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By U. Yorik. Georgetown University. 2018.

The PAH gene and its PKU mutations are particular protein cheap 200 mg diflucan otc, and is made up of a molecular found on chromosome 12 in the human genome buy 150 mg diflucan mastercard. Each gene is detail discount diflucan 50 mg online, PKU mutations can involve many different types found on a precise location on a chromosome generic diflucan 200mg mastercard. The term autosomal means that the gene for inheritance and expression of a genetic mutation buy 150mg diflucan visa. A recessive genetic trait generic diflucan 50mg amex, such as PKU, is one true or chronological age and multiplies that ratio that is expressed—or shows up—only when two copies by 100. A person with one normal and one PKU gene is Metabolism—The total combination of all of the called a carrier. A carrier does not display any symptoms chemical processes that occur within cells and tis- of the disease because their liver produces normal quan- sues of a living body. However, PKU carriers can Mutation—A permanent change in the genetic pass the PKU genetic mutation onto their children. Two material that may alter a trait or characteristic of carrier parents have a 25% chance of producing a baby an individual, or manifest as disease, and can be with PKU symptoms, and a 50% chance having a baby transmitted to offspring. Although PKU conforms to these basic genetic patterns of inheritance, the actual Myelin—A fatty sheath surrounding nerves in the expression, or phenotype, of the disease is not strictly an peripheral nervous system, which help them con- “either/or” situation. Although some PKU Nervous system—The complete network of mutations cause rather mild forms of the disease, others nerves, sense organs, and brain in the body. The more severe the PKU mutation, the Phenylalanine—An essential amino acid that must greater the effect on cognitive development and perform- be obtained from food since the human body can- ance (mental ability). Also, it must be remembered that human cells con- Protein—Important building blocks of the body, tain two copies of each type of gene. Different combina- composed of amino acids, involved in the forma- tions of any two PKU mutations tend to produce a wide tion of body structures and controlling the basic spectrum of physiological and psychological symptoms. For example, patients who receive two “severe” PKU Recessive—Genetic trait expressed only when mutations from their parents can potentially develop present on both members of a pair of chromo- more serious symptoms than people who possess a com- somes, one inherited from each parent. To further complicate the genetic picture of PKU, 920 GALE ENCYCLOPEDIA OF GENETIC DISORDERS other types of genes have been identified which seem to be responsible for the abnormal processing of phenylala- nine in brain tissue. These abnormalities add to the sever- ity of PKU symptoms experienced by patients who inherit these genes. In more detail, the association of multiple types of genes with a single condition, such as PKU, is referred to as molecular heterogeneity. Demographics One in 50 individuals in the United States have inherited a gene for PKU. Studies indicate that the incidence of this disease in Caucasian and Native American populations is higher than in African- American, Hispanic, and Asian populations. Signs and symptoms Untreated PKU patients develop a broad range of symptoms related to severely impaired cognitive func- tion, sometimes referred to as mental retardation. Other symptoms can include extreme patterns of behavior, delayed speech development, seizures, a characteristic body odor, and light body pigmentation. The light pig- mentation is due to a lack of melanin, which normally colors the hair, skin, and eyes. Melanin is made from the amino acid tyrosine, which is lacking in untreated cases of PKU. Physiologically, PKU patients show high levels of phenylalanine and low levels of tyrosine in the blood. Babies do not show any visible symptoms of the disease A technician is performing a test to screen for PKU. Diagnosis elevated phenylalanine levels may be caused by some medical condition other than PKU. Another, more accurate test procedure for procedure is referred to as the Guthrie test (Guthrie bac- PKU measures the ratio (comparison) of the amount of terial inhibition assay).

Typically generic diflucan 50 mg free shipping, the average threshold for evoking movement with intracortical stimulation in a premotor area is somewhat higher than that in M1 purchase diflucan 150 mg amex, and the probability of evoking movement at any given site is lower in the premotor areas than in M1 diflucan 50 mg with mastercard. Electrical stimulation of the SMA generated a complete map of the body with a rostral to caudal orientation of its face discount diflucan 50 mg overnight delivery, arm discount diflucan 200mg on line, and leg representations (Figure 1 buy diflucan 200 mg with visa. The medial wall is unfolded and reflected upward to display the medial wall in an “upside down” orientation. The boundaries between cytoarchitectonic areas (dotted lines), the fundus of the cingulate sulcus (dashed line), and the lips of the cingulate sulcus (solid lines) are indicated. Movements were evoked by short- or long-train intracortical stimulation in a macaque monkey. ArSs: rostral limit of the superior limb of the arcuate sulcus; Fgc: frontal granular cortex; Skc: somatic koniocortex. Nevertheless, sites within the arm representation of the SMA that evoked movements of distal joints tended to be located ventral to sites where movements of proximal joints were evoked. Intracortical stimulation with parameters that were effective in the SMA did not evoke movement in the preSMA which lies just rostral to the SMA on the medial wall of the hemisphere (Figures 1. Movements elicited in the preSMA were typically slow, involved multiple joints, and resembled natural postural movements. PreSMA neurons often responded to visual but not to somatosensory stimuli, whereas SMA neurons had the opposite characteristics, responding to somato- sensory but not visual stimuli. The intracortical stimulation maps, however, are more fractured, are punctuated with nonresponsive areas, and reflect a lower sampling frequency than in the anatomical experiments. Movements of the arm and leg were elicited in each cingulate motor area, but face movements were evoked only, and infrequently, in the CMAr (Figure 1. Longer pulse trains and higher currents were required to evoke movements within the CMAr. This observation is congruent with the relatively low density of corticospinal neurons found in this area (Figure 1. Thorough exploration of the CMAr was limited to one animal, where arm and leg movements were found to be somewhat intermingled. Systematic mapping of the PMd with intracortical stimulation has been limited to one study,101 although numerous studies have reported the results of partial explorations of this region. These stimulation effects could be mediated directly via corticospinal efferents from each premotor area or indirectly by projections from each premotor area to M1 and henceforth via the corticospinal efferents from M1. Following removal of M1, intracortical stimulation of the SMA could still evoke movements with stimulus currents that were in the range of prelesion values. This observation suggests that electrical activation of corticospinal efferents in the SMA is sufficient to generate muscle contraction. This conclusion reinforces the view that independent and parallel pathways for motor control originate in the SMA and M1. Copyright © 2005 CRC Press LLC RP1 #239 Ar Spur CgS 26 25 27 28 29 30 32 33 34 36 35 Thumb Fingers Wrist Elbow, Shoulder Orofacial Upper Trunk Eye Blink 2 mm No Response FIGURE 1. A cross- section from a macaque brain (Macaca nemestrina) illustrates the location of electrode penetrations and the movements evoked at each stimulation site within the posterior bank of the inferior limb of the arcuate sulcus. Thresholds for evoking movement are indicated by symbol size (large symbols = #15 µA, small symbols = 16–50 µA). Digital photomicro- graphs of spinal cord sections viewed under dark-field illumination with polarized light. Arrow points to terminations in the dorsolateral part of lamina IX that contains motoneurons. Compared to SMA terminations, M1 terminations are denser and more extensive in lamina IX, and extend further into the base of the dorsal horn. The extent of M1 terminations within the motor nuclei of the spinal cord changes during development129,131,132 and varies between different species. Terminations here were concentrated at three locations: (1) the dorsolateral portion of laminae V–VII; (2) the dorsomedial portion of lamina VI at the base of the dorsal columns; and (3) the ventromedial portion of lamina VII and adjacent lamina VIII.

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While not approved as a dietary supplement by the FDA purchase diflucan 50 mg online, lutein is ubiquitous in foods diflucan 200 mg lowest price. It may play an impor- Mai Tran tant role in maintaining vision and preventing such eye Teresa G cheap diflucan 150mg. Odle diseases as ARMD and cataracts buy diflucan 50 mg with mastercard, the two leading causes of vision loss in adults proven diflucan 150 mg. The carotenoid may accomplish Lupus see Systemic lupus erythematoses this by protecting eye tissue from free radical damage and shielding the eyes from potentially destructive sunlight order diflucan 150mg. Research also indicates that getting adequate amounts of lutein may decrease the risk of colon cancer and heart disease. Lutein may offer protection against the latter two Lutein diseases by acting as an antioxidant, since free radical Description damage is believed to contribute to the development of cardiovascular disease as well as certain cancers. Found in certain fruits and vegetables as well as egg yolks, lutein is a nutrient with a number of potentially The results of an earlier study, published in the beneficial effects. It is a member of the carotenoid family, British Medical Journal in 1992, shed light on the possi- a group of chemicals related to vitamin A. The objective of carotene, the precursor of vitamin A, may be the most fa- the study was to examine the relationship between 1244 GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 cataracts and intake of carotenoids, vitamins C and E, their intake of foods known to contain lutein. Researchers studied the dietary habits are the richest source and also contain a large amount via questionnaires of over 50,000 registered nurses aged of zeaxanthin. Other sources of lutein include corn, red 45 years and over for a period of eight years and found seedless grapes, kiwi fruit, squash, and green vegeta- that those who reported consuming the most vitamin A bles such as zucchini, spinach, collard greens, kale, leaf and carotenoids were found to have a lower risk of de- lettuce, celery, peas, broccoli, and leeks. Spinach, which is a rich source of orange juice, tomatoes, and carrots also prove good lutein, appeared to offer the most protection against the sources of lutein. The researchers concluded that the carotenoids concentrations of lutein are higher in the peels of fruits present in food may decrease the risk of developing se- than in the pulp. Getting too much lutein through food and drink is not considered a significant risk be- Lutein may also help to prevent the development of cause the nutrient is only present in relatively small colon cancer, according to a study published in the amounts in plants and animals. This study examined the risk of colon cancer and dietary in- take of lutein and other carotenoids such as alpha- Precautions carotene, beta-carotene, lycopene, zeaxanthin, and beta- cryptoxanthin. The researchers examined the eating Lutein is not known to be harmful when taken in habits of over 4,000 people. Roughly half the partici- recommended dosages, though it is worth remembering pants were between the ages of 30 and 79 and already that the long-term effects of taking lutein supplements had colon cancer, while the remainder made up the can- are unknown. The results indicated that men lutein should be used with caution in children, women and women who had consumed large amounts of lutein who are pregnant or breast-feeding, and people with were less likely to develop the disease. Side effects The evidence regarding lutein and heart disease is When taken in recommended dosages, lutein is not indirect but intriguing. A study reported in 2001 found associated with any bothersome or significant side ef- that carotid arteries in those with higher lutein levels fects. A human study also provides some indirect evi- Interactions dence that higher levels of lutein and other carotenoids may play a role in preventing the development of cardio- Lutein is not known to interact adversely with any vascular disease. Toulouse, who have a much lower rate of heart disease, had lutein levels about twice as high as those from PERIODICALS Belfast, where the incidence of cardiovascular disease is Carlson, Mike, et al. GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 1245 roots are usually harvested in the spring, although they KEY TERMS can be dug any time of the year. Lycium is also called Chinese Age-related macular degeneration (ARMD)—The wolfberry. General use Antioxidant—An organic substance that is able to The first recorded use of lycium fruit as a medicinal counteract the damaging effects of oxidation in herb is from the first century A. It is used as both a jing (yin) tonic for pigments that are chemically similar to carotene. To re- main healthy, yin aspects must be kept in balance with Cataracts—The clouding of the eye lens, which yang aspects. Retina—The layer of light-sensitive cells located at Health is restored by taking herbs and treatments that re- the back of the eye.

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Estriol is produced in high concentrations by Other Actions of Estrogens the placenta in pregnant women cheap diflucan 50mg on-line. The high levels of estrogens and progesterone associ- Under the influence of high levels of estrogen or pro- ated with pregnancy may alter liver function and glu- gesterone generic 50 mg diflucan with visa, the physicochemical composition of cervical cose metabolism 50 mg diflucan with visa. High circulating levels of estrogen can mucus may reduce sperm motility and provide a barrier cause mild glucose intolerance discount diflucan 50 mg without prescription. Modifications at positions the formation of high-density lipoproteins and reducing C6 and C7 increase their progestational activity diflucan 50mg without a prescription. Reductions in serum albumin Examples of these synthetic progestins include me- and antithrombin III synthesis can occur in the pres- droxyprogesterone and megestrol acetate (Megace) purchase diflucan 200mg free shipping. These compounds are metabolized in the same manner In males, estrogens stimulate the growth of the stro- as progesterone and are excreted in the urine. SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMs) SYNTHETIC AGENTS ACTING VIA ESTROGEN AND PROGESTERONE Selective ER modulators (SERMs) are nonhormonal RECEPTORS pharmacological agents that bind to ERs. A characteris- tic feature of the SERMs is that a given agent will act as Long-acting semisynthetic estrogens and progestins an estrogen agonist in one or more tissues and as an es- contain esterified lipophilic substituents. Esterification trogen antagonist in one or more other estrogen target of steroids prolongs their release from depot injection organs. Medroxyprogesterone acetate (Amen, Cyctin, rate (Clomid, Serophene) and raloxifene (Evista) are Provera, Depo-Provera) is a widely used long-acting examples of nonsteroidal SERMs. SERM is tamoxifen citrate, a drug formerly character- Synthetic steroid hormones retain the common ized as an antiestrogen. The two most thus is used as a treatment and chemopreventative for widely used synthetic steroid estrogens are ethinyl estra- breast cancer. Tamoxifen is a full agonist in bone and diol (Estinyl) and mestranol, found in oral contracep- endometrium, and prolonged use of tamoxifen leads to tives. Synthetic steroids containing an ethinyl substitution a fourfold to fivefold increase in the incidence of en- are metabolized more slowly. See Chapter 56 for a detailed discus- hormones have better oral absorption properties and ex- sion of the use of tamoxifen in breast cancer. Raloxifene (Evista) is a new SERM approved for Approximately 50% of a dose of mestranol is de- use in the treatment and prevention of osteoporosis be- methylated to form ethinyl estradiol. Subsequently, the metabo- estrogen antagonist in both breast and endometrial tis- lism of these two synthetic estrogens proceeds by means sues. The estrogenlike properties of raloxifene result in of the same pathways as the natural steroid hormones. Absorp- thetic steroid estrogens, in contrast to the natural estro- tion of raloxifene is impaired by cholestyramine. Tamoxifen, clomiphene, and raloxifene are orally ac- One chemical class of synthetic progestins is derived tive. The primary route of excretion of all three drugs is from testosterone and is referred to as the 19-nortestos- in the feces. These compounds have progestational activity yet of these SERMs are increased frequency of hot flashes retain some androgenic activity. Both effects nor, Nor-QD) and norethindrone acetate (Aygestin) are are attributable to their estrogenic activity. In phase III clinical trials faslodex tivity of norethindrone and norethindrone acetate be- showed good activity against advanced breast cancer. Norethindrone is metabolized by hydroxylation and conjugation, just as are the natural CLINICAL USES progestins.

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