bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Fab-fragment of a PAI-1 Inhibiting Antibody Reduces Thrombus Size and Restores Blood Flow in a Rat Model of Arterial Thrombosis
Authors: van Giezen J J J , Wahlund G , Nerme V , Abrahamsson T 
Published: July 2018

SummaryThe effect of PRAP-1, a Fab-fragment of a PAI-1 -inhibiting polyclonal antibody, on thrombus size and arterial blood flow was studied in a rat model of arterial thrombosis. It was shown that exposure of the carotid artery to FeCl3 led to the rapid formation of an occlusive thrombus with a morphology similar to that of arterial thrombi found in humans. Tranexamic acid (50 mg/kg), an inhibitor of fibrinolysis, increased thrombus size (p = 0.014) when given intravenously (i.v.) prior to the FeCl3-exposure. Heparin (1000 U), when given i.v. after FeCl3, did not affect the thrombus size per se, but caused a reduction in the interindividual variation of the size of the thrombus (p <0.05). Thus, heparin was included in all the subsequent experiments. An i.v. infusion of t-PA (1 mg/kg/h), starting before thrombus formation, induced a 3.3 fold increase in the perfusion rate (p = 0.006) and a 67% reduction in the thrombus size (p <0.001). PRAP-1, an inhibitor of rat PAI-1 activity, was given i.v. as a bolus followed by an infusion. Two doses of PRAP-1 were studied (7.5 and 15 mg/kg/h), and the administration of the PAI-1 inhibitor was started 10 min before FeCl3. The lower PRAP-1 dose caused a 3.8 fold increase in perfusion rate (p = 0.036), a 1.44 fold increase in the time to occlusion (p = 0.034), and the thrombus size was decreased by 18% (p = 0.104). The corresponding effects of the high PRAP-1 dose were a 6.5 fold increase in perfusion rate (p <0.001), a 1.6 fold increase in time to occlusion (p = 0.038) and a 32% reduction in thrombus size (p = 0.016). It is concluded that an inhibitor of PAI-1 activity, PRAP-1, caused a moderate decrease in thrombus size and partly restores blood flow in a rat model of arterial thrombosis. This finding suggests a potential role for an inhibitor of PAI-1 in the treatment of arterial thrombosis.
von Willebrand Factor without the A2 Domain Is Resistant to Proteolysis
Authors: Lankhof Hanneke , Damas Conchi , Schiphorst Marion E , Ijsseldijk Martin J W , Bracke Madelon , Furlan Miha , Tsai Han-Mou , de Groot Philip G , Sixma Jan J , Vink Tom 
Published: July 2018

Summaryvon Willebrand factor (vWF) is a complex multimeric plasma glycoprotein, that plays a critical role in the mediation of platelet adhesion to the damaged vascular wall, and functions as a carrier protein for factor VIII. vWF has a domain structure consisting of repeated A, B, C, and D domains. The A1 domain is involved in binding to the platelet receptor glycoprotein (GP) lb, and the A3 domain has a binding site for collagen. A function of the A2 domain has not been described, although point mutations identified in von Willebrand disease (vWD) type 2A patients are localized in this domain. To study the role of the A2 domain a deletion mutant was constructed which lacked the A2 domain, ΔA2- vWF. Previous studies have shown that this approach is a powerful tool to study the function of a domain in a protein since it does not affect the activity of other domains. After expression in baby hamster kidney (BHK) cells, ΔA2-vWF was compared to wild-type (WT) vWF, and to ΔAl-vWF (Lankhof et al., Blood 86: 1035,1995). Ristocetin induced platelet binding was slightly increased but botrocetin induced platelet binding was normal as was binding to heparin and collagen type III. Adhesion studies to surface coated purified ΔA2-vWF or to ΔA2-vWF preincubated on collagen under flow conditions showed no abnormalities. Incubation with normal human plasma showed that ΔA2-vWF like WT-vWF was not sensitive to proteolysis. After addition of urea, WT-vWF becomes sensitive to the protease, indicating that unfolding of the molecule is necessary for exposure of the cleavage site. ΔA2- vWF tested under the same conditions was resistant, indicating that the protease sensitive site is located in the A2 domain.
Plasminogen: An Important Hemostatic Parameter in Septic Patients
Authors: Duboscq Cristina , Quintana Irene , Bassilotta Ethel , Bergonzelli Gabriela E , Porterie Pablo , Sassetti Beatriz , Haedo Ana S , Wainsztein Nestor , Kruithof Egbert K O , Kordich Lucía 
Published: July 2018

