Characterization of Antithrombotic Effects of Antiplatelet Drugs and Anticoagulants in Experimental Thrombosis

1979 ◽  
Author(s):  
R. Zimmermann ◽  
C. Zeltsch ◽  
L. Zieboll ◽  
D. Lange ◽  
A. Petri

Drugs with possible antithrombotic properties have to be investigated in models for inducing experimentalthrombosis. Some of the well known antiplatelet drugs and anticoagulants were studied in the venous (4 models, 370 experiments) and arterial system (2 models,200 experiments). Thrombi were produced by different endothelial lesions, by stasis and hypercoagulability or a combination of these thrombogenic factors. In the venous system heparin reduced the thrombus size in comparison with controls by 98% (significantly, p<0.05 = s), phenprocoumon 91% (s), acetylsalicylic acid (ASA) 30%, ASA and dipyridamole (DIPY) 69%, carbenicillin 54%. In the arterial system a minor effect could be seen: Carbenicillin 72 %(s), ASA and DIPY 36%, ASA 8%, heparin 52%, phenprocoumon 17 %. Dependent on the experimental conditions ASA may demonstrate venous thrombus size reductions by 0, 6 or 30% and heparin by 33,98,81,68 or 88%, respectively. Comment: A drug may demonstrate an effect in one model but not necessarily in another one. The antithrombotic efficacy of new substances has to be investigated in models characterized by their thrombogenic conditions and thrombus structure and compared with that of well known antithrombotic substances.

Author(s):  
Layla T. Yassen ◽  
Saad L. Hamed ◽  
Ban O. Abdulsattar ◽  
Asmaa A. Hussein

The aim of this study was purification and characterization of CTX-M-15 as a medically important enzyme from locally Klebsiella pneumoniae isolate, CTX-M-15 enzyme was subjected to two purification steps including: precipitation with 80% ammonium sulfate saturation and gel filtration chromatography by using Sepharose -6B column. Specific activity of purified enzyme has been increment up to 21.9 IU/mg with 7.3 purification folds and 69% enzyme recapture. Characterization study of purified enzyme demonstrated that the M.wt. of CTX-M-15 produced by K. pneumoniae was almost 32.2 kDa. The maximal enzyme activity at (pH 7.0), and enzyme settled at pH 6-7. The enzyme also revealed a full activity at a range of temperature between 30-37oC. Enzyme activity has inhibited powerfully in the existence of EDTA and calcium chloride, when added separately at a constant concentration. Moreover, copper chloride, and ferric chloride also caused a strong inhibition to the enzyme activity while cloxacillin showed a minor effect on enzyme activity.


1940 ◽  
Vol 24 (2) ◽  
pp. 169-188 ◽  
Author(s):  
Anthony J. Glazko ◽  
John H. Ferguson

1. A new technique for studying the progressive inactivation of thrombin is described. 2. Thrombin inactivation follows the kinetics of a first order reaction. 3. The rate constant of the inactivation reaction increases with temperature and pH (5.0 → 10.0), and also with the presence of crystalline trypsin, or serum. The rate varies for different thrombin preparations, even under the same experimental conditions. 4. The temperature characteristics of the reaction indicate that thrombin is associated with protein. 5. Thrombin preparations are most stable at pH 4 to 5, even when trypsin or serum is added. 6. The progressive inactivation is believed to be due to two mechanisms: (1) a major effect, thought to be the action of a "serum-tryptase," which is usually present in the thrombin preparations, and (2) a minor effect, probably attributable to denaturation of thrombin-protein. 7. Sources of the thrombinolytic factor (serum-tryptase) and its implications in the general theory and practical problems of blood coagulation and antithrombic action are briefly discussed.


1995 ◽  
Vol 15 (3) ◽  
pp. 1144-1153 ◽  
Author(s):  
H Sheng ◽  
Z Hou ◽  
T Schierer ◽  
D L Dobbs ◽  
E Henderson

