scholarly journals Nanoencapsulation Enhances Anticoagulant Activity of Adenosine and Dipeptide IleTrp

Nanomaterials ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 1191
Author(s):  
Trung Dinh Nguyen ◽  
The Ngoc Nguyen ◽  
Trang Thuy Thi Nguyen ◽  
Igor A. Ivanov ◽  
Khoa Cuu Nguyen ◽  
...  
Keyword(s):  
Biological Activity ◽  
Bleeding Time ◽  
Anticoagulant Activity ◽  
The Body ◽  
Clot Formation ◽  
Pluronic P123 ◽  
Transmission Electron ◽  
Clot Formation Time

It is well-known that drugs administered into an organism intravenously or through the gastrointestinal tract are degraded by enzymes of the body, reducing their therapeutic effect. One of the ways to decrease this undesirable process is through the inclusion of drugs in nanomaterials. Earlier strong anticoagulant activity was demonstrated for dipeptide IleTrp (IW) and adenosine (Ado). In this work, the effect of inclusion in nanomaterials on the biological activity of IW and Ado was studied. For this purpose, Ado and IW were incorporated into thermosensitive nanogel composed of pluronic P123-grafted heparin. The prepared nanocarrier was characterized by transmission electron microscopy, dynamic light scattering, and ζ-potential. Biological activity was determined by measuring the bleeding time from mouse tail in vivo and the time of clot formation in vitro. It was found that encapsulation of Ado and IW into nanomaterial significantly increased their effects, resulting in an increase in the bleeding time from mouse tail and clot formation time. Thus, inclusion of low molecular weight anticoagulants Ado and IW into nanomaterials may be considered a way to increase their biological activity.

Interaction of heparin and protamine in presence of overdosage: in vitro study

2020 ◽  
pp. 021849232095506
Author(s):  
Alexander A Hanke ◽  
Ines Severloh ◽  
Felix Flöricke ◽  
Christian F Weber ◽  
Thomas Lang
Keyword(s):  
In Vitro Study ◽  
Vitro Study ◽  
Clot Formation ◽  
Rotational Thromboelastometry ◽  
Significant Prolongation ◽  
Heparin Neutralization ◽  
Positive Effect ◽  
Clot Formation Time

Background Heparin is used for anticoagulation during cardiopulmonary bypass. After weaning from bypass, protamine is administered to neutralize the effects of heparin and thus reestablish hemostasis. Rotational thrombelastometry has been shown to discriminate between heparin and other impairing effects on coagulation. We analyzed the interaction of heparin and protamine under different conditions of overdosage in an in-vitro trial. Methods Blood samples were taken from 17 healthy volunteers, separated, and spiked in vitro with heparin, protamine for heparin neutralization, an overdosage of protamine, and two dosages of re-heparinization to evaluate heparin effects under the condition of protamine overdosage. All samples were analyzed in a standard ROTEM rotational thromboelastometry device after intrinsic activation with and without addition of heparinase. Coagulation time, maximum clot firmness, and clot formation time were recorded. Results Heparin led to prolongation of coagulation and clot formation times in the test without heparinase. Adequate protamine addition normalized the test, and overdosage of protamine led to significant prolongation of both times. Addition of heparin in the presence of protamine overdosage normalized these parameters. Conclusion We reconfirmed that the ROTEM device enables discrimination of the effects heparin and protamine on coagulation and detection of the coagulation-impairing effects of protamine overdosage. Furthermore, we were able to show a positive effect on coagulation times by heparin in the presence of protamine overdosage. Because this was an in-vitro study, these findings need to be confirmed in vivo, requiring further research.

scholarly journals Slounase, a Batroxobin Containing Activated Factor X Effectively Enhances Hemostatic Clot Formation and Reducing Bleeding in Hypocoagulant Conditions in Mice

2021 ◽  
Vol 27 ◽  
pp. 107602962110185
Author(s):  
Reheman Adili ◽  
Madeline Jackson ◽  
Livia Stanger ◽  
Xiangrong Dai ◽  
Mandy Li ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Fibrin Clot ◽  
Biochemical Properties ◽  
Clot Formation ◽  
Factor X ◽  
Wild Type ◽  
Fibrin Formation ◽  
Uncontrolled Bleeding

Uncontrolled bleeding associated with trauma and surgery is the leading cause of preventable death. Batroxobin, a snake venom-derived thrombin-like serine protease, has been shown to clot fibrinogen by cleaving fibrinopeptide A in a manner distinctly different from thrombin, even in the presence of heparin. The biochemical properties of batroxobin and its effect on coagulation have been well characterized in vitro. However, the efficacy of batroxobin on hemostatic clot formation in vivo is not well studied due to the lack of reliable in vivo hemostasis models. Here, we studied the efficacy of batroxobin and slounase, a batroxobin containing activated factor X, on hemostatic clot composition and bleeding using intravital microcopy laser ablation hemostasis models in micro and macro vessels and liver puncture hemostasis models in normal and heparin-induced hypocoagulant mice. We found that prophylactic treatment in wild-type mice with batroxobin, slounase and activated factor X significantly enhanced platelet-rich fibrin clot formation following vascular injury. In heparin-treated mice, batroxobin treatment resulted in detectable fibrin formation and a modest increase in hemostatic clot size, while activated factor X had no effect. In contrast, slounase treatment significantly enhanced both platelet recruitment and fibrin formation, forming a stable clot and shortening bleeding time and blood loss in wild-type and heparin-treated hypocoagulant mice. Our data demonstrate that, while batroxobin enhances fibrin formation, slounase was able to enhance hemostasis in normal mice and restore hemostasis in hypocoagulant conditions via the enhancement of fibrin formation and platelet activation, indicating that slounase is more effective in controlling hemorrhage.

scholarly journals The Efficacy of Cholesterol-Based Carriers in Drug Delivery

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4330
Author(s):  
Ngonidzashe Ruwizhi ◽  
Blessing Atim Aderibigbe
Keyword(s):  
Drug Delivery ◽  
Biological Activity ◽  
Wide Distribution ◽  
Therapeutic Agents ◽  
The Body ◽  
In Vivo Studies ◽  
Routes Of Administration ◽  
Bioactive Agents

Several researchers have reported the use of cholesterol-based carriers in drug delivery. The presence of cholesterol in cell membranes and its wide distribution in the body has led to it being used in preparing carriers for the delivery of a variety of therapeutic agents such as anticancer, antimalarials and antivirals. These cholesterol-based carriers were designed as micelles, nanoparticles, copolymers, liposomes, etc. and their routes of administration include oral, intravenous and transdermal. The biocompatibility, good bioavailability and biological activity of cholesterol-based carriers make them potent prodrugs. Several in vitro and in vivo studies revealed cholesterol-based carriers potentials in delivering bioactive agents. In this manuscript, a critical review of the efficacy of cholesterol-based carriers is reported.

scholarly journals Modern Approaches to Determination of the Biological Activity of Insulin and its

2019 ◽  
Vol 9 (2) ◽  
pp. 85-92
Author(s):  
T. A. Batuashvili ◽  
L. V. Simutenko ◽  
P. V. Shadrin ◽  
N. P. Neugodova
Keyword(s):  
Biological Activity ◽  
Animal Models ◽  
Insulin Analogues ◽  
Quality Parameters ◽  
The Body ◽  
Animal Testing ◽  
Biological Potency

The paper considers insulin’s specific action on the patient’s body, types of insulin preparations and insulin analogues which are used for the treatment of diabetes, as well as applicable requirements for these products. It was demonstrated that determination of biological activity is one of the key quality parameters of this type of medicines. The paper summarises the methods used for evaluation of insulin and its analogues, which are based both on the hormone’s general action on the body (in vivo: double crossing, euglycemic clamp, etc.), and on certain aspects of the hormone’s interaction with the body systems (in vitro: receptor-binding assay, phosphorylation, metabolic methods). Due to the appearance of insulin biosimilars on the pharmaceutical market, the article raises the issue that the «Biological potency» parameter tested in animals should be kept as part of the product specification. The analysis of the in vivo and in vitro methods of biological activity determination convincingly demonstrates that animal models can not be replaced with the modern analytical methods based on cell cultures. Consequently, animal models are still necessary, as they allow for an adequate assessment of the quality of insulins in terms of «Biological potency». Taking into account the global trend towards reduction of animal testing, the authors point out the need to develop modern methods, the results of which will be comparable to the results of in vivo determination of the biological activity.

Hog and Beef Mucosal Heparin - In Vitro Study Using Different Assay Procedures

1979 ◽  
Author(s):  
Martine Aiach ◽  
A. Kher ◽  
J. Mardiguian
Keyword(s):  
Biological Activity ◽  
Anticoagulant Activity ◽  
In Vitro Study ◽  
Vitro Study ◽  
In Vivo Studies ◽  
Factor X ◽  
Thrombosis Research ◽  
Manufacturing Procedure

In a previous study, on healthy volunteers two purified heparin preparations, obtained from hog and beef mucosausing the same manufacturing procedure, were compared for anticoagulant activity. Heparin levels measured by anti Xa assays and AFTT were not statistically different following subcutaneous or intravenous heparin injection, (M. Aiach, A. Kher, A. Kichaud, J. Mardiguian, M. Trillou, M. Leclerc - Thrombosis Research, to be published). An in vitro study was undertaken to evaluate the biological activity of these two heparins : thrombin clotting time was performed in plasma. Anti Xa activities were compared in purified system using human antithrombin III, or in plasma, and bovine and human activated factor X were used. Residual F Xa was evaluated with chromogenic substrate and in a clotting assay. The results will be reported in detail.In conclusion, the biological activity in vitro is higher for hog mucosal than for beef mucosal heparin when evaluated with sensitive and accurate methods. The in vivo study does not confirm these data. This discrepancy between in vitro and in vivo studies could be explained by individual variation of in vivo response to heparin and by dissimilarities in the distribution of molecular weight between these two heparins.

