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1.
Nutrients ; 16(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38999733

RESUMO

Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants-genipin, patent blue V, and brilliant blue FCF-on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1-200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.


Assuntos
Coagulação Sanguínea , Plaquetas , Corantes de Alimentos , Iridoides , Humanos , Iridoides/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Corantes de Alimentos/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Hemostasia/efeitos dos fármacos , Tempo de Tromboplastina Parcial , Adesividade Plaquetária/efeitos dos fármacos , Fibrinogênio/metabolismo , Benzenossulfonatos/farmacologia , Tempo de Protrombina , Corantes de Rosanilina/farmacologia , Hemostáticos/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Tempo de Trombina
2.
Cell Biochem Funct ; 42(5): e4085, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38951992

RESUMO

This review rigorously investigates the early cerebral changes associated with Alzheimer's disease, which manifest long before clinical symptoms arise. It presents evidence that the dysregulation of calcium (Ca2+) homeostasis, along with mitochondrial dysfunction and aberrant autophagic processes, may drive the disease's progression during its asymptomatic, preclinical stage. Understanding the intricate molecular interplay that unfolds during this critical period offers a window into identifying novel therapeutic targets, thereby advancing the treatment of neurodegenerative disorders. The review delves into both established and emerging insights into the molecular alterations precipitated by the disruption of Ca2+ balance, setting the stage for cognitive decline and neurodegeneration.


Assuntos
Doença de Alzheimer , Autofagia , Cálcio , Mitocôndrias , Mitofagia , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Cálcio/metabolismo , Animais , Hemostasia , Homeostase
3.
PLoS One ; 19(7): e0304231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985805

RESUMO

Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from trauma patients with level I activations (N = 34) within 60 min of hospital arrival, as well as healthy volunteer controls (N = 10). Samples were perfused through a microfluidic model of injury at venous and arterial shear rates, and a subset of experiments were performed after incubation with fluorescent anti-CD41 to quantify platelets. Complete blood counts were performed as well as plasma-based assays to quantify coagulation times, fibrinogen, and von Willebrand factor (VWF). Exploratory correlation analyses were employed to identify relationships with microfluidic hemostatic parameters. Trauma patients had increased microfluidic bleeding times compared to healthy controls. While trauma patient samples were able to deposit a substantial amount of clot in the model injury site, the platelet contribution to microfluidic hemostasis was attenuated. Trauma patients had largely normal hematology and plasma-based coagulation times, yet had elevated D-Dimer and VWF. Venous microfluidic bleeding time negatively correlated with VWF, D-Dimer, and mean platelet volume (MPV), while arterial microfluidic bleeding time positively correlated with oxygenation. Arterial clot growth rate negatively correlated with red cell count, and positively with mean corpuscular volume (MCV). We observed changes in clot composition in trauma patient samples reflected by significantly diminished platelet contribution, which resulted in reduced hemostatic function in a microfluidic model of vessel injury. We observed a reduction in platelet clot contribution under both venous and arterial flow ex vivo in trauma patient samples. While our population was heterogenous and had relatively mild injury severity, microfluidic hemostatic parameters correlated with different patient-specific data depending on the flow setting, indicating potentially differential mechanistic pathways contributing to platelet hemostatic capacity in the context of TIC. These data were generated with the goal of identifying key features of platelet dysfunction in bleeding trauma patients under conditions of flow and to determine if these features correlate with clinically available metrics, thus providing preliminary surrogate markers of physiological platelet dysfunction to be further studied across larger cohorts. Future studies will continue to explore those relationships and further define mechanisms of TIC and their relationship with patient outcomes.


Assuntos
Plaquetas , Hemostasia , Microfluídica , Ferimentos e Lesões , Humanos , Plaquetas/metabolismo , Masculino , Feminino , Adulto , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações , Microfluídica/métodos , Pessoa de Meia-Idade , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/sangue , Fator de von Willebrand/metabolismo , Fibrinogênio/metabolismo , Estudos de Casos e Controles , Tempo de Sangramento
4.
Nat Commun ; 15(1): 5557, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956415

RESUMO

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.


