CHAPTER 6 TRACE ELEMENTAL ANALYSIS IN EPILEPTIC CHILDREN

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1 CHAPTE 6 TACE ELEMENTAL ANALYSIS IN EPILEPTIC CHILDEN 6.1 Intoduction 6.2 eview of the Liteatue 6.3 Mateials and Method 6.4 esults 6.5 Discussion 6.6 Conclusion 119

2 6.1 Intoduction The object of the pesent chapte is to investigate the extensive examination of the most pominent tace element, which has been epeatedly found to play a majo ole in human health and disease. Ou main aim is to locate tace elemental high concentations with special efeence to epilepsy. Seveal mineal elements exist in living tissue in such small amounts that is the past it was not possible to measue thei pecise concentations with the analytical methods. Thee ae lots of elements found in the human body 25 to be exact and we have discussed only seven types of tace elements. The elements that ae pesent in living tissues in small amounts ae called tace elements. Thee ae many types of tace elements like coppe, ion, zinc, sodium, potassium, calcium, magnesium, selenium, molybdenum, fluoine, iodine, chloine, cobalt, lithium, silicon, lead, vanadium, asenic and bomine. These ae all necessay fo ou body to function popely. Tace elements ae essential nutients fo human beings. In ode to maintain vital pocesses tace elements must be pesent in the oganism within cetain concentation anges. They fulfill special biological functions e.g. as catalysts in the synthesis of poteins and enzymes, as active centes of poteins and as stuctue foming pats of molecule in body fluids many mental containing poteins ae pesent. Tace elements occu in the tissue of animals, plants, and micooganism in low concentations. The concentations of these elements change highly among many elements. Thee concentations ae also diffeent among vaious living oganisms and thei pats. These diffeences ae also seen in nutitionally essential elements and also in those elements, which ae associated with no vital function. Tace elements compise only a faction of total body weight. These ae cucial fo many body functions. These include tanspoting oxygen, nomalizing the cental nevous system (CNS) and simulating gowth, maintenance and epai of tissues and bones [247]. It has been noticed that the egulation of tace elements balance in the body is essential to suvival. Each cell is a living oganism and we must ty to maintain its intenal 120

3 envionment. The movement of the tace elements acoss cell membanes, between the exta cellula and intacellula fluid foms the basis fo the body s most pimay functions. Electical activity may be initiated; heat beats, neve cells signals, muscles may espond, blood vessels may tighten o elax. Wate balance should be maintained [248]. It has been epoted in the liteatue that most of the tace elements found in the tissues and body fluids ae also pesent in the blood. Many of the metallic elements have a specific metabolic function and the pesence of these is not meely the esult of contamination fom ou envionment. Biologically active tace elements poduce thei effects though enzyme systems. Metalloenzymes and metal potein complexes ae the two systems. Metalloenzymes have a fixed amount of specific metallic ion pe molecule of potein addition of an agent which binds the metal inactivates the enzyme. Metal-potein complexes ae lage goup of poteins loosely bound to metal. Metals may substitute fo each othe with fluctuating degees of affinity and they can be emoved by the pocess of dialysis. Some of these complexes may have 12enzymatic activity only. ests of these ae concened with tanspotation pocess only. Chelation affects these two types of activity of enzymes [249]. The essential metals at tace levels play a ole in the human body and can cause some diseases when pesent beyond the limit of nomal concentation [250, 251]. Tace elements have divegent oles to play depending upon thei chemical fom o combination and thei position in the body tissues and fluids. The functional foms of the tace elements and thei chaacteistic concentations ought to be maintained with naow limits if the functional and stuctual integity of the tissues is to be safeguad and the gowth, health and fetility of the individual have to be unaffected. Continued ingestion of diets that ae deficient, imbalanced, o excessively high in a paticula tace element invaiably induces changes in the functioning foms activities, o amount of these elements in the tissue o fluids, so that they fall below, o ise above the nomal and pemissible limits o anges. In these situations, biochemical distubances develop, physiological functions ae influenced and stuctual disodes may aise in ways which change with elements. The degee and duation of the dietay deficiency o toxicity, age, sex and species ae impotant factos associated with the tace elements [9]. 121

