scholarly journals TITANIUM NANOPARTICLES CONJUGATED WITH STREPTOKINASE AS A MODIFIED THROMBOLYTIC AGENT

Author(s):  
HAYDER H. ABED ◽  
ESTABRAQ AR. ALWASITI ◽  
AMIR T. TAWFEEQ

Objective: Blood clots are the main cause of death worldwide by stroke and myocardial infarction. Streptokinase a thrombolytic agent that is used in the treatment of circulatory disorders. Methods: Titanium Nanoparticles was supplied from Changsha Santech Co. Its characterized were studied using (FT-IR, XRD, AFM, FE-SEM). Streptokinase at concentration 0.1 mg/ml was conjugated with Titanium nanoparticles using PH equal to 5.2 with continuous stirring. Formation of Streptokinase loading Titanium nanoparticles confirmed using FT-IR, Ninhydrine’s test and Bradford protein assay. Physicochemical Properties were studied in vitro. Thrombolytic activity in vitro was determined using d–dimer indicator and weight of blood clot after treatment as indicators of thrombolytic activity. Results: Titanium nanoparticles show particle size at range 31 nm. The thrombolytic activity of streptokinase loading Titanium nanoparticles shows significant value in d-dimer and weight of blood clot compared with the control group and non-significant compared with an equivalent amount of streptokinase alone. Conclusion: Titanium nanoparticles conjugated with streptokinase show high thrombolytic activity against blood clots in vitro.

2018 ◽  
Vol 8 (6-s) ◽  
pp. 101-104
Author(s):  
Prerna Alawa ◽  
Mayank Tenguria ◽  
Vijayshree Nilofey

Blood clotting is an important and vital process that takes places in humans, animals and birds. At the same time blood clots sometimes considered an issue when developed in the circulatory system due to failure of hemostasis causes vascular blockage and leads to serious consequences in thrombolytic diseases such as acute myocardial or cerebral infarction which may cause death. Certain substances like Alteplase, anistreplase, streptokinase, urokinase, tissue plasminogen activator, Heparin and Aspirin are used as clot dissolving agents. Plants have also been proved to perform such activity. Calotropis gigantea L. is a traditional medicinal plant with several pharmacological properties belongs to the family Apocyanaceae of Asclepiadaceous was investigated for its efficacy for blood clot dissolving activity under in vitro conditions when incorporated into carbomer based gels. The ethanolic extract of the leaves of C. gigantea was prepare by soxhlation which upon analysis reported to contain alkaloids, glycosides, flavonoids, tannins, terpenoids and saponins as usual components as were reported in earlier investigations. There were 3 gels with ethanolic leaf extract C. gigantea with 1 mg, 0.5 mg and 0.25 mg per gram of 1% Carbopol-940 gel containing methyl paraben, glycerol and water. The two gels containing sterile distilled water and 0.1 mg per gram gel streptokinase enzyme served as –ve and positive controls respectively. The in vitro thrombolytic of clot dissolving activity war performed on goat blood collected from slaughter houses. From the results the percentage clot dissolving activity of gels containing 1 mg, 0.5 mg and 0.25 mg C. gigantea extract per gram were reported as 34%, 27% and 14% respectively considered significant when compared to the activity of standard streptokinase in the gel. The activity of these experimental gels describes the possibility of development of new safe, and non reactive topical anti-clot gel products using herbal or plant components like C. gigantea extracts. Keywords: Calotropis gigantea L, Streptokinase, Thrombolytic activity, Carbopol gel, Biopharmaceutical.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Leela Goel ◽  
Huaiyu Wu ◽  
Bohua Zhang ◽  
Jinwook Kim ◽  
Paul A. Dayton ◽  
...  

AbstractOne major challenge in current microbubble (MB) and tissue plasminogen activator (tPA)-mediated sonothrombolysis techniques is effectively treating retracted blood clots, owing to the high density and low porosity of retracted clots. Nanodroplets (NDs) have the potential to enhance retracted clot lysis owing to their small size and ability to penetrate into retracted clots to enhance drug delivery. For the first time, we demonstrate that a sub-megahertz, forward-viewing intravascular (FVI) transducer can be used for ND-mediated sonothrombolysis, in vitro. In this study, we determined the minimum peak negative pressure to induce cavitation with low-boiling point phase change nanodroplets and clot lysis. We then compared nanodroplet mediated sonothrombolysis to MB and tPA mediate techniques. The clot lysis as a percent mass decrease in retracted clots was 9 ± 8%, 9 ± 5%, 16 ± 5%, 14 ± 9%, 17 ± 9%, 30 ± 8%, and 40 ± 9% for the control group, tPA alone, tPA + US, MB + US, MB + tPA + US, ND + US, and ND + tPA + US groups, respectively. In retracted blood clots, combined ND- and tPA-mediated sonothrombolysis was able to significantly enhance retracted clot lysis compared with traditional MB and tPA-mediated sonothrombolysis techniques. Combined nanodroplet with tPA-mediated sonothrombolysis may provide a feasible strategy for safely treating retracted clots.