Assuntos
DNA , Armadilhas Extracelulares , Hemostasia , Hemostáticos , Hidrogéis , Cicatrização , Animais , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/efeitos dos fármacos , DNA/química , Masculino , Hidrogéis/química , Hidrogéis/farmacologia , Ratos , Hemostasia/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Hemostáticos/farmacologia , Hemostáticos/química , Ratos Sprague-Dawley , Hemorragia , Humanos , Neutrófilos/metabolismo , Modelos Animais de Doenças
5.
Molecules ; 29(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38998951

RESUMO

In our search for a biocompatible composite hemostatic dressing, we focused on the design of a novel biomaterial composed of two natural biological components, collagen and sodium alginate (SA), cross-linked using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) and oxidized sodium alginate (OSA). We conducted a series of tests to evaluate the physicochemical properties, acute systemic toxicity, skin irritation, intradermal reaction, sensitization, cytotoxicity, and in vivo femoral artery hemorrhage model. The results demonstrated the excellent biocompatibility of the collagen/sodium alginate (C/SA)-based dressings before and after crosslinking. Specifically, the femoral artery hemorrhage model revealed a significantly shortened hemostasis time of 132.5 ± 12.82 s for the EDC/NHS cross-linked dressings compared to the gauze in the blank group (hemostasis time of 251.43 ± 10.69 s). These findings indicated that C/SA-based dressings exhibited both good biocompatibility and a significant hemostatic effect, making them suitable for biomedical applications.


Assuntos
Alginatos , Bandagens , Colágeno , Hemostáticos , Alginatos/química , Alginatos/farmacologia , Animais , Colágeno/química , Colágeno/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Camundongos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Teste de Materiais , Hemorragia/tratamento farmacológico , Masculino , Ratos , Hemostasia/efeitos dos fármacos , Artéria Femoral
6.
Nat Cell Biol ; 26(7): 1110-1123, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38997457

RESUMO

Migrasomes are organelles that are generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found that a large number of neutrophil-derived migrasomes exist in the blood of mice and humans. Compared with neutrophil cell bodies and platelets, these migrasomes adsorb and enrich coagulation factors on the surface. Moreover, they are highly enriched with adhesion molecules, which enable them to preferentially accumulate at sites of injury, where they trigger platelet activation and clot formation. Depletion of neutrophils, or genetic reduction of the number of these migrasomes, significantly decreases platelet plug formation and impairs coagulation. These defects can be rescued by intravenous injection of purified neutrophil-derived migrasomes. Our study reveals neutrophil-derived migrasomes as a previously unrecognized essential component of the haemostasis system, which may shed light on the cause of various coagulation disorders and open therapeutic possibilities.


Assuntos
Coagulação Sanguínea , Plaquetas , Camundongos Endogâmicos C57BL , Neutrófilos , Neutrófilos/metabolismo , Animais , Humanos , Plaquetas/metabolismo , Camundongos , Hemostasia , Movimento Celular , Ativação Plaquetária , Masculino , Fatores de Coagulação Sanguínea/metabolismo , Fatores de Coagulação Sanguínea/genética
7.
Zhonghua Yi Xue Za Zhi ; 104(23): 2142-2147, 2024 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-38871471

