Serum Components

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

Miscellaneous Serum Components. The discussion of the tests most commonly done in the Laboratory of Neonatology, above, illustrates the various types of instrumentation used. Here, various other procedures will be discussed at random in order to illustrate some basic principles, which have many applications. 

Materials. Egg phosphatidylcholine (PC), bovine brain phosphatidylserine (PS) were obtained from Avanti Polar Lipids Inc. (Birmingham, AL) and cholesterol was from Sigma (St. Louis, MO). Ganglioside GMj, bovine, was obtained from Calbiochem (San Diego, CA). Diethylenetriamine pentaacetic acid distearylamide complex (DPTA-SA) was synthesized according to ref. 17 and nlIn-DTPA-SA was prepared as described (7). This lipophilic radiolabel is not transferred to the serum components from liposomes (unpublished data), nor is it rapidly metabolized in vivo (7). The synthesis of N-(glutaryl)phosphatidylethanolamine(NGPE) has been described (18). Dipalmitoyl deoxyfluorouridine(dpFUdR) was synthesized as described (24). 

Zelphati O, et al. Effect of serum components on the physico-chemical properties of cationic lipid/oligonucleotide complexes and on their interactions with cells. Biochim Biophys Acta 1998 1390 119. 

Purines, pyrimidines, and the corresponding nucleosides have been separated in reversed phase systems. The five mqior nucleosides as well as inosine and xanthosine and the corresponding seven bases were separated by Hartwick and Brown (405). The selective determination of adenosine in the presence of other serum components has been reported (406). 

Kolar, C. K. and Brunner, J. R. 1970. Proteose-peptone fraction of bovine milk Lacteal serum components 5- and 8-casein-associated glycoproteins. J. Dairy Sci. 53, 997-1008. 

The injection of serum components of another species into human patients has not been without problems. A condition known as serum sickness develops in an alarmingly high proportion of those treated in this... 

Borchard, G. and Kreuter, J. (1993) Interaction of serum components with poly(methyl methacrylate) nanoparticles and the resulting body distribution after intravenous injection inJt te jg Target 1 15-93. 

TCDD in vitro on lymphocytes, the dependence of those effects on serum components, and the requirements for high concentrations of 2,3,7,8-TCDD are all consistent with an indirect mechanism of... 

Table 5.3 Serum components and their functions in the animal cells cultured in vitro (adapted from Freshney, 2005)...

PDGF is one of the most common serum components (40-60 ng/ml). It is also secreted by endothelial and placenta cells, and by several cell lines such as BHK and 3T3-fibroblasts. PDGF has synergetic action with EGF and IGF-1 and is a potent mitogen. 

H36. Husby, G., and Natvig, J. B., A serum component related to nonimmunoglobulin amyloid protein AS, a possible precursor of the fibrils. J. Clin. Invest. 53, 1054-1061 (1974). 

L12. Levin, M., Pras, M., and Franklin, E. C., Immunologic studies of the major nonimmunoglobulin protein of amyloid. I. Identification and partial characterization of a related serum component. ] Exp. Med. 138, 373-380 (1973). 

L15. Linke, R. P., Sipe, J. D., Pollock, P. S, Ignaczak, T. F., and Glenner, G. G., Isolation of a low-molecular-weight serum component antigenically related to an amyloid fibril protein of unknown origin. Proc. Natl. Acad. Sci. U.S.A. 72, 1473-1476 (1975). 

R18. Rosenthal, C. J., and Franklin, E. C., Variation with age and disease of an amyloid A protein-related serum component. J. Clin. Invest. 55, 746-753 (1975). 

Reducing vascular permeability. EC modulates mass exchange between blood and adjacent tissues, and prevents the random infiltration of serum components or blood cells, which mostly occurs when EC divides or receives external stimulation by thrombin/histamine involvement or mechanical (shear) stress. 

Whilst growth factors in the serum provide specific proliferative stimuli, studies with cultured cells have indicated other important components for cell proliferation [18]. For example, insulin is required to facilitate glucose and amino-acid uptake, and transferrin, which binds iron, makes it available to the cell. Serum is also believed to supply trace elements such as selenium, copper and zinc as well as fatty acids important for cell growth. Some serum components such as ascorbate, a-tocopherol, caeruloplasmin and albumin may serve important antioxidant functions [19]. 

As already mentioned (section 2.2) serum is a source of growth factors, so it is perhaps not surprising that the withdrawal of serum from the growth media of most cultured mammalian cells results in notably reduced rates of cell proliferation [18]. Another readily observed feature of serum deprivation is an increase in the level of cellular lipid peroxidation [39], In part this may be a function of the absence of serum components that might provide an antioxidant function, e.g. a-tocopherol, ascorbate, urate, caeruloplasmin, etc. (see also... 

Red kidney-bean extracts formed precipitates with several, normal, animal sera, as well as with individual serum-components.I05 I07,742 744... 

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