Thrombogenicity Results Of Cold Sterilized (ß-Propiolactone/Ultraviolet Irradiation) PPSB In Chimpanzees

1981 ◽  
Author(s):  
R Kotitschke ◽  
W Stephan ◽  
A M Prince ◽  
B Brotman
Keyword(s):  
Body Weight ◽  
Platelet Count ◽  
Ultraviolet Irradiation ◽  
In Vitro Tests ◽  
In Vivo Models ◽  
Peptide Substrates ◽  
At Iii

In vitro tests were demonstrated to be insufficient for the determination of the thrombogenicity of PPSB preparations with peptide substrates or the TGt50 and the NAPTT. Unequivocal determinations of the thrombogenicity of PPSB preparations are possible only up to now in in vivo models. As an alternative to the up to now proposed dog or hemophilia B dog models we have determined the thrombogenicity of cold sterilized PPSB in chimpanzees. PPSB isolated from ß-propiolactone treated and UV irradiated plasma was injected into the chimpanzees at a dose of approximately 100 units/kg body weight. An FDA licensed PPSB preparation served as a control.15 minutes, 1 h, 4 h, and 24 h after the PPSB application the following parameters were determined in the chimpanzee blood: factors II, VII, IX, X, VIII, fibrinogen, AT III, thrombin coagulase, Quick value, APTT and platelet count.Neither the untreated control preparation nor the PPSB from ß-propiolactone treated and UV irradiated plasma showed signs of a thrombogenic effect in this chimpanzee model.

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. 

Comparison of Two Different In Vivo Models and an In Vitro Model for Caloric Determination of Four Novel Fiber Ingredients

2013 ◽  
Vol 61 (50) ◽  
pp. 12374-12379 ◽  
Author(s):  
Sarah Cervantes-Pahm ◽  
Brenda K. Knapp ◽  
Beob G. Kim ◽  
Yanhong Liu ◽  
Carl M. Parsons ◽  
...  
Keyword(s):  
In Vitro Model ◽  
In Vivo Models ◽  
Vitro Model

scholarly journals The in Vivo Evaluation of the Hemostatic Function of Stored Human Platelets

1977 ◽  
Author(s):  
M. Blajchman ◽  
A. Senyi ◽  
J. Hirsh
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Bleeding Time ◽  
Human Subjects ◽  
Human Platelets ◽  
In Vitro Tests ◽  
In Vivo Evaluation ◽  
Ethyl Palmitate

The assessment of the hemostatic function of stored human platelets is difficult to assess in human subjects. The use of thrombocytopenic rabbits treated with ethyl palmitate to produce reticuloendothelial blockade, has made it possible to study the hemostatic function of human platelets in vivo. The assessment of hemostatic function has been made using both a jugular bleeding time technique and an ear bleeding time technique, and in both, a close correlation between bleeding time and platelet count has been established. Using both methods, both fresh and human platelets stored for 72 hours at 22°C correct the bleeding time of thrombocytopenic animals to levels appropriate to the platelet count achieved. Platelets stored at 4°C using standard methods of preparation and storage were ineffective hemostatically after 24 hours storage. Platelets prepared and stored at 4°C at a pH of 6.4 were hemostatically effective in thrombocytopenic rabbits for as long as 10 days of storage. No correlation, however, was noted between the hemostatic effect of stored platelets and in vitro tests of platelet function. Similarly, the intravenous infusion of ADP and collagen produced similar falls in platelet count for both hemostatically effective and non-effective platelets. These studies provide further evidence for the limitations of in vitro tests of platelet function for the assessment of the potential in vivo function of stored human platelets. Furthermore, these findings raise the possibility for the prolongued liquid storage of human platelets at conditions which minimize bacterial contamination, yet maintain hemostatic efficacy.

Molecular Targets and Early Response Biomarkers for the Prediction of Developmental Toxicity In Vitro

2007 ◽  
Vol 35 (3) ◽  
pp. 335-342 ◽  
Author(s):  
Michael Stigson ◽  
Kim Kultima ◽  
Måns Jergil ◽  
Birger Scholz ◽  
Henrik Alm ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Developmental Toxicity ◽  
Molecular Targets ◽  
Toxicity Testing ◽  
Early Response ◽  
In Vitro Tests ◽  
In Vivo Models ◽  
Response Biomarkers

There is an urgent need for new in vitro methods to predict the potential developmental toxicity of candidate drugs in the early lead identification and optimisation process. This would lead to a reduction in the total number of animals required in full-scale developmental toxicology studies, and would improve the efficiency of drug development. However, suitable in vitro systems permitting robust high-throughput screening for this purpose, for the most part, remain to be designed. An understanding of the mechanisms involved in developmental toxicity may be essential for the validation of in vitro tests. Early response biomarkers — even a single one — could contribute to reducing assay time and facilitating automation. The use of toxicogenomics approaches to study in vitro and in vivo models in parallel may be a powerful tool in defining such mechanisms of action and the molecular targets of toxicity, and also for use in finding possible biomarkers of early response. Using valproic acid as a model substance, the use of DNA microarrays to identify teratogen-responsive genes in cell models is discussed. It is concluded that gene expression in P19 mouse embryocarcinoma cells represents a potentially suitable assay system, which could be readily used in a tiered testing system for developmental toxicity testing.

A Comprehensive Review on the Screening Models for the Pharmacological Assessment of Antiulcer Drugs

2019 ◽  
Vol 14 (3) ◽  
pp. 175-196 ◽  
Author(s):  
Abhinav P. Mishra ◽  
Ankit Bajpai ◽  
Suresh Chandra
Keyword(s):  
Abdominal Pain ◽  
Gastrointestinal Disorder ◽  
Research Area ◽  
In Vitro Models ◽  
Antiulcer Activity ◽  
Ulcer Formation ◽  
In Vivo Models

Background:Due to inappropriate diet, smoking, alcohol consumption, regular use of drugs like NSAIDs and sedentary lifestyle, one may feel upper abdominal pain which may be the predictor of the gastrointestinal disorder called Peptic Ulcer. When an imbalance occurs between the defensive factor and aggressive factor of the stomach, ulcer formation in the esophageal lining, stomach, or duodenum takes place. This leads to the formation of small sores that cause pain. Another condition that synergizes the abdominal pain is vomiting materials which look like coffee grounds, blood in the stool, black or tarry stools. This pain may increase after lunch or dinner. This problem persists, that often leads to the gastroenterologist's consultation.Objective:There are many antiulcer screening models present for the determination of antiulcer activity of the drug molecule. The main objective of this study is to find which model is best for the determination of antiulcer activity.Methods:A literature search was conducted on the databases namely Science direct and PubMed with the help of different keywords such as "Anti-ulcer", "In-vitro models" and "In-vivo models". The search was customized by applying the appropriate filters so as to get the most relevant articles to meet the objective of this review article.Result:There are different research and review papers based on the antiulcer screening models for the determination of antiulcer activity of new drug molecules.Conclusion:On the basis of our study, we found some useful models for the antiulcer activity of drugs and suggested that, if we use in-vitro and in-vivo methods together, then we may obtain the most relevant result in our research area.

In Vivo Activation of the Extrainsic Pathway by F.E.I.B.A

1979 ◽  
Author(s):  
G. Mariani ◽  
D. Romoli ◽  
C. Salvitti ◽  
G. Avvisati ◽  
H.J. Hassan ◽  
...  
Keyword(s):  
Platelet Count ◽  
Blood Coagulation ◽  
High Titre ◽  
Factor Vii ◽  
Disappearance Time ◽  
At Iii ◽  
Coagulation Pathway ◽  
Different Doses

