Dosing, whole-organism

When single micronutrients are applied for prevention or even intervention in diseases of organs or tissues, they are usually administered in higher doses for a longer period of time. The hope is to accumulate it this way sufficiently in the tissue and to thus be able to ensure the therapeutic success. This procedure, however, leads to a flooding of the whole organism with micronutrients and their potential enrichment in tissues which would usually not accumulate the respective micronutrient. Thus, unexpected side effects may occur. 

Figure 5.3. A binding curve is simply a dose-response curve determined at the biomolecular level. In contrast to the dose-response curve determined on a whole organism, it is easier to ensure that the substance has good access to the protein, metabolism can be eliminated and the full range of a response will be available. In this graph, the binding curves of two different substances capable of binding to the same protein are shown. Substance A occupies 50% of the binding sites at one-tenth the concentration needed to bring about the same degree of occupancy with Substance B.

After a peel, the skin needs to heal as quickly as possible in order to maintain homeostasis of the whole organism. Tretinoin accelerates re-epithelialization if used before the peeling. For this it must be used at a dose of 0.05%-0.1%, sometimes to the point of irritative dermatitis. Ideally, the treatment should start 3-4 weeks before a TCA-SAS peel. It is accepted scientifically that the preventive application of tretinoin promotes post-peel healing of the skin. In contrast, applying tretinoin during the post-peel period appears to slow down skin regeneration. Not all peels require this help with re-epitheliazation. 

Percentage of injected dose per whole organ n Data not available. 

A RfD is derived by first examining the available human or animal toxicity data to identify a dose or exposure that corresponds to a no-observed-adverse-effect level (NOAEL) or a lowest-observed-adverse-effect level (LOAEL). The NOAEL is the exposure level at which there are no statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control. Effects may be produced at this level, but they are not considered to be adverse if they do not result in functional impairment or pathological lesions that affect the performance of the whole organism or which reduce an organism s ability to cope with additional chal-... 

Cylindrospermopsin s existence was first realized after 149 people were poisoned on Palm Island off the north-east Australian coastline when their freshwater dam became contaminated by C. raciborskii. The molecular mechanism by which this toxin exerts its toxicity is yet to be elucidated. Liver toxicity, however, is the main toxic manifestation but lesions in the kidney, heart, and thymus occur when tested on mice and rats. Orally, cylindrospermopsin has a median lethal dose to mice of 6 mg kg whereas intraperitoneal injection of mice yields an LD50 of 0.2 mg kg Other whole organism assays used to measure cylindrospermopsin toxicity include the brine shrimp Artemia saUna (LD5o = 0.7pgml after 72 h) and the crustacean Thamnocephalus platyurus. 

It is necessary to take into account the different sensitivities of various tissues and organs to the induction of deleterious health effects to the whole organism. The effective dose (E) is defined as a summation of the tissue equivalent doses multiplied by the appropriate tissue weighting factor W[. According to this definition. 

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