Commercially available analogues of GnRH and LH secretion

Abstract. Six agonistic derivatives of GnRH, four of which have already been evaluated in clinical trials, were compared with GnRH itself in an in vitro test system (incubation of rat pituitary glands). It was investigated 1) how the release of LH was affected when the pituitary glands were incubated in the presence of these analogues or GnRH, and 2) how the release of LH continued after removal of the analogues or GnRH from the medium. It was also investigated how an in vivo pretreatment for 6 days with several doses of 5 of these analogues or GnRH affects 3) the plasma concentration of LH, 4) the pituitary content of LH, and, in vitro, 5) the autonomous and 6) agonist-stimulated secretion of LH. Each of the analogues showed for each of the six investigated parameters a 10- to 100-fold higher potency than GnRH itself. Between the six analogues there were only minor differences. It is discussed how the six investigated parameters may be the expression of one single property of all these analogues, namely a long retention in the pituitary gland with a strong binding to the GnRH receptor.

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

Blood ◽

10.1182/blood.v30.2.176.176 ◽

1967 ◽

Vol 30 (2) ◽

pp. 176-188 ◽

Cited By ~ 19

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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An in vivo-in vitro test system for the detection of DNA repair and chromosome damage in cells of the respiratory tract of rodents

Mutation Research/Environmental Mutagenesis and Related Subjects ◽

10.1016/0165-1161(87)90040-9 ◽

1987 ◽

Vol 182 (5) ◽

pp. 288

Author(s):

A.H. Poth ◽

A. Timm ◽

H.G. Miltenburger

Keyword(s):

Dna Repair ◽

Respiratory Tract ◽

Test System ◽

Chromosome Damage ◽

In Vitro Test ◽

Vitro Test ◽

In Cells

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Hepatocytes as in vitro test system to investigate metabolite patterns of pesticides in farmed rainbow trout and common carp: Comparison between in vivo and in vitro and across species

Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology ◽

10.1016/j.cbpc.2016.05.003 ◽

2016 ◽

Vol 187 ◽

pp. 62-73 ◽

Cited By ~ 8

Author(s):

Ina Bischof ◽

Jessica Köster ◽

Helmut Segner ◽

Christian Schlechtriem

Keyword(s):

Rainbow Trout ◽

Common Carp ◽

Test System ◽

In Vitro Test ◽

Vitro Test

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Synthesis and evaluation trypanosomicidal activity of new derivatives of megazol

Pharmaceutical and Biological Evaluations ◽

10.26510/2394-0859.pbe.2018.05 ◽

2018 ◽

Vol 5 (2) ◽

pp. 40

Author(s):

Helena B. Leites ◽

Flávia S. Damasceno ◽

Ariel M. Silber ◽

Ronaldo Z. Mendonça ◽

Cristina Northfleet de Albuquerque

Keyword(s):

Cell Proliferation ◽

Positive Control ◽

In Vitro Test ◽

Biological Part ◽

Amide Derivatives ◽

Vitro Test ◽

South Americans ◽

Derivatives Of

Objective: This work aims at the synthesis of megazol analogs with antitrypanosomicidal activity. Chagas’disease is caused by Trypanosoma cruzi and is a debilitating disease that has both acute and chronic forms. Many South Americans suffer from the chronic form of Chagas’disease, and there is no treatment currently available.Methods: In the chemical part, classical techniques of heterocyclic synthesis as well as usual methods of identification were used. In the biological part the cell proliferation test was used in vitro and the IC 50.Results: We synthesized a series of derivatives of 2-(1-methyl-5-nitro-2-imidazolyl)-5-substituted-1,3,4-thiadiazoles where 1-acetyl, 1-propyl and 1-nonyl were used as the substituent (4,6,7). Derivatives without nitro group were also synthesized (3,12) along with thiosemicarbazones (8,9,10) and a 5-(5-nitro-2-furanyl)-1,3,4-thiadiazol-2-amine (11). These compounds were evaluated using an in vitro test where were measured the cell proliferation. The derivatives that obtained the best results underwent further tests, in which their IC50 was calculated. The data revealed that two compounds (4,6) were effective against the parasite (IC50= 0.354 µM; IC50= 2.13 µM) and besides that, obtained the same results as the positive control, antimycim and rotenone. All proposed structures were obtained in satisfactory yields and purities.Conclusions: In conclusion, the in vitro trypanocidal activity makes these compounds promising leads in the development of an effective therapeutic agent. However, this study must be completed by additional tests with in vitro amastigote/macrophage models or in vivo mouse models. Analyzing the amide derivatives, compounds (4) and (6) were the ones that presented the best results.

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Comparison of the developmental potential of in vivo and in vitro maturated bovine oocytes in an in vitro test system

Theriogenology ◽

10.1016/0093-691x(96)84746-7 ◽

1996 ◽

Vol 45 (1) ◽

pp. 273 ◽

Cited By ~ 7

Author(s):

E.E. van de Leemput ◽

P.L.A.M. Vos ◽

E.C. Zeinstra ◽

M.M. Bevers ◽

S.J. Dieleman

Keyword(s):

Test System ◽

In Vitro Test ◽

Developmental Potential ◽

Vitro Test ◽

Bovine Oocytes

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In Vitro Toxicology Methods in Risk Assessment

Alternatives to Laboratory Animals ◽

10.1177/026119299602400305 ◽

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.

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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?

Alternatives to Laboratory Animals ◽

10.1177/026119299502300110 ◽

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.

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