Anticoagulant And Antithrombotic Properties Of D-PHE-PRO-ARG-H /1/, BOC-D-PHE-PRO-ARG-H /2/, BZ-D-ALE-PRO-ARG-H /3/ And β-D-Phenyl-Lactyl-PRO-ARG-H /4/

1981 ◽  
Author(s):  
D Bagdy ◽  
É Barabás ◽  
S Banusz ◽  
E Széll ◽  
I Boaor
Keyword(s):  
Blood Clotting ◽  
Competitive Inhibitor ◽  
Thrombin Time ◽  
In Vivo Experiments ◽  
Anticoagulant Action ◽  
Antithrombotic Effects ◽  
Conscious Rabbits ◽  
Dose Dependent

A series of tripeptide derivatives was synthetized and studied for blood clotting inhibition in vitro and in vivo experiments. Whole blood clotting time /WBCT/, activated partial thromboplastin time /APTT/, thrombin time /TT/ and prothrombin time /PT/ were measured in Thrombelastograph and Coagulometer, resp. using heparin and hirudin as reference substances. The inhibition by /1-4/ of platelet aggregation /PA/ was tested in Chrono-Log Aggregometer. The anticoagulant action of /1-4/ in vivo was investigated in mice, rats, rabbits, dogs and monkeys, resp. by different ways of administration. /1/ was found to be a non competitive inhibitor of thrombin according to Dixon plots /Ki = 7.5 × l0-8 M /. /1-4/ inhibited the thrombin induced PA specifically. By giving to animals i.v.,i.m.,s.c. and orally, resp. /1-4/ proved to be effective in all species and the anticoagulant action was dose dependent. In the course of continuous i.v.infusions to conscious rabbits and narcotized dogs, resp. /3-4 mg pro kg/hr for 3 to 6 hrs / WBCT, APTT and TT prolonged to 3-5 times of the starting values. The anticoagulant effect appeared 15 min after starting and returned to normal within 1-2 hrs after stop the infusions. No change either in blood pressure or in respiration could be observed during the infusions. ED50 and LD50 of i.v. infusion in conscious rabbits was found to be 1.3 and 58 mg, resp.. Our results suggest that /1-4/ represent powerful anticoagulant and antithrombotic effects and can be regarded as a new tyoe of anticoagulants.

A Comparison of Anticoagulation Activity of a Potent Heparin Preparation in Different Test

1979 ◽  
Author(s):  
A.S. Bhargava ◽  
J. Heinick ◽  
Chr. Schöbel ◽  
P. Günzel
Keyword(s):  
Blood Clotting ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Thrombin Time ◽  
Beagle Dogs ◽  
Clotting Time ◽  
Relative Potencies ◽  
Heparin Preparation

The anticoagulant effect of a new potent heparin preparation was compared with a commercially available heparin in vivo after intravenous application in beagle dogs. The anticoagulant activity was determined using thrombin time, activated partial thromboplastin time and whole blood clotting time after 5, 10 and 30 minutes of application. The relative potency of the new heparin preparation (Scherinq) was found to be 1.62 to 2.52 times higher than heparin used for comparison (150 USP units/mg, Dio-synth). The anticoagulant properties of both preparations were also studied in vitro using dog and human plasma. The relative potencies in vitro correlated well with those obtained in vivo. Further characterization with amidolytic method using chromogenic substrate for factor Xa and thrombin (S-2222 and S-2238 from KABI, Stockholm) showed that heparin (Schering) contains 243 to 378 USP units/raq depending upon the test systems used to assay the anticoagulation activity and in addition, proves the validity of the amidolytic method.