RESUMO

Objective: To evaluate the influence of thromboelastography-guided hemostatic algorithm on allogeneic transfusion requirements during pediatric hemispherectomy. Methods: Clinical data of 38 children who underwent hemispherectomy from January 1, 2011 to October 31, 2023 at Xuanwu Hospital of Capital Medical University were retrospective collected. Patients were divided into study group (n=17) and control group (n=21) according to whether thromboelastography was employed to guide hemostatic algorithm. Demographic data and surgical data were recorded. The primary outcomes were allogeneic transfusion rates, including RBC transfusion rate, plasma transfusion rate, and platelets transfusion rate. The second outcomes were estimated blood loss, postoperative seizures during hospitalization, thromboembolic events, and length of hospital stay. Results: There were 13 boys and 4 girls with mean age of (5.7±3.3) years old in study group, and 16 boys and 5 girls with mean age of (7.4±3.4) years old in control group. The surgery duration, anesthesia duration and the proportion of prophylactic administration of tranexamic acid in study group were (424.5±98.5) min, (542.8±106.9) min, and 94.1% (16/17), which were higher than (353.1±85.3) min, (445.3±87.9) min, and 47.6% (10/21) in control group (all P<0.05). The rates of intra- and perioperative allogeneic plasma transfusion in study group were 52.9% (9/17) and 64.7% (11/17) respectively, which were lower than 90.5% (19/21) and 95.2% (20/21) in control group (all P<0.05). The ratio of fibrinogen concentrates administration in study group was 58.8% (10/17), which was higher than that in control group [4.8% (1/21), P=0.001]. There were no statistically differences in intra- and perioperative allogeneic RBC transfusion rates between the two groups (all P>0.05). No platelets were transfused in both groups. There were no statistically differences in estimated blood loss, postoperative seizures during hospitalization and the length of hospital stay between the two groups (all P>0.05). No postoperative thromboembolic events were observed. Conclusion: Thromboelastography-guided hemostatic algorithm can reduce allogeneic plasma transfusion requirements but not RBC transfusion requirements during pediatric hemispherectomy.


Assuntos
Hemisferectomia , Tromboelastografia , Humanos , Feminino , Masculino , Criança , Estudos Retrospectivos , Pré-Escolar , Algoritmos , Transfusão de Sangue , Perda Sanguínea Cirúrgica/prevenção & controle , Hemostasia
8.
Clin Appl Thromb Hemost ; 30: 10760296241255959, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38831596

RESUMO

The purpose of the study was to investigate baseline inflammatory, hemostatic indicators and new-onset deep vein thrombosis (DVT) with the risk of mortality in COVID-19 inpatients. In this single-center study, a total of 401 COVID-19 patients hospitalized in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were enrolled from December 1, 2022 to January 31, 2023. The basic information, first laboratory examination results, imaging examination, and outcome-related indicators were compared between patients in the moderate and severe subgroups. We found that baseline D-dimer and baseline absolute neutrophil count (ANC) levels were associated with new-onset DVT and death in severe hospitalized patients with COVID-19. The odds ratio (OR) of baseline D-dimer and baseline ANC with mortality was 1.18 (95% confidence interval [CI], 1.08-1.28; P < .001) and 1.13 (95% CI, 1.06-1.21; P < .001). Baseline ANC was associated with the risk of death in severe hospitalized COVID-19 patients, irrespective of the DVT status. In addition, a significantly higher serum neutrophil activity was observed in severe COVID-19 inpatients with DVT or those deceased during hospital stay. New-onset DVT partially mediated the association between baseline D-dimer (indirect effect: 0.011, estimated mediating proportion: 67.0%), baseline ANC (indirect effect: 0.006, estimated mediating proportion: 48.7%), and mortality in severe hospitalized patients with COVID-19. In summary, baseline D-dimer and baseline absolute neutrophil count (ANC) levels were associated with the mortality in severe hospitalized patients with COVID-19, especially DVT inpatients. New-onset DVT partially mediated the association between baseline D-dimer, baseline ANC, and mortality in severe hospitalized patients with COVID-19.


Assuntos
COVID-19 , Produtos de Degradação da Fibrina e do Fibrinogênio , SARS-CoV-2 , Humanos , COVID-19/mortalidade , COVID-19/sangue , COVID-19/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Idoso , Neutrófilos , Trombose Venosa/sangue , Trombose Venosa/mortalidade , Inflamação/sangue , Fatores de Risco , Índice de Gravidade de Doença , Hemostasia , Pacientes Internados/estatística & dados numéricos , Contagem de Leucócitos , Adulto , China/epidemiologia
9.
J Vis Exp ; (207)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38856226

