In Vitro and In Vivo Evaluation of Amino Acid-Functionalized Cellulose Beads for Whole Blood Hemoperfusion

2005 ◽  
Vol 288-289 ◽  
pp. 393-396 ◽  
Author(s):  
Yong Jian Wang ◽  
Yao Ting Yu
Keyword(s):  
Rheumatoid Arthritis ◽  
Amino Acid ◽  
Whole Blood ◽  
Blood Perfusion ◽  
In Vitro Test ◽  
Rheumatoid Factors ◽  
In Vivo Evaluation ◽  
Vitro Test

Phenylalanine linked to cellulose beads was designed as an adsorbent in whole blood hemoperfusion for the therapy of rheumatoid arthritis. In whole blood perfusion tests, the adsorbent adsorbed rheumatoid factors directly from whole blood. In vitro test showed that the adsorbent had good biocompability properties. No acute systemic toxicity and dermal irritancy with extremely low skin sensitizing activity were observed. In vivo animal test with satisfactory results was perfumed with rabbits. Experimental results show that the adsorbent holds promise as a highly effective and safe hemoadsorbent in clinical therapy for rheumatoid arthritis patients by hemoperfusion.

IN VITRO DEMONSTRATION OF "HEPARIN REBOUND"

1987 ◽  
Author(s):  
C Taylor ◽  
R F Baugh
Keyword(s):  
Whole Blood ◽  
Cardiovascular Surgery ◽  
Anticoagulant Activity ◽  
Blood Levels ◽  
In Vitro Test ◽  
Neutralizing Activity ◽  
Vitro Test ◽  
The Stability

"Heparin rebound", the in vivo appearance of measurable heparin anticoagulant activity following theapparent neutralization of heparin by protamine, hasbeen a problem sporadically associated with the use of heparin in cardiovascular surgery. A number of mechanisms have been proposed to explain rebound, and to some extent each may contribute to the phenomena. As yet no reliable, predictable method has been demonstrated for measuring, reproducing or quantifying "heparin rebound".We have demonstrated and measured the appearance of heparin anticoagulant activity following neutralization with protamine in citrated whole blood. The reappearance of heparin anticoagulant activity was associated with a rapid loss of protamine. The loss of protamine followed 1st order enzyme kinetics, and was indicative of the action of an enzyme. The anticoagulant activity which eappeared could be titrated againwith protamine. The loss of protamine neutralizing activity, in whole blood, could be followed by titration with heparin using a recalcified activated clotting time. The rate of loss varied with both individual blood donors and with the type and source of protamine. The rate of loss of protamine was great enough to influence in. vivo heparin/protamine neutralization ratios, i.e. at 4 units of heparin/ml, 1 unit/ml anticoagulant activity was routinely recovered within 30 minutes following initial neutralization. The indications for cardiovascular surgery are:1)the in vivo neutralization ratio should be adjusted to account for loss of protamine activity, 2) the higherthe blood levels of heparin used during surgery, themore significant the potential for heparin rebound, and 3) protamines may be evaluated in an in vitro test which measures the stability of protamine neutralizing activity in whole blood.

scholarly journals Assessment of Three In Vitro Tests and an In Vivo Test for Chloroquine Resistance in Plasmodium falciparumClinical Isolates

1998 ◽  
Vol 36 (1) ◽  
pp. 243-247 ◽  
Author(s):  
Jean Bickii ◽  
Leonardo K. Basco ◽  
Pascal Ringwald
Keyword(s):  
Host Factors ◽  
Chloroquine Resistance ◽  
In Vitro Assays ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
In Vivo Evaluation ◽  
In Vivo Test ◽  
Vitro Test

Three in vitro assays (the isotopic semimicrotest [700 μl per well; 24-well plates], the isotopic microtest [200 μl per well; 96-well plates], and the rapid in vitro test) and the standard in vivo test for chloroquine resistance were compared for 99 clinical isolates of Plasmodium falciparum obtained from symptomatic African patients. The 50% inhibitory concentrations determined by the two isotopic tests were similar and were highly correlated (r = 0.965; P < 0.05), showing a high concordance between the semimicrotest and the microtest. There was a moderate agreement between these two isotopic tests and the in vivo test. Most of the discordant results were probably due to host factors, including reinfections, pharmacokinetic variations, and immunologic response, which are eliminated in in vitro assays. The rapid in vitro test based on the inhibition of chloroquine efflux in the presence of verapamil was poorly concordant with the other tests. Despite some discordant results, isotopic in vitro assays are useful to characterize the phenotypes of individual isolates without the interference of host factors and are complementary to in vivo evaluation of drug efficacy. However, in vitro assays need to be standardized to allow direct comparison of results between different laboratories.