4 Deposition of Tace Elements in the Human Body Food is the basic necessity of the life of a living oganism. Eveybody eats food whethe it is vegetaian o non-vegetaian. Scientists wee vey cuious about the food they consumed. Food passes in the body and affects the body. Food is the substance taken into the body that will help meet the body s need fo enegy. It helps in maintaining good health, gowth and epoduction. A lage numbe of mineals and tace elements ae ciculating in the human body. Some of these elements fom pat of body stuctual component and some othes act as catalytic agents in diffeent body eactions. Bones and skeleton ae made up of calcium, magnesium, phosphous and ion is a component of blood. Mineals like zinc, molybdenum, coppe, manganese and magnesium ae eithe a stuctual pat o activate a lage numbe of enzyme systems. Iodine is a pat of homone, thyoxin, sodium, potassium ae impotant elements pesent in fluids within the outside the cells and along with ions like chloide, bicabonate and cabonate keep wate and acid base balance. If we see the case of gowing infant and childen, intake of additional amount of seveal mineals ae essential to ensue adequate gowth of tissues. It has been epoted somewhee in the liteatue that the addition of vitamins and mineals to food can be effective public health intevention to coect inadequate intake of nutients in both the geneal society [252]. Zumkley [255] stated that clinical expeimental and epidemiological studies indicate that a lage numbe of tace elements may be involved in the aetiology of diffeent human body disodes. Both inceased levels of any tace element o evese of this can influence the development of disease. S. No. Type of element Place whee found Pecentage Oxygen Oxygen Oxygen Silica Aluminium Ion Eath cust Ocean Atmosphee Eath cust Eath cust Eath cust

5 7. Calcium Eath cust Sodium Eath cust Sodium Ocean Potassium Eath cust Magnesium Eath cust Magnesium Ocean Titanium Eath cust Chloide Ocean Nitogen Atmosphee Agon Atmosphee Cabon dioxide Atmosphee Neon Atmosphee Helium Atmosphee Kypton Atmosphee Hydogen Ocean Hydogen Atmosphee Table Elements found in the eath s cust, ocean and atmosphee. It has been established somewhee else in the liteatue that though geophysical foces, mixing of the eath s cust with wate may povide vitually evey mineal fo ou body, which equies to maintain health. The wate is compatable with moe substances than any known solvent [253]. It is an ideal medium fo tanspoting nutients in the cells fo the chemical eactions of cellula metabolism to take place. Ou body contains lot of element out of 25 ae divided into mainly thee categoies such as majo, mino components and tace elements. The majo components, which make up 96% of human body, ae composed of oxygen, nitogen, cabon and hydogen. It has been established that majo elements found in the biological molecules such as poteins, nucleic acids, fats and cabohydates these ae capable to make-up the body. Hydogen ions ae vey impotant fo ou cells to make ATP o enegy. Wate is also a medium fo all the chemical eactions taken place in the human body. Wate is a mixtue of oxygen and hydogen atoms [254]. 123

6 Mino components make up 4% of ou body. They may include calcium, phosphous, potassium, sulfu, sodium, chloine and magnesium. Some of these ae necessay fo chemical pocesses to un coectly. Ou muscles need calcium in ode fo them to twitch popely. Enough calcium is equied to ou body. Tace elements make up 0.1% of ou body. They include coppe, zinc, selenium, molybdenum, fluoine, iodine, manganese, cobalt, ion, lithium, stontium, aluminium, silicon, lead, vanadium, asenic and bomine. These elements ae necessay fo ou body to function popety. ole of Tace Elements in Human Body with a Detailed Desciption Indian saint Swami Dayanand Saaswati quoted somewhee else in the liteatue anything consumed in excess is poison. By the beautiful quotation we can estimate ou body in tems of tace elemental analysis and can assue the excess of one element may cause a divese effect on the body. Tace elements may play an impotant ole in human beings. We may pesent a detail desciption egading tace elemental effect on human body with an impact of deficiency of tace element may cause a seious disease. It is planned to discuss some of the tace elements in detailed and desciptive knowledge of few elements. These ae coppe, zinc, ion, magnesium, calcium, sodium and potassium. We ae familia with all these elements. We have a suitable position of these elements in the peiodic table. We shall discuss each and evey element in detailed desciption. Coppe: The pesence of coppe in animals and plants is vey essential. Coppe is most abundant tace element in the human beings. This element is caied mostly in the bloodsteam on a plasma potein. We may call it is ceuloplasmin. Coppe is fistly absobed in the gut and tanspoted to the live bound to albumin. This tace element is found in a vaiety of enzymes, including the coppe cente of cytochome C oxidase. Ou body needs coppe fo nomal gowth and health. It is said that coppe is equied to help body use anothe tace element such as ion. Coppe is vey impotant fo neve function, bone gowth and to help body use suga. This element is a component of a 124