RESUMO

Hemostasis, the process of normal physiological control of vascular damage, is fundamental to human life. We all suffer minor cuts and puncture wounds from time to time. In hemostasis, self-limiting platelet aggregation leads to the formation of a structured thrombus in which bleeding cessation comes from capping the hole from the outside. Detailed characterization of this structure could lead to distinctions between hemostasis and thrombosis, a case of excessive platelet aggregation leading to occlusive clotting. An imaging-based approach to puncture wound thrombus structure is presented here that draws upon the ability of thin-section electron microscopy to visualize the interior of hemostatic thrombi. The most basic step in any imaging-based experimental protocol is good sample preparation. The protocol provides detailed procedures for preparing puncture wounds and platelet-rich thrombi in mice for subsequent electron microscopy. A detailed procedure is given for in situ fixation of the forming puncture wound thrombus and its subsequent processing for staining and embedding for electron microscopy. Electron microscopy is presented as the end imaging technique because of its ability, when combined with sequential sectioning, to visualize the details of the thrombus interior at high resolution. As an imaging method, electron microscopy gives unbiased sampling and an experimental output that scales from nanometer to millimeters in 2 or 3 dimensions. Appropriate freeware electron microscopy software is cited that will support wide-area electron microscopy in which hundreds of frames can be blended to give nanometer-scale imaging of entire puncture wound thrombi cross-sections. Hence, any subregion of the image file can be placed easily into the context of the full cross-section.


Assuntos
Microscopia Eletrônica , Trombose , Animais , Camundongos , Microscopia Eletrônica/métodos , Trombose/patologia , Hemostasia , Punções/métodos
10.
ACS Appl Mater Interfaces ; 16(24): 30742-30754, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38841831

RESUMO

Uncontrolled hemorrhage and infection are the principal causes of mortality associated with trauma in both military and civilian medical settings. Modified starch granules have emerged as a safe hemostatic agent for irregular and noncompressible wounds, but their performance is constrained by limited hemostasis efficiency and modest antibacterial activity. This study reported a directed self-assembly approach for a multifunctional mesoporous starch-based microparticle loaded with chitosan and calcium ions (Ca@MSMP) used for rapid hemostasis and wound healing. Directed self-assembly of uniform Ca@MSMP with a hierarchical hollow structure in the presence of chitosan was confirmed by scanning electron microscopy (SEM) analysis and pore structure analysis. The resulting Ca@MSMP exhibited a well-defined spherical shape and uniform size of 1 µm and demonstrated excellent antibacterial activity (>95%) without hemolytic activity. Importantly, Ca@MSMP enhanced blood coagulation and platelet aggregation via the synergistic effect of rapid calcium release and chitosan-mediated electrostatic interactions, leading to a significant decrease in blood loss and reduction in hemostasis time in rat tail amputation and liver injury models. In comparative analyses, Ca@MSMP significantly outperformed the commercial hemostatic agent Quickclean, notably enhancing the healing of full-thickness skin wounds in vivo by effectively preventing infection. These results underscore the potential of this innovative hemostatic material in diverse clinical scenarios, offering effective solutions for the management of bleeding in wounds that are irregularly shaped and noncompressible.


Assuntos
Quitosana , Hemostasia , Hemostáticos , Amido , Cicatrização , Animais , Amido/química , Amido/farmacologia , Cicatrização/efeitos dos fármacos , Ratos , Hemostáticos/química , Hemostáticos/farmacologia , Hemostasia/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Porosidade , Ratos Sprague-Dawley , Cálcio/química , Antibacterianos/farmacologia , Antibacterianos/química , Coagulação Sanguínea/efeitos dos fármacos , Masculino , Hemorragia/tratamento farmacológico , Humanos , Staphylococcus aureus/efeitos dos fármacos
11.
Int J Biol Macromol ; 272(Pt 2): 132930, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38848843

RESUMO

The rapid absorption of water from the blood to concentrate erythrocytes and platelets, thus triggering quick closure, is important for hemostasis. Herein, expansion-clotting chitosan fabrics are designed and fabricated by ring spinning of polylactic acid (PLA) filaments as the core layer and highly hydrophilic carboxyethyl chitosan (CECS) fibers as the sheath layer, and subsequent knitting of obtained PLA@CECS core spun yarns. Due to the unidirectional fast-absorption capacity of CECS fibers, the chitosan fabrics can achieve erythrocytes and platelets aggregate quickly by concentrating blood, thus promoting the formation of blood clots. Furthermore, the loop structure of coils formed in the knitted fabric can help them to expand by absorbing water to close their pores, providing effective sealing for bleeding. Besides, They have enough mechanical properties, anti-penetrating ability, and good tissue-adhesion ability in wet conditions, which can form a physical barrier to resist blood pressure during hemostasis and prevent them from falling off the wound, thus enhancing hemostasis synergistically. Therefore, the fabrics exhibit superior hemostatic performance in the rabbit liver, spleen, and femoral artery puncture injury model compared to the gauze group. This chitosan fabric is a promising hemostatic material for hemorrhage control.


