scholarly journals Effects of Post-Translational Modifications of Fibrinogen on Clot Formation, Clot Structure, and Fibrinolysis

2020 ◽  
Vol 40 (3) ◽  
pp. 554-569 ◽  
Author(s):  
Judith J. de Vries ◽  
Charlotte J.M. Snoek ◽  
Dingeman C. Rijken ◽  
Moniek P.M. de Maat

Objective: Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current literature on post-translational modifications of fibrinogen and their effects on fibrin formation and clot characteristics. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was performed to find studies reporting post-translational modifications of fibrinogen and the effects on clot formation and structure. Both in vitro studies and ex vivo studies using patient material were included. One hundred five articles were included, describing 11 different modifications of fibrinogen. For the best known and studied modifications, conclusions could be drawn about their effect on clot formation and structure. Oxidation, high levels of nitration, and glycosylation inhibit the rate of polymerization, resulting in dense clots with thinner fibers, while low levels of nitration increase the rate of polymerization. Glycation showed different results for polymerization, but fibrinolysis was found to be decreased, as a consequence of increased density and decreased permeability of clots. Acetylation also decreases the rate of polymerization but results in increased fiber diameters and susceptibility to fibrinolysis. Other modifications were studied less or contrasting results were found. Therefore, substantial gaps in the knowledge about the effect of post-translational modifications remain. Conclusions: Overall, post-translational modifications do affect clot formation and characteristics. More studies need to be performed to reveal the effects of all post-translational modifications and the effects on thrombotic diseases. Expanding the knowledge about modifications of fibrinogen can ultimately contribute to optimizing treatments for thrombotic diseases.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4053-4053
Author(s):  
Don A. Gabriel ◽  
Brett E. Skolnick ◽  
Stephanie Seremetis ◽  
Philip Leese ◽  
David Mathews

Abstract The generation of thrombin is a critical step in clot formation and securing hemostasis. Inadequate thrombin generation may result in excessive bleeding, while uncontrolled thrombin production has the potential to induce thromboses. Recombinant FVIIa has been shown to control bleeding in hemophilia patients with inhibitors to coagulation factors VIII and IX, and several other clinical conditions in which life- and limb-threatening bleeding may occur. However, for non-hemophilia patients the dose and dosing regimen still require refinement. The use of ex-vivo assessment systems (Thromboelastograph assay, Hemodyne Hemostasis Analyzer) to generate an in vitro model of hemostasis may be useful to determine the effect of rFVIIa on the dynamics of clot formation, particularly in a patient population where clinical trials are difficult. A series of pilot studies were performed to establish an optimal punch biopsy location and biopsy size to create an effective bleeding site for further study. The current study (48 subjects consented for an IRB approved protocol) examined, in an ascending dose-escalation manner, the effect of an individual dose of rFVIIa on bleeding time, blood loss volume, coagulation parameters and coagulation status in healthy volunteers. All patients underwent three punch biopsies: the first (baseline biopsy) with no treatment, the second and third biopsy with either a low or high rFVIIa dose administered prior to biopsy. The treatment pair sequences were placebo/10, 10/20, 20/40, 40/80, 80/120, and 120/160 μg/kg. Blood samples were drawn 15 minutes pre-, 15 minutes post-, 1 hour and 5 hours post-biopsy to conduct ex-vivo assessments of hemostasis. The results indicate that overall there was a trend towards an increase in platelet contractile force and clot elastic modulus with an apparent maximal effect at 1 hour post-biopsy. At the higher doses this effect, although reduced, does not return to pre-treatment values by 5 hours post-biopsy. For the lower doses these values decreased to levels comparable to those at pre-treatment. These observations are consistent with the reports of a dose-related half-life of rFVIIa. These data imply that the administration of rFVIIa may have an effect in non-coagulopathic individuals. Although the heterogenity observed in this sample of patients may limit interpretations, it is proposed that this ex-vivo model with further refinements may be useful for evaluating the effects of future pro-hemostatic agents. Figure Figure


2021 ◽  
Vol 10 (2) ◽  
pp. e7810212093
Author(s):  
Millena Silva Cardoso ◽  
Laís Ferrante de Faria ◽  
Camila Moreira Lima ◽  
Fabíola Pessôa Pereira Leite ◽  
Laércio Almeida de Melo

