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The cells contain numerous granu- lar endoplasmic reticulum buy hydrea 500mg cheap symptoms migraine, lysosome buy 500mg hydrea overnight delivery symptoms knee sprain, and golgi complex discount hydrea 500 mg with amex symptoms 8 days after iui. Iodine Metabolism Thyroid Hormone Synthesis Iodide uptake is the first and crucial step in the thyroid Steps of Thyroid Hormone Synthesis hormone synthesis purchase hydrea cheap medications hyperkalemia. Thyroid Iodide Trapping gland is the principal organ that takes up iodine to form thyroid hormone. Normally, about 120 µg of iodide is taken up by the active transport of iodide from circulation into the col thyroid gland per day for thyroid hormone synthesis. On average, 480 µg of iodine is excreted in the urine basolateral membrane of thyrocytes where it facili and 20 µg is excreted in the stool. The Na is pumped back into the interstitium by Na + and in mountainous regions all over the world. Therefore, iodide is pumped into the results in goiter, hypothyroidism and cretinism. Note, normally a balance is maintained between the amount of iodide presented to extracellular fluid from intestine and the amount excreted from the body (in urine and stool). The other tissues that accumulate iodide are salivary Iodide that is actively transported into the colloids of thy gland, placenta, choroid plexus, mammary gland, gas roid follicles is immediately converted to iodine by means tric mucosa, and ciliary body; however, they do not – of oxidation. Mutation of pendrin gene leads to Pendred syndrome, which is characterized by defective organification of iodine, goiter and sensorineural deafness. Thyroglobulin Synthesis Thyroglobulin is the glycoprotein with two subunits and the molecular weight of 660,000. It is synthesized in the endoplasmic reticulum of thyroid cells, packaged in Golgi apparatus and then, secreted into the colloid by exocytosis. The thyroid hormones are synthesized in the thyroglobulin molecule and remain bound with the thyroglobulin till they are secreted. Note, thyroxine contains four iodine atoms, at 3, 5, 3´ and 5´ positions, and triiodothyronine con- Once reactive iodine is formed (by oxidation of iodide to tains three iodine atoms at 3, 5 and 3´ positions of the thyronine iodine), it binds immediately with the tyrosine molecule, ring structures. They actively accumulate iodide from blood for syn Intramolecular Coupling thesis of thyroid hormones. For the positions of iodine atoms in thyroid hormones, thyroxine and triiodo Secretion of Thyroid Hormones thyronine are abbreviated as T and T respectively. The lysosomal enzymes digest the peptide bonds Metabolism of Thyroid Hormones between iodinated residues and thyroglobulin. In circu nated by the microsomal enzyme iodotyrosine deiodi- lation, most of the thyroid hormones bind with the plasma nase. As physiological effects of thyroid hormones depend on their free-form level in plasma, and the free hormone component influences feedback control of hypothalamo- pituitary-thyroid axis, in thyroid dysfunctions, mainly the free hormone concentrations are measured. However, it is ideal to measure both total and free level of hormones in blood for diagnosing thyroid dysfunctions. The opposite phenomenon occurs when level of Protein Binding plasma binding protein decreases in plasma. Thus, initial change observed in thyroid hormones due teins: to change in plasma proteins is a temporary effect. Therefore, the halflives of circulat site on it for a molecule of thyroid hormone. Normally, about 35% of secreted T4 is converted to (cancer chemotherapeutic drug). Salicylates, pheny T3 in the circulation by the enzyme 5´-deiodinase toin (anticonvulsant), mitotane (cancer chemothera peutic drug) and 5fluorouracil inhibit binding of T (Flowchart 57. As 5´deiodinase is present in high concentration in 4 pituitary and cerebral cortex, the ratio of T3/T4 is very Albumin high in these structures. Effect of Diet the concentration of free T3 and T4 depends on the concentration of plasma proteins that bind these hor Fasting decreases conversion of T4 to T3. Regulation of Secretion Secretion of thyroid hormones is regulated by a feedback control mechanism. The secretion the selenium in the amino acid is essential for their is less during the day. D3 is present in brain and repro by influencing almost all the steps involved in it. D1 and D2 are 5´-deiodinase that convert T4 to T3 and sis of T and T (coupling reaction), secretion of thy 3 4 maintain the intracellular T3 in their target tissues. Therefore, mild to moderate hyperthyroidism is observed in tumors of placental origin like choriocarcinoma. With few exceptions like adult brain and gonads, receptors for thyroid hormones are pre sent in all tissues and organs. Though the developing neu rons in infants and children are highly sensitive to thyroid Fig. Note, the mechanism hormones, it is not clear why the adult neurons are not so of thyroxine action is similar to steroid hormones. T3 and T4 enter the cells of the target organs by carrier mediated (energy dependant) transport. Chapter 57: Thyroid Gland 489 General Effects on Basal Metabolism of endogenous protein and fat. Thus, significant weight loss occurs promptly in increased thyroid activity, without