Assuntos
Quitosana , Hemorragia , Hemostáticos , Quitosana/química , Animais , Hemorragia/tratamento farmacológico , Hemorragia/prevenção & controle , Coelhos , Hemostáticos/química , Hemostáticos/farmacologia , Poliésteres/química , Têxteis , Coagulação Sanguínea/efeitos dos fármacos , Hemostasia/efeitos dos fármacos
12.
Biomater Adv ; 162: 213932, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38917648

RESUMO

Clay minerals have attracted wide attention as biomedical materials due to the unique crystal structure, abundant morphology and good biocompatibility. However, the relevant studies on the abundant natural mixed clay deposits were scarcely reported. Herein, the hemostatic performance of natural mixed-dimensional attapulgite clay (MDAPT) composed of one-dimensional attapulgite and multiple two-dimensional clay were systematically investigated based on the structural evolution using oxalic acid for different time. The results of hemostatic evaluation showed that MDAPT leached by oxalic acid with 1 h presented the shortest clotting time (134 ± 12.17 s), a 15.09 % and 41.74 % reduction of relative hemoglobin absorbance at 180 s and 120 s when compared with the control group, respectively, and an increase of 19.45 % of the blood clotting index in vitro, as well as MDAPT obtained the shortest bleeding time (158.5 ± 6.9 s), nearly 66 % and 31 % reduction blood loss as compared to the blank group and the YNBY group in vivo. This improvement was primarily ascribed to the synergistic effect of lamellar non-expandable illite, and nano rod-like attapulgite. Furthermore, the rapid hemostasis of MDAPT was also due to the joint effect of superhydrophobic property toward blood, minimizing blood loss, surface negative charge, metal ions from MDAPT structural skeleton, promoting an average increase of 21 % for platelet activation. The results suggested that MDAPT could be served as a promising efficient inorganic hemostatic materials, which provided a feasible strategy to realize the high-valued utilization of natural mixed clay resources.


Assuntos
Argila , Compostos de Magnésio , Compostos de Silício , Compostos de Magnésio/química , Compostos de Magnésio/farmacologia , Argila/química , Animais , Compostos de Silício/química , Hemostáticos/farmacologia , Hemostáticos/química , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Hemostasia/efeitos dos fármacos , Hemostasia/fisiologia , Silicatos de Alumínio/química , Humanos
13.
J Med Eng Technol ; 48(1): 12-24, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38857023

RESUMO

Haemorrhage is the leading cause of battlefield deaths and second most common cause for civilian mortality worldwide. Biomaterials-based haemostatic agents are used to aid in bleeding stoppage; mesoporous bioactive glasses (MBGs) are candidates for haemostasis. Previously made Tantalum-containing MBG (Ta-MBG) powders' compositions were fabricated as electrospun fibres for haemostatic applications in the present study. The fibres were fabricated to address the challenges associated with the powder form: difficult to compress without gauze, getting washed away in profuse bleeding, generating dust in the surgical environment, and forming thick callus-difficult to remove for surgeons and painful for patients. Ta-MBGs were based on (80-x)SiO2-15CaO-5P2O5-xTa2O5 mol% compositions with x = 0 (0Ta), 0.5 (0.5Ta), 1 (1Ta), and 5 (5Ta) mol%. The present study details the fibres' in vitro analyses, elucidating their cytotoxic effects, and haemostatic capabilities and relating these observations to fibre chemistry and previously fabricated powders of the same glasses. As expected, when Ta addition is increased at the expense of silica, a new FTIR peak (non-bridging oxygen-silicon, Si-NBO) develops and Si-O-Si peaks become wider. Compared to 0Ta and 1Ta fibres, 0.5Ta show Si-O peaks with reduced intensity. The fibres had a weaker intensity of Si-NBO peaks and release fewer ions than powders. A reduced ion profile provides fibres with a stable matrix for clot formation. The ion release profile for 1Ta and 5Ta fibres was significantly lower than 0Ta and 0.5Ta fibres. Ta-MBGs were not found to be cytotoxic to primary rat fibroblasts using a methyl thiazolyl tetrazolium (MTT) assay. Furthermore, a modified activated partial thromboplastin time assay analysing the fibrin absorbance showed that the absorption increases from physiological clotting < 0Ta < 0.5Ta < 5Ta < commercial haemostat, Surgical SNoWTM, Ethicon, USA < 1Ta. Higher absorption signifies a stronger clot. It is concluded that Ta-MBG fibres can provide stable matrix for clot formation and 1Ta can potentially enhance clotting best among other Ta-MBGs.