scholarly journals Detrimental effects of geldanamycin on adults and larvae of Trichinella spiralis

2016 ◽  
Vol 53 (2) ◽  
pp. 126-132 ◽  
Author(s):  
A. A. Othman ◽  
Z. S. Shoheib
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Trichinella Spiralis ◽  
Heat Shock Protein 90 ◽  
The Body ◽  
Transmission Electron ◽  
Larval Count ◽  
Different Doses

SummaryTrichinellosis is a zoonotic disease affecting mainly the temperate regions. The treatment is a challenge for the physician, and the available therapy is far from ideal. Therefore, this work aimed to evaluate the effect of heat shock protein 90 inhibitor, geldanamycin, on the adult worms and larvae of Trichinella spiralis. This research comprised an in vivo study in which T. spiralis-infected mice were treated by two different doses of geldanamycin, thereafter larval count and pathological changes were determined in the muscles. Meanwhile, the in vitro study investigated the effect of two different concentrations of geldanamycin on adult worms and larvae of T. spiralis via transmission electron microscopy. The in vivo study showed significant reduction of muscle larval counts under the effect of geldanamycin. Moreover, characteristic changes were noted as regards the parasite and the inflammatory response. The in vitro study revealed degenerative changes in the body wall of larvae and adults of T. spiralis under the influence of geldanamycin. In conclusion, heat shock protein 90 inhibitor, geldanamycin, seems to have detrimental effects on the adults and larvae of T. spiralis. It, or one of its derivatives, could be an adjuvant to anthelmintic therapy of trichinellosis, but more studies are warranted to establish its usefulness.

scholarly journals Structure and anticoagulant properties of sulfated glycosaminoglycans from primitive Chordates

2002 ◽  
Vol 74 (1) ◽  
pp. 105-112 ◽  
Author(s):  
MAURO S. G. PAVÃO
Keyword(s):  
Dermatan Sulfate ◽  
Thrombus Formation ◽  
Anticoagulant Activity ◽  
The Body ◽  
Heparin Cofactor Ii ◽  
Styela Plicata ◽  
Iduronic Acid ◽  
Bleeding Effect

Dermatan sulfates and heparin, similar to the mammalian glycosaminoglycans, but with differences in the degree and position of sulfation were previously isolated from the body of the ascidian Styela plicata and Ascidia nigra. These differences produce profound effects on their anticoagulant properties. S. plicata dermatan sulfate composed by 2-O-sulfatedalpha-L-iduronic acid and 4-O-sulfated N-acetyl-beta-D-galactosamine residues is a potent anticoagulant due to a high heparin cofactor II activity. Surprisingly, it has a lower potency to prevent thrombus formation on an experimental model and a lower bleeding effect in rats than the mammalian dermatan sulfate. In contrast, A. nigra dermatan sulfate, also enriched in 2-O-sulfated alpha-L-iduronic acid, but in this case sulfated at O-6 of the N-acetyl-beta-D-galactosamine units, has no in vitro or in vivo anticoagulant activity, does not prevent thrombus formation but shows a bleeding effect similar to the mammalian glycosaminoglycan. Ascidian heparin, composed by 2-O-sulfated alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (75%) and alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (25%) disaccharide units has an anticoagulant activity 10 times lower than the mammalian heparin, is about 20 times less potent in the inhibition of thrombin by antithrombin, but has the same heparin cofactor II activity as mammalian heparin.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

The Anticoagulant Properties of a Modified Form of Protein S

1988 ◽  
Vol 60 (02) ◽  
pp. 298-304 ◽  
Author(s):  
C A Mitchell ◽  
S M Kelemen ◽  
H H Salem
Keyword(s):  
Monoclonal Antibody ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Factor Xa ◽  
Protein S ◽  
Human Neutrophil Elastase ◽  
Factor X ◽  
Sds Page

SummaryProtein S (PS) is a vitamin K-dependent anticoagulant that acts as a cofactor to activated protein C (APC). To date PS has not been shown to possess anticoagulant activity in the absence of APC.In this study, we have developed monoclonal antibody to protein S and used to purify the protein to homogeneity from plasma. Affinity purified protein S (PSM), although identical to the conventionally purified protein as judged by SDS-PAGE, had significant anticoagulant activity in the absence of APC when measured in a factor Xa recalcification time. Using SDS-PAGE we have demonstrated that prothrombin cleavage by factor X awas inhibited in the presence of PSM. Kinetic analysis of the reaction revealed that PSM competitively inhibited factor X amediated cleavage of prothrombin. PS preincubated with the monoclonal antibody, acquired similar anticoagulant properties. These results suggest that the interaction of the monoclonal antibody with PS results in an alteration in the protein exposing sites that mediate the observed anticoagulant effect. Support that the protein was altered was derived from the observation that PSM was eight fold more sensitive to cleavage by thrombin and human neutrophil elastase than conventionally purified protein S.These observations suggest that PS can be modified in vitro to a protein with APC-independent anticoagulant activity and raise the possibility that a similar alteration could occur in vivo through the binding protein S to a cellular or plasma protein.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

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