the metabolism of a cell depends on the rate of its oxy adequate nutrient supplementation. T3 also stimulates the transcription of genes for both + + in last six months of fetal life and first six months of post α and b subunits of Na K pump. During this period, thyroid hormones initiate strongly perceived that increased oxygen consumption + + and facilitate the process of differentiation and matura- stimulated by thyroid hormones is mediated by Na K tion of brain cells. Thyroid hormones are required for following neural Target tissues: the increased consumption of oxygen functions: by thyroid hormone is observed in all tissues of the body, 1. Growth of cerebral and cerebellar cortices, and basal which is prominent especially in skeletal muscle, liver, ganglia. Receptors for thyroid hormones roid hormones induce formation of enzymes essential are almost absent in adult brain. Basal metabolic rate: In the resting stage, oxygen for neurotransmitter synthesis. Increase in number of receptors on different brain tis roid state, it increases to about 400 mL/min. Synthesis of proteins and various enzymes like succinic Mitochondrial mechanism: Metabolism is increased dehydrogenase that are required for energy genera by thyroid hormones not only by increased oxygen con tion in neurons. General alertness and responsiveness to various stim cytochrome oxidase activity. This is why thyroid deficiency in newborn oxidation of nutrients and heat production. Thyroid hormones enter the brain in adults Effects Secondary to Metabolic or and found in gray matter of various parts of the brain. After thyroid 4 3 Increased body metabolism increases nitrogen excre- ectomy, D2 type 2 deiodinase activity in brain increases tion.
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The Michaelis spectrum of the acceptor molecule overlaps with that of the constant is equivalent to the concentration substrate when the emission spectrum of the donor and takes place via resonance reaction velocity is half maximal buy discount hydrea 500mg on-line medications for gout. There is no need for direct contact between the two molecules for energy transfer buy 500mg hydrea mastercard symptoms night sweats. If the acceptor molecule is nonfuorescent purchase 500 mg hydrea fast delivery treatment ingrown toenail, Intrinsic association constant describes univalent ligand diminution of energy occurs through nonradiation processes buy hydrea 500mg amex symptoms 6 days before period. Fluorescence quenching techniques can techniques that determine bound and free ligand concentra- provide very sensitive quantitative data on antibody–hapten tions evaluate the intrinsic association constant. Intrinsic affnity is a synonym for intrinsic association An antigen–antibody complex is a product of the union constant. The materials needed for a precipitation reac- tion include antigen, antibody, and electrolyte. The reaction of soluble antigen and antibody in the precipitation test may be observed in liquid or in gel media. Following 4000 discovery of the precipitation reaction by Kraus in 1897, only quantitative and semiquantitative measurements of antibody could be made. The term precipitinogen is some- times employed to designate the antigen, and precipitin is the antibody in a precipitation reaction. Dichloro- ﬂuorescein ( ) and ﬂuorescein ﬂuorescence ( ) in A precipitin test is an assay in which antibody interacts buﬀer alone are shown in the left-hand ﬁgure with soluble antigen in the presence of electrolyte to produce figure 8. When the interaction takes place in vitro, it is called the precipitin reaction, but it may also take place in Precipitin reaction: See precipitin test, precipitation, pre- vivo. The relative proportion in which antigen and antibody cipitation curve, and precipitation in gel media. Excess antigen may lead to soluble complexes, whereas excess antibody may lead to Precipitin reaction curve: See Precipitation curve. In vivo, soluble complexes are more likely to produce tissue injury, whereas larger insoluble com- the zone of equivalence is that point in a precipi- plexes are often removed by reticuloendothelial system cells. All Immune elimination is the accelerated removal of an antigen molecules of each have reacted to produce antigen– antibody from the blood circulation following its interaction with specifc precipitate. When a similar reaction occurs in vivo, immune antibody and elimination of the antigen–antibody complexes complexes are deposited in the microvasculature, and serum through the mononuclear phagocyte system. While the quantity macrophages express Fc receptors that bind antigen–antibody of antiserum is held constant, varying dilutions of antigen complexes and also complement receptors which bind those are added and the tube contents are mixed. It is followed by removal of immune complexes through the phago- in this tube that the ratio of antigen to antibody is in optimal cytic action of mononuclear phagocytes. Heidelberger and Kendall used the tech- nique extensively, employing pneumococcus polysaccha- Antigen ride antigen and precipitating antibody in which nitrogen determinations refected a quantitative measure of antibody content. The classic precipitin reaction may be illustrated using the serum of a rabbit immunized with egg albumin Antibody (Figure 