The Source Of Thromboxane Formation Associated With Complement-Mediated Pulmonary Leukostasis In Sheep

1981 ◽  
Author(s):  
J W D McDonald ◽  
M Ali ◽  
J D Cooper ◽  
E R Townsend
Keyword(s):  
Pulmonary Artery ◽  
Blood Clotting ◽  
Ex Vivo ◽  
Lung Parenchyma ◽  
Mechanical Obstruction ◽  
Vascular Response ◽  
In Vivo Experiments ◽  
Pulmonary Arterial

The infusion of plasma containing Zymosan-activated complement (ZAC) into sheep produces leukopenia with pulmonary leukostasis and transient pulmonary arterial hypertension (PAH). Previous work has related PAH to elevations of plasma thromboxane B2 (TXB2) rather than to mechanical obstruction by sequestered leukocytes (WBC). We have investigated the source of the TXB2 formation in this model. Incubation of platelet-poor WBC preparations with arachi- donate resulted in negligible TXB2 formation. WBC-poor platelet preparations on the other hand formed significant amounts of TXB2 (approximately 6-18 ng/108 platelets). Incubation of whole sheep blood or plasma with ZAC failed to generate significant amounts of TXB2. Thus, WBC agglutination in vitro did not induce platelet TXB2 formation.Pretreatment of sheep with aspirin (ASA)(10 mg/kg IV) completely blocked TXB2 formation and PAH in response to infusion of plasma containing ZAC. The infusion of 10-50% nonnal platelets into sheep 4 hours after ASA pretreatment failed to restore TXB2 formation and pulmonary vascular response to subsequent challenge with ZAC. TXB2 formation during blood clotting ex vivo was restored by the platelet infusions. These experiments make it appear unlikely that platelets are the source of the TXB2. It is possible that the transfused platelets respond to thrombin but are unable to interact with sequestered leukocytes. Sheep lung and pulmonary artery were incubated in vitro with arachidonate. Lung formed 630 ng TXB2 and 39 ng 6-keto-PGF1α/g of wet tissue. Pulmonary artery formed 9 ng TXB2 and 180 ng 6-keto-PGF1α/g of wet tissue. The relative proportions of TXB2 and 6-keto-PGF1α formed by lung parenchyma but not pulmonary artery resemble the proportions observed in previous in vivo experiments with ZAC. It appears that lung tissue is the most likely source of TXB2 formation causing PAH in response to ZAC-mediated pulmonary leukostasis.

scholarly journals On the effect of salvarsan on blood clotting. Trost (Arch. f. Derm. u. Syph., 1922, Bd. 139)

2021 ◽  
Vol 19 (1) ◽  
pp. 107-107
Author(s):  
N. Yasnitsky
Keyword(s):  
Blood Clotting ◽  
Arsenic Compounds ◽  
In Vivo Experiments ◽  
Organic Arsenic

In order to find out the effect of organic arsenic compounds in the form of salvarsan and its derivatives on blood clotting the author set a series of in vitro and in vivo experiments by the methods of Brkеrʹa and Schultz'a. These experiments convinced the author that organic arsenic compounds such as salvarsan already in minimal amounts cause in vitro clotting retardation.

Vitamin D as a Regulator of Adipocyte Differentiation Effects in vivo and in vitro

2018 ◽  
Vol 69 (3) ◽  
pp. 731-734
Author(s):  
Alin Constantin Pinzariu ◽  
Teodor Oboroceanu ◽  
Florin Zugun Eloae ◽  
Ioana Hristov ◽  
Victor Vlad Costan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipocyte Differentiation ◽  
Dependent Manner ◽  
Omental Adipose Tissue ◽  
In Vivo Experiments ◽  
Dose Dependent ◽  
Stromal Stem Cells

The age-associated adiposity and the effect of long-term vitamin D was studied in vitamin D deficient rats. In in vivo experiments, the influence of a 9 months of vitamin D treatment (weekly oral gavage with 0.125 mg vitamin D3 (5000 IU)/100g body weight) on the adipocyte precursors from the omental adipose tissue was examinated. In in vitro experiment, rat adipose-derived mesenchymal stromal/stem cells (ASCs) were induced to differentiate into adipocytes in the presence or absence of 25(OH)D3 (0.25, 25, and 2500 nmol/L). ASCs derived from vitamin D-treated animals showed an increase adipogenic potential as compared to vitamin D-deficient rats. The addition of 25(OH)D3 inhibits the adipocyte differentiation and lipid deposition in a dose dependent manner.