2020 ◽  
Vol 12 (3) ◽  
pp. 379-390
Author(s):  
F. I. Penu ◽  
S. M. Ivy ◽  
F. Ahmed ◽  
J. Uddin ◽  
M. S. Hossain ◽  
...  

The present study was carried out to investigate phytochemical, antioxidant; antimicrobial, thrombolytic activity and estimate total phenolic, total flavonoid content of Pandanus odoratissimus (p.odoratissimus) leaves of methanol extract. In thrombolytic activity, aqueous soluble fraction (AQSF) exhibited highest percentage (46.58 %) of potential to lyse blood clot compared to standard drug streptokinase (69.52 %). In antimicrobial assay, dichloromethane soluble fraction (DCMSF) explored the highest diameter of clear zone of inhibition against both gram positive (19.60 ± 0.12 mm) and gram negative (20.00 ± 0.20 mm) bacteria compared to standard antibiotic, Kanamycin (50.00 ± 0.19). Levels of antioxidant were determined by DPPH assay followed by calculated IC50 values of different Kupchan extracts. The methyl soluble fraction (MSF) showed the lowest level of IC50 value (36.70 ± 0.32 µg/mL) in comparison to ascorbic acid (12.48 ± 0.09 µg/mL) while MSF disclosed the maximum level (62.19 ±  0.26 mg of GAE/g of extract) of total phenolic content in the extracts of P. odoratissimus. This study was conducted to validate the P. odoratissimus leaves used as a folk medicine such as, antioxidant, thrombolytic, and antimicrobial potential.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Stephen J D’Auria ◽  
Filip Istvanic ◽  
Francois Yu ◽  
Xucai Chen ◽  
John Pacella

Introduction: Microvascular obstruction (MVO) occurs frequently during successful PCI for acute myocardial infarction. Our previous work has demonstrated the potential of using ultrasound targeted microbubbles (MBs) cavitation to relieve MVO, termed sonoreperfusion (SRP). Hypothesis: In the present study, we aim to develop a tPA loaded MB in order to utilize the thrombolytic effects of locally delivered tPA to enhance SRP, with a decreased tPA dose to limit the bleeding risk. Methods: tPA (1 mg/mL) was first modified via a maleimide linkage using BMCC-biotin, leading to a biotinylated protein. The biotinylated tPA (0.87 mg/mL) was then mixed with streptavidin labeled lipid shelled MB (1х10^9MB/mL) via biotin-streptavidin bridging. The enzymatic activity of the tPA in these tPA loaded MBs were was tested with whole porcine blood thrombus and with a tPA chromogenic activity kit. The loading capability of tPA onto the MBs was determined by BCA protein assay. The SRP efficacy of the loaded tPA MB was tested in an in vitro model of MVO and compared with full dose systemic tPA as well as modified MB. Results: tPA loaded MB showed successful lysis of whole porcine blood clot in vitro , as evidenced by decreased thrombus weight. Subsequent analysis of tPA activity showed that there was no significant difference in the activity of stock tPA when compared to the BMCC labeled tPA (42.0±3.4 IU vs 44.7±1.1 IU, p =0. 17). tPA was loaded onto MB at volumetric ratios of 3 units of tPA at 0.87 mg/mL to 1 unit (3:1) of MB at 1e9 MB/mL (43.5±2.2 IU, p =0.38) and 6:1 (39.3±1.5 IU, p =0.15). There was decreased activity in the 1:1 group. The loading capability of tPA for the 3:1 tPA loaded MB was 6.2e-7 μg per MB, with a loading efficiency of 10.4% of the stock tPA. Early in vitro work showed the tPA loaded MB to be non-inferior at relieving MVO with SRP when compared to infusion of full dose tPA and SRP with standard unmodified tPA. Conclusions: We successfully loaded tPA onto the surface of a lipid encapsulated MB, with retention of the enzymatic activity of tPA. The loading efficiency was 10.4% of the stock tPA. The tPA loaded MB demonstrated similar reperfusion efficacy to full systemic dose tPA. Thus, this approach of targeted local delivery of tPA may provide a means to mitigate bleeding risk without sacrificing drug efficacy.