7 cofacto fo diffeent enzymes, appoximately. These enzymes ae fifty in numbe and equied coppe to function popely. Coppe is an essential nutient, which plays an impotant ole in the poduction of hemoglobin, myelin, collagen and melanin. This element woks with vitamin C also to help in making a component of connective tissues known as elastin. It is a citical functional component of a numbe of essential enzymes. These enzymes ae cupoenzymes. Coppe is an essential component of the natual dak pigment and melanin. This melanin is needed to colou the skin, hai and eyes. The cupo-enzyme, tyosinase, is equied fo the fomation of the pigment melanin. Melanin is fomed in cells called melanocytes and plays a ole in the pigmentation of hai, skin and eyes. This element is a stong antioxidant. It woks togethe with an antioxidant enzyme, supeoxide dismutase (SOD), to potect cell membanes fom being destoyed by fee adicals. Coppe is needed to make adenosine tiphosphate (ATP), which is equied to un the body. Coppe may play a ole in staving off heat, hythm disodes and high blood pessue. The anti-inflammatoy actions of the coppe may help in educing athitis symptoms. Many impotant oxidation eduction eactions in the body ae catalyzed by coppe. It helps the fomation of wate fom the fee hydogen and oxygen pesent in the cells. The catalytic action of coppe educes the impact of this eaction. This eaction could be explosive if the coppe is absent. The sense of taste, which geneated in the human tongue, is influenced completely by the pesence of coppe. Coppe must be available in sufficient amount in the human body to allow fo the full utilization of ion. The absoption of ion into the body is simulated by coppe. On an aveage, a young peson equies one hunded to one hunded fifty milligam of coppe daily. Coppe in highe concentation is found in live, hai, muscle and lung [256]. Absobed coppe is fistly attached to plasma albumin and then taken by the live. It is eleased afte the elapsed of time and bound to specific coppe-caying potein ceuloplasmin. Coppe is an impotant component of so many metalloenzymes including cytochome C oxidase. Coppe absoption and etention depends on the chemical foms in which the metal is ingested, the dietay levels of othe mineals and oganic substances, and the acidity of the intestinal contents in the absoptive aea. The mechanisms of absoption of coppe is not known and still an open question. 125

8 Coppe in the plasma is bound to seum albumin evesibly. It foms diect eacting pool of plasma. coppe and it is distibuted widely to the tissues. The coppe-albumin seum pool eceives coppe fom tissues. Coppe in ceuloplasmin does not appea to be so eadily available fo exchange o fo tansfe. Small amount of faction of seum coppe is ultafiltable and consists of coppe, i.e., fee and anothe small faction that is liganded to the amino acids. The coppe eaching the live is incopoated into the mitochondia, micosomes, nuclei and soluble faction of the paenchymall cells in popotions that vay with the age, the stain and coppe status of human beings. Only a small amount of coppe appoximately 10 to 60 μg is exceted in uine daily in human. Negligible amount of coppe ae lost in the pocess of sweat. Duing the menstual cycle 0.5 mg of coppe may be lost in females. This loss may account fo less than 0.02 mg/day negative balance in females who ae in thei epoductive phase of life. The adult human beings contain 80 mg of coppe. Newbon child has 4.7 pat pe million (ppm) and vey young people contain moe coppe pe unit of body weight than adults appoximately 1.7 ppm. A total of 23 mg in the live, heat, spleen, kidneys, bain and blood of nomal healthy subjects. Of this total, 8 mg may pesent in the live and supisingly, 8 mg in the bain. Highly vaiable concentation of coppe occus in the tissue of all human beings. The glands such as postate, pituitay, thyoid and thymus ae examples of tissues which contain low coppe; spleen, panceas, muscles, skin, and bones contain intemediate concentations of coppe and the live, bain, kidneys, heat and hai ae tissues which have high concentation of coppe. It has been epoted in the liteatue vey specifically that vaiation of coppe levels with age, the bain is the only ogan in which the concentation inceases fom bith to about double the level at the age of matuity, i.e., 25 yeas. Exceptionally high concentation of coppe occus in the pigmented pats of the eye. High live coppe concentations ae the indicato of a numbe of diseases of human beings. These diseases include thalasemia, hemochomatosis, cihosis and yellow atophy of the live, tubeculosis, cacinoma and sevee chonic diseases accompanied by 126