scholarly journals HgS Inhibits Oxidative Stress Caused by Hypoxia through Regulation of 5-HT Metabolism Pathway

2019 ◽  
Vol 20 (6) ◽  
pp. 1364 ◽  
Author(s):  
Qiangqiang He ◽  
Ji Ma ◽  
Praveen Kumar Kalavagunta ◽  
Liangliang Zhou ◽  
Junyi Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prescription Drug ◽  
In Vivo Experiments ◽  
Behavioral Abnormalities ◽  
Experimental Drug ◽  
Pharmacologic Effect ◽  
Dose Dependent ◽  
And Oxidative Stress

This study aims to reveal the potential relationship between 5-HT and oxidative stress in the organism. Our in vitro experiments in RIN-14B cells showed that anoxia leads the cells to the state of oxidative stress. Administration of exogenous 5-HT exacerbated this effect, whereas the inhibition of Tph1, LP533401 alleviated the oxidative stress. Several research articles reported that Cinnabar (consists of more than 96% mercury sulfide, HgS), which is widely used in both Chinese and Indian traditional medicine prescriptions, has been involved in the regulation of 5-HT. The present research revealed that HgS relieved the level of oxidative stress of RIN-14B cells. This pharmacological activity was also observed in the prescription drug Zuotai, in which HgS accounts for 54.5%, and these effects were found to be similar to LP533401, an experimental drug to treat pulmonary hypertension. Further, our in vivo experiments revealed that the administration of cinnabar or prescription drug Zuotai in zebrafish reduced the reactive oxygen species (ROS) induced by hypoxia and cured behavioral abnormalities. Taken together, in organisms with hypoxia induced oxidative stress 5-HT levels were found to be abnormally elevated, indicating that 5-HT could regulate oxidative stress, and the decrease in the 5-HT levels, behavioral abnormalities after treatment with cinnabar and Zuotai, we may conclude that the therapeutic and pharmacologic effect of cinnabar and Zuotai may be based on the regulation of 5-HT metabolism and relief of oxidative stress. Even though they aren’t toxic at the present dosage in both cell lines and zebrafish, their dose dependent toxicities are yet to be evaluated.

Quantitation of the Coagulation Inhibition in Vivo Due to Breakdown Products of Fibrin

1970 ◽  
Vol 23 (03) ◽  
pp. 477-485 ◽  
Author(s):  
P. S Mitchell ◽  
F. K Beller
Keyword(s):  
Blood Clotting ◽  
Fibrinogen Level ◽  
Degradation Products ◽  
Thrombin Time ◽  
Clotting Time ◽  
Human Fibrinogen ◽  
Quantitative Basis ◽  
Coagulation Inhibition

SummaryDegradation products of human fibrinogen were prepared by in vitro lysis of fibrin clots by urokinase activation and injected into rabbits on a quantitative basis. The dose necessary to anticoagulate the animal was equal to 2½ to 3 times the animals’ fibrinogen level. The effect on whole blood clotting time and thrombin time lasted for approximately 2 hrs. The “r” time of the TEG returned to normal after 1 hr while the “Max” value remained abnormal for more than 120 min. Degradation product E was shown to clear more rapidly than D by immunochemical techniques. The overall T ½ clearance was found to be approximately 12 hrs.