Objetivo: O objetivo dessa revisão sistemática foi avaliar a influência das diferentes concentrações do ácido hidrofluorídrico (HF) no condicionamento das cerâmicas vítreas. Materiais e Métodos: Esta revisão reuniu estudos in vitro a partir de buscas nas bases Cochrane Library, Lilacs, PubMed, SciElo, Scopus e Web of Science, através dos descritores “Veneers”, “Crowns”, “Ceramics”, “Ceramic”, “Surface Treatments”, “Surface”, “Hydrofluoric Acid Concentration”, “Acid Concentration”, “Adhesion”, “Hydrofluoric Acid”. Foram incluídos estudos que investigaram os efeitos da concentração do ácido hidrofluorídrico através de diferentes concentrações entre grupos. O nível de evidência dos artigos selecionados seguiu os princípios do Oxford Center for Evidence-Based Medicine. Esta revisão seguiu as recomendações do PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyzes). Resultados: As estratégias de busca encontraram 151 títulos, dos quais 8 foram eleitos e incluídos nessa revisão. Os parâmetros de avaliação incluíram a influência da concentração do ácido quanto a resistência a flexão, rugosidade superficial, ângulo de molhamento e resistência ao microcisalhamento. Nos estudos, as cerâmicas foram condicionadas com diferentes tipos de concentração e, no geral, o HF a 5% teve o melhor desempenho. Conclusão: Os estudos encontraram mais resultados negativos para as concentrações mais baixas (1% e 3%). Apesar de algumas vantagens, o HF a 10% também não teve os melhores resultados, os quais foram de autoria do HF a 5%. Além disso, a concentração não pode ser vista como o único e principal fator importante na qualidade de adesão das cerâmicas.


2022 ◽  
Vol 9 (1) ◽  
pp. 14
Author(s):  
Inês Francisco ◽  
Raquel Travassos ◽  
Catarina Nunes ◽  
Madalena Ribeiro ◽  
Filipa Marques ◽  
...  

Background: There has been an increase in demand for orthodontic treatment within the adult population, who likely receive restorative treatments using ceramic structures. The current state of the art regarding the most effective method to achieve an appropriate bond strength of brackets on ceramic surfaces isn’t consensual. This systematic review aims to compare the available surface treatments to ceramics and determine the one that allows to obtain the best bond strength. Methods: This systematic review followed the PRISMA guidelines and the PICO methodology was used, with the question “What is the most effective technique for bonding brackets on ceramic crowns or veneers?”. The research was carried out in PubMed, Web of Science, Embase and Cochrane Library databases. In vitro and ex vivo studies were included. The methodological quality was evaluated using the guidelines for reporting of preclinical studies on dental materials by Faggion Jr. Results: A total of 655 articles searched in various databases were initially scrutinized. Sevety one articles were chosen for quality analysis. The risk of bias was considered medium to high in most studies. The use of hydrofluoric acid (HF), silane and laser afforded the overall best results. HF and HF plus laser achieved significantly highest bond strength scores in felsdphatic porcelain, while laser was the best treatment in lithium disilicate ceramics. Conclusions: The most effective technique for bonding brackets on ceramic is dependent on the type of ceramic.


2020 ◽  
Vol 21 (17) ◽  
pp. 6361
Author(s):  
Mohamad Assi ◽  
Boris Pirlot ◽  
Vincent Stroobant ◽  
Jean-Paul Thissen ◽  
Patrick Jacquemin

KRAS is a powerful oncogene responsible for the development of many cancers. Despite the great progress in understanding its function during the last decade, the study of KRAS expression, subcellular localization, and post-translational modifications remains technically challenging. Accordingly, many facets of KRAS biology are still unknown. Antibodies could be an effective and easy-to-use tool for in vitro and in vivo research on KRAS. Here, we generated a novel rabbit polyclonal antibody that allows immunolabeling of cells and tissues overexpressing KRAS. Cell transfection experiments with expression vectors for the members of the RAS family revealed a preferential specificity of this antibody for KRAS. In addition, KRAS was sensitively detected in a mouse tissue electroporated with an expression vector. Interestingly, our antibody was able to detect endogenous forms of unprenylated (immature) and prenylated (mature) KRAS in mouse organs. We found that KRAS prenylation was increased ex vivo and in vivo in a model of KRASG12D-driven tumorigenesis, which was concomitant with an induction of expression of essential KRAS prenylation enzymes. Therefore, our tool helped us to put the light on new regulations of KRAS activation during cancer initiation. The use of this tool by the RAS community could contribute to discovering novel aspects of KRAS biology.