The effect on extrinsic blood coagulation pathway of the infusion of different doses (10 to 100 U./Kg b.w.) of FEIBA in three hemophiliacs with high-titre inhibitor was studied. The concentrate induces a striking shortening of Thrombotest strictly related to the infused dose. The shortening of Thrombotest seems to be due to an activation of factors VII and X. The antigen related to factor VII remains always at the prelnfusion levels. Factor VII-like activity induced in vivo by FEIBA is dramatically reduced after a 24 hrs, in vitro incubation at 4°C with heparin (1 U./ml). No significant changes were observed concerning Fibrinogen, FDP, At-III (amidolytic) and Platelet count, whatever dose was given. These data suggest that FEIBA induces in vivo a strong activation of recipient’s own factor VII and X) proportional to the dose. This activation is short living and its 50% disappearance time is of 210 minutes.

scholarly journals Water as a Blood Model for Determination of CO2 Removal Performance of Membrane Oxygenators

Membranes ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 356
Author(s):  
Benjamin Lukitsch ◽  
Raffael Koller ◽  
Paul Ecker ◽  
Martin Elenkov ◽  
Christoph Janeczek ◽  
...  
Keyword(s):  
Boundary Layer ◽  
Removal Rate ◽  
In Vitro Tests ◽  
Co2 Removal ◽  
Reliable Determination ◽  
Fluid Properties ◽  
Membrane Oxygenators

CO2 removal via membrane oxygenators has become an important and reliable clinical technique. Nevertheless, oxygenators must be further optimized to increase CO2 removal performance and to reduce severe side effects. Here, in vitro tests with water can significantly reduce costs and effort during development. However, they must be able to reasonably represent the CO2 removal performance observed with blood. In this study, the deviation between the CO2 removal rate determined in vivo with porcine blood from that determined in vitro with water is quantified. The magnitude of this deviation (approx. 10%) is consistent with results reported in the literature. To better understand the remaining difference in CO2 removal rate and in order to assess the application limits of in vitro water tests, CFD simulations were conducted. They allow to quantify and investigate the influences of the differing fluid properties of blood and water on the CO2 removal rate. The CFD results indicate that the main CO2 transport resistance, the diffusional boundary layer, behaves generally differently in blood and water. Hence, studies of the CO2 boundary layer should be preferably conducted with blood. In contrast, water tests can be considered suitable for reliable determination of the total CO2 removal performance of oxygenators.

scholarly journals Characterization of Fibrous Wollastonite NYAD G in View of Its Use as Negative Standard for In Vitro Toxicity Tests

Minerals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1378
Author(s):  
Dario Di Giuseppe ◽  
Valentina Scognamiglio ◽  
Daniele Malferrari ◽  
Luca Nodari ◽  
Luca Pasquali ◽  
...  
Keyword(s):  
Biological Response ◽  
Toxicity Tests ◽  
In Vitro Toxicity ◽  
In Vitro Tests ◽  
In Vivo Models ◽  
Mineral Fibre ◽  
In Vivo Testing ◽  
Positive Controls

Today, despite considerable efforts undertaken by the scientific community, the mechanisms of carcinogenesis of mineral fibres remain poorly understood. A crucial role in disclosing the mechanisms of action of mineral fibres is played by in vitro and in vivo models. Such models require experimental design based on negative and positive controls. Commonly used positive controls are amosite and crocidolite UICC standards, while negative controls have not been identified so far. The extensive characterisation and assessment of toxicity/pathogenicity potential carried out in this work indicate that the commercial fibrous wollastonite NYAD G may be considered as a negative standard control for biological and biomedical tests involving mineral fibres. Preliminary in vitro tests suggest that wollastonite NYAD G is not genotoxic. This material is nearly pure and is characterized by very long (46.6 µm), thick (3.74 µm) and non-biodurable fibres with a low content of metals. According to the fibre potential toxicity index (FPTI) model, wollastonite NYAD G is an inert mineral fibre that is expected to exert a low biological response during in vitro/in vivo testing.

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

1973 ◽  
Vol 29 (02) ◽  
pp. 490-498 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Itsuro Kobayashi ◽  
Tadahiro Sano ◽  
Takio Shimamoto
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
The Other ◽  
Endothelial Surface ◽  
Important Interaction ◽  
Blood Coagulability ◽  
The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

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