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The serpent has been a symbol of long life, healing, and knowledge among almost all cul tures and religions since the beginning of recorded history. The serpent adopted as a logo type by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin. The National Academy of Sciences is a private, nonprofit, selfperpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. It is autonomous in its administration and in the selection of its mem bers, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engi neering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. Close attention was given throughout the report to the evidence relating macronutrient intakes to risk reduction of chronic disease and to amounts needed to maintain health. Thus, the report includes guidelines for partitioning energy sources (Acceptable Macronutrient Distribution Ranges) compatible with decreasing risks of various chronic diseases. Thus, although governed by scientific rationales, informed judgments were often required in setting reference values. The quality and quantity of information on overt deficiency diseases for protein, amino acids, and essential fatty acids available to the com mittee were substantial. Unfortunately, information regarding other nutri ents for which their primary dietary importance relates to their roles as energy sources was limited most often to alterations in chronic disease biomarkers that follow dietary manipulations of energy sources. Also, for most of the nutrients in this report (with a notable exception of protein and some amino acids), there is no direct information that permits estimating the amounts required by children, adolescents, the elderly, or pregnant and lactating women. These information gaps and inconsistencies often precluded setting reli able estimates of upper intake levels that can be ingested safely. The report provides recommended levels of energy expenditure that are considered most com patible with minimizing risks of several chronic diseases and provides guid ance for achieving recommended levels of energy expenditure. Inclusion of these recommendations avoids the tacit false assumption that light sedentary activity is the expected norm in the United States and Canada. With more experience, the proposed models for establishing reference intakes of nutrients and other food components that play significant roles in pro moting and sustaining health and optimal functioning will be refined. Many of the questions that were raised about requirements and recommended intakes could not be answered satisfactorily for the reasons given above. The research agenda is anticipated to help future policy decisions related to these and future recommendations.
Diseases
- Agoraphobia
- Midline defects recessive type
- Cerebro oculo dento auriculo skeletal syndrome
- Spinal muscular atrophy
- Copper transport disease
- Chromosome 9, duplication 9q21
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Bioavailability data for specific nutrients must be considered and incorporated into the risk assessment process. Supplemental forms of some nutrients may require special consideration if they have higher bioavailability since they may present a greater risk of producing adverse effects than equivalent amounts from the natural form found in food. Excessive intake of one nutrient may interfere with absorp tion, excretion, transport, storage, function, or metabolism of a second nutrient. With regard to the form of intake, fatsoluble vitamins, such as vitamin A, are more readily absorbed when they are part of a meal that is high in fat. Nutrient supplements that are taken separately from food require special consideration because they are likely to have different bioavailabilities and therefore may repre sent a greater risk of producing adverse effects. The primary types of data used as background for identifying nutrient hazards in humans are: Human studies. Human data provide the most relevant kind of infor mation for hazard identification and, when they are of sufficient quality and extent, are given the greatest weight. However, the number of con trolled human toxicity studies conducted in a clinical setting is very limited because of ethical reasons. Such studies are generally most useful for identifying very mild (and ordinarily reversible) adverse effects. Observa tional studies that focus on welldefined populations with clear exposures to a range of nutrient intake levels are useful for establishing a relation ship between exposure and effect. Sometimes a series of case reports, if it shows a clear and distinct pattern of effects, may be reasonably con vincing on the question of causality. Most of the available data used in regulatory risk assess ments come from controlled laboratory experiments in animals, usually mammalian species other than humans. Moreover, there is a longstanding history of the use of animal studies to identify the toxic properties of chemical substances, and there is no inherent reason why animal data should not be relevant to the evalua tion of nutrient toxicity. They can, for example, be readily controlled so that causal relationships can be recognized. The effects of chronic exposures can be identified in far less time than they can with the use of epidemio logical methods. All these advantages of animal data, however, may not always overcome the fact that species differences in response to chemical substances can sometimes be profound, and any extrapolation of animal data to predict human response needs to take this possibility into account. Key issues that are addressed in the data evaluation of human and animal studies are described below (see Box 41). Evidence of Adverse Effects in Humans the hazard identification step involves the examination of human, animal, and in vitro published evidence that addresses the likelihood of a nutrient eliciting an adverse effect in humans. Decisions about which observed effects are adverse are based on scientific judgment.
