Thrombogenic Properties of Surface Factor; Evidence for an Anti-Surface Factor Activity in Canine Plasma.

1964 ◽  
Vol 12 (01) ◽  
pp. 035-048 ◽  
Author(s):  
Sotirios G. Iatridis ◽  
John H. Ferguson ◽  
Panayotis G. Iatridis ◽  
Ronald Mauldin
Keyword(s):  
Mode Of Action ◽  
Clotting Factor ◽  
In Vitro Tests ◽  
Inhibitory Mechanism ◽  
Factor Activity ◽  
Activation Product ◽  
Canine Plasma ◽  
Surface Factor

SummaryPurified surface factor (SF or activation product) was prepared from canine plasma and its effect was studied on 22 dogs. It was shown that intravenous injection of SF increased the coagulability of the circulating blood (in vitro tests) and induced thrombosis in areas of vascular stasis (in vivo assay). The hypercoagulability was associated with the injected SF preparation and with no other known clotting factor increase. A second injection performed 61 minutes after the first was less effective. The survival period of injected SF seemed to be relatively short. This might be attributable, in part, to an inhibitory mechanism acting against SF (anti-SF) in plasma. Experimental evidence of the existence of such an inhibitor and its “progressive” mode of action is provided. Anti-SF has a variable titer normally, but appears to increase after the intravenous SF injection in dogs.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

Role of in vivo and in vitro Tests in the Diagnosis of Severe Cutaneous Adverse Reactions (SCAR) to Drug

2019 ◽  
Vol 25 (36) ◽  
pp. 3872-3880 ◽  
Author(s):  
Marcel M. Bergmann ◽  
Jean-Christoph Caubet
Keyword(s):  
Adverse Reactions ◽  
Lymphocyte Transformation ◽  
Stevens Johnson Syndrome ◽  
In Vitro Tests ◽  
High Morbidity ◽  
Patch Tests ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCAR) are life-threatening conditions including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Diagnosis of causative underlying drug hypersensitivity (DH) is mandatory due to the high morbidity and mortality upon re-exposure with the incriminated drug. If an underlying DH is suspected, in vivo test, including patch tests (PTs), delayed-reading intradermal tests (IDTs) and in vitro tests can be performed in selected patients for which the suspected culprit drug is mandatory, or in order to find a safe alternative treatment. Positivity of in vivo and in vitro tests in SCAR to drug varies depending on the type of reaction and the incriminated drugs. Due to the severe nature of these reactions, drug provocation test (DPT) is highly contraindicated in patients who experienced SCAR. Thus, sensitivity is based on positive test results in patients with a suggestive clinical history. Patch tests still remain the first-line diagnostic tests in the majority of patients with SCAR, followed, in case of negative results, by delayed-reading IDTs, with the exception of patients with bullous diseases where IDTs are still contra-indicated. In vitro tests have shown promising results in the diagnosis of SCAR to drug. Positivity is particularly high when the lymphocyte transformation test (LTT) is combined with cytokines and cytotoxic markers measurement (cyto-LTT), but this still has to be confirmed with larger studies. Due to the rarity of SCAR, large multi-center collaborative studies are needed to better study the sensitivity and specificity of in vivo and in vitro tests.

Hemostatic wound dressings: Predicting their effects by in vitro tests

2019 ◽  
Vol 33 (9) ◽  
pp. 1285-1297 ◽  
Author(s):  
Cornelia Wiegand ◽  
Martin Abel ◽  
Uta-Christina Hipler ◽  
Peter Elsner ◽  
Michael Zieger ◽  
...  
Keyword(s):  
Blood Clot ◽  
Wound Dressings ◽  
In Vitro Tests ◽  
Regenerated Cellulose ◽  
Oxidized Regenerated Cellulose ◽  
Inflammatory Reactions ◽  
In Vitro Techniques ◽  
Cotton Gauze