8. In this technique, a constant volume and concentration of rab- bit antibody is placed in a row of serological tubes. Let us say there is no precipitate in tube 1, a slight quantity in tube 2, a heavy amount in tubes 3, 4, and 5, a slight figure 8. All tubes are centri- Coprecipitation is the addition of an antibody specifc for fuged and the supernatants tested for both unreacted antigen either the antigen portion or the antibody portion of immune and antibody. There is excess antigen but no free antibody in complexes to effect their precipitation. In the supernatant of tube 4 there is neither added instead to precipitate soluble immune complexes. The antigen nor antibody, therefore this tube is called the equiva- procedure may be employed to quantify low concentrations of lence tube, where antigen and antibody are in identical pro- radiolabeled antigen that are combined with excess antibody. In the supernatants of tubes After soluble complexes have formed, antiimmunoglobulin 5, 6, and 7 there is antibody but no antigen. Both tubes contained anti- gen as well as antibody which reacted but did not form aggre- Ring precipitation test: (Figure 8. Therefore, an excess of either antigen or antibody may inhibit precipitation, A ring test is a qualitative precipitin test used for more than particularly an excess of antigen. If amount of antibody or antigen by a gel diffusion method such the antigen and antibody are specifc for each other, a ring of as single radial diffusion or Laurell rocket assay. Milligrams of antibody in the precipitate are plotted on the ordinate and the milligrams of antigen added are plotted on Quantitative precipitin reaction is an immunochemical the abscissa of a graph (Figure 8. The precipitin curve assay based on the formation of an antigen– antibody precip- contains an ascending and a descending limb and zones of itate in serial dilutions of the reactants, permitting combi- antibody excess, equivalence, and antigen excess. The with the homologous reagents, unreacted antibodies and anti- ratio of antibody to antigen is graded sequentially from one gens can be detected in the supernatants. The optimal proportion of antigen and anti- geneous or if antibodies specifc for only one of a mixture of body is present in the tube that shows the most rapid foc- antigens are studied by the precipitin reaction, none of the culation and yields the greatest amount of precipitate. After supernatants contain both unreacted antibodies and unre- washing, the precipitate can be analyzed for protein content acted antigens that can be detected. Antigen–Antibody Interactions 297 Antibody-excess Equivalence Antigen-excess zone zone zone excess Ab Supernatants excess Ag Antibody precipitated Antigen Added figure 8. The ascending limb of the precipitation curve represents the occurs when there is an overlap between the zone of antigen zone of antibody excess where free antibody molecules are excess in one antigen–antibody combination with the zone present in the supernatants. The descending limb represents of antibody excess of a separate antigen–antibody system the zone of antigen excess where free antigen is present in (Figure 8. Precipitation is maximum in the zone of equivalence (or equivalence point) where neither antigen nor the lattice theory (Figure 8. When the ratio of antibody to antigen is above Excess Excess Antibody Antigen Antigen Used figure 8. However, when the ratio is epitopes recognized by the antibody molecules present, the less than 1, soluble complexes result and remain in the more extensive the complex formation. Also termed pre- the incremental addition of antigen to an optimal amount cipitin curve. This dem- the lattice theory is the concept that soluble antigen and onstrates the presence of both precipitating and nonprec- antibody combine with each other in the precipitation reaction ipitating antibodies. Although the nonprecipitating variety to produce an interconnecting structure of molecules. This cannot lead to the formation of insoluble antigen–antibody structure has been likened to a criss-cross pattern of wooden complexes, they can be assimilated into precipitates that cor- strips fastened together to reveal a series of diamond-shaped respond to their specifcity. Lattice formation requires interaction of bivalent was once believed, they may merely have a relatively low antibodies with multivalent antigens to produce a connect- affnity for the homologous antigen. Monogamous bivalency, ing linkage of many molecules to produce a complex whose which describes the combination of high affnity antibody density becomes suffcient to settle out of solution. The more with two antigenic determinants on the same antigen par- ticle, represents an alternative explanation of the failure of these molecules to participate with their homologous antigen. The formation of nonprecipitating antibodies, which usually represents 10 to 15% of the antibody population produced, is dependent on such variables as heterogeneity of the antigen, characteristics of the antibody, and animal species. Factors that affect the precipitin reaction are pH, salt concen- tration (ionic strength), temperature, the presence of comple- ment in the sera used, and time curve. The precipitin reaction usually remains unaffected by changes of pH in the range of 6.