Biological evaluation

The classical method for the biological testing of vitamin K-active substances is the measuring of their effect on the blood clotting time of the vitamin K-deficient chick. Dam et al. (1951) have described a modified method, by which a linear relationship between vitamin K dosage and clotting time was obtained. 

In a second method the antidotal effect of vitamin K to Dicumarol and related substances in different laboratory animals, such as rats, rabbits, dogs, has been employed, and the first quantitative results have recently been published by Lowenthal and Taylor (1958), with the rat as the test animal. 

Dam and S0ndergaard (1953a) found that in the usual test with vitamin K-deficient chicks, using an assay period of 20 hours or more, the activities of vitamin Ki and menadione are approximately equal on a molar basis. However, on intravenous administration and measurement of the prothrombin time within the first 2 hours, it could be shown that vitamin Ki acts more rapidly than menadione. There was no difference between vitamin Ki and menadione after 2 hours. 

Equal activities for vitamin Ki and menadione were found by Fisher et al. (1956) in the dog, where vitamin K deficiency had been produced by chronic lack of bile. On oral administration the water-soluble menadione was more active than the oily solution of vitamin Ki. 

Similar differences in activity between menadione bisulfite, menadione, and vitamin Ki have been observed in chicks under practical feeding conditions, and most probably are due to better absorption of the water-soluble forms (Frost and Spruth, 1955 Frost et al., 1956 Perdue et at., 1957a,b). 

The abilities of compounds 37-39,42-44, 68-78, and 82 to enhance pseudo-tubule sprouting on endothelial cells are reported in Table 7.1, and have been compared to the parent octasaccharide 12, used as the reference compound because of its standard sulfation pattern. 

Entry Compound Main features of GlcN residue Tubule formation on endothelial cells 

Taken together, these data clearly show that the number as well as the exact location of primary O-sulfonates plays a major role in the FGF2/FGFR activation system. The results presented here also indicate that the introduction of carefully selected alkyl/aryl moieties at the anomeric position and/or at position 2 of GlcN results in an increase of biological activity. 

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Center for Biologies Evaluation and Research (CBER). This center is responsible for the regulation and approval of ah biological products intended for use in the treatment, prevention, or cure of diseases or injuries to humans. A biological product is any vims, therapeutic semm, toxin, antitoxin, vaccine, blood or blood component or derivative, or analogous product (5). It also includes products produced by biotechnology, such as interferons and erythropoietins. 

J. Cross and E. J. Singer, Cationic Suf actants Analytical and Biological Evaluation, Surfactant Science Series, Vol. 53, Marcel Dekker, Inc., New York, 1994. CSMA Detergents Division, Test Methods Compendium, 2nd ed., CSMA, Inc., Washington, D.C., 1985. 

Standardization and Testing". The Center for Biologies Evaluation and Research has set guidelines for the vaccine which include standards for si2e of the individual polysaccharides and specifications for both purity (absence of protein and nucleic acid) and chemical and immunological identity. 

Structure-Activity Relationships. Biological evaluation of peniciUias yields information such as in vitro and in vivo antibacterial activities. 

ANSI/ADA specification no. 14 provides a requirement for removable partial dentures of a combined minimum of 85% by weight of chromium, cobalt, and nickel or, for alloys failing to meet that minimum, at least 20% chromium. Bio-compatibiUty is demonstrated by passing the pertinent criteria of ANSI/ADA specification no. 41, Recommended Standard Practices for Biological Evaluation of Dental Materials. 

Cationic Surfactants Analytical and Biological Evaluation, edited by John Cross and Edward J. Singer... 

Chemistry, synthesis, and biological evaluation of purine 7-A-oxides relative to nucleic acids 97H(44)573. 

I am deeply gi ateful to a number of gi aduate students and undergraduates. Were it not for their hard work and dedication, the effort described herein could not have been accomplished. I also express cordial gi atitude to Pi of. H. Shigenobu (Toho University School of Phaimaceutical Science) for biological evaluations of l-hydroxyyohimbine derivatives. 

With its structure known, the synthesis of a peptide can then be undertaken— perhaps to obtain a larger amount for biological evaluation. A simple amide might be formed by treating an amine and a carboxylic acid with dicyclo-hexylcarbodiimide (DCC Section 21.7), but peptide synthesis is a more difficult problem because many different amide bonds must be formed in a specific order rather than at random. 

