Genetic and Physiological Factors

In view of this uneasiness and on the strength of experimental observations, to be described, the authors have found it necessary in this chapter to consider the question whether or not serum alkaline phosphatase in normal healthy nonpregnant individuals may be essentially a mixture of unmodified and metabolically modified intestinal alkaline phosphatases, whose relative proportions are predetermined by genetic and physiological factors. The basis of this statement and its implications constitute a major point of this chapter. 

Human perception creates difficulty ia the characterization of flavor people often, if not always, perceive flavors differently due to both psychological and physiological factors. For example, certain aryl thiocarbamates, eg, phenylthiocarbamide, taste exceedingly bitter to some people and are almost tasteless to others (5). This difference is genetically determined, and the frequency of its occurrence differs from one population to another 40% of U.S. Caucasians are nontasters, whereas only 3% of the Korean population caimot perceive the strong bitter taste of the aryl thiocarbamates (6). Similar differences were found ia the sense of smell for compounds such as menthol, carvone, and ethyl butyrate (7). 

The etiology of obesity is usually unknown, but it is likely multifactorial and related to varying contributions from genetic, environmental, and physiologic factors. 

Animal models of human disease can also be informative for physiological studies of genetic and environmental factors, and can be used to test novel therapeutics (7,8). For both Mendelian and complex diseases, genes that modify disease severity can also be investigated in animal models by studying animal strains that are severely or mildly affected by the same gene defect, combined with knock-out and knock-in models. 

The success of core-top temperature calibrations indicates that physiological state, genetic variability, and depth and seasonality of production play secondary roles to the control on the sedimentary U37 index exerted by mean annual near-surface temperature. In most cases, these factors produce errors at the level of 1.5 °C or less in the global core-top calibration. To this observer s opinion, core-top data cannot be reconciled with the large variations in the U 7 index attributed to genetic or physiological factors by some culture studies. This does not indicate that the culture data are wrong in a technical sense, but that their results cannot always be extrapolated to the natural environment (Popp et al., 1998). 

Obesity is a condition that is influenced by genetic and environmental factors (such as energy intake and expenditure, fetal nutrition, culture). There are four major physiological causes of obesity endocrine disorders (growth hormone deficiency, Cushing syndrome), genetic syndromes (Prader-Willi syndrome or Alstrom syndrome), disorders of the central nervous system (tumor, trauma) or the most common cause, multifactorial or primary obesity (caused by an interaction of multiple genes). 

The globalization of pharmaceutical research and development is expected to shorten the time required for product approval and registration, by increasing the number of subjects available for research studies and broadening an investigational product s exposure to ethnic intrinsic factors (genetic and physiological) and extrinsic factors (cultural and environmental). 

Figure 7. A hypothetical model of the interactions among the MHC, bacteria, diet and other genetic, environmental and physiological factors which may be involved in the production of urinary odors of individuality in rodents.

Only 6 percent of our schizophrenic subjects were found by our tests not to be low in any of the three vitamins. A complete understanding of vitamins in relation to schizophrenia has not yet been obtained. There is uncertainty as to the relative contributions of genetic and environmental factors, and to the effect of the schizophrenic episodes and of hospitalization on the biochemical and physiological functioning of the patients. There is no uncertainty, however, about the fact that the great majority, 94 percent, of the hospitalized schizophrenic subjects studied by us show a low urinary excretion of one or more of the three vitamins which we have studied, and that this is an indication of a low content of vitamins in the body, which can be rectified by the methods of orthomolecular psychiatry—the increased daily intake of the vitamins, as discussed in other chapters of this book. 

Elevated serum MMA and tHcy concentrations can be considered alternative specific metabolic parameters of cobalamin deficiency. Measurement of functional metabolite MMA requires sophisticated equipment and is, therefore, unsuitable for routine use. Total homocysteine is a more sensitive analyte than tfii2 in diagnosing subclinical vitamin B12 deficiency because its plasma levels increase before clinical symptoms appear. However, the lack of specificity of this analyte represents a serious limit to its use. Total homocysteinemia depends on genetic or physiological factors, life style, diseases in progress, and drugs. HHCY is caused by folate or vitamin Bg deficiency and renal failure. 

More than 100 components have been identified in milk. Two glasses (1 pt) of whole milk provides approximately 23 g of carbohydrate (total), 16.3 g of fat, 16 g of protein, 3.5 g of minerals, plus fat-soluble and water-soluble vitamins. But the composition of milk varies in response to physiological factors (inherited or genetic) and environmental factors. Variations in composition occur among breeds, between milkings, and between milk taken from different sections of the udder. Also, the composition of milk is affected by the feed, the environment temperature, the season, and the age of the cow. 

Aside from their utility for the treatment of multiple skin manifestations, psoralens and UVA radiation could be used as a therapeutic alternative for several immune-mediated disorders as Crohn s disease and ulcerative colitis. Both are chronic inflammatory diseases of the gastrointestinal tract and are collectively known as inflammatory bowel disease. This disorder is produced by a dysfunction of the immtme system that leads to the accumulation of abtmdant lymphocytes and monocytes in the mucosa of the bowel, together with the secretion of cytokines and proinflammatory mediators. There are several genetic, environmental, and physiological factors that contribute to the pathogenesis of inflammatory bowel disease [151]. 

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