Biological factors

Key factors for the successful scale-up of cell culture include using the best available cell line, inoculating cells that are in prime condition and ensuring that nutritional, physiological and physicochemical conditions are optimized. 

Scale (1) System Area (cm ) (batch size) Cells per batch (cells L )  

As one scales up, culture conditions become more demanding on the cells and the logistics of preparing large-cell inocula and maintaining sterility become more difficult. Therefore, do not be over-ambitious in the scale-up steps. 

In this overview an explanation has been given for the wide and complex range of cell culture bioreactor systems that are available. This is to put some perspective on the ones that are described in more detail in the following chapters. The selection of a suitable system follows the adage horses for courses , i.e. a process is selected that fulfils the particular criteria for the cell, product, scale and quantity required, plus the resources in facilities, manpower and experience that are available. 

There are some additional general factors to be taken into consideration. First, upstream processing is only part of the total process, which starts at the initiation of a cell line and finishes with a purified and packaged product, and therefore should not be treated in isolation. Secondly, increasing unit productivity does not 

There are many different examples of species differences in the toxicity of foreign compounds, some of which are commercially useful to man, as in the case of pesticides and antibiotic drugs where there is exploitation of selective toxicity. Species differences in toxicity are often related to differences in the metabolism and disposition of a compound, and an understanding of such differences is extremely important in the safety evaluation of compounds in relation to the extrapolation of toxicity from animals to man and hence risk assessment. 

Species differences in the toxicity of the drug digitoxin have been suggested because of differences in the concentration required to inhibit Na+/K+-ATPase, which is more sensitive in sensitive species. An alternative suggestion is that differences in metabolism catalyzed by CYP3A4 are responsible. 

Absorption. Absorption of foreign compounds from various sites is dependent on the physiological and physical conditions at these sites. These, of course, may be subject to species variations. Absorption of compounds through the skin shows considerable species variation. Table 5.2 gives an example of this and shows the species differences in toxicity of an organophosphorus compound absorbed percutaneously. Human skin is generally less permeable to chemicals than that of rabbits, mice, and rats, although there is variation. For some compounds, rat skin has similar permeability to human skin and seems to be less permeable than that of the rabbit. 

Distribution. The distribution of foreign compounds may vary between species because of differences in a number of factors such as proportion and distribution of body fat, rates of metabolism and excretion and hence elimination, and the presence of specific uptake systems in organs. For instance, differences in localization of methylglyoxal-bis-guanyl hydrazone (Fig. 5.6) in the liver account for its greater hepa to toxicity in rats than in mice. The hepatic concentration in mice is only 0.3% to 0.5% of the dose after 48 hours, compared with 2% to 8% in the rat. 

The plasma-protein concentration is a species-dependent variable, and the proportions and types of proteins may also vary. The concentration may vary from about 20 g L-1 in certain 

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Precise kinetic electroanalytical data permit to describe quantitatively the kinetics of the whole process with a precision that has never been achieved before by patch-clamp techniques or spectroscopic near-field methods. This enables to investigate finely these events and to identify the exact physicochemical nature of all the individual physicochemical and biological factors which concur to produce vesicular release. 

It is the determination of volatile organic compounds produced from natural products that requires separation techniques that allow isolation of stereoisomers. The most commonly determined groups are the terpene and sesquiterpene species present in essential oils, which are used as key indicators of biological factors such as the growth season, geographic location, climate, etc. These species are also released directly into the atmosphere by very many plants and trees, and make a substantial contribution to global biogeochemical cycles. 

The condition of any soil represents a stage in the changing process of soil evolution. Soils develop, mature and change with the passage of time. Whereas the time required for a true soil to develop from the parent rock of the earth may be thousands of years, rapid changes can result in a few years when soils are cultivated, irrigated, or otherwise subjected to man s manipulation. The type of soil that develops from the parent material will depend upon the various physical, chemical and biological factors of the environment. 

Biological factors Microorganisms, fungi, bacteria, animals, insects can destroy materials or change their properties... 

G. Neumann, E. George, and V. Romheld, White lupin—a model plant to study mechanisms involved in root-induced mobilization of sparingly available P-sources, International Workshop on Role of Environmental and Biological Factors of To.xic and Essential Elements by Plants. Research Institute of Pomology and Floriculture, Skierniewice, Poland, 1998, p. 27. 

C. Holmstrom and S. Kjelleberg, The effect of external biological factors on settlement of marine invertebrate and new antifouling technology. Biofouling, 1994, 8, 147. 

Non-biologic factors that affect drug response... 

We have thus far focused on the biological factors that affect drug responses but recovery from illness often takes place in the context of interactions among individuals. In these interactions, both patient and clinician bring their own knowledge, predispositions, values, priorities, modes of thinking, and belief systems into play. Within this transaction, issues such as patient compliance, expectation effect ... 

Biological factors that may influence pharmacological response and side effects include pharmacokinetics such as protein binding, distribution, metabolism, or... 

Sociocultural, illness, and biological factors affect individual attitudes towards psychotropic medications. Health beliefs or explanatory models, particularly causal attributions regarding the illness and the treatment options afforded within such models, exert a profound influence on patients attitudes and behavior regarding medications (Smith, Lin Mendoza, 1993). Such effects can be subtle and can occur during the course of treatment even if there has been initial successful negotiation about the nature of the illness and treatment. In psychiatric illness little research has been leveled at the personal meaning that patients bring to treatment practices such as electro-convulsive therapy (ECT), oral medications, and depot injections, or to the transition between different administrative routes and types of medications. 

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