2017 ◽  
Vol 23 (3) ◽  
pp. 607-617 ◽  
Author(s):  
Albe C. Swanepoel ◽  
Odette Emmerson ◽  
Etheresia Pretorius

AbstractCombined oral contraceptive (COC) use is a risk factor for venous thrombosis (VT) and related to the specific type of progestin used. VT is accompanied by inflammation and pathophysiological clot formation, that includes aberrant erythrocytes and fibrin(ogen) interactions. In this paper, we aim to determine the influence of progesterone and different synthetic progestins found in COCs on the viscoelasticity of whole blood clots, as well as erythrocyte morphology and membrane ultrastructure, in an in vitro laboratory study. Thromboelastography (TEG), light microscopy, and scanning electron microscopy were our chosen methods. Our results point out that progestins influence the rate of whole blood clot formation. Alterations to erythrocyte morphology and membrane ultrastructure suggest the presence of eryptosis. We also note increased rouleaux formation, erythrocyte aggregation, and spontaneous fibrin formation in whole blood which may explain the increased risk of VT associated with COC use. Although not all COC users will experience a thrombotic event, individuals with a thrombotic predisposition, due to inflammatory or hematological illness, should be closely monitored to prevent pathological thrombosis.


2012 ◽  
Vol 1 (12) ◽  
pp. 431-435 ◽  
Author(s):  
Mohammad Arif Dar ◽  
Nahida Tabassum

Thrombosis, the formation of blood clots, is a cause not only of heart attacks and strokes, but of deep venous thrombosis (DVT) and pulmonary embolism as well. The number one killer of Americans is a blood clot that blocks blood flow to the heart or to the brain and approximately half of all morbidity and mortality in the United States can be attributed to heart attack or stroke. All the blood clot related conditions are life-threatening, and so there is a need for safe, effective and preventive treatment. A natural substance rutin, also called rutoside, is a citrus flavonoid glycoside found in Fagopyrum esculentum (buckwheat), the leaves and petioles of Rheum species, and Asparagus. This flavonoid compound has shown effective thrombolytic activity (prevents the formation of blood clots) by blocking the enzyme protein disulfide isomerase (PDI) found in all cells involved in blood clotting. Food and Drug Administration (FDA) has established that rutin is safe and, thus provides a safe and inexpensive drug that could reduce recurrent clots and help save thousands of lives.DOI: http://dx.doi.org/10.3329/icpj.v1i12.12454 International Current Pharmaceutical Journal 2012, 1(12): 431-435


2019 ◽  
Vol 7 (9) ◽  
pp. 328 ◽  
Author(s):  
Tomas Puidokas ◽  
Mantas Kubilius ◽  
Donatas Nomeika ◽  
Gintaras Januzis ◽  
Erika Skrodeniene

Alveolar osteitis (AO) is a common, painful postoperative complication after tooth extraction. Fibrinolytic activity in the extraction socket is one etiological factor. Platelet concentrates are used to prevent and treat AO. The aim of this study was to find out whether the positive effect of platelet concentrates can be related to resistance to bacteria-induced fibrinolysis. Blood from 45 human volunteers was used to prepare four media: blood clot medium as control group; PRF and PRGF first fraction (PRGF I) and PRGF second fraction (PRGF II) as study groups. Additionally, collected blood was used for blood plasma preparation on which evaluation of initial value of d-dimer concentration was performed. A solution of five different microbes (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Bacillus cereus, and Candida albicans) was adjusted to 0.5 McFarland (1 × 108 CFU/mL) and then diluted to 0.25 McFarland (0.5 × 108 CFU/mL). The d-dimer concentration was evaluated after one and three hours of bacteria exposure. The resistance to fibrinolysis was not statistically distinguished among any media groups at any time. S. pneumoniae was statistically active in PRF after three hours. C. albicans was statistically active in PRGF II after one hour and in PRF between the first and third hour and after three hours. S. aureus and B. cereus were statistically active in PRGF II after three hours. S. pyogenes was statistically active after one hour, between the first and third hour, and after the third hour in all groups. S. pyogenes was the most active bacterium. Different blood formulations were not distinguishable based on resistance to bacteria-induced fibrinolysis. Low fibrinolytic properties of the found major microbes suggests that bacteria-induced fibrinolysis is one of the leading causes of absence of a clot in a post-extraction socket to be clinically insignificant. The initial absence of a clot or its mechanical elimination during formation or the healing period are major causes of dry socket.


