP) at 135 μM Ca2+ showed increased rates of aggregation for patients relative to normal controls. For ADP-stimulated aggregation, increased maximal rates (Vmax) and decreased doses for half-maximal rates were observed. With collagen-stimulated aggregation, patient samples showed only decreased ED50 values relative to normal controls. The changes in these values are linearly correlated with the elevation of resting dense tubular Ca2+ level determined by the calcium-CTC test carried out at 2 mM external Ca2+. For ADP-stimulated aggregation this relationship can be mimicked by pre-incubating normal platelets with subcritical concentrations of the Ca2+ ionophore A23187.

These results suggest that elevated cytoplasmic and dense tubular Ca2+ in the “resting state” is a major factor in arterial thrombosis, rendering the platelet more sensitive to the stimulation by physiologic agents.
HIV Antibody Status and Immunological Abnormalities in Polish Haemophiliacs
Authors: Lopaciuk S , Kacperska E , Gloskowska-Moraczewska Z , Maslanka K , Uhrynowska M , Kraj M , Seyfried H
Published: July 2018

Sera of 520 multitransfused haemophiliacs were examined for antibody to HIV; 447 patients had haemophilia A and 73 had haemophilia B. In 382 patients with haemophilia A and in 62 with haemophilia B solely Polish-made blood products were used for replacement therapy. The remaining haemophiliacs had also received imported clotting factor concentrates prior to the investigation. Only 8 patients (haemophilia A - 7, haemophilia B - 1) developed anti-HIV and all of them had been exposed to commercial concentrates. The analysis of T-cell subsets demonstrated an inverted T4/T8 ratio (less than 1.0) in 7 (30%) of the 23 haemophiliacs treated solely with domestic cryoprecipitate and in 3 (37%) of the 8 seropositive recipients of commercial concentrates. The most frequent alteration in both subgroups was a reduced ratio with either normal absolute numbers or an increase in T8 cells. Increased serum IgG levels were found in 82% of the users of cryoprecipitate and in 75% of the seropositive patients. Serum beta-2-microglobulin level was elevated in 69 and 62% of each subgroup, respectively. The observed immunological abnormalities, at least in the cryoprecipitate treated subgroup, may be causally related to factors other than HIV infection.
Testosterone Effects on Biosynthesis of Coagulation Proteins
Authors: Owens Michael R , Cimino Catherine D , Donnelly Joan
Published: July 2018

Studies were performed to assess the effects of testosterone on synthesis of selected coagulation proteins using the isolated rat liver perfused in vitro for 10 hours, as well as effects of testosterone on plasma levels of these same proteins. Pretreatment of castrated male rat liver donors for 14 days with pellets containing placebo or testosterone, 0.5 mg, 5.0 mg or 15.0 mg had no significant effects on cumulative biosynthesis of Factor II, Factor VII, anti thrombin III, plasminogen or fibrinogen. Plasma concentrations of these proteins in liver donor animals were also unchanged by such hormonal manipulations. In contrast, biosynthesis of fibronectin was increased significantly by increasing doses of testosterone, and plasma concentrations of fibronectin in liver donor rats showed a similar effect.
Antithrombin III in Full-Term and Pre-Term Newborn Infants : Three Cases of Neonatal Diagnosis of AT III Congenital Defect
Authors: De Stefano V , Leone G , De Carolis M P , Ferrelli R , De Carolis S , Pagano L , Tortorolo G , Bizzi B
Published: July 2018

Antithrombin III (AT III) plasma levels were investigated in 18 full term neonates and 14 healthy preterm neonates. A control group of 20 healthy adults was also studied. AT III was measured as antigen concentration (Ag) and antithrombin or anti-factor Xa heparin cofactor (H. C.) activities. Crossed immunoelectrophoresis on heparin-agarose (H-CIE) was carried out on plasma samples; moreover the distribution of isoantithrombins was investigated on whole plasma by a technique of crossed immunoelectrofocusing (CIEF). AT III plasma levels in full term infants were significantly lower as compared to the adult values. The preterm newborns group showed a further significant decrease in AT III levels as compared to the full term neonates. In all infants AT III H-CIE runs displayed a single fast moving anodal peak, so that a normal binding to heparin was demonstrated. The CIEF AT III plasma pattern of the adults as well as of all neonates displayed three major peaks at pH range 5.2-4.9, a small amount of AT III at pH 4.9-4.8 and a minor peak at pH 4.8-4.6, so that it was concluded that the isoantithrombins plasma distribution in neonatal age is identical to that of the adult subjects. Four neonates whose mothers were affected by AT III congenital defect were also investigated: diagnosis of congenital deficiency was established in three cases.
Inhibition of Fibrin Polymerization by Serum Amyloid P Component and Heparin
Authors: Meyer Keith , Smith Robert , Williams Eliot C
Published: July 2018