Assuntos
Vidro , Tantálio , Tantálio/química , Vidro/química , Hemostáticos/química , Hemostáticos/farmacologia , Hemostasia/efeitos dos fármacos , Animais , Porosidade , Humanos , Ratos , Materiais Biocompatíveis/química
14.
Eur J Sport Sci ; 24(7): 899-906, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38874882

RESUMO

This study was conducted to investigate the effects of 12 weeks of aerobic exercise (AT) and saffron supplementation on hemostasis, inflammatory markers, and insulin resistance in obese women diagnosed with type 2 diabetes (T2D). A total of 44 women with T2D (mean age: 54.12 ± 5.63 years, mean BMI: 31.15 ± 1.50 kg/m2, HbA1c: 85 ± 4.2 mmol/mol) were included in a randomized, double-blind, placebo-controlled study. We were randomly assigned to one of four groups (n = 11 per group): saffron + training (ST), placebo + training (PT), saffron supplement (SS), and placebo (P). The ST and PT groups completed 12 weeks of AT (three sessions per week of mild to moderate intensity). The ST and SS groups were administered a daily dose of 200 mg of saffron powder for 12 weeks. Fasting blood samples were collected 48 h before the first AT session and/or nutritional supplementation and 48 h after the last AT session and/or nutritional supplementation. Post-evaluation, homeostatic model assessment of insulin resistance value (HOMA-IR, p < 0.001) and serum levels of glucose (p < 0.001), fibrinogen (FIB, p < 0.001), homocysteine (HCY, p < 0.001), interleukin-6 (IL-6, p < 0.001), and tumor necrosis factor α (TNFα, p < 0.001) showed significant reduction in the ST, PT, and SS groups compared to the P group (p < 0.05). In particular, the ST group showed a more significant reduction in all variables compared to the PT and SS groups (p < 0.05). Our results suggest that a 12-week intervention with AT and saffron supplementation can independently improve markers related to hemostasis, inflammation, and insulin resistance. However, their combination showed the greatest effectiveness on the above markers.


Assuntos
Biomarcadores , Crocus , Diabetes Mellitus Tipo 2 , Suplementos Nutricionais , Exercício Físico , Resistência à Insulina , Humanos , Feminino , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Pessoa de Meia-Idade , Biomarcadores/sangue , Exercício Físico/fisiologia , Inflamação/sangue , Interleucina-6/sangue , Obesidade/terapia , Obesidade/sangue , Glicemia/análise , Fator de Necrose Tumoral alfa/sangue , Hemostasia
15.
ACS Appl Mater Interfaces ; 16(27): 34684-34704, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38919152