9 anemia, etc. The coppe in blood plasma occus in two foms (i) fimly bound to ceuplasmin and (ii) evesibly bound to albumin. Plasma coppe does not incease following meals o decease duing fasting. Seum coppe levels inceases in women who ae taking oal contaceptives. Pegnant women have an elevated level of coppe in compaison to healthy contols. Zinc: The ole of zinc in human subject as a nutitional point of view has been geat impotance to the eseach scientists in the field of Biophysics and Biochemisty fo the past so many yeas. The impotance has also been well established. Zinc is a necessay tace metal of suitable impotance in the dietay management of many human body complex disodes. A young peson has 3 gm of zinc. A calculation shows that this is appoximately half of the body ion, but ten to fifteen times geate than coppe. This tace element is found in all ou cells. This element is essential fo all foms of life. Many poteins contain stuctues called zinc finges may help to egulate genes. The distibution of zinc in the human tissues is well documented in the liteatue. Live, kidney, bone, etina, postate and muscle appea to be vey ich in zinc. It has been epoted in the liteatue that zinc in BC is ten times that of plasma and in human seum is 16% highe than plasma. The highe content of zinc in seum has also been attibuted to the libeation of zinc fom the platelets duing the pocess of clotting and to invisible hemolysis of ed cells. The estimation of zinc in plasma of healthy contols has been studied by many scientists and found simila and good in ageement. Plasma zinc levels in the newbon child ae in the same as in adults. The metalloenzyme cabonic anhydase is a zinc-containing enzyme. It is well documented that thee ae moe than 80 othe enzymes found, which possesses zinc including alkaline phosphate and alcohol dehydogenease. The vey high zinc content in the etina aises due to the metallo-enzyme etenene eductase, which sets up a elationship between the metabolism of vitamin A and zinc. Cabohydate metabolism and DNA-synthesis equie zinc. Most of the ed cells zinc is tightly bound to enzyme cabonic anhydase. It is exchangeable with plasma zinc. Whole of plasma zinc is found with poteins. Sixty pecent zinc is bound to albumin, 30% has binding with alpha 2 macoglobulin and the emainde with low molecula weight poteins including amino acids [257]. 127

10 The binding of zinc to amino acids and seum potein was studied by Pasad and Obeleas [258]. Histidine, glutamine, theonine, cystine and lysine showed the most makable effects. The amino-acid-bound faction of zinc may have an impotant ole in biological tanspot of zinc. The stable zinc content is highe in albumin faction. Simila concentations of zinc wee found in the α-, β- and γ- globulins. It is well established that zinc is a constituent of a numbe of metalloenzymes. Due to the popety of colous, ion and coppe enzymes have been ecognized fo some time. Zinc metalloenzymes have emeged few yeas back. Kelin and Mann [259] have shown the fist demonstation of a specific biological function citically dependent on the pesence of zinc. They have also shown that cabonic anhydase contains zinc and it is essential to the mechanism of action. iodan and Vallee [260] have epoted in the liteatue that thee ae moe than seventy zinc metalloenzymes. Zinc metalloenzymes exhibit a divesity both of catalytic function and of the ole played by the metal atom. Chemical stability may be an aspect of the utilization of zinc in divese biological pocesses such as hydolysis, tansfe, and addition to double bonds and even oxidoeduction. ole of zinc in edox enzymes does not donate o accept electons. A zinc metalloenzymes may be defined as a catalytically active metallopotein containing stoichiometic amounts of zinc fimly bound at its active site. The metal atoms ae so tightly bound that they do not dissociate fom the potein duing the isolation pocedue. When the metal is not tightly bound, the association is chemically and functionally moe tenuous and the destination metallo-enzyme ae complex. The metal in zinc metalloenzymes paticipate in the actual catalytic pocess. One may speculate that the level of zinc in cells contols the physiological pocesses though the fomation of egulation of activity, o both of zinc-dependent enzymes. Besides the bone and the intestine, the kidneys and stomach may also have educed activity of alkaline phosphatase in zinc deficiency. In tissues such as blood, stomach and intestine in which cabonic anhydase has a majo functional ole, educed activities have been well established. 128