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Aspirin can cause gastrointestinal bleeding, and acetaminophen (such as Tylenol) can cause liver damage if too much of the drug is taken. Recent evidence suggests that good control of symptoms, including pain, actually helps people to live longer! One method is to remove the source of the pain, if possible, through surgery, chemotherapy, radiation and/or some other form of treatment. Physicians prescribing drugs for pain relief must also be made fully aware of all other medications the patient is taking. Before purchasing pain relievers, it is advisable to first check the ingredients to see whether the product contains Benzocaine. Benzocaine is associated with a rare but serious condition called methemoglobinemia, which greatly reduces the amount of oxygen carried through the bloodstream. Additionally, some people experienced a significant decrease in neuropathyinduced pain when they took a prescription antidepressant drug called Cymbalta (Duloxetine). Certain medications such as Gabapentin (Gralise, Neurontin) and Pregabalin (Lyrica), which were developed to treat epilepsy, may relieve nerve pain. Potassium and magnesium supplements can also be helpful in relieving muscle cramps, as can Epsom salt baths. This may help prevent pain messages traveling along that nerve pathway from reaching the brain. The pain pump is an implanted drug infusion system that releases prescribed amounts of pain medication directly to the pain receptors (nerves) near the spine. The pump, whose purpose is to store and deliver pain medication, is surgically placed in the abdomen. The catheter is inserted into the intrathecal (spinal canal) space surrounding the spinal cord. The pump sends the medication through the catheter directly to the spinal area where pain receptors are located. Patients return to their doctor for more medicine when the pump needs to be refilled. Before having the pump implanted, an epidural screening test provides a temporary evaluation period so that patients can determine whether the targeted drug delivery truly relieves the pain.
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The second meiotic division follows the first division without a normal interphase. Each chromosome divides and each half, or chromatid, is drawn to a different pole; thus, the haploid number of chromosomes (23) is retained and each daughter cell formed by meiosis has the reduced haploid number of chromosomes, with one representative of each chromosome pair (now a singlechromatid chromosome). The second meiotic division is similar to an ordinary mitosis except that the chromosome number of the cell entering the second meiotic division is haploid. Meiosis Provides constancy of the chromosome number from generation to generation by reducing the chromosome number from diploid to haploid, thereby producing haploid gametes. Allows random assortment of maternal and paternal chromosomes between the gametes. Relocates segments of maternal and paternal chromosomes by crossing over of chromosome segments, which "shuffles" the genes and produces a recombination of genetic material. If involved in fertilization, these gametes with numerical chromosome abnormalities cause abnormal development such as occurs in infants with Down syndrome (see Chapter 20). Spermatogonia, which have been dormant in the seminiferous tubules of the testes since the fetal period, begin to increase in number at puberty. Oogonia are not shown in this figure because they differentiate into primary oocytes before birth. The number designates the total number of chromosomes, including the sex chromosome(s) shown after the comma. Note that (1) following the two meiotic divisions, the diploid number of chromosomes, 46, is reduced to the haploid number, 23; (2) four sperms form from one primary spermatocyte, whereas only one mature oocyte results from maturation of a primary oocyte; and (3) the cytoplasm is conserved during oogenesis to form one large cell, the mature oocyte. The homologous chromosomes approach each other and pair; each member of the pair consists of two chromatids. Observe the single crossover in one pair of chromosomes, resulting in the interchange of chromatid segments. H, Distribution of parental chromosome pairs at the end of the first meiotic division. The drawings show how nondisjunction results in an abnormal chromosome distribution in gametes. Although nondisjunction of sex chromosomes is illustrated, a similar defect may occur in autosomes. When nondisjunction occurs during the first meiotic division of spermatogenesis, one secondary spermatocyte contains 22 autosomes plus an X and a Y chromosome, and the other one contains 22 autosomes and no sex chromosome. Similarly, nondisjunction during oogenesis may give rise to an oocyte with 22 autosomes and two X chromosomes (as shown) or may result in one with 22 autosomes and no sex chromosome.
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