Background Application of controlled in vitro techniques can be used as a screening tool for the development of new hemostatic agents allowing quantitative assessment of overall hemostatic potential. Materials and methods Several tests were selected to evaluate the efficacy of cotton gauze, collagen, and oxidized regenerated cellulose for enhancing blood clotting, coagulation, and platelet activation. Results Visual inspection of dressings after blood contact proved the formation of blood clots. Scanning electron microscopy demonstrated the adsorption of blood cells and plasma proteins. Significantly enhanced blood clot formation was observed for collagen together with β-thromboglobulin increase and platelet count reduction. Oxidized regenerated cellulose demonstrated slower clotting rates not yielding any thrombin generation; yet, led to significantly increased thrombin-anti-thrombin-III complex levels compared to the other dressings. As hemostyptica ought to function without triggering any adverse events, induction of hemolysis, instigation of inflammatory reactions, and initiation of the innate complement system were also tested. Here, cotton gauze provoked high PMN elastase and elevated SC5b-9 concentrations. Conclusions A range of tests for desired and undesired effects of materials need to be combined to gain some degree of predictability of the in vivo situation. Collagen-based dressings demonstrated the highest hemostyptic properties with lowest adverse reactions whereas gauze did not induce high coagulation activation but rather activated leukocytes and complement.

In Vitro Methods as a Tool in Neurotoxicity Studies

1995 ◽  
Vol 23 (4) ◽  
pp. 491-496
Author(s):  
Hanna Tähti ◽  
Leila Vaalavirta ◽  
Tarja Toimela
Keyword(s):  
Risk Evaluation ◽  
Toxicity Testing ◽  
In Vitro Models ◽  
In Vitro Tests ◽  
Industrial Chemicals ◽  
Mercury Compounds ◽  
Toxicological Data ◽  
In Vivo Tests

— There are several hundred industrial chemicals with neurotoxic potential. The neurotoxic risks of most of these chemicals are unknown. Additional methods are needed to assess the risks more effectively and to elucidate the mechanisms of neurotoxicity more accurately than is possible with the conventional methods. This paper deals with general tasks concerning the use of in vitro models in the evaluation of neurotoxic risks. It is based on our previous studies with various in vitro models and on recent literature. The induction of glial fibrillary acidic protein in astrocyte cultures after treatment with known neurotoxicants (mercury compounds and aluminium) is discussed in more detail as an important response which can be detected in vitro. When used appropriately with in vivo tests and with previous toxicological data, in vitro neurotoxicity testing considerably improves risk assessment. The incorporation of in vitro tests into the early stages of risk evaluation can reduce the number of animals used in routine toxicity testing, by identifying chemicals with high neurotoxic potential.

Vasopressin as a neuroendocrine regulator of anterior pituitary hormone secretion

1993 ◽  
Vol 129 (6) ◽  
pp. 489-496 ◽  
Author(s):  
Andreas Kjær
Keyword(s):  
Arginine Vasopressin ◽  
Mode Of Action ◽  
Anterior Pituitary ◽  
Hormone Secretion ◽  
Pituitary Hormones ◽  
Pituitary Hormone ◽  
Anterior Pituitary Hormones ◽  
Anterior Pituitary Hormone

Secretion of the anterior pituitary hormones adrenocorticotropin (ACTH), β-endorphin and prolactin (PRL) is complex and involves a variety of factors. This review focuses on the involvement of arginine-vasopressin (AVP) in neuroendocrine regulation of these anterior pituitary hormones with special reference to receptor involvement, mode of action and origin of AVP. Arginine-vasopressin may act via at least two types of receptors: V1− and V2−receptors, where the pituitary V1−receptor is designated V1b. The mode of action of AVP may be mediating, i.e. anterior pituitary hormone secretion is transmitted via release of AVP, or the mode of action may be permissive, i.e. the presence of AVP at a low and constant level is required for anterior pituitary hormones to be stimulated. Under in vivo conditions, the AVP-induced release of ACTH and β-endorphin is mainly mediated via activation of hypothalamic V1− receptors, which subsequently leads to the release of corticotropin-releasing hormone. Under in vitro conditions, the AVP-stimulated release of ACTH and β-endorphin is mediated via pituitary V1b− receptors. The mode of action of AVP in the ACTH and β-endorphin response to stress and to histamine, which is involved in stress-induced secretion of anterior pituitary hormones, is mediating (utilizing V1− receptors) as well as permissive (utilizing mainly V1− but also V2−receptors). The AVP-induced release of PRL under in vivo conditions is conveyed mainly via activation of V1−receptors but V2−receptors and probably additional receptor(s) may also play a role. In stress- and histamine induced PRL secretion the role of AVP is both mediating (utilizing V1 −receptors) and permissive (utilizing both V1− and V2− receptors). Arginine-vasopressin may be a candidate for the PRL-releasing factor recently identified in the posterior pituitary gland. Arginine-vasopressin of both magno- and parvocellular origin may be involved in the regulation of anterior pituitary hormone secretion and may reach the corticotrophs and the lactotrophs via three main routes: the peripheral circulation, the long pituitary portal vessels or the short pituitary portal vessels.