11 It is becoming evident that zinc in small quantities is pesent in vaious cell membanes. Most of the membane-bound zinc is linked to a distinct macomolecule constituent lipopotein faction. The effect of zinc and othe metals an aggegation of platelets and elease of H 3 seotonin activated eithe by collagen o epinephine [261]. The inteaction of zinc with calcium on the ed cell membane was discoveed. The effect of manganese ion, which was shown to displace Ca++, thus modifying functions of the platelet membane. Plasma zinc levels in the new bon ae in the same ange as in the adults. It has been epoted somewhee in the liteatue that the level of zinc falls to just below adult level within the fist week of life. This continues till the next 90 days. This level eached finally to the adult level at the 4 months of age. At the age above sixty yeas, the plasma zinc values goes down. The use of pedialyzed albumin, haptoglobin, ceuloplasmin, α-macoglobulin, tansfein and IgG, incubated with Zn, evealed that zinc was bound to all these poteins, and that the binding of zinc to IgG was electostatic in natue. Only a small pecentage of ingested dietay zinc is absobed. Absoption is difficult to ascetain pecisely, and intake-output studies ae well documented. The nutitional status of zinc in infants and young childen has been vey limited. In addition to vomiting, the symptoms of zinc toxicity in human beings may include dehydation, electolyte imbalance, abdominal pain, nausea, lethagy, dizziness, and muscula incoodination. If the peson takes zinc chloide in suitable amount of dosage, the chances of enal failue may be ceased. The daily dosage of zinc in man is admissible fom mg. It is well established that zinc and coppe compete with each othe fo simila potein binding sites. One thing is to be noted that one may induce coppe deficiency in subjects eceiving high amount of zinc fo seveal months. A syndome of ion deficiency anaemia, hepatosplenomegaly and dwafism has been found to be associated with malfunctioning of zinc metabolism [262]. Though this epesents a human zinc deficiency syndome, definite conclusions may be complicated because othe nutitional deficiencies also exist in such type of patients. 129

12 Othopedic and cental nevous system have elatively slow zinc uptake. This element emains tightly attached fo a lengthy span of time. The deficiency of zinc leads to gowth etadation o failue, lesions of the skin and its appendages, and impaied epoductive development and function. Psychological distubances ae epoted in individuals suffeing fom acodematitis en-teopathic [263]. Zinc induced deficiencies in human beings have been associated with neuological symptoms such as depession, poo concentation, nevousness and moodiness [264]. The hippocampus is ich in zinc. Zinc deficiency is associated with leaning and memoy defects simila to behavio syndomes esulting fom destuction of the hippocampus [265]. Acute oal zinc toxicity has been epoted to poduce dowsiness and somnolence. Ion: This tace element is one of the fist mino elements. It is essential fo the gowth of a child duing the pocess of gowing. Ion was consideed to be celestial oigin in ancient civilizations of the easten mediteanean aea. The metal of heaven was vey much used in Egypt and Mesopotamia fo theapeutic puposes. Ion compounds wee used by medical pactitiones in the Geco-oman peiod. The theapeutic indications fo ion duing the oman ea included alopecia, acne, dematitis, wounds, hemohoids, gout, pulmonay diseases, diahoea, vomiting, weakness, edema, feve and cystitis [266]. Many clinical disodes wee shown to be associated with low seum ion. McCance and Widdson [267] have concluded fom thei eseach and have epoted that once the ion was absobed by the human body, its excetion was vey minimal and was not contolled eithe by gastointestinal tact o by the kidneys. The plasma ion was in equilibium with tissue ion. The level of plasma ion influenced the ate of ion absoption. The intestine egulates the ate of ion absoption. adioactive ion was used in the yea 1938 by the scientists to undestand the metabolism of ion. Gamick [268] adopted and extended the hypothesis of feitin as the mucosal egulato of ion absoption. This hypothesis was used and named as mