Effect of Immobilized Antithrombin III on the Thromboresistance of Polycarbonate Urethane.
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ABSTRACT:
SUBMITTER: Lukas K
PROVIDER: S-EPMC5506919 | biostudies-other | 2017 Mar
REPOSITORIES: biostudies-other
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Project description:PurposeSince the treatment options for symptomatic total meniscectomy patients are still limited, an anatomically shaped, polycarbonate urethane (PCU), total meniscus replacement was developed. This study evaluates the in vivo performance of the implant in a goat model, with a specific focus on the implant location in the joint, geometrical integrity of the implant and the effect of the implant on synovial membrane and articular cartilage histopathological condition.MethodsThe right medial meniscus of seven Saanen goats was replaced by the implant. Sham surgery (transection of the MCL, arthrotomy and MCL suturing) was performed in six animals. The contralateral knee joints of both groups served as control groups. After three months follow-up the following aspects of implant performance were evaluated: implant position, implant deformation and the histopathological condition of the synovium and cartilage.ResultsImplant geometry was well maintained during the three month implantation period. No signs of PCU wear were found and the implant did not induce an inflammatory response in the knee joint. In all animals, implant fixation was compromised due to suture breakage, wear or elongation, likely causing the increase in extrusion observed in the implant group. Both the femoral cartilage and tibial cartilage in direct contact with the implant showed increased damage compared to the sham and sham-control groups.ConclusionThis study demonstrates that the novel, anatomically shaped PCU total meniscal replacement is biocompatible and resistant to three months of physiological loading. Failure of the fixation sutures may have increased implant mobility, which probably induced implant extrusion and potentially stimulated cartilage degeneration. Evidently, redesigning the fixation method is necessary. Future animal studies should evaluate the improved fixation method and compare implant performance to current treatment standards, such as allografts.
| S-EPMC4507942 | biostudies-literature
Project description:The inactivation of thrombin by heat and by its physiological inhibitor, antithrombin-III, shows quite different dependence on heparin concentration. Heparin at 250 microgram/ml protects thrombin against heat inactivation, and thrombin behaves heterogeneously in this reaction. In the absence of heparin, the thermodynamic activation parameters change with temperature (deltaH+ = 733 kJ/mol and 210 kJ/mol at 50 and 58 degrees C respectively). When heparin is present, heat inactivation of the protected thrombin species proceeds with deltaH+ = 88 kJ/mol and is independent of temperature in the same range. On the other hand, heparin at 0.125-2.5 microgram/ml accelerates the thrombin-antithrombin-III reaction. Thrombin does not show heterogeneity in this reaction and the time courses at any heparin concentration and any temperature between 0 and 37 degrees C appear to follow first-order kinetics. Activation enthalpy is independent of heparin concentration or temperature, deltaH+ = 82-101 kJ/mol, varying slightly with antithrombin-III concentration and thrombin specific activity. Heparin seems to exert its effect by increasing activation entropy. On the basis of these data we suggest a mechanism of action of heparin in the thrombin-antithrombin-III reaction which accounts for all the important features of the latter and seems to unify the different hypotheses that have been advanced.
| S-EPMC1185853 | biostudies-other
Project description:Background: The evaluation of treatment response to antidepressant therapy commonly depends on neuropsychologic assessments, as there are currently no suitable biomarkers. Previous research has identified a panel of increased proteins in patients with major depressive disorder (MDD), including antithrombin III (ATIII), as potential biomarkers of depression. Methods: A total of 90 MDD patients were recruited. Of these, 74 patients received occipital repetitive transcranial magnetic stimulation (rTMS) as individualized, standard, or sham treatment for 5 days, and underwent the complete procedure, including clinical assessments, blood collection, and protein measurement. Results: After treatment, ATIII was significantly decreased in both the individualized and standard groups (both p < 0.001) relative to the sham group. In the individualized group, reduction in ATIII was associated with improvements in several neuropsychological assessments. Furthermore, ATIII at baseline in the standard group and after individualized rTMS showed good performance for evaluating or predicting the response to five-day treatment (AUC = 0.771, 95% CI, 0.571-0.971; AUC = 0.875, 95% CI, 0.714-1.000, respectively) and remission at follow-up (AUC = 0.736, 95% CI, 0.529-0.943; AUC = 0.828, 95% CI, 0.656-1.000, respectively). Lastly, both baseline ATIII and change in ATIII showed good predictive value for the 24-item Hamilton Depression Rating Scale at follow-up (p = 0.024 and 0.023, respectively). Conclusion: Our study revealed a reduction in ATIII after occipital rTMS in MDD patients and a relationship between change in ATIII and therapeutic response. Taken together, these findings provide evidence for the potential of ATIII as a biomarker for the evaluation and prediction of antidepressive effects.
| S-EPMC8580946 | biostudies-literature
Project description:Pelvic organ prolapse (POP) is the herniation of the pelvic organs into the vaginal space, resulting in the feeling of a bulge and organ dysfunction. Treatment of POP often involves repositioning the organs using a polypropylene mesh, which has recently been found to have relatively high rates of complications. Complications have been shown to be related to stiffness mismatches between the vagina and polypropylene, and unstable knit patterns resulting in mesh deformations with mechanical loading. To overcome these limitations, we have three-dimensional (3D)-printed a porous, monofilament membrane composed of relatively soft polycarbonate-urethane (PCU) with a stable geometry. PCU was chosen for its tunable properties as it is comprised of both hard and soft segments. The bulk mechanical properties of PCU were first characterized by testing dogbone samples, demonstrating the dependence of PCU mechanical properties on its measurement environment and the effect of print pathing. The pore dimensions and load-relative elongation response of the 3D-printed PCU membranes under monotonic tensile loading were then characterized. Finally, a fatigue study was performed on the 3D-printed membrane to evaluate durability, showing a similar fatigue resistance with a commercial synthetic mesh and hence its potential as a replacement.
| S-EPMC10259470 | biostudies-literature
Project description:The kinetics of inhibition of human and bovine alpha-thrombin and human factor Xa by antithrombin III were examined under pseudo-first-order conditions as a function of the concentration of pentosan polysulphate [a fully sulphated (beta 1-4)-linked D-xylopyranose with a single laterally positioned 4-O-methyl-alpha-D-glucuronic acid]. Double-reciprocal plots of the observed first-order rate constant against concentration of pentosan polysulphate gave straight lines, intercepts on the axes giving values for maximum increase in second-order rate constant (by calculation) and apparent dissociation constant. These values were: for human alpha-thrombin 1.52 X 10(7) M-1 . min-1 and 3.6 microM respectively, for bovine alpha-thrombin 6.56 X 10(6) M-1 . min-1 and 0.16 microM and for factor Xa 6.86 X 106 M-1 . min-1 and 20 microM. In the presence of pentosan polysulphate the dissociation constant for the initial complex of antithrombin III and thrombin was shown to be reduced from approx. 2 X 10(-3) M to 61 X 10(-6) M without apparent change in the limiting rate constant of 750 min-1. An oligosaccharide (primarily 8-10 saccharide units) prepared from heparin and with high affinity for antithrombin III but low potency in the thrombin-antithrombin III interaction did not diminish the rate of interaction catalysed by pentosan polysulphate. The catalysis was shown to be due to a weak electrostatic interaction, since it was completely reversed by concentrations of NaCl greater than 0.3 M. It is concluded that the mechanism is independent of the heparin high-affinity binding site on antithrombin III and is probably due to binding of the high-charge-density polysaccharide to the proteinase. It is calculated that the acceleration in rate achieved, although lower than that of heparin, approaches that required to be of physiological significance and may be of importance in the anticoagulation role of antithrombin III at sites of high charge density which may occur in vivo.
