Liver extract

In a study by Stresser and co-workers, the effect on tumor modulation by 227 has been investigated. HPLC on liver extracts from Fisher 344 rats revealed two major compounds, 3,3 -bisindolylmefliane (133) and a linear trimer, together with a < l(KX)-fold lower content of 4 in comparison with the two major substances. The HPLC isolate was derivatized with /V-methyl-/V-bis(trifluoroacetamide) that, upon MS detection, gave a compound identical to /V,W -ditrifluoroacetylindolo-[3,2-()]carbazole. The content of 4 in this system was estimated to be 0.(XKX)13% of the total dose of 227 given. Thus, it was concluded that the beneficial effect of oral distribution of 227 is due to the total content of derivatives formed (95MI5). 

In historical terms, folates are among the most recently identified of the vitamins. Wills was the first to describe a form of anaemia associated with pregnancy and malnutrition which could be cured by yeast or liver extract (Wills, 1933 Wills et al, 1937). The active constituent of these dietary... 

De Meester C, Duverger-Van Bogaert M, Lambotte-Vandepaer M, et al. 1979. Liver extract mediated mutagenicity of acrylonitrile. Toxicology 13 7-15. 

In the USA, purity alone often facilitates patenting of a product of nature (Table 4.1). The US Patent and Trademark Office (PTO) recognizes purity as a change in form of the natural material. For example, although vitamin B12 was a known product of nature for many years, it was only available in the form of a crude liver extract, which was of no use therapeutically. Development of a suitable... 

Shenoy, K. G., and Ramasarma, G. B., Iron as a stabilizer of vitamin B12 activity in liver extracts and the nature of so-called alkali-stable factor. Arch. Bio-chem. Biophys. 55, 293-295 (1955). 

The total number of cell divisions that take place in the supplemented top agar. This is controlled by the supply of nutrients, in particular, histidine. Rat liver extracts may also supply trace amounts of limiting nutrients, resulting in a slight increase in the spontaneous yield of mutants in the presence of S9 mix. 

There was no indication that either the fresh or salt water bivalves could metabolize any of the aromatic hydrocarbons or the N- and 0-heterocyclic compounds. All the compounds were transformed in positive controls with cunner liver extracts, however (Table III). 

On this first-pass the entire dose is subjected to liver extraction and the fraction of the dose reaching the systemic circulation (F) can be substantially reduced (even for completely absorbed drugs) as shown in the following equation ... 

All these compounds are moderately lipophilic and should show excellent ability to cross biological membranes by transcellular absorption. Propranolol, betaxolol and metoprolol all have minimal gut first-pass metabolism, as shown by the low value for E(g. i.). Metabolism and first pass effects for these compounds are largely confirmed to the liver as shown by the values for E(g. i.). In contrast talinolol shows high extraction by the gastrointestinal tract with low liver extraction [13]. These effects are illustrated graphically in Figure 3.9 which shows the bioavailability predicted from hepatic extraction contrasted with that seen in vivo in man. 

The assessment of metabolites often requires complex preclinical studies and there are currently no cell-based assays that fully reproduce the in vivo metabolism of the human liver, or other tissues. The rodent S9 liver extracts used as an exogenous source of metabolism are incomplete metabolic surrogates, and perhaps more relevantly here, their properties are inappropriate for handling on an automated HTS platform. 

Karlin, J. M. (1979). Occupational asthma to clam s liver extract. J. Allergy Clin. Immunol. 63, 197. 

A.D. 23 Romans investigate the possibility that liver extracts from rabid dogs could protect against rabies... 

Most of the oral formulations contain one of the iron compound with many vitamins, amino acids, liver extract, minerals, folic acid, appetite stimulants (cyproheptadine like compound). 

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