Biological evaluation of our synthetic A-Factor confirmed its activity we thank Dr. Richard Monaghan and his group at Merck Sharp and Dohme Research Labs for performing these tests. 

The Center for Biologies Evaluation and Research (CBER) is responsible for the oversight of what might be considered more traditional biological products, such as... 

Once the FDA receive the initial submission, an IND reference number is assigned. The application is then passed on to the appropriate review centre either the Center for Drug Evaluation and Research (CDER), or the Center for Biologies Evaluation and Research (CBER). Various experts will then review the submitted documents, the purpose being to ensure that the safety of subjects is not compromised and, in the case of Phase II and III studies, that the quality of study design is scientifically adequate. The FDA are allowed 30 days to complete the initial review, after which the study can commence, provided that it has been approved by an Institutional Review Board (IRB). 

Chitosan acetate and lactate salt films have been tested as wound-healing materials. Mechanical, bioadhesive and biological evaluation of the films were carried out. The results were compared to Omiderm . Chitosan lactate exhibited a lower tensile strength, however, it was more flexible and bioadhesive than chitosan acetate. Chitosan lactate and Omiderm did not cause any allergic reactions in contrast, chitosan acetate produced skin irritation clearly due to the anion. Nevertheless, no sign of toxicity was encountered when the extracts of three preparations were administered parenterally [244]. 

In 2004, Alterman et al. apphed their cyanation protocol to the synthesis of N-(t-butyl)-3-(4-cyanobenzyl)-5-isobutylthiophene-2-sulfonamide [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloroformate finally gave the target compoimd for biological evaluation as a selective angiotensin 11 AT2 receptor agonist (Scheme 65). The cyano derivative, however, showed only a low affinity for the AT2 receptor (Ki value >10 p,M). 

Anzini M, Canullo L, Braile C, et ah Synthesis, biological evaluation, and receptor docking simulations of 2-[(acylamino)ethyl]-1,4-benzodiazepines as kappa-opioid receptor agonists endowed with antinociceptive and antiamnesic activity. J Med Chem 46 3833-3864, 2003... 

A potential major benefit of a cyclohexene-based template was the capacity to mimic more closely the putative transition state sialosyl cation by the placement of a double bond in the correct position. While the ring conformation in Neu5Ac2en 4 is very similar to the sialosyl cation transition state 5, these two stracmres are essentially isomers due to the fact that the double bond is either between the ring oxygen and C-2 in 5 or C-2 and C-3 in 4. The synthesis and biological evaluation of... 

Liu B, Lewis AK, Shen W (2009) Physical hydrogels photo-cross-linked from self- assembled macromers for potential use in tissue engineering. Biomacromolecules 10 3182-3187 Vandermeulen GWM, Tziatzios C, Duncan R et al (2005) Peg-based hybrid block copolymers containing alpha-helical coiled coil peptide sequences control of self- assembly and preliminary biological evaluation. Macromolecules 38 761-769... 

Peukert S, Brendel J, Pirard B, Strtibing C, Kleemann HW, Bohme T, Hemmerle H. Pharmacophore-based search, synthesis, and biological evaluation of anthra-nilic amides as novel blockers of the Kvl.5 channel. Bioorg Med Chem Lett 2004 14 2823-7. 

Wu YQ, Belyakov S, Chi Choi, Limburg D, Thomas BE IV, Vaal M, Wei L, Wilkinson DE, Holmes A, Fuller M, McCormick J, Connolly M, Moeller T, Steiner J, Hamilton, GS. Synthesis and biological evaluation of non-peptidic cyclophilin ligands. J Med Chem 2003 46 1112-15. 

U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) and Center for Biologies Evaluation and Research (CBER). Guidance for Industry Population Pharmacokinetics. http //www.fda.gov/cder/guidance/1852fnl.pdf (accessed October 1,... 

US Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research. Center for Biologies Evaluation and Research. 

Jonck, L. M., Grobbelaar, C. J. Strating, H. (1989b). Biological evaluation of glass-ionomer cement (Ketac-0) as an interface material in total joint replacement. A screening test. Clinical Materials, 4, 201-24. 

Kawahara, H., Imanishi, Y. Oshima, H. (1979). Biological evaluation on glass-ionomer cement. Journal of Dental Research, 58, 1080-6. 

Keller, J. C., Hammond, B. D., Kowlay, K. K. Brauer, G. M. (1988). Biological evaluation of zinc hexyl vanillate cement using two in vivo test methods. Dental Materials, 4, 341-50. 

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