Pyrogenic factors

Interestingly, the antipyretic activity is exclusively caused due to the direct interferences, with such phenomena with the aid of which pyrogenic factors give rise to fever however, they are found... 

Factors to be considered in maldng the selection of chromatography processing steps are cost, sample volume, protein concentration and sample viscosity, degree of purity of protein product, presence of nucleic acids, pyrogens, and proteolytic enzymes. Ease with which different types of adsorbents can be washed free from adsorbed contaminants and denatured proteins must also be considered. 

Sterility, freedom from pyrogens, and acceptably low level of extraneous particulate matter are critical quality attributes of all injectable products. Additional critical quality attributes depend on the clinical use of the product. For example, for IV, IM, and SC routes, isotonicity and physiological pH (7.4) are always desirable in order to minimize potential irritation upon injection. Other factors may preclude this, however. If the required dose of drug must be administered in a small volume, it may not be feasible to formulate an isotonic solution. Likewise, solubility or stability considerations may preclude formulation at physiological pH. This explains why formulation pH for injectable drugs varies from about pH 2 to about pH 11. 

As a consequence of the various approaches adopted in naming and classifying cytokines, it is hardly surprising to note that many are known by more that one name. IL-1, for example, is also known as lymphocyte activating factor (LAF), endogenous pyrogen, leukocyte endogenous mediator, catabolin and mononuclear cell factor. This has led to even further confusion in this field. 

IL-l is also known as lymphocyte-activating factor (LAF), endogenous pyrogen and catabolin. It displays a wide variety of biological activities and has been appraised clinically in several trials. 

These unusual concerns include irritation (vascular, muscular, or subcutaneous), pyrogenicity, blood compatibility, and sterility (Avis, 1985). The background of each of these, along with the underlying mechanisms and factors that influence the level of occurrence of such an effect, are briefly discussed below. 

The parenteral routes include three major ones IV (intravenous), IM (intramuscular), and SC (subcutaneous) and a number of minor routes (such as intraarterial) that are not considered here. Administration by the parenteral routes raises a number of special safety concerns in addition to the usual systemic safety questions. These include irritation (vascular, muscular, or subcutaneous), pyrogenicity, blood compatibility, and sterility (Avis, 1985 Ballard, 1968). The background of each of these, along with the underlying mechanisms and factors that influence the level of occurrence of such an effect, are discussed in Chapter 11. 

Several factors of design and manufacture are of great importance sterility, absence of pyrogens and foreign particulate matter, and tonicity. The last, when adjusted to the osmotic pressure of body fluids in the case of aqueous solutions, reduces the risk of tissue irritation and pain,... 

Van Damme J, De Ley M, Opdenakker G, Billiau A, et al. 1985. Homogenous interferon-inducing 22 K factor is related to endogenous pyrogen and interleukin-1. Nature. 314 266-268. 

Keywords Endotoxin Limulus amoebocyte lysate test LAL Molecular cloning Pyrogene assay Recombinant Factor C... 

Various enzymes, lysozyme, catalase, phosphatase, malate/formate dehydrogenase, adenylase kinase, pymvate decarboxylase, alkaline phospatase, serum albumin, lipoprotein, interferon, growth factor, polypeptide hormone DNA, RNA, y-globulin, proteinase, carboxypeptidase, endotoxins, pyrogen, IgG, trypsin inhibitor, transferrin, casein, L-benzoyl arginine ethyl ester, cytocrome C IgG, heparin... 

Endotoxin pyrogen induces fever by an indirect process. On entry into the circulatory system, endotoxin is bound to LPS-binding protein (LPB) that transports it to receptor cells in the reticuloendothelial system. The main target cells are circulating mononuclear cells, which produce proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-a (TNFot). These cytokines are involved in acute and chronic inflammation, induce fever, and modulate the host s response to bacterial infection. ° ... 

However, additional factors must be considered in order to understand and fuially predict the rheological behavior of silica-resin mixtures. In particular, the type and strength of particle interactions and the influence of adsorption processes on these interactions are key factors which govern the rheology of liquid media containing pyrogenic silica for rheology control. 

Sauder, D.N., Mounessa, N.L., Kary, S.I., Dinarello, C.A. and Gallin, J.l. (1984). Chemotactic cytokines the role of leukocyte pyrogen and epidermal cell thymocyte activating factor in neutrophi chemotaxis. J. Immunol. 132, 828-837. 

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