SummaryBackground: Previously we observed in some but not all septic patients a low plasma concentration of plasminogen. Objectives: To investigate prospectively whether plasma levels of plasminogen or the ratio of plasminogen to alpha-2-antiplasmin have a prognostic value for survival from sepsis and to study the variation of other hemostatic parameters during septicemia. Patients: The study population consisted of 45 consecutive patients with septicemia, 15 non-septic patients from the same intensive care unit and 30 healthy volunteers. Measurements and Main Results: Plasminogen concentrations were significantly lower (p <0.001) in plasma of septic patients (median 0,62 IU/ml range: 15-1,06) than in plasma of healthy controls (median 1.00 IU/ml, range: 0.75-1.10) or of non-septic intensive care patients (median 00 IU/ml, range: 0.82-1.08). Among the other parameters tested, plasminogen activator inhibitor (PAI-1) antigen concentration and PAI activity were similar in septic and non-septic intensive care patients, but higher than in healthy controls. Concentrations of elastase-alpha-1- protease inhibitor or of thrombin-antithrombin complexes were higher in septic patients than in non-septic intensive care patients or healthy controls. A degraded form of plasminogen of 38 kDa was detected by Western blot analysis in the plasma of septic patients, but not in plasma of non-septic intensive care patients or controls. Plasminogen alone or the ratio of plasminogen to antiplasmin were good markers for survival from septicemia. E.g. for plasminogen at a cut off of 0.65 IU/ml, sensitivity was 90.5% and specificity 66.7%, whereas for the ratio of plasminogen over antiplasmin at a cut off ratio of 0,65 IU/ml, sensitivity was 95.2% and specificity 70.8%. Conclusion: Plasminogen or the ratio of plasminogen to antiplasmin are sensitive markers for survival in patients with septicemia.
Isolation of Human Fibrinogen of High Purity and in High Yield Using Polyethylene Glycol 1000
Authors: Masri Marwan A , Masri Saad A , Boyd Nigel D 
Published: July 2018

SummaryFibrinogen was isolated from human plasma using a polyethylene glycol 1000 fractionation procedure that eliminates problems of denaturation, degradation and contamination encountered with other procedures (1). The technique is simple, rapid, gives a high yield and gram amounts of fibrinogen can be readily obtained.
Platelet Adhesion to Subendothelium - Effect of Shear Rate, Hematocrit and Platelet Count on the Dynamic Equilibrium Between Platelets Adhering to and Detaching from the Surface
Authors: Remuzzi Andrea , Raffaella Languino Lucia , Costantini Vincenzo , Guardabasso Vincenzo , Gartano Giovanni de , Dejana Elisabetta 
Published: July 2018

SummaryThe adherence of human 3H-adenine-labeled platelets to rat subendothelium was quantitated using a rotating probe device. Platelet adhesion increased in relation to the rotation time, reaching a plateau value in about 4-6 min without any further increase. A non-linear fitting analysis of experimental data allowed calculations of initial rate and plateau value of platelet adhesion. Increasing the shear rates (from 35 to 150 sec-1) or the hematocrit (from 10% to 40%), both the adhesion rate and the plateau value were increased. When different platelet concentrations were used the adhesion rate and the plateau calculated increased with platelet concentration. Different plateau values were obtained in the experimental conditions considered. This suggests that the plateau was not reached for the complete occupation of the subendothelial surface by the adherent platelets. Experiments using two different vessels rotated in the same platelet suspension or, viceversa, the same vessel rotated successively in two fresh platelet suspensions, showed that the plateau was not determined by reduced platelet reactivity. Rotating the same vessel first in radiolabeled platelets, until the plateau was reached, and secondly in non labeled platelets, or viceversa, showed that the plateau was indeed a dynamic condition where the number of platelets adhering and detaching reached equilibrium. These observations suggest that the platelet adhesion to subendothelium is the final equilibrium of two platelet fluxes, one adhering to the surface and another detaching from the surface.
A Two-Site, Monoclonal Antibody-Based Immunoassay for von Willebrand Factor -Demonstration that vWF Function Resides in a Conformational Epitope
Authors: Chand S , McCraw A , Hutton R , Tuddenham E G D , Goodall A H 
Published: July 2018