Anticoagulant Kinetics Following Bolus Injection of Heparin

1979 ◽  
Vol 42 (04) ◽  
pp. 1248-1260 ◽  
Author(s):  
Lyle F Mockros ◽  
Samuel D Hirsch ◽  
Leon Zuckerman ◽  
Joseph A Caprini ◽  
William P Robinson ◽  
...  
Keyword(s):  
Whole Blood ◽  
Blood Clotting ◽  
Anticoagulant Effect ◽  
Post Injection ◽  
Clotting Time ◽  
Sequential Samples ◽  
Dose Dependent ◽  
Blood Clotting Time

SummaryBolus injections of beef-lung heparin at doses of 50, 100 and 200 u/kg body weight were administered to mongrel dogs. Neutralization of the anticoagulant effect was evaluated using sequential samples withdrawn from the animals (in vivo samples) and aliquots from a 100 ml sample withdrawn from the dog at 30 minutes post-injection (in vitro samples). Tests of the activated partial thromboplastin time (APTT) and prothrombin time (PT) did not indicate the degree of anticoagulation. Tests of the whole blood clotting time (WBCT), celite- activated whole blood clotting time (ACT), and celite-activated thromboelastography (ATEG) indicated pronounced hypocoagulability immediately after the injection, followed by a fairly rapid decay in anticoagulability, and a slight Ziype/coagulability at three to four hours post injection. The results from the in vitro ATEG samples were essentially identical to those on the in vivo samples, whereas the in vitro WBCT and ACT generally indicated higher degrees of anticoagulation. Calculated half-lives of the anticoagulant effect are significantly shorter than previously reported, being 18 to 36 minutes, and slightly dose dependent. The decay of the effects, however, does not appear to follow a single exponential curve, dropping very rapidly immediately post-injection and at a somewhat slower rate 60 or more minutes post-injection.

P6275Role of autophagy in imatinib-induced cardiotoxicity

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kobara ◽  
N Naseratun ◽  
Y Watanabe ◽  
H Toba ◽  
T Nakata
Keyword(s):  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Cardiac Tissue ◽  
Oxygen Species ◽  
In Vitro Experiments ◽  
In Vivo Experiments ◽  
Myocyte Apoptosis ◽  
Dose Dependent

Abstract Background Cardiotoxicity is one of the severe adverse effects of chemotherapeutic agents. Imatinib, a therapeutic agent for chronic myelogenous leukemia, has been reported to induce cardiotoxicity. Autophagy is an intracellular bulk protein and organelle degradation process, but it is unclear whether autophagy functions as pro-death or pro-survival program during disease conditions. We examined whether imatinib induces myocyte autophagy and the role of autophagy in imatinib-induced cardiotoxicity in in vitro and in vivo experiments. Methods In in vitro experiments, neonatal rat cardiac myocytes were treated with imatinib (1, 5, 10 μM; 1–6 hrs). Inhibition of autophagy was performed using 3-methyl-adenine (3MA), an autophagic inhibitor, and transfection with Atg5-targeted siRNA. Myocyte apoptosis was detected by morphological change in nuclei and caspase 3 activity. Mitochondria-derived reactive oxygen species production was detected using MitoSOX and mitochondrial membrane potential was assessed by TMRM staining. Expressions of cytochrome c in mitochondria and cytosole were examined by Werstern blotting. Myocyte autophagy was assessed by monodansylcadaverine staining and microtubule-associated protein light chain (LC) 3-II expression. In in vivo experiments, C57BL6 mice were treated with imatinib (50 and 200 mg/kg/day) for 5 weeks in the presence or absence of 3MA. Cardiac function was examined by echocardiography. In cardiac tissue, apoptotic myocytes were examined by TUNEL assay and autophagy was examined by LC3-II expression. Results In in vitro experiments, imatinib increased apoptotic nuclei and caspase 3 activity, in a dose-dependent manner. Consequently, imatinib augmented production of mitochondria-derived reactive oxygen species, loss of mitochondrial membrane potential, and the release of cytochrome c from mitochondria to cytosole, suggesting that imatinib induced mitochondrial-apoptotic pathway. On the other hand, imatinib significantly increased monodansylcadaverine stained dots and LC3-II expression, suggesting that imatinib increased autophagy. 3MA and Atg5 siRNA augmented imatinib-induced apoptosis by 60% and 30%, respectively. In in vivo experiments, imatinib (200 mg) exhibited the dilatation of left ventricle by 15% and the depression of left ventricular fractional shortening by 23%. Ratio of apoptotic myocytes was significantly increased and LC3-II expression in cardiac tissue was enhanced by imatinib in a dose-dependent fashion. Co-treatment with 3MA and imatinib further impaired imatinib-induced myocyte apoptosis by 3 fold and LV dysfunction by 20%. Conclusion These results indicate that imatinib induced myocyte apoptosis, leading to cardiac dysfunction. Imatinib enhanced myocyte autophagy as a consequence of apoptosis and autophagy was a beneficial phenomenon in this condition.

