scholarly journals Correlating Labeling Chemistry and in-vitro Test Results with the Biological Behavior of Radiolabeled Proteins

1986 ◽  
Vol 1 (3) ◽  
pp. 111-120 ◽  
Author(s):  
Suresh C. Srivastava ◽  
George E. Meinken

A study of the effect of various rediochemical labeling parameters on the in-vivo behavior of proteins, in particular of monoclonal antibodies, was carried out. Both radioiodination, and radiometal labeling (using protein-chelating agent conjugates), of antimelanoma, antiplatelet, and anticolon carcinoma monoclonal antibodies (222.28s, 7E3, and GA-733 respectively), as well as the direct labeling of human serum albumin with 99m Tc, were investigated. Different aspects of the biological behavior are affected in relation to the labeling chemistry involved. These include the immunoreactivity, blood clearance and tissue uptake kinetics, and rates and routes of excretion. Individual radionuclide effects have often to be addressed separately. Some antibodies are more susceptable to alteration from labeling conditions than others. Careful optimization of labeling and purification procedures is thus necessary for particular radionuclide/antibody combinations in order to obtain predictable and reproducible in-vivo results for both immunoscintigraphy and immunotherapy applications.

2020 ◽  
Vol 31 (1) ◽  
pp. 21
Author(s):  
Anella Retna Kumala Sari ◽  
Firdaus Auliya Rahmah ◽  
Syamsuddin Djauhari

<em></em><em>One of the important diseases on chili is anthracnose caused by </em>Colletotrichum capsici<em>. </em>Curcuma<em> extracts and </em><em>their essential oils were known as antifungal, but nonessential compounds have not been widely tested. This study aimed to assay the effectiveness of nonessential compounds of </em>Curcuma longa<em>, </em>C. zedoaria<em>, and </em>C. aeruginosa<em> to </em>C. annuum<em>. This study was conducted in November 2014 until Mei 2015 at Brawijaya University. The nonessential compound was obtained by soaking rhizome of </em>C. longa,   C.   zedoaria<em>,  and </em>C.   aeruginosa<em> in methanol, then distilled by</em><em>using rotary vacuum evaporator. Nonessential chemical compunds were identified by using HPLC. Effectiveness evaluation of nonessential compounds from three species of </em>Curcuma<em> was done by in </em>vitro<em> and </em>in vivo<em> test. Tested treatments were three species of </em>Curcuma<em> spp and 6 concentration levels of nonessential compounds (0 ppm, 4 ppm, 6 ppm, 8 ppm, 10 ppm, and</em><em> 12 ppm). The xperiment was performed in Factorial Complete Randomized Design, with 18 treatments combination, and replicated three times. Results of HPLC analysis showed the rhizomes of the three </em>Curcuma<em> species contained curcumin and </em>desmethoxycurcumin<em> in various concentrations. The highest </em><em>level was found in the </em>C. longa<em> extract (13.792 ppm curcumin and 67.156 ppm </em>desmethoxycurcumin<em>). However, in vitro test results showed nonessential compound of </em>C. zedoaria<em> was most effective in inhibiting </em>C. annuum<em> growth.  The 10 ppm concentration inhibited 81.53 % of fungal growth.  Further, the in vivo test, also indicated the same, it’s most effective in hampering the growth of anthracnose symptoms. Therefore, curcumin and </em>desmethoxycurcumin<em> from three species of </em>Curcuma<em> have potential to be developed as botanical fungicide.</em>


1992 ◽  
Vol 20 (4) ◽  
pp. 537-548
Author(s):  
Virginia C. Gordon

The EYTEX™ system is an in vitro method for predicting in vivo ocular irritation via a target biomacromolecular approach. EYTEX™ uses changes of relevant macromolecules upon exposure to chemicals and formulations to predict in vivo irritancy and toxicity endpoints. The EYTEX™ system is based on alterations in the conformation and hydration of an ordered macromolecular matrix. An oligomeric protein with a molar mass of approximately 300,000g/mol is the major active component of the reagent. This oligomer, characterised by 12 subunits, associates itself into strands which are then incorporated into a gel network. This network also includes smaller proteins, peptides, amino acids, aminoglycans and mucopolysaccharides, which contribute to the overall response of the macromolecular matrix to a diverse array of test compounds, such as acids, bases, salts, solvents, surfactants, lubricants, preservatives, emulsions, dyes, amines, amides and many others. The method has been extensively evaluated using chemicals and formulations from diverse classes and with different ranges of toxicity, representing various mechanisms of ocular toxicity. Results using the in vitro test correlate broadly with the Draize in vivo eye irritancy test results. Quantification of the EYTEX™ method is based on measurement of changes in optical density of the matrix, which are sensitive to the conformation and hydration of protein, as well as the order in the matrix. These changes, which occur when the matrix is exposed to chemicals and formulations, can be used to predict in vivo ocular irritancy. Calibrators and controls provide assay standardisation with a 4–8% coefficient of variation. Multiple dose and time variables relating to irritancy potential can be assessed and compared with Draize in vivo results. The EYTEX™ system provides a comprehensive set of four protocols suitable for analysing chemicals and formulations with varying degrees and mechanisms of ocular irritancy.


1995 ◽  
Vol 2 (2) ◽  
pp. 99-103 ◽  
Author(s):  
Marcel Gielen

An overview of the in vitro test results on several human tumour cell lines of several series of organotin compounds synthesized at the Free University of Brussels VUB. Several compounds exhibit excellent antitumour activities. in vivo screening also gave very promising results.


1996 ◽  
Vol 24 (3) ◽  
pp. 325-331
Author(s):  
Iain F. H. Purchase

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.


1995 ◽  
Vol 23 (1) ◽  
pp. 61-73
Author(s):  
Coenraad Hendriksen ◽  
Johan van der Gun

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.


2019 ◽  
Vol 9 (15) ◽  
pp. 3066 ◽  
Author(s):  
Emmanuel Reginald Jacques ◽  
Paschalis Alexandridis

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.


2016 ◽  
Vol 720 ◽  
pp. 130-140
Author(s):  
Berrak Bulut ◽  
Ziya Engin Erkmen ◽  
Eyup Sabri Kayali

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.


Blood ◽  
1967 ◽  
Vol 30 (2) ◽  
pp. 176-188 ◽  
Author(s):  
MARTIN J. CLINE

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.


1987 ◽  
Author(s):  
C Taylor ◽  
R F Baugh

"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.


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