2020 ◽  
Vol 12 (4) ◽  
pp. 455-460
Author(s):  
Yuan Wu ◽  
Cuizhong Liu ◽  
Ming Gao ◽  
Qiang Liang ◽  
Yu Jiang

This study aimed to observe the effect of titanium nanomaterials on osteoblastsin vitro. Osteoblasts were identified using histochemical staining, and they were examined using an MTT (3-(4,5Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay to determine the proliferation and differentiation of osteoblasts. In addition, we observed the effect of titanium nanomaterials on the function of osteoblasts. Compared with the control group, titanium nanomaterials promoted the growth, proliferation, and differentiation of osteoblasts. Our findings showed that titanium nanomaterials can significantly promote the proliferation of osteoblasts and enhance their osteogenic activity.


2016 ◽  
Vol 27 (2) ◽  
pp. 160-168 ◽  
Author(s):  
Aline Cristina Silva ◽  
Camilla Christian Gomes Moura ◽  
Jessica Afonso Ferreira ◽  
Denildo de Magalhães ◽  
Paula Dechichi ◽  
...  

Abstract The aim of this study was to evaluated the root surfaces modifications resulted by application of different chemicals agents, and their influence on the fibrin network and fibroblasts attachment. From 96 anterior mandibular human extracted incisor teeth, 192 dentin blocks of buccal and lingual surface were obtained and randomly divided into 6 groups: Cont- control group, which received no treatment; Root surface scaling and root planing (Srp); Citric acid-Srp; EDTA-Srp; Tetracycline capsule-Srp; Tetracycline gel-Srp. After dentin treatments the specimens were analyzed as follows: 1) demineralization level and residues of the product by scanning electron microscopy (SEM); 2) adhesion of blood components after 20 min of surface treatment by SEM; 3) fibroblast attachment after 24 h by SEM; 4) cell metabolism after 24 h by MTT assay. Data were analyzed using Fisher Exact, One-way ANOVA test followed by Dunn's test, Tukey test and Dunnett test (α=0.05). Citric acid, EDTA and Tetracycline gel resulted in adequate demineralization with no completely smear layer and smear plug removal on root dentin surface. Tetracycline capsule produced great tetracycline residues with several demineralization areas. Tetracycline gel and EDTA groups presented more fibroblast fixation than other experimental groups. The highest mean blood clot adhesion score was observed in roots treated with tetracycline gel. EDTA and Tetracycline gel surface treatment removed the smear layer over dentin surface and promoted adhesion of fibrin network and fibroblast cells attachment.


Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 983
Author(s):  
Xueqin Gao ◽  
Haizi Cheng ◽  
Xuying Sun ◽  
Aiping Lu ◽  
Joseph J. Ruzbarsky ◽  
...  

Background. Fibrin sealant has been used as a scaffold to deliver genetically modified human muscle-derived stem cells (hMDSCs) for bone regeneration. Alternatively, autologous blood clots are safe, economic scaffolds. This study compared autologous blood clot (BC) with fibrin sealant (FS) as a scaffold to deliver lenti-BMP2/GFP-transduced hMDSCs for bone regeneration. Methods. In vitro osteogenic differentiation was performed using 3D pellet culture and evaluated using microCT and Von Kossa staining. The lenti-GFP transduced cells were then mixed with human blood for evaluation of osteogenic differentiation. Furthermore, a murine critical- sized calvarial defect model was utilized to compare BC and FS scaffolds for lenti-BMP2/GFP-transduced hMDSCs mediated bone regeneration and evaluated with micro-CT and histology. Results. Lenti-BMP2/GFP transduced hMDSCs formed significantly larger mineralized pellets than non-transduced hMDSCs. hMDSCs within the human blood clot migrated out and differentiated into ALP+ osteoblasts. In vivo, BC resulted in significantly less new bone formation within a critical-sized calvarial bone defect than FS scaffold, despite no difference observed for GFP+ donor cells, osteoclasts, and osteoblasts in the newly formed bone. Conclusions. Human lenti-BMP2/GFP-transduced hMDSCs can efficiently undergo osteogenic differentiation in vitro. Unexpectedly, the newly regenerated bone in BC group was significantly less than the FS group. The autologous blood clot scaffold is less efficacious for delivering stem cells for bone regeneration than fibrin sealant.


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