| S-EPMC1144217 | biostudies-other
Project description:Analysis of pollution of the ocean plastics is presently being extensively carried out but special attention should be direct to matters. It is widely believed that plastic dose not decompose in the ocean. Certain contaminants, bisphenol-A (BPA) that serves the material for polycarbonate (PC) and epoxy resin (EPX) both of which may possibly be elute or degrade from commercial products, have often been detected in rivers, lakes and oceans. To clarify in detail the extend of this impact of this situation, purified PC (BPA free) was decomposed at temperatures range 50-230 °C. PC was seen to start decomposing at 50 °C over a 3 day period to generated 11 μg kg-1 BPA. Based on the rate constants of BPA, the activation energy was calculated 42.0 kJ mol-1. Since this value is almost same as the EPX and polystyrene (PS) of each decomposition. Based on the PC decomposition rate and the actual BPA value in the deep sea, the 280 million metric tons (MT) BPA in the world ocean was estimated. Unlike plastics, BPA shows endocrine disrupting in fish. It should thus be considered that degraded PC and EPX pose a serious threat to the marine ecosystem, directly.
| S-EPMC10568682 | biostudies-literature
Project description:Confluent passage-2 HUVECs in Falcon T12.5 flasks grown in the presence or absence of VEGF-165 (10ng/mL) (R&D systems) were treated with human native, cleaved or latent antithrombins (20 5g/mL) for 24 hours in 3 mL M-199 with 2% heat-inactivated FBS and antibiotics. Following this treatment, total RNA was extracted from the cells by the Trizol method (Invitrogen). The total RNA was subjected to one cycle of linear RNA amplification using the MessageAmp aRNA kit according to the manufacturers instructions (Ambion, Austin, TX). The quality of the antisense RNA was verified on a denaturing agarose gel. Only samples showing a distribution of sizes from 250-5500 nt with a peak centered at 1000-1500 nt were used to generate the test cDNA samples for the subsequent array experiments. DNA labeling and hybridizations were performed essentially as described (Pollack et al., 1999, Nat. Genet.), with slight modifications. Briefly, the test endothelial cell antisense RNA samples together with Universal Human Reference RNA (Stratagene, Cedar Creek, TX) were used to generate Cy3/Cy5 (Amersham Biosciences) labeled cDNA for array hybridization on the Stanford 43K human cDNA microarray (www.microarray.org/sfgf). The Stanford microarray used in this study consists of 18,416 named genes with UniGene symbol, 4,145 ESTs with known function, 19,365 ESTs with unknown function and ~1,000 repeated spots as internal controls. Hybridized arrays were scanned on a GenePix 4000B scanner (Axon Instruments), and fluorescence ratios (test/reference) calculated using the Stanford Microarray Database software (available at http://genomewww5. A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Keywords: Computed
2005-12-31 | GSE3956 | GEO
Project description:Antithrombin III (ATIII) is a key antiproteinase involved in blood coagulation. Previous investigations have shown that ATIII is degraded by Staphylococcus aureus V8 protease, leading to release of heparin binding fragments derived from its D helix. As heparin binding and antimicrobial activity of peptides frequently overlap, we here set out to explore possible antibacterial effects of intact and degraded ATIII. In contrast to intact ATIII, the results showed that extensive degradation of the molecule yielded fragments with antimicrobial activity. Correspondingly, the heparin-binding, helix D-derived, peptide FFFAKLNCRLYRKANKSSKLV (FFF21) of human ATIII, was found to be antimicrobial against particularly the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Fluorescence microscopy and electron microscopy studies demonstrated that FFF21 binds to and permeabilizes bacterial membranes. Analogously, FFF21 was found to induce membrane leakage of model anionic liposomes. In vivo, FFF21 significantly reduced P. aeruginosa infection in mice. Additionally, FFF21 displayed anti-endotoxic effects in vitro. Taken together, our results suggest novel roles for ATIII-derived peptide fragments in host defense.
