Effects of fibrinolytic agents and heparin on blood coagulation in dogs

1964 ◽  
Vol 207 (5) ◽  
pp. 1049-1052 ◽  
Author(s):  
Jessica H. Lewis ◽  
Mitsuru Shirakawa

In vitro experiments demonstrated that incubation of dog plasma with Thrombolysin or Actase caused marked falls in factors I, VIII, and IX, a moderate fall in factor V, and the appearance of a heat-labile clot inhibitor. Incubation of dog plasma with streptokinase (SK), staphylokinase, trypsin, bromelain, or dog fibrinolysin in amounts similar to those used in in vivo studies had little effect on these coagulation factors. If the streptokinase concentration were increased 10- to 15-fold results similar to those found with Thrombolysin were observed. Intravenous infusions of Thrombolysin or Actase resulted in marked depressions of factors I, VIII, and V, minimal depressions of factors II, VII, and IX, and the development of a clot inhibitor. Seven dogs who received SK showed no coagulation changes, while three showed moderate fibrinogenolysis and inhibitor formation.

1974 ◽  
Vol 31 (03) ◽  
pp. 420-428 ◽  
Author(s):  
M Fainaru ◽  
S Eisenberg ◽  
N Manny ◽  
C Hershko

SummaryThe natural course of defibrination syndrome caused by Echis colorata venom (ECV) in five patients is reported. All patients developed afibrinogenemia within six hours after the bite. Concomitantly a depression in factor V was recorded. Factor VIII and thrombocyte count in blood were normal in most patients. In the light of the known effects of ECV on blood coagulation in vivo and in vitro it is concluded that the afibrinogenemia is due to intravascular clotting.Four patients had transient renal damage, manifested by oliguria, azotemia, albuminuria and cylindruria, ascribed to microthrombi in the renal glomeruli.After the bite, the natural course was benign, no major bleeding was observed, and all signs of coagulopathy reverted to normal within 7 days. Therefore we recommend no specific treatment for this condition. In the case of heavily bleeding patients, administration of antiserum against ECV and/or heparin should be considered.


1962 ◽  
Vol 39 (1) ◽  
pp. 129-140 ◽  
Author(s):  
D. J. CANDY ◽  
B. A. KILBY

1. In vivo studies on 5th instar and adult locusts revealed that chitin formation in thorax, abdomen, hind leg and wing was greatest during the first few days after moulting. 2. Wing extracts were used for in vitro experiments, and evidence was obtained for the presence of the following enzymes: hexokinase, phosphohexose isomerase, glutamine transaminase, phosphoglucosamine transacetylase, acetyl coenzyme-A synthetase, phosphoacetylglucosamine mutase and uridine diphosphate N-acetylglucosamine pyrophosphorylase. 3. The results are discussed, and a tentative scheme is presented for the biosynthesis of chitin in the wing of Schistocerca gregaria.


1981 ◽  
Author(s):  
E Szwarcer ◽  
R Giuliani ◽  
E Martinez Aquino

For studying heparin effect on blood coagulation and on inhibitors, the drug was added at increasing amounts to a normal platelet poor plasma (PPP), and to plasmas of patients with variable amounts of clotting factors (cirrhotic, pregnant, etc) -IN VITRO STUDIES-, and infused to the same individuals -IN VIVO STUDIES-. Modifications on two clotting assays (KCCT-TT) were compared to heparin potentiating effect on AntiXa (Denson & Bonnar tech).When studied IN VITRO, the sensibility of KCCT, TT, and AntiXa techniques for heparin measurement was similar. IN VIVO, an apparently greater sensibility using AntiXa technique was observed.For determining if this phenomena was related to a specific enhanced potentiating effect of the inhibitor against Xa, exerted by heparin IN VIVO, experiences were repeated IN VITRO and IN VIVO, measuring heparin effect on KCCT, TT, and on the inhibitor, studied against Xa and thrombin. A personal technique was used for the measurement of Antithrombin III heparin potentiating effect, using diluted platelet poor test plasma, heated (56°C 15’) and incubated with thrombin during a fixed time, and reading residual thrombin on citrated human PPP. IN VITRO, all techniques were similar in their ability to show heparin presence.IN VIVO, the potentiating effect of heparin on the inhibitor, measured against Xa or thrombin, was greater than the changes obtained on KCCT or TT.So, AntiXa-Antithrombin III techniques seem to be more sensitive for heparin measurement IN VIVO.This “dissociation” of results in between the potentiating effect on the inhibitor, that is not simultaneously exerted on global coagulation, is interpreted as a heparin pro-coagulant effect, exerted by the drug IN VIVO.


1977 ◽  
Author(s):  
F. Elsinger

FEIBA IMMUNO is a preparation in which a new activity is generated capable of bypassing factor VIII. The preparation which is used to treat patients with inhibitors (especially inhibitors to factor VIII) is standardized in FEIBA units, i.e. in terms of its in vitro capacity to shorten the activated PTT of a factor VIII inhibitor plasma.It could be concluded from different in vitro experiments that none of the classic’ activated coagulation factors is responsible for the factor VIII bypassing reaction; FEIB-activity seems to be correlated to a new complex of coagulation factors.To get an answer to the question which coagulation factors are essential for FEIB-activity, we tried to generate this activity from different deficient plasmas; from these experiments the following conclusions could be drawn:, the presence of at least factors VII, IX, and X is essential for the generation of the molecular species responsible for factor VIII as well as factor X bypassing activity, but factor V is not bypassed. This activity is not factor Xa itself. Factors VIII and V are not necessary for the generation of this active principle, but factor V is finally needed for its bypassing action.


1961 ◽  
Vol 05 (02) ◽  
pp. 187-200 ◽  
Author(s):  
E. A Loeliger ◽  
A Hensen

SummaryAfter a brief review of the data concerning the cases of Hageman trait hitherto reported in the literature, a patient with severe Hageman factor (HF) “deficiency” (HF-activity below 0.05% of normal) is described. The patient has no haemorrhagic diathesis.In vitro, intrinsic coagulability and fibrinolytic activity are grossly disturbed. On the basis of a diminished fibrinolytic activity in vivo, the rather high activity of several coagulation factors in patient’s plasma could be explained.Thromboplastin formation, once initiated, is normal as to rate; the amount of thromboplastin formed is possibly slightly diminished. Prothrombin consumption is normal. These findings are in agreement with a normal rate ot clot formation, as measured by means of thrombelastography.Normal HF seems to be an initiator of blood coagulation only and not an activator or a substrate involved in thromboplastin formation.The weak anticoagulant property of Hageman trait plasma, described by several authors, is not necessarily due to an inhibitor; it can be explained by the assumption that, in Hageman trait, HF shows normal glass adsorbability and only a very deficient glass activation.


1987 ◽  
Author(s):  
A Kornberg ◽  
S Kaufman ◽  
L Silber ◽  
J Ishay

The extract from the venom sac of Vespa orientalis (VSE) inactivates exogenous and endogenous thromboplastin (Joshua and Ishay, Toxicon, 13:11-20,1975). The prolongation of both prothrombin time (PT) and recalcification time suggests inactivation of other factors. The aim of the present study is to investigate the effect of VSE on clotting factors. A lyophilized VSE with protein concentration of 5 mg/ml was used. Studies were performed in vitro with human plasma and in vivo in cats. Routine methods were employed for the assay of PT, activated tissue thromboplastin (APTT), thrombin time (TT), fibrinogen degradation products (FDP), fibrinogen and factors V,VII,VIII,IX,X. Human plasma was incubated with various concentrations of VSE (0,1,5,10,50,100 μg/ml) for 60 min and for various incubation times (0,5,15,30,+ 60,90,120 min) with 50 μg/ml VSE (n=8). 1 μg/ml VSE prolonged PT from 13.5 to 16 sec (p<0.05) and APTT from 62 to 180 sec. PT was maximal (17.7 sec) with 10 μg/ml and APTT (442 sec) with 50 μg/ml VSE. Factors V,VII,X decreased gradually from 94-105% to 11%,11% and 29% with 100 μg/ml VSE and VIII and IX to 1% even with 1 μg/ml VSE. After 5 min with constant concentration of VSE (50 μg/ml) PT was 14.9 sec (normal 13 sec) and APTT 165 sec (normal 54 sec). Both were maximal (17.5 and 298 sec) after 60 min. Factors VII and X decreased to 13% and 32% and VIII and IX to >1% after 60 min of incubation. Injection of 5 mg/kg VSE to cats (n=6-8) resulted in prolongation of PT from 9.4 to 11.2 sec and of APTT from 19.5 to 63 sec after 5 min. Both were maximal after 90 min (12.3 and 127 sec). Factors V,VII and X decreased from 100% to 7.6%, 13% and 37% and VIII and IX to 1% after 10 min. In all experiments TT and plasma fibrinogen were not affected and FDP were normal. Heating of VSE for 5 min at 80°C abolished completely the anticoagulant activity but dialysis for 24 hr at 4°C had no effect on it. The activity was eluted on Sephadex-25 both in void and post void volumes. The results show that VSE has a potent anticoagulant activity against various factors. Factors VIII and IX are markedly decreased. The effect on V, VII and X is moderate. Plasma fibrinogen is not affected. The nature and clinical significance of the anticoagulant activity merit further investigation.


1978 ◽  
Vol 30 (1) ◽  
pp. 100-102 ◽  
Author(s):  
Franz Klink ◽  
Ruediger Grosspietzsch ◽  
Lebrecht Von Klitzing ◽  
Wolfgang Endell ◽  
Wolfdietrich Husstedt ◽  
...  