2021 ◽  
Vol 10 (2) ◽  
pp. e18819212240
Author(s):  
Laís Ferrante de Faria ◽  
Millena Silva Cardoso ◽  
Camila Moreira Lima ◽  
Laércio Almeida de Melo ◽  
Fabíola Pessôa Pereira Leite

Objetivo: Objetivou-se avaliar a influência do tempo de condicionamento do Ácido Hidrofluorídrico (HF) em diferentes cerâmicas vítreas, a fim de estabelecer o melhor protocolo que viabilize uma adequada adesão protética do material restaurador. Metodologia: Trata-se de uma revisão sistemática de estudos in vitro. Para a sua realização, utilizou-se os descritores “Veneers”, “Crowns”, “Ceramics”, “Ceramic”, “Etching Time”, “Application Time”, “Surface Treatments”, “Hydrofluoric Acid” e “Adhesion” nas bases Scopus, PubMed, Cochrane Library, SciElo, Web of Science e Lilacs. Estudos que investigaram os efeitos do tempo de aplicação do HF sobre a adesão de cerâmicas vítreas foram incluídos. O nível de evidência dos artigos selecionados seguiu os princípios do Oxford Center for Evidence-Based Medicine. Esta revisão seguiu as recomendações do Preferred Reporting Items for Systematic Reviews and Meta-analyzes (PRISMA). Resultados: A estratégia de busca resultou em 290 estudos, dos quais 5 foram incluídos na revisão. Os estudos demonstraram diferentes parâmetros avaliativos como rugosidade microestrutural, molhabilidade, resistência ao cisalhamento, resistência à flexão biaxial e microdureza das cerâmicas, a fim de investigar a influência do tempo de condicionamento do HF nas cerâmicas vítreas, incluindo feldspáticas, de silicato de lítio reforçada por zircônia e dissilicato de lítio. O condicionamento com HF por 60s é recomendado para cerâmicas feldspáticas, enquanto para cerâmicas de silicato de lítio reforçada por zircônia e de dissilicato de lítio é indicado por 20s. Conclusão: O tempo de condicionamento da cerâmica com HF influencia na adesão. Tempos prolongados de condicionamento são prejudiciais às cerâmicas vítreas, refletindo em redução da adesão protética.


2017 ◽  
Vol 28 (6) ◽  
pp. 657-668 ◽  
Author(s):  
Luiz A. Chisini ◽  
Marcus C.M. Conde ◽  
Guillermo Grazioli ◽  
Alissa S. San Martin ◽  
Rodrigo Varella de Carvalho ◽  
...  

Abstract Although the biological properties of mesenchymal stem cells (MSC) are well-characterized in vitro, MSC clinical application is still far away to be achieved, mainly due to the need of xenogeneic substances for cell expansion, such as fetal bovine serum (FBS). FBS presents risks regarding pathogens transmissions and internalization of animal’s proteins, which can unleash antigenic responses in patients after MSC implantation. A wide range of venous blood derivatives (VBD) has been reported as FBS substitutes showing promising results. Thus, the aim of this study was to conduct a systematic scoping review to analyze whether VBD are effective FBS substitutes for MSC ex vivo expansion. The search was performed in SciVerse ScopusTM, PubMed, Web of ScienceTM, BIREME, Cochrane library up to January 2016. The keywords were selected using MeSH and entry terms. Two independent reviewers scrutinized the records obtained considering specific inclusion criteria. The included studies were evaluated in accordance with a modified Arksey and O’ Malley’s framework. From 184 found studies, 90 were included. Bone marrow mesenchymal stem cells (BMMSC) were presented in most of these studies. Overall, VBD allowed for either, maintenance of MCS’s fibroblast-like morphology, high proliferation, high colony-formation ability and maintenance of multipotency. Besides. MSC expanded in VBD supplements presented higher mitogen activity than FBS. VBD seems to be excellent xeno-free serum for ex vivo expansion of mesenchymal stem cells. However, an accentuated heterogeneity was observed between the carried out protocols for VBD isolation did not allowing for direct comparisons between the included studies.


1997 ◽  
Vol 3 (S2) ◽  
pp. 329-330
Author(s):  
John W. Weisel

Fibrin clot formation is necessary for maintaining the integrity of the vasculature via physiological processes of hemostasis and wound healing and is also involved in pathological processes, such as thrombosis and atherosclerosis. A variety of structural and biophysical approaches has been used to examine intermediates in the formation of clots and to visualize in vitro clots and ex vivo thrombi.Structures at all stages of polymerization have been examined to learn about molecular mechanisms of assembly. Fibrinogen is a polyfunctional, multi-domain protein that is essential for platelet aggregation and for the formation of the three-dimensional network of fibrin fibers which is the structural basis of the clot. Distinctive functions for several of fibrinogen's domains in the fibrin assembly process have been elucidated. Enzymatic removal of the fibrinopeptides exposes binding sites in the central region which then interact with complementary sites at the ends of a neighboring molecule to yield fibrin oligomers.