The effects of serum amyloid P component (SAP) and heparin on the thrombin-catalyzed formation of polymeric fibrin from purified fibrinogen were examined using a turbidometric method to quantify fibrin polymerization. SAP and heparin acted synergistically to inhibit the lateral aggregation of fibrin fibrils, resulting in the formation of fibrils with a smaller mass to length ratio. Heparin did not enhance the incorporation of SAP into fibrin clots, and the effect of heparin and SAP did not seem to be related to inhibition of thrombin or of fibrinopeptide release. The evidence suggests that a soluble complex of SAP and heparin inhibits fibrin polymerization.
The Primary Structure of the Inhibitor of Tissue Plasminogen Activator Found in the Seeds of Erythrina caffra
Authors: Joubert F J , Dowdle E B D
Published: July 2018

Trypsin and tissue plasminogen activator inhibitor DE-3 from Erythrina caffra contains 172 amino acids, including 4 half-cystine residues, and resembles the Kunitz-type inhibitors. Limited hydrolysis of DE-3 with trypsin at pH 3.2 produced two fragments, FI and F2, containing 63 and 109 amino acids, respectively. Amino-terminal sequence studies showed that FI was the N-terminal and that F2 was the C-terminal fragment. The complete amino acid sequence of the fragments were then determined on peptides produced by enzymatic digestion with trypsin. The sequence of trypsin and tissue plasminogen activator inhibitor DE-3 from E. caffra seeds shows a high degree of homology to that of trypsin and tissue plasminogen activator inhibitor DE-3 from E. latissima seeds and revealed only four amino acids which were replaced.
Hypertensive Disorders of Pregnancy and Preterm Birth Rates among Black Women
Authors: Baer Rebecca , Jelliffe-Pawlowski Laura , Norton Mary , Premkumar Ashish
Published: July 2018

Objective The objective of this study was to investigate the role of gestational hypertension (gHTN) and chronic hypertension (cHTN) on rates of preterm birth (PTB) among black women.

Study Design Singleton live births between 20 and 44 weeks' gestation among black women in California from 2007 to 2012 were used for analysis. Risk of PTB by subtype and gestational age among women with cHTN or gHTN, including preeclampsia, was calculated via Poisson's logistic regression modeling. Risks were adjusted for maternal factors associated with increased risk of PTB.

Results A total of 154,950 women met the inclusion criteria. Of the 5,948 women in the sample with cHTN, 26.2% delivered preterm; for the 11,728 women with gHTN, 21.6% delivered preterm. Women with gHTN or cHTN had a higher risk of medically indicated and spontaneous PTB, both at less than 32 and 32 to 36 weeks, when compared with nonhypertensive women (adjusted relative risks [aRRs]: 3.4–11.6). Women with superimposed preeclampsia had higher risks of spontaneous (aRR: 2.8, 95% confidence interval [CI]: 2.3–3.4) and medically indicated PTB (aRR: 2.8, 95% CI: 2.0–3.8), especially PTB < 32 weeks, when compared with women with preeclampsia.

Conclusion Among black women, superimposed preeclampsia increased the risk for spontaneous and medically indicated PTB, especially PTB < 32 weeks.
Febrile Infection-Related Epilepsy Syndrome (FIRES) with Multifocal Subcortical Infarcts, A New Imaging Phenotype
Authors: Tan Ai
Published: July 2018

Febrile infection-related epilepsy syndrome (FIRES) is a catastrophic epileptic encephalopathy of unknown etiology which occurs predominantly in school-aged children, following a febrile illness. The term FIRES was first proposed in 2010 by van Baalen et al. The etiology of FIRES remains elusive, although most believed that it is likely related to inappropriate activation of the innate immune system. It is often a diagnosis of exclusion as it lacks specific clinical criteria and/or confirmatory tests. Familiarity with the range of imaging phenotypes associated with FIRES is crucial as this will assist timely recognition and institution of appropriate treatment plan. With this in mind, the author would like to present a rare case of FIRES with extensive subcortical infarcts, predominantly in the temporo-occipital lobes. This has never been reported before and may represent a new imaging phenotype of FIRES. A detailed literature review, focusing on the various pattern of imaging phenotypes, in relation to patients' age and clinical outcome, will also be included.
Pediatric Cervical Lymphadenitis
Authors: Jaggi Preeti , Walz Patrick , Hecht Shaina
Published: July 2018