| S-EPMC4207992 | biostudies-literature
Project description:The present study deals with the conformation in solution of two heparin octasaccharides containing the pentasaccharide sequence GlcN(NAc,6S)-GlcA-GlcN(NS,3,6S)-IdoA(2S)-GlcN(NS,6S) [AGA*IA; where GlcN(NAc,6S) is N-acetylated, 6-O-sulfated alpha-D-glucosamine, GlcN(NS,3,6S) is N,3,6-O-trisulfated alpha-D-glucosamine and IdoA(2S) is 2-O-sulfated IdoA (alpha-L-iduronic acid)] located at different positions in the heparin chain and focuses on establishing geometries of IdoA residues (IdoA(2S) and IdoA) both inside and outside the AGA*IA sequence. AGA*IA constitutes the active site for AT (antithrombin) and is essential for the expression of high anticoagulant and antithrombotic activities. Analysis of NMR parameters [NOEs (nuclear Overhauser effects), transferred NOEs and coupling constants] for the two octasaccharides indicated that between the 1C4 and 2S0 conformations present in dynamic equilibrium in the free state for the IdoA(2S) residue within AGA*IA, AT selects the 2S0 form, as previously shown [Hricovini, Guerrini, Bisio, Torri, Petitou and Casu (2001) Biochem. J. 359, 265-272]. Notably, the 2S0 conformation is also adopted by the non-sulfated IdoA residue preceding AGA*IA that, in the absence of AT, adopts predominantly the 1C4 form. These results further support the concept that heparin-binding proteins influence the conformational equilibrium of iduronic acid residues that are directly or indirectly involved in binding and select one of their equi-energetic conformations for best fitting in the complex. The complete reversal of an iduronic acid conformation preferred in the free state is also demonstrated for the first time. Preliminary docking studies provided information on the octasaccharide binding location agreeing most closely with the experimental data. These results suggest a possible biological role for the non-sulfated IdoA residue preceding AGA*IA, previously thought not to influence the AT-binding properties of the pentasaccharide. Thus, for each AT binding sequence longer than AGA*IA, the interactions with the protein could differ and give to each heparin fragment a specific biological response.
| S-EPMC1609903 | biostudies-literature
Project description:BackgroundThrombophilia is a coagulation disorder closely associated with venous thromboembolism. Hereditary antithrombin III (AT III) deficiency is a type of genetic thrombophilia. In China, genetic thrombophilia patients mainly suffer from deficiencies in AT III, protein S, and protein C. Multiple mutations in the serpin family C member 1 (SERPINC1) can affect AT III activity, resulting in thrombosis.Case presentationThis case presented a 17-year-old adolescent female who developed lower extremity venous thrombosis and subsequently pulmonary embolism (PE) following a right leg injury. A missense mutation in gene SERPINC1 of c.331 T > C, p.S111P was detected on the patient, resulting in a decreased AT III activity and an elevated risk of thrombosis. The patient received anticoagulation treatment for approximately 5 months. During follow-up, the blood clot gradually dissolved, and there have been no recurrent thrombotic events reported thus far.DiscussionHereditary AT deficiency can be classified into two types based on the plasma levels of the enzymatic activity and antigen. Type I is a quantitative defect, while Type II is a qualitive defect. Until 2021, 486 SERPINC1 gene mutations have been registered, more than 18% of which are point mutations. The SERPINC1 mutation c.331 T > C in was firstly reported in 2017, which was classified into type I AT III deficiency.ConclusionHereditary thrombophilia is a coagulation disorder with a high omission diagnostic rate. Minor mutations in the SERPINC1 gene can also lead to hereditary AT III deficiency, which in turn can cause PE. We emphasized the importance of etiological screening for hereditary thrombophilia in venous thromboembolism patients without obvious high-risk factors. Long-term anticoagulation treatment and avoidance of potential thrombosis risk factors are critical for such patients.
| S-EPMC10919460 | biostudies-literature