RESUMO

Effective bleeding management strategies in uncontrollable and noncompressible massive hemorrhage are becoming important in both clinical and combat situations. Here, a novel approach was developed to create a superporous and highly absorbable hemostatic sponge through a facile chemical gas-foaming method by cross-linking long-chain polyphosphate along with nanokaolin and Ca2+ in an alginate structure to synergistically activate the coagulation pathway. Natural kaolin obtained from the Marand mine in East Azarbaijan was converted into pseudohexagonal-shaped kaolin nanoparticles (30 to 150 nm) using ball milling followed by a newly developed glow discharge plasma treatment method. The obtained ultralight sponges (>90% porosity) exhibit ultrarapid water/blood absorption capacity (∼4000%) and excellent shape memory, which effectively concentrates coagulation factors. The results of in vitro tests demonstrated that the proposed sponges exhibited enhanced blood clotting ability (BCI < 10%) and superior cohesion with red blood cells (∼100) and platelets (∼80%) compared to commercially available hemostatic products. The in vivo host response results exhibited biosafety with no systemic and significant local inflammatory response by hematological, pathological, and biochemical parameter assessments. In a rat femoral artery complete excision model, the application of alginate/k/polyp nanocomposite sponges resulted in a complete hemostasis time of 60 s by significant reduction of hemostasis time (∼6.7-8.3 fold) and blood loss (∼2-2.8-fold) compared to commercially available hemostatic agents (P < 0.001). In conclusion, distinct physical characteristics accompanied by unique chemical composition multifunctional sponges activate hemostasis synergistically by triggering the XII, XI, X, IX, V, and II factors and the contact pathway and have the ability of rapid hemostasis in noncompressible severe bleeding.


Assuntos
Hemorragia , Nanopartículas Metálicas , Polifosfatos/química , Caulim/química , Nanopartículas Metálicas/química , Alginatos/química , Fatores de Tempo , Humanos , Hemostasia , Hemorragia/terapia , Porosidade , Sobrevivência Celular , Linhagem Celular , Masculino , Animais , Ratos
16.
Int J Biol Macromol ; 273(Pt 1): 133032, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38862053

RESUMO

Collagen's unique properties promise hemostatic potential, but its sponge form's stability and mechanics need improvement. In this study, we developed a series of homeostatic sponges by co-assembling collagen and curdlan at different ratios into hydrogels, followed by freeze-drying treatment. The incorporation of curdlan into collagen sponges has been found to significantly enhance the sponge's properties, including increased porosity, elevated water uptake, improved elasticity, and enhanced resistance to degradation. In vitro cytotoxicity and hemolysis assays have demonstrated the biocompatibility and nontoxicity of composite sponges. In mouse liver perforation and incision models, the composite sponges achieved rapid coagulation within 67 s and 75 s, respectively, outperforming gauze and gelatin sponge in reducing blood loss. Furthermore, composite sponges demonstrated superior wound healing potential in mice full-thickness skin defects model, with accelerated healing rates observed at days 3, 7, and 14 compared to the control group. Overall, collagen/curdlan composite sponge show promise for hemostasis and wound healing applications.


Assuntos
Colágeno , Hemostasia , Cicatrização , beta-Glucanas , Animais , Cicatrização/efeitos dos fármacos , Colágeno/química , Colágeno/farmacologia , beta-Glucanas/farmacologia , beta-Glucanas/química , Camundongos , Hemostasia/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/lesões , Hidrogéis/química , Hidrogéis/farmacologia , Hemólise/efeitos dos fármacos , Hemostáticos/farmacologia , Hemostáticos/química , Porosidade , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Masculino
17.
Expert Rev Hematol ; 17(7): 391-403, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38889268

RESUMO

BACKGROUND: Platelet storage is complicated by deleterious changes, among which reduction of ristocetin-induced platelet aggregation (RIPA) has a poorly understood mechanism. The study elucidates the mechanistic roles of all the possible players in this process. RESEARCH DESIGN AND METHODS: PRP-platelet concentrates were subjected to RIPA, collagen-induced platelet aggregation (CIPA), and flowcytometric analysis of GPIbα and PAC-1 binding from days 0 to 5 of storage. Platelet-poor plasma was subjected to colorimetric assays for glucose/LDH evaluation and automatic analyzer to examine VWF antigen and activity. RESULTS: From day three of platelet storage, reducing CIPA but not RIPA was correlated with the reduction of both metabolic state and integrin activity. RIPA reduction was directly related to the decreased levels of total-content/expression of GPIbα, and inversely related to its shedding levels during storage. Re-suspension of 5-day stored platelet in fresh plasma compensated CIPA, but not RIPA. VWF concentration and its activity did not change during storage while they had no correlation with RIPA. CONCLUSIONS: This study identified the irreversible loss of platelet GPIbα, but not VWF status, as the primary cause of the storage-dependent decrease of RIPA. Unlike CIPA, this observation was not compensated by plasma refreshment, suggesting that some evidence of PSL may not be recovered after transfusion.


Assuntos
Plaquetas , Preservação de Sangue , Agregação Plaquetária , Complexo Glicoproteico GPIb-IX de Plaquetas , Ristocetina , Fator de von Willebrand , Humanos , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Ristocetina/farmacologia , Plaquetas/metabolismo , Preservação de Sangue/métodos , Fator de von Willebrand/metabolismo , Hemostasia/efeitos dos fármacos
18.
Bull Exp Biol Med ; 176(6): 731-735, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38904932

RESUMO

We studied the effectiveness of Xe/O2 mixture inhalation (30% Xe and 70% O2, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the studied mixture decreased the intensity of the inflammatory process in the lung tissue assessed by the temperature response of animals, changed lung weight and lung weight coefficient. At acute stage of pneumonitis, an increase in xenon consumption was recorded due to its retention in the gas exchange zone and a natural decrease in oxygen consumption due to partial alveolar/capillary block. The formation of pneumonitis was accompanied by a pronounced procoagulant shift in the regulation system of the aggregate state of blood. The Xe/O2 inhalations ensured physiologically optimal levels of prothrombin and activated partial thromboplastin time against the background of a moderate decrease in fibrinogen level throughout the experiment. At the same time, the activity of the natural anticoagulant antithrombin III increased from day 5 to day 14.


Assuntos
Oxigênio , Pneumonia , Xenônio , Animais , Pneumonia/sangue , Pneumonia/patologia , Masculino , Oxigênio/metabolismo , Xenônio/administração & dosagem , Xenônio/farmacologia , Hemostasia/efeitos dos fármacos , Administração por Inalação , Fibrinogênio/metabolismo , Tempo de Tromboplastina Parcial , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Antitrombina III/metabolismo , Ratos , Tromboplastina/metabolismo , Protrombina/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Coagulação Sanguínea/efeitos dos fármacos
19.
Thromb Res ; 240: 109045, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38834002

RESUMO

INTRODUCTION: Thrombin generation assays (TGAs) assess the overall functionality of the hemostatic system and thereby provide a reflection of the hemostatic capacity of patients with disorders in this system. Currently, four (semi-)automated TGA platforms are available: the Calibrated Automated Thrombogram, Nijmegen Hemostasis Assay, ST Genesia and Ceveron s100. In this study, we compared their performance for detecting patients with congenital single coagulation factor deficiencies. MATERIALS AND METHODS: Pooled patient samples, healthy control samples and normal pooled plasma were tested on all four platforms, using the available reagents that vary in tissue factor and phospholipid concentrations. The TGA parameters selected for analysis were peak height and thrombin potential. Results were normalized by using the calculated mean of healthy controls and a correction for between-run variation. Outcomes were presented as relative values, with the mean of healthy controls standardized to 100 %. RESULTS: Across all platforms and reagents used, thrombin potentials and peak heights of samples with coagulation factor deficiencies were lower than those of healthy controls. Reagents designed for bleeding tendencies yielded the lowest values on all platforms (relative median peak height 19-32 %, relative median thrombin potential 19-45 %). Samples representing more severe coagulation factor deficiencies generally exhibited lower relative peak heights and thrombin potentials. CONCLUSIONS: Thrombin generation assays prove effective in differentiating single coagulation factor deficient samples from healthy controls, with modest discrepancies observed between the platforms. Reagents designed for assessing bleeding tendencies, featuring the lowest tissue factor and phospholipid concentrations, emerged as the most suitable option for detecting coagulation factor deficiencies.


Assuntos
Trombina , Humanos , Trombina/metabolismo , Trombina/análise , Trombina/biossíntese , Testes de Coagulação Sanguínea/métodos , Transtornos de Proteínas de Coagulação/sangue , Transtornos de Proteínas de Coagulação/diagnóstico , Hemostasia
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