2016 ◽  
Vol 2016 ◽  
pp. 1-12
Author(s):  
Chang-Chieh Wu ◽  
Fu-Ming Tsai ◽  
Mao-Liang Chen ◽  
Semon Wu ◽  
Ming-Cheng Lee ◽  
...  

Antipsychotic drugs (APDs) used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the underlying mechanism remains unknown. We first analyzed platelet aggregation and clot formation in platelets treated with APDs, risperidone, clozapine, or haloperidol, using an aggregometer and rotational thromboelastometry (ROTEM). Our data indicated that platelet aggregation was inhibited, that clot formation time was increased, and that clot firmness was decreased in platelets pretreated with APDs. We also examined the role two major adenosine diphosphate (ADP) receptors, P2Y1and P2Y12, play in ADP-mediated platelet activation and APD-mediated suppression of platelet aggregation. Our results show that P2Y1receptor stimulation with ADP-induced calcium influx was inhibited by APDs in human and rats’ platelets, as assessed byin vitroorex vivoapproach, respectively. In contrast, APDs, risperidone and clozapine, alleviated P2Y12-mediated cAMP suppression, and the release of thromboxane A2 and arachidonic acid by activated platelets decreased after APD treatment in human and rats’ platelets. Our data demonstrate that each APD tested significantly suppressed platelet aggregation via different mechanisms.


2021 ◽  
Vol 10 (2) ◽  
pp. 316
Author(s):  
Irini Fagogeni ◽  
Tomasz Falgowski ◽  
Joanna Metlerska ◽  
Mariusz Lipski ◽  
Maciej Górski ◽  
...  

The aim of this review is to evaluate of effectiveness of bleaching procedures used to treat discolored teeth subsequent to regenerative endodontic procedures (REPs) based on the review of in vitro and in vivo studies. This literature review was carried out according to the PRISMA guidelines. Four databases (PubMed, Scopus, the Cochrane Library, and Web of Science databases) were searched electronically, until 30 January 2020 without a year limit. The quality of studies was assessed using a modified methodological index for non-randomized studies. After analyzing 1405 studies, 6 in vitro and 9 in vivo studies were eligible for this review. In in vitro studies, effectiveness of bleaching was assessed in teeth discolored by antibiotic pastes, blood, and barrier materials in various combinations. In all analyzed studies, bleaching was effective in teeth discolored by antibiotic pastes as well as by blood and barrier materials. Of 26 treated teeth in the in vivo studies, 17 teeth were bleached successfully. In six cases, there was improvement of the shade. In three cases, bleaching was not sufficient. Bleaching material, techniques, and times differed between studies. Whitening of discolored teeth after REPs is achievable. However, to establish precise guidelines, further long-term clinical studies should be performed.


2020 ◽  
Vol 9 (10) ◽  
pp. e6839109154
Author(s):  
Laércio Almeida de Melo ◽  
Camila Moreira Lima ◽  
Lucas Lactim Ferrarez ◽  
Delano Neves Silva ◽  
Fabíola Pessôa Pereira Leite

Objetivo: Avaliar a precisão da adaptação de próteses totais confeccionadas pela tecnologia utilizando o desenho e a manufatura assistidas por computador (CAD/CAM).Metodologia: Foi realizada uma revisão sistemática de estudos laboratoriais através das bases de dados Medline-PubMed, Scopus, Scielo, Lilacs, Web of Science e Cochrane Library, usando os descritores: “Complete denture”, “Complete dentures”, “Total denture”, “Total dentures”, “Complete prosthesis”, “Complete prostheses”, “Total prosthesis”, “Total prostheses”, “Computer Aied Design”, “Computer Aied Manufacturing”, “CAD/CAM”, Adaptation” e “Precision”. Três revisores calibrados obtiveram dados e compararam os resultados. Todos os estudos avaliaram a precisão da adaptação de próteses totais confeccionadas pela tecnologia CAD/CAM. Esta revisão seguiu as recomendações do Preferred Reporting Items for Systematic Reviews and Meta-analyzes (PRISMA). Resultados: A estratégia utilizada de busca eletrônica e manual resultou em 863 títulos e resumos. Destes, 10 foram selecionados pelos critérios de inclusão e exclusão e lidos na íntegra. Ao final, 7 foram eleitos para inclusão na revisão. Os estudos selecionados demonstraram resultados satisfatórios em relação a adaptação e efetividade sobre as próteses confeccionadas a partir do processo CAD/CAM quando comparadas aos métodos convencionais. Conclusão: Os estudos in vitro demonstraram que o processo de fabricação de prótese total por meio do sistema CAD/CAM apresenta melhor precisão de adaptação quando comparados ao método convencional. O método de fresagem apresentou resultados superiores quando comparado ao por impressão 3D.


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