Haemostatic Platelet Plug Formation in the Isolated Rabbit Mesenteric Preparation - An Analysis of Red Blood Cell Participation

1980 ◽  
Vol 44 (01) ◽  
pp. 006-008 ◽  
Author(s):  
D Bergqvist ◽  
K-E Arfors
Keyword(s):  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
In Vitro Test ◽  
Pharmacological Agents ◽  
Vitro Test ◽  
Releasing Effect ◽  
Plug Formation

SummaryIn a model using an isolated rabbit mesenteric preparation microvessels were transected and the time until haemostatic plugs formed was registered. Perfusion of platelet rich plasma gave no haemostasis whereas whole blood did. Addition of chlorpromazine or adenosine to the whole blood significantly prolonged the time for haemostasis, and addition of ADP to the platelet rich plasma significantly shortened it. It is concluded that red cells are necessary for a normal haemostasis in this model, probably by a combination of a haemodynamic and ADP releasing effect.The fundamental role of platelets in haemostatic plug formation is unquestionable but there are still problems concerning the stimulus for this process to start. Three platelet aggregating substances have been discussed – thrombin, adenosine diphosphate (ADP) and collagen. Evidence speaking in favour of thrombin is, however, very minimal, and the discussion has to be focused on collagen and ADP. In an in vitro system using polyethylene tubings we have shown that "haemostasis" can be obtained without the presence of collagen but against these results can be argued that it is only another in vitro test for platelet aggregation (1).To be able to induce haemostasis in this model, however, the presence of red blood cells is necessary. To further study this problem we have developed a model where haemostatic plug formation can be studied in the isolated rabbit mesentery and we have briefly reported on this (2).Thus, it is possible to perfuse the vessels with whole blood as well as with platelet rich plasma (PRP) and different pharmacological agents of importance.

In Vitro Toxicology Methods in Risk Assessment

1996 ◽  
Vol 24 (3) ◽  
pp. 325-331
Author(s):  
Iain F. H. Purchase
Keyword(s):  
Risk Assessment ◽  
Hazard Assessment ◽  
Human Health Risk ◽  
In Vitro Test ◽  
In Vitro Methods ◽  
New Concepts ◽  
Vitro Test

The title of this paper is challenging, because the question of how in vitro methods and results contribute to human health risk assessment is rarely considered. The process of risk assessment usually begins with hazard assessment, which provides a description of the inherent toxicological properties of the chemical. The next step is to assess the relevance of this to humans, i.e. the human hazard assessment. Finally, information on exposure is examined, and risk can then be assessed. In vitro methods have a limited, but important, role to play in risk assessment. The results can be used for classification and labelling; these are methods of controlling exposure, analogous to risk assessment, but without considering exposure. The Ames Salmonella test is the only in vitro method which is incorporated into regulations and used widely. Data from this test can, at best, lead to classification of a chemical with regard to genotoxicity, but cannot be used for classification and labelling on their own. Several in vitro test systems which assess the topical irritancy and corrosivity of chemicals have been reasonably well validated, and the results from these tests can be used for classification. The future development of in vitro methods is likely to be slow, as it depends on the development of new concepts and ideas. The in vivo methods which currently have reasonably developed in vitro alternatives will be the easiest to replace. The remaining in vivo methods, which provide toxicological information from repeated chronic dosing, with varied endpoints and by mechanisms which are not understood, will be more difficult to replace.

Animal Models and Alternatives in the Quality Control of Vaccines: Are In Vitro Methods or In Vivo Methods the Scientific Equivalent of the Emperor's New Clothes?

1995 ◽  
Vol 23 (1) ◽  
pp. 61-73
Author(s):  
Coenraad Hendriksen ◽  
Johan van der Gun
Keyword(s):  
Quality Control ◽  
Test Methods ◽  
In Vitro Test ◽  
Large Numbers ◽  
Alternative Approach ◽  
Inactivated Vaccines ◽  
Vitro Test

In the quality control of vaccine batches, the potency testing of inactivated vaccines is one of the areas requiring very large numbers of animals, which usually suffer significant distress as a result of the experimental procedures employed. This article deals with the potency testing of diphtheria and tetanus toxoids, two vaccines which are used extensively throughout the world. The relevance of the potency test prescribed by the European Pharmacopoeia monographs is questioned. The validity of the potency test as a model for the human response, the ability of the test to be standardised, and the relevance of the test in relation to the quality of the product are discussed. It is concluded that the potency test has only limited predictive value for the antitoxin responses to be expected in recipients of these toxoids. An alternative approach for estimating the potency of toxoid batches is discussed, in which a distinction is made between estimation of the immunogenic potency of the first few batches obtained from a seed lot and monitoring the consistency of the quality of subsequent batches. The use of animals is limited to the first few batches. Monitoring the consistency of the quality of subsequent batches is based on in vitro test methods. Factors which hamper the introduction and acceptance of the alternative approach are considered. Finally, proposals are made for replacement, reduction and/or refinement (the Three Rs) in the use of animals in the routine potency testing of toxoids.