Telomeric DNA of Tetrahymena thermophila consists of a long stretch of (TTGGGG)n double-stranded repeats with a single-stranded (TTGGGG)2 3' overhang at the end of the chromosome. We have identified and characterized a protein that specifically binds to a synthetic telomeric substrate consisting of duplex DNA and the 3' telomeric repeat overhang. This protein is called TEP (telomere end-binding protein). A change from G to A in the third position of the TTGGGG overhang repeat converts the substrate to a human telomere analog and reduces the binding affinity approximately threefold. Changing two G's to C's in the TTGGGG repeats totally abolishes binding. However, permutation of the Tetrahymena repeat sequence has only a minor effect on binding. A duplex structure adjacent to the 3' overhang is required for binding, although the duplex need not contain telomeric repeats. TEP does not bind to G-quartet DNA, which is formed by many G-rich sequences. TEP has a greatly reduced affinity for RNA substrates. The copy number of TEP is at least 2 x 10(4) per cell, and it is present under different conditions of cell growth and development, although its level varies. UV cross-linking experiments show that TEP has an apparent molecular mass of approximately 65 kDa. Unlike other telomere end-binding proteins, TEP is sensitive to high salt concentrations.


2006 ◽  
Vol 6 (1) ◽  
pp. 1-9
Author(s):  
V. Miska ◽  
J.H.J.M. van der Graaf ◽  
J. de Koning

Nowadays filtration processes are still monitored with conventional analyses like turbidity measurements and, in case of flocculation–filtration, with phosphorus analyses. Turbidity measurements have the disadvantage that breakthrough of small flocs cannot be displayed, because of the blindness regarding changes in the mass distributions. Additional particle volume distributions calculated from particle size distributions (PSDs) would provide a better assessment of filtration performance. Lab-scale experiments have been executed on a flocculation–filtration column fed with effluent from WWTP Beverwijk in The Netherlands. Besides particle counting at various sampling points, the effect of sample dilution on the accuracy of PSD measurements has been reflected. It was found that the dilution has a minor effect on PSD of low turbidity samples such as process filtrate. The correlation between total particle counts, total particle volume (TPV) and total particle surface is not high but is at least better for diluted measurements of particles in the range 2–10 μm. Furthermore, possible relations between floc-bound phosphorus and TPV removal had been investigated. A good correlation coefficient is found for TPV removal versus floc-bound phosphorus removal for the experiments with polyaluminiumchloride and the experiments with single denitrifying and blank filtration.


2001 ◽  
Vol 66 (9) ◽  
pp. 1315-1340 ◽  
Author(s):  
Vladimir J. Balcar ◽  
Akiko Takamoto ◽  
Yukio Yoneda

The review highlights the landmark studies leading from the discovery and initial characterization of the Na+-dependent "high affinity" uptake in the mammalian brain to the cloning of individual transporters and the subsequent expansion of the field into the realm of molecular biology. When the data and hypotheses from 1970's are confronted with the recent developments in the field, we can conclude that the suggestions made nearly thirty years ago were essentially correct: the uptake, mediated by an active transport into neurons and glial cells, serves to control the extracellular concentrations of L-glutamate and prevents the neurotoxicity. The modern techniques of molecular biology may have provided additional data on the nature and location of the transporters but the classical neurochemical approach, using structural analogues of glutamate designed as specific inhibitors or substrates for glutamate transport, has been crucial for the investigations of particular roles that glutamate transport might play in health and disease. Analysis of recent structure/activity data presented in this review has yielded a novel insight into the pharmacological characteristics of L-glutamate transport, suggesting existence of additional heterogeneity in the system, beyond that so far discovered by molecular genetics. More compounds that specifically interact with individual glutamate transporters are urgently needed for more detailed investigations of neurochemical characteristics of glutamatergic transport and its integration into the glutamatergic synapses in the central nervous system. A review with 162 references.


Water ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 1757
Author(s):  
Yesica Vicente-Martínez ◽  
Manuel Caravaca ◽  
Antonio Soto-Meca ◽  
Miguel Ángel Martín-Pereira ◽  
María del Carmen García-Onsurbe

This paper presents a novel procedure for the treatment of contaminated water with high concentrations of nitrates, which are considered as one of the main causes of the eutrophication phenomena. For this purpose, magnetic nanoparticles functionalized with silver (Fe3O4@AgNPs) were synthesized and used as an adsorbent of nitrates. Experimental conditions, including the pH, adsorbent and adsorbate dose, temperature and contact time, were analyzed to obtain the highest adsorption efficiency for different concentration of nitrates in water. A maximum removal efficiency of 100% was reached for 2, 5, 10 and 50 mg/L of nitrate at pH = 5, room temperature, and 50, 100, 250 and 500 µL of Fe3O4@AgNPs, respectively. The characterization of the adsorbent, before and after adsorption, was performed by energy dispersive X-ray spectroscopy, scanning electron microscopy, Brunauer-Emmett-Teller analysis and Fourier-transform infrared spectroscopy. Nitrates can be desorbed, and the adsorbent can be reused using 500 µL of NaOH solution 0.01 M, remaining unchanged for the first three cycles, and exhibiting 90% adsorption efficiency after three regenerations. A deep study on equilibrium isotherms reveals a pH-dependent behavior, characterized by Langmuir and Freundlich models at pH = 5 and pH = 1, respectively. Thermodynamic studies were consistent with physicochemical adsorption for all experiments but showed a change from endothermic to exothermic behavior as the temperature increases. Interference studies of other ions commonly present in water were carried out, enabling this procedure as very selective for nitrate ions. In addition, the method was applied to real samples of seawater, showing its ability to eliminate the total nitrate content in eutrophized waters.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonathan Brassac ◽  
Quddoos H. Muqaddasi ◽  
Jörg Plieske ◽  
Martin W. Ganal ◽  
Marion S. Röder

AbstractTotal spikelet number per spike (TSN) is a major component of spike architecture in wheat (Triticumaestivum L.). A major and consistent quantitative trait locus (QTL) was discovered for TSN in a doubled haploid spring wheat population grown in the field over 4 years. The QTL on chromosome 7B explained up to 20.5% of phenotypic variance. In its physical interval (7B: 6.37–21.67 Mb), the gene FLOWERINGLOCUST (FT-B1) emerged as candidate for the observed effect. In one of the parental lines, FT-B1 carried a non-synonymous substitution on position 19 of the coding sequence. This mutation modifying an aspartic acid (D) into a histidine (H) occurred in a highly conserved position. The mutation was observed with a frequency of ca. 68% in a set of 135 hexaploid wheat varieties and landraces, while it was not found in other plant species. FT-B1 only showed a minor effect on heading and flowering time (FT) which were dominated by a major QTL on chromosome 5A caused by segregation of the vernalization gene VRN-A1. Individuals carrying the FT-B1 allele with amino acid histidine had, on average, a higher number of spikelets (15.1) than individuals with the aspartic acid allele (14.3) independent of their VRN-A1 allele. We show that the effect of TSN is not mainly related to flowering time; however, the duration of pre-anthesis phases may play a major role.


Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 382
Author(s):  
Camelia-Maria Toma ◽  
Silvia Imre ◽  
Camil-Eugen Vari ◽  
Daniela-Lucia Muntean ◽  
Amelia Tero-Vescan

Plasma protein binding plays a critical role in drug therapy, being a key part in the characterization of any compound. Among other methods, this process is largely studied by ultrafiltration based on its advantages. However, the method also has some limitations that could negatively influence the experimental results. The aim of this study was to underline key aspects regarding the limitations of the ultrafiltration method, and the potential ways to overcome them. The main limitations are given by the non-specific binding of the substances, the effect of the volume ratio obtained, and the need of a rigorous control of the experimental conditions, especially pH and temperature. This review presents a variety of methods that can hypothetically reduce the limitations, and concludes that ultrafiltration remains a reliable method for the study of protein binding. However, the methodology of the study should be carefully chosen.


Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 9
Author(s):  
Kristina Ritter ◽  
Jan Christian Sodenkamp ◽  
Alexandra Hölscher ◽  
Jochen Behrends ◽  
Christoph Hölscher

Anti-inflammatory treatment of chronic inflammatory diseases often increases susceptibility to infectious diseases such as tuberculosis (TB). Since numerous chronic inflammatory and autoimmune diseases are mediated by interleukin (IL)-6-induced T helper (TH) 17 cells, a TH17-directed anti-inflammatory therapy may be preferable to an IL-12-dependent TH1 inhibition in order to avoid reactivation of latent infections. To assess, however, the risk of inhibition of IL-6-dependent TH17-mediated inflammation, we examined the TH17 immune response and the course of experimental TB in IL-6- and T-cell-specific gp130-deficient mice. Our study revealed that the absence of IL-6 or gp130 on T cells has only a minor effect on the development of antigen-specific TH1 and TH17 cells. Importantly, these gene-deficient mice were as capable as wild type mice to control mycobacterial infection. Together, in contrast to its key function for TH17 development in other inflammatory diseases, IL-6 plays an inferior role for the generation of TH17 immune responses during experimental TB.


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