SummaryTwo monoclonal antibodies (RFF-VIII: R/l and RFF-VIII:R/ 2) which recognise the same epitope on von Willebrand factor (vWF) have been used in a simple, two-site, solid-phase immunoradiometric (IRMA) or enzyme-linked assay (ELISA) to analyse vWF in plasma from normal individuals and from patients with von Willebrand’s disease (vWD). Results obtained confirm our previous findings (using RFF-VIII :R/2 in a one-site, fluid-phase IRMA) that the MAbs detect the presence of an epitope on the vWF molecule that reflects its function. This epitope is involved in vWF binding to the GPIb protein on platelets. It is reduced in all types of vWD, including type II (or variant) vWD. It is present in normal plasma, in vWF released from normal platelets and from cultured umbilical cord vein endothelial cells. The epitope is, however, found to be reduced in serum. Studies on SDS-treated vWF prove that this GPIb-binding site is dependent on the conformation of the vWF multimers.
Platelet Activation Induced by a Human Neuroblastoma Tumor Cell Line Is Reduced by Prior Administration of Ticlopidine
Authors: Bastida Eva , Escolar G , Almirall L , Ordinas A 
Published: July 2018

SummaryTiclopidine (250 mg twice daily) was administered to human volunteers for seven days and the response of their heparinized platelet-rich plasma to SKNMC (ADP-dependent) human neuroblastoma cells was examined. The first wave of platelet aggregation, characteristic of ADP-dependent human tumor cell lines, was completely abolished but was replaced by a lag period prior to the onset of aggregation. In the Baumgartner perfusion apparatus there was a marked inhibition in the thrombus generated by the presence of SKNMC cells with a concomitant increase in the percentage of surface coverage. These results suggest that the administration of ticlopidine could be useful to prevent some of the steps of metastatic dissemination in which activated platelets may play a role.
International Collaborative Study for the Establishment of the Second International Reference Preparation of Plasmin
Authors: Gaffney P J , Mussett M V 
Published: July 2018

SummaryAn international collaborative study involving seven laboratories was undertaken to assess the suitability of a freeze- dried preparation of human plasmin to replace the current International Reference Preparation (IRP) for plasmin. Chromogenic and fibrinolytic assays were used by all participating laboratories to assess the potencies of the Proposed International Reference Preparation (PIRP) and two other freeze-dried plasmins, one of human and one of porcine originThe data suggest that the PIRP is a more suitable standard for plasmin than the IRP in that the former binds to fibrin whereas only 50% of the latter binds. The PIRP compared well to other plasmin preparations and the potency assays were independent of the assay procedure and substrate used. Degradation studies indicated that the PIRP was far more stable than the glycerol solution of the IRP, surviving for 12 months at 37° C with no significant loss in either amidolytic or fibrinolytic activity. The International Committee for Thrombosis and Haemostasis (Bergamo, 1982) has recommended the use of this material as a standard and it has been established by the Expert Committee on Biological Standardization of the World Health Organization as the second International Reference Preparation for Plasmin with a defined potency of 10 International Units of Plasmin per ampoule.
The Glymphatic System: A Review
Authors: Oliveira Louise , Figueiredo Eberval , Peres Carlos 
Published: July 2018

AbstractThe brain represents ∼ 2% of the adult body mass; conversely, it is responsible for 20% to 25% of the glucose and 20% of the oxygen consumption, receiving 15% of the cardiac output. This substantial metabolic rate is associated with a significant production of biological debris, which is potentially toxic. Therefore, a complex and efficient clearance system is required to prevent the accumulation of byproducts and ensure optimal function. However, until today, there is little knowledge about this topic. The glymphatic system, also known as perivascular pathway, is a recently described glial-dependent network that is responsible for the clearance of metabolites from the central nervous system (CNS), playing a role equivalent to the one played by the lymphatic vessels present in other organs. Studies have demonstrated that the glymphatic pathway has a paramount role in protein homeostasis, and that the malfunction of this system may be related to the development of neurodegenerative disorders such as Alzheimer disease and normal pressure hydrocephalus. They also showed that body posture, exercise and the state of consciousness influence the glymphatic transport. In this context, the understanding of this clearance system could not only clarify the pathophysiology of several diseases, but also contribute to future therapeutic interventions. In the present article, we will evaluate the glymphatic pathway, focusing on the factors that regulate its flow, as well as on its role in CNS physiology and in disease initiation and progression, including dementia, hydrocephalus, glaucoma and traumatic brain injury. Ultimately, this review also aims to encourage further research on novel therapeutic targets.
Clinical Decision Support Improves Adherence to Pediatric Antimicrobial Renal Dosing Guidelines
Authors: Quach Andrew , Ateya Mohammad , Zimmerman Christopher 
Published: July 2018

Background Antimicrobial drug dosage selection requires consideration of patient demographics, renal function, and indication(s) of use. We developed a strategy that employed upfront passive dose-guidance clinical decision support (CDS) in addition to noninterruptive/interruptive maximum dose warnings to guide providers to order renally appropriate antimicrobial drug therapy.
Objectives Our objective was to assess the impact of passive dose-guidance CDS, along with a successive CDS strategy that provided renal dosing assistance at multiple points throughout order entry, on provider adherence to pediatric antimicrobial dosing guidelines.
Methods A single-center, observational, retrospective cohort study at an academic pediatric hospital. The study compared the proportion of orders adherent to the institutional guidelines across three time points: a historical control (October 2014 to March 2015), phase I implementation (March 2015 to May 2015), and phase II implementation (May 2015 to October 2015).
Results The proportion of adherent orders with respect to dose and frequency was 74% in the control period, 76% (odds ratio [OR] = 1.11; 95% confidence interval [CI], 0.76–1.16, p = 0.6) in phase I of the study, and increased to 81% (OR = 1.54; 95% CI, 1.16–2.03, p = 0.003) in phase II of the study.
Conclusion Provider adherence to institutional antimicrobial dosing guidelines improved following the implementation of a successive CDS combining passive and noninterruptive/interruptive approaches. This study displays the value of designing CDS that occurs at multiple points within ordering workflow and minimizes intrusiveness. Our CDS strategy can be considered for implementation by other institutions using similar electronic health record systems.
Mediated electrochemical synthesis of metal nanoparticles
Authors: Yanilkin Vitaliy V. , Nasretdinova Gul’naz R. , Kokorekin Vladimir A. 
Published: July 2018

The review integrates and analyzes data of original studies on the mediated electrosynthesis of metal nanoparticles — a new efficient and environmentally attractive process for obtaining these particles in the solution bulk. The general principles and specific features of electrosynthesis of metal nanoparticles by mediated electroreduction of metal ions and complexes are considered. The discussed issues include the role of cyclic voltammetry in the development of this method, the method efficiency, some aspects of selection of mediators, and aggregation, stabilization and catalytic activity of the metal nanoparticles thus obtained. Analysis of the results of mediated electrosynthesis of Pd, Ag, PdAg, Au, Pt and Cu nanoparticles stabilized by various compounds and mediated electrogeneration of highly active metal particles is used as basic data for discussion.The bibliography includes 247 references.
Electrical water bath stunning for Halal poultry meat production: animal welfare issues and compatibility with the Halal rules.
Authors: Fuseini A. , Teye M. , Wotton S. B. , Lines J. A. , Knowles T. G. 
Published: July 2018

Abstract
The use of electrical water bath stunning for the 'humane' slaughter of poultry has drawn criticism from some animal welfare research scientists and animal welfare organizations throughout the world. During water bath stunning, birds are shackled and inverted prior to entry into an electrified water bath, current is passed from the head, through the body and legs to earth via stainless steel shackles. From a Halal perspective, the rules stipulate that the welfare of animals is protected at all times and that animals must be alive (not conscious) at the point of neck-cutting. Some Muslim authorities have therefore questioned the suitability of water bath stunning for Halal meat production due to its negative impact on animal welfare and the possibility of some birds dying prior to exsanguination. This paper examines possible welfare compromises during water bath stunning and how these may affect compatibility with the rules of Halal meat production.
Electric field determination in air plasmas from intensity ratio of nitrogen spectral bands: II. Reduction of the uncertainty and state-of-the-art model
Authors: Bílek Petr , Obrusník Adam , Hoder Tomáš , Šimek Milan , Bonaventura Zdeněk 
Published: July 2018

Abstract
An established and widely used method for remote electric field determination is based on the ratio of the spectral band intensities of the first negative and second positive spectral systems of molecular nitrogen which does, however, require theoretically or experimentally obtained dependence

R
(
E

/

N
)

. The aim of this work is to reduce the overall uncertainty in the theoretical dependence