scholarly journals Tablet Scoring: Current Practice, Fundamentals, and Knowledge Gaps

2019 ◽  
Vol 9 (15) ◽  
pp. 3066 ◽  
Author(s):  
Emmanuel Reginald Jacques ◽  
Paschalis Alexandridis
Keyword(s):  
Prescription Drugs ◽  
In Vitro Test ◽  
Dose Administration ◽  
Solid Dosage ◽  
Non Invasive ◽  
Health Care Practitioners ◽  
Tablet Splitting ◽  
Vitro Test

Oral solid dosage formulations and/or tablets have remained the preferred route of administration by both patients and health care practitioners. Oral tablets are easy to administer, they are non-invasive and cause less risk adversity. Because of the lack of commercially available tablet dose options, tablets are being split or partitioned by users. Tablet scoring refers to the breakage of a tablet to attain a desired efficacy dose and is an emerging concept in the pharmaceutical industry. The primary reason for the tablet scoring practice is to adjust the dose: dose tapering or dose titrating. Other reasons for tablet partitioning are to facilitate dose administration, particularly among the pediatric and the geriatric patient population, and to mitigating the high cost of prescription drugs. The scope of this review is to: (1) evaluate the advantages and inconveniences associated with tablet scoring/portioning, and (2) identify factors in the formulation and the manufacturing of tablets that influence tablet splitting. Whereas tablet partitioning has been a common practice, there is a lack of understanding regarding the fundamentals underpinning the performance of tablets with respect to splitting. Several factors can influence tablet partitioning: tablet size, shape, and thickness. A requirement has recently been set by the European Pharmacopoeia and the U.S. Food and Drug Administration for the uniformity of mass of subdivided tablets. For breaking ease, an in-vivo reference test and a routinely applicable in-vitro test need to be established.

Characteristics and Biocompatibility of the Hydroxyapatite Based Two Ternary Biocomposites

2016 ◽  
Vol 720 ◽  
pp. 130-140
Author(s):  
Berrak Bulut ◽  
Ziya Engin Erkmen ◽  
Eyup Sabri Kayali
Keyword(s):  
Mechanical Properties ◽  
Physical And Mechanical Properties ◽  
Secondary Phase ◽  
In Vitro Test ◽  
Compression Tests ◽  
Vitro Test ◽  
Dental Applications ◽  
The Ideal

Hydroxyapatite (HA) is a very popular bioceramic for orthopedic and dental applications. Although HA has excellent biocompatibility, its inferior mechanical properties make it unsuitable for load-bearing implant applications. Therefore, HA should be strengthened by a secondary phase for robust mechanical properties. The aim of this study was to compare the properties of HA-Al2O3 (HAC) and HA-ZrO2 (HZC) composites with the addition of 5 and 10 wt% commercial inert glass (CIG); independently. The mixture powders were pressed and then, the pellets were sintered between 1000-1300 °C for 4 hours. Microstructural characterizations were carried out using SEM + EDS and XRD, while hardness and compression tests were done to measure mechanical properties. In order to investigate the biocompatibility behavior of the samples in vitro and in vivo tests were performed. The mechanical properties of HAC composites increased with rising CIG content and increasing sintering temperature. For HZC composites, increasing CIG content caused an elevation in hardness and a decrease in compressive strength values at 1300 °C. The composites having the best physical and mechanical properties also showed improved bioactive properties at in vitro test. In this study, the ideal composite was selected as HZC5 sintered at 1200 °C depending on the microstructure, mechanical and biocompatibility properties.

scholarly journals Prediction of in Vivo Cytotoxicity of Chemotherapeutic Agents by Their Effect on Malignant Leukocytes in Vitro

Blood ◽  
1967 ◽  
Vol 30 (2) ◽  
pp. 176-188 ◽  
Author(s):  
MARTIN J. CLINE
Keyword(s):  
Test System ◽  
Chemotherapeutic Agents ◽  
Response To Treatment ◽  
In Vitro Test ◽  
Malignant Cells ◽  
Vitro Test ◽  
In Vitro Effects ◽  
In Vivo Cytotoxicity

Abstract In order to develop a test system for predicting the response to chemotherapeutic agents, leukocytes from patients with leukemia and leukolymphosarcoma were cultured in vitro and the effect of several drugs on the incorporation of H3-uridine into ribonucleic acid was measured. Cortisol, vincristine and cytosine arabinoside at concentrations near the therapeutic range produced inhibition of H3-uridine incorporation in sensitive leukocytes. The in vitro effects of 6-mercaptopurine and methotrexate were variable. In 39 trials on 25 patients with leukemia or lymphosarcoma, the in vitro test was used successfully to predict the response to treatment with prednisone and vincristine. It was concluded that the in vitro test system can predict the in vivo cytotoxicity of certain drugs for malignant cells, although it cannot be used to predict the likelihood of the induction of remissions with these drugs.

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