Enlargement of the lymph nodes in the head and neck region is a common presenting symptom in the pediatric population as the upper aerodigestive tract is a common source of inoculation of many infectious agents. While infectious processes—both viral and bacterial and both acute and chronic—are the most likely etiology of enlargement of cervical lymph nodes, other potential causes including inflammatory conditions and malignancy should be considered in the evaluation of cervical adenopathy. In this article, the anatomy and physiology as well as pathophysiology of the head and neck lymphatic system will be reviewed as this relates to clinical presentation of cervical lymphadenitis. Also, the myriad causes for cervical adenopathy will be discussed with a comprehensive review of the epidemiology of infectious etiologies. An evidence-based framework for the diagnostic workup and therapeutic interventions available to appropriately manage infectious cervical lymphadenitis will be reviewed, and the complications that can result from failure to adequately diagnose and treat cervical lymphadenitis will be discussed.
Secondary Bone Defect in Neuromuscular Diseases in Childhood: A Longitudinal “Muscle-Bone Unit” Analysis
Authors: Ribstein C. , Courteix D. , Rabiau N. , Bommelaer C. , Bourdeau Y. , Pereira B. , Sarret Catherine
Published: July 2018

To evaluate the potential bone defect in neuromuscular diseases, we conducted a longitudinal study including three groups of patients: 14 Duchenne muscular dystrophies (DMD) and 2 limb-girdle muscular dystrophies (LGMD); 3 Becker muscular dystrophies (BeMD) and 7 spinal muscular atrophies (SMA). Yearly osteodensitometries assessed body composition and bone mineral density (BMD) associated with bone markers and leptin. Along the 7-year study, 107 osteodensitometries showed that bone status evolved to osteopenia in most patients except BeMD. When analyzing the crude values, BMD improved with age in BeMD and SMA but not in DMD/LGMD. The correlation using the Z-scores displayed a decrease in BMD with age in DMD/LGMD for all regions, in SMA at total body less head, whereas BMD increased in BeMD at lumbar spine. As observed in healthy persons, muscular mass and bone tissue were significantly correlated. Glucocorticoids were deleterious on trabecular and cortical bone. Leptin was high in most patients and correlated to fat mass and bone parameters. This study confirms a secondary bone defect in neuromuscular diseases, further confirming the functional relationship between bone and muscle and arguing for regular bone follow-up in patients to prevent fracture risk. Adipose tissue seems to interfere with bone remodeling in neuromuscular diseases.
Identification of Two Novel Mutations in Aminomethyltransferase Gene in Cases of Glycine Encephalopathy
Authors: Lingappa Lokesh , Naushad Shaik , Radha Rama Devi Akella
Published: July 2018

In this study, we report three cases of nonketotic hyperglycinemia (NKHG) diagnosed biochemically and molecularly. Clinical exome analysis in two families revealed two novel mutations in the aminomethyltransferase (AMT) gene, that is, c.14_15insT (p.Ser6LysfsTer22) and c.259–2A > T, both of them adversely affecting the protein. This is the first report of AMT gene mutations in NKHG from India. Prenatal diagnosis in the first family showed an unaffected fetus in the third pregnancy. The role of AMT protein is pivotal for the synthesis of 5,10-methylene tetrahydrofolate, the first metabolite in one-carbon metabolism that regulates DNA synthesis, repair, and methylation.
Ödembehandlung in der Ergotherapie – Schwellung … was nun?
Authors: Bringezu Günther
Published: July 2018

Immer wieder bekommen Patienten entweder Ergo- oder Physiotherapie verordnet. Häufig wäre jedoch beides angezeigt. Beispielsweise bei Patienten mit einem Ödem, das eine manuelle Lymphdrainage erfordern würde, weil die Schwellung eine aktive Therapie noch nicht zulässt. Warum sollten Ergotherapeuten in diesen Fällen ihren Patienten keine Komplexbehandlung ermöglichen?
Novel scintillator-based x-ray spectrometer for use on high repetition laser plasma interaction experiments
Authors: Rusby D. R. , Armstrong C. D. , Brenner C. M. , Clarke R. J. , McKenna P. , Neely D.
Published: July 2018

The characterisation of x-rays from laser-plasma interactions is of utmost importance as they can be useful for both monitoring electron dynamics and also applications in an industrial capacity. A novel versatile scintillator x-ray spectrometer diagnostic that is capable of single shot measurements of x-rays produced from laser-plasma interactions is presented here. Examples of the design and extraction of the temperature of the spectrum of x-rays produced in an intense laser-solid interaction (479 ± 39 keV) and the critical energy from a betatron source (30 ± 10 keV) are discussed. Finally, a simple optimisation process involving adjusting the scintillator thickness for a particular range of input spectra is demonstrated.