Anticoagulant and Antithrombotic Action of Novel Specific Inhibitors of Thrombin

1980 ◽  
Vol 43 (02) ◽  
pp. 118-123 ◽  
Author(s):  
J Hauptmann ◽  
B Kaiser ◽  
F Markwardt ◽  
G Nowak
Keyword(s):  
Time Course ◽  
Anticoagulant Effect ◽  
Thrombin Time ◽  
Anticoagulant Action ◽  
Derivatives Of ◽  
Specific Inhibitors

SummaryA series of new specific inhibitors of thrombin, cyclic amides of Nα-arylsulfonyl-amidinophenylalanine, was studied for anticoagulant action in vitro and in vivo. The inhibitors showed strong anticoagulant effects in vitro. The time course of the anticoagulant effect of the inhibitors in rabbits and rats was monitored using plasma thrombin time determinations. In rats, the inhibitors prevented the formation of experimental venous thrombi and of thrombin-induced microthrombosis. The new derivatives of benz-amidine presented may be useful as immediately acting anticoagulants.

Clinical And Experimental Studies On The Ionic And Nonionic Contrast Media Interactions With Anticoagulant Drugs

1981 ◽  
Author(s):  
Z Parvez ◽  
H L Messmore ◽  
R Moncada ◽  
A C Anderson ◽  
J Fareed
Keyword(s):  
Contrast Media ◽  
Partial Thromboplastin Time ◽  
Experimental Studies ◽  
Thrombin Time ◽  
Dextran 40 ◽  
Sodium Heparin ◽  
In Vivo Experiments ◽  
Anticoagulant Action ◽  
Anticoagulant Drugs

Interactions of ionic and non-ionic radiologic contrast media (CM) with anticoagulant drugs like heparin and Dex- tran-40 have been investigated. Renografin-60 (Squibb and Sons, Princeton, New Jersey), P-297, ioxigalic acid and iothalamic acid (Laboratoire Guerbet, Paris, France) were used. Human, monkey, dog and rabbit plasmas were incubated with CM, CM + heparin, CM + Dextran-40 and saline; prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time (TT) were determined. In human plasma, Renografin-60 (final cone. 30 mg/ml) produced a strong anticoagulant effect and clotting times PT, PTT, and TT were prolonged by 1-1.5X their base value. When Renografin-60 was supplemented with 0.2u/ml heparin, the TT was greatly elevated, >100 secs, (control < 20 secs). No such prolongation of TT was noted when Dextran-40 was mixed into CM + plasma mixture. Iothalamic acid also showed potent anticoagulant action. P-297, which is a .non-ionic CM, showed the least anticoagulant action by itself, but did manifest some synergistic reaction with 0.2 - 0.4u/ml heparin (TT >100 secs, with 10 NIH u/ml thrombin). Similar results were obtained with monkey, dog and rabbit plasmas. In the in vivo experiments, dogs weighing 11-18kg were injected intravenously with 100-150 u sodium heparin/kg body weight, along with 50-100 ml Renografin-60. Blood samples were drawn at 1 hr., 3 hrs., 4 hrs., and 6 hrs., post injection and assayed for clotting times. 5 ml/kg CM injected with 25 u/kg heparin prolonged the activated partial thromboplastin time (APPT) and TT for upto 6 hours, while sodium heparin along produced anticoagulant effects for shorter duration (< 4 hours). Our studies indicate that ionic forms of CM produce relatively stronger antithrombotic response in animals as compared to non-ionic ones and utmost care should be exercised in their usage in patients on anticoagulant drugs.

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