1999 ◽  
Vol 13 (3) ◽  
pp. 239-244
Author(s):  
Sílvia Magaly Sasso CARVALHO ◽  
Ana Cristina M. POLIZELLO ◽  
Denise Pimenta da Silva LEITÃO ◽  
Augusto César Cropanese SPADARO

A mouthrinse containing cetylamine fluoride (230 ppm in fluoride) was prepared for in vitro studies of fluoride clearance and adsorption by enamel and/or hydroxyapatite using a device that simulates the oral cavity. In vivo studies of fluoride clearance from this mouthrinse were conducted and compared with other fluoride sources. The amount of fluoride adsorbed to tooth blocks or powdered hydroxyapatite, both treated with this cetylamine fluoride mouthrinse once or twice a day, was determined. The results of these studies showed that it is possible to prepare a mouthrinse with cetylamine fluoride for alternative use by patients for the prevention and therapy of dental caries.


2020 ◽  
Vol 10 (9) ◽  
pp. 397
Author(s):  
Kimihiko Takada ◽  
Mayuko Takano ◽  
Aiko Kunii ◽  
Kei Harayama ◽  
Akira Ito ◽  
...  

Background: Nobiletin is contained in Shiikuwasa fruit, a popular citrus fruit from Okinawa Prefecture in Japan. Nobiletin reportedly acts as a strong antioxidant, an anti-inflammatory agent, and an anti-cancer agent, and it suppresses the expression of TF which triggers blood coagulation. However, in vivo verification of in vitro reports is necessary. This study used a rat model of LPS-induced microthrombosis based on the in vivo studies as previously reported. Sustained intravenous injection of LPS changed all blood coagulation indicators in the direction of thrombus formation. The aim of this study was to determine if intake of nobiletin could suppress DIC-like symptoms.Methods: Experimental SD rats were fully anesthetized and fixed to an operating table. Either LPS alone or nobiletin (50 mg/kg) plus LPS was given to rats to investigate the repressive effects of nobiletin on the expression of blood coagulation factors.Results: After 4 h of LPS infusion (12.5 mg/kg/h, i.v.), PLT counts and Fbg levels in rat plasma decreased by 80% and 74%, respectively. PT and APTT were extended by 180% and 256%, respectively. TF activity and PAI-1 antigen levels were remarkably increased (54- and 86-fold, respectively vs. control). Pretreatment on nobiletin (50 mg/kg, p.o.) reduced or suppressed fluctuations in blood coagulation indices caused by LPS. TF activity was repressed almost completely by nobiletin pretreatment. After 4 h, PAI-1 antigen levels in nobiletin-treated animals were repressed 82.6% compared to LPS-treated rats. Nobiletin repressed LPS-induced changes in TF and PAI-1 more effectively than other parameters. Further, nobiletin repressed fibrin thrombi  formation in the renal glomeruli induced by LPS treatment.Conclusions: Nobiletin was found to reduce LPS-induced DIC-like symptoms in rats. In the fluctuations of blood indices related to the coagulation cascade, nobiletin suppressed the LPS-induced expression of PAI-1 and TF more effectively than other indices. The binding sites of transcription factors that are activated by LPS-induced signals reside in the promoter areas of TF and PAI-1 gene sequences. Thus, the suppression of TF and PAI-1 expression by nobiletin appears similar to mechanisms previously evaluated during in vitro experiments. Importantly, nobiletin repressed fibrin deposition in the renal glomeruli induced by LPS treatment and improved overall health. Nobiletin may function as an anti-thrombogenic agent when ingested daily. Keywords: nobiletin; LPS; DIC model; blood coagulation; anti-thrombogenic


2002 ◽  
Vol 1 (2) ◽  
pp. 153535002002021
Author(s):  
Mian M. Alauddin ◽  
Atranik Shahinian ◽  
Erlinda M. Gordon ◽  
Peter S. Conti

2′-Deoxy-2′-flouro-5-methyl-1-β-d-arabinofuranosyluracil (FMAU) has been evaluated in HT-29 cells as a potential positron emission tomography (PET) radiotracer for imaging HSV-tk gene expression in vivo. In vitro experiments demonstrate that the accumulation of [14C]-FMAU in HSV-tk-expressing cells is 2.4-fold ( p < .02), 4.0-fold ( p < .001), and 5.3-fold ( p < .001) higher than the wild-type cells at 1, 3, and 5 hr, respectively. In vivo studies revealed that the tumor uptake in HSV-tk-expressing cells was 2.3-fold ( p < .001), 3.0-fold ( p < .001), and 5.5-fold ( p < .001) higher than the control cells at 1, 2, and 5 hr, respectively. FMAU was found to be more sensitive compared to our earlier studies using 9-[(3-18F-fluoro-1-hydroxy-2-propoxy)methyl]-guanine ([18F]-FHPG) and 9-(4-[18F]-fluoro-3-hydroxy-methylbutyl)guanine ([18F]-FHBG) in the same cell lines, although, the specificity was less than FHBG. These results suggest that while FMAU labeled with PET isotopes may be useful for imaging HSV-tk-expressing tumors in vivo, multitracer studies across additional tumor models are necessary in order to identify an optimal PET radiotracer.


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