R
(
E

/

N
)

calculated in part I of this work. We present an in-depth review of the kinetic and cross section data that are available in literature for the most influential processes. By tracking the historical evolution of the kinetic data, their cross-validation by independent authors and by taking into account advances in the experimental methods, we separate datasets that have not been rendered inaccurate by later works. By doing so, we reduce the uncertainty of the theoretical

R
(
E

/

N
)

dependence and propose corresponding confidence band to be used by scientific community.
Artificial intelligence–derived 3-Way Concentration-dependent Antagonism of Gatifloxacin, Pyrazinamide, and Rifampicin During Treatment of Pulmonary Tuberculosis
Authors: Pasipanodya Jotam G , Smythe Wynand , Merle Corinne S , Olliaro Piero L , Deshpande Devyani , Magombedze Gesham , McIlleron Helen , Gumbo Tawanda 
Published: July 2018

AbstractBackgroundIn the experimental arm of the OFLOTUB trial, gatifloxacin replaced ethambutol in the standard 4-month regimen for drug-susceptible pulmonary tuberculosis. The study included a nested pharmacokinetic (PK) study. We sought to determine if PK variability played a role in patient outcomes.MethodsPatients recruited in the trial were followed for 24 months, and relapse ascertained using spoligotyping. Blood was drawn for drug concentrations on 2 separate days during the first 2 months of therapy, and compartmental PK analyses was performed. Failure to attain sustained sputum culture conversion at the end of treatment, relapse, or death during follow-up defined therapy failure. In addition to standard statistical analyses, we utilized an ensemble of machine-learning methods to identify patterns and predictors of therapy failure from among 27 clinical and laboratory features.ResultsOf 126 patients, 95 (75%) had favorable outcomes and 19 (15%) failed therapy, relapsed, or died. Pyrazinamide and rifampicin peak concentrations and area under the concentration-time curves (AUCs) were ranked higher (more important) than gatifloxacin AUCs. The distribution of individual drug concentrations and their ranking varied significantly between South African and West African trial sites; however, drug concentrations still accounted for 31% and 75% of variance of outcomes, respectively. We identified a 3-way antagonistic interaction of pyrazinamide, gatifloxacin, and rifampicin concentrations. These negative interactions disappeared if rifampicin peak concentration was above 7 mg/L.ConclusionsConcentration-dependent antagonism contributed to death, relapse, and therapy failure but was abrogated by high rifampicin concentrations. Therefore, increasing both rifampin and gatifloxacin doses could improve outcomes.Clinical Trials RegistrationNCT002216385.
The association of calcium oxalate deposition in kidney allografts with graft and patient survival
Authors: Palsson Ragnar , Chandraker Anil K , Curhan Gary C , Rennke Helmut G , McMahon Gearoid M , Waikar Sushrut S 
Published: July 2018

Abstract

Background
Whether calcium oxalate (CaOx) deposition in kidney allografts following transplantation (Tx) adversely affects patient outcomes is uncertain, as are its associated risk factors.

Methods
We performed a retrospective cohort study of patients who had kidney allograft biopsies performed within 3 months of Tx at Brigham and Women’s Hospital and examined the association of CaOx deposition with the composite outcome of death or graft failure within 5 years.

Results
Biopsies from 67 of 346 patients (19.4%) had CaOx deposition. In a multivariable logistic regression model, higher serum creatinine [odds ratio (OR) = 1.28 per mg/dL, 95% confidence interval (CI) 1.15–1.43], longer time on dialysis (OR = 1.11 per additional year, 95% CI 1.01–1.23) and diabetes (OR = 2.26, 95% CI 1.09–4.66) were found to be independently associated with CaOx deposition. CaOx deposition was strongly associated with delayed graft function (DGF; OR = 11.31, 95% CI 5.97–21.40), and with increased hazard of the composite outcome after adjusting for black recipient race, donor type, time on dialysis before Tx, diabetes and borderline or acute rejection (hazard ratio 1.90, 95% CI 1.13–3.20).

Conclusions
CaOx deposition is common in allografts with poor function and portends worse outcomes up to 5 years after Tx. The extent to which CaOx deposition may contribute to versus result from DGF, however, cannot be determined based on our retrospective and observational data. Future studies should examine whether reducing plasma and urine oxalate prevents CaOx deposition in the newly transplanted kidney and whether this has an effect on clinical outcomes.