A battery of in vivo and in vitro tests useful for genotoxic pollutant detection in surface waters

2006 ◽  
Vol 77 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Claudia Pellacani ◽  
Annamaria Buschini ◽  
Mariangela Furlini ◽  
Paola Poli ◽  
Carlo Rossi
Keyword(s):  
Surface Waters ◽  
In Vitro Tests ◽  
Pollutant Detection

Effect of steroids on cartilage metabolism "in vitro"

1986 ◽  
Vol 113 (4_Suppl) ◽  
pp. S35-S40 ◽  
Author(s):  
Marc V.L. DU CAJU ◽  
Raoul P. ROOMAN
Keyword(s):  
Growth Factor ◽  
Thymidine Incorporation ◽  
Normal Serum ◽  
Synthetic Analogue ◽  
Factor Activity ◽  
Poor Growth ◽  
Cartilage Metabolism ◽  
Glucocorticoid Administration

ABSTRACT Conditions characterized by high levels of glucocorticoids are associated with poor growth. Serum somatomedin or insulin-like growth factor activity measured by cartilage bioassay systems is low, but is generally not accompanied by a fall in somatomedin concentration. Hydrocortisone and a synthetic analogue, dexamethasone, impaired the serum stimulated "in vitro" 35S sulphate and 3H-thymidine incorporation in porcine rib cartilage at physiological concentrations. Hydrocortisone added at a concentration of 0,1 μg/ml decreased the potency of normal serum to 50 % of controls. Dexamethasone was at least 10 times more potent. Removal of "in vitro" or "in vivo" administered hydrocortisone with dextran-coated charcoal restored the sulphate and thymidine activity to normal. We conclude that physiological amounts of glucocorticoids inhibit the "in vitro" porcine cartilage metabolism. Glucocorticoid administration "in vivo" does not abolish the activity of the cartilage stimulating effect of serum but affects cartilage metabolism directly or by the induction of locally produced inhibitors of cartilage metabolism.

scholarly journals Comparative Characteristics of Determination of Antioxidant Activity of Sea Buckthorn Fruits by Various Methods

2019 ◽  
Vol 8 (4) ◽  
pp. 48-52
Author(s):  
O. V. Trineeva
Keyword(s):  
Antioxidant Activity ◽  
Medicinal Plant ◽  
Plant Material ◽  
Natural Antioxidants ◽  
Sea Buckthorn ◽  
In Vitro Tests ◽  
Medicinal Plant Material

Introduction. Recently, much attention has been paid to the primary assessment of the pharmacological effect of various drugs using in vivo and in vitro tests. It is known that such a medicinal plant as sea buckthorn, in its phytochemical composition is rich in natural antioxidants: carotenoids, tocopherols, flavonoids, ascorbic acid, etc. In some publications there is information about the antioxidant activity of sea buckthorn and fatty oil based on them. However, information on the comparative characteristics of the use of various methods for determining the antioxidant activity of this type of medicinal plant material and the results obtained are not found in the scientific literature.Aim. The aim of this work was a comparative determination of the antioxidant activity of medicinal plant material of buckthorn fruits of various species of buckthorn.Materials and methods. The total antioxidant activity of water and water-alcohol extracts from the fruits of sea buckthorn fruits was determined using various techniques recommended in the literature. The antioxidant activity of the extracts was determined by permanganometric titration, in vitro inhibition of adrenaline autooxidation, and also in a biological model, Parametium caudatum cell culture.Results and discussion. The effect of the extractant polarity on the value of antioxidant activity was studied. It was found that the highest content of antioxidants in the extraction is observed when using 96 % ethanol as an extractant.Conclusion. Using three methods, the prospects of using sea buckthorn fruits and preparations based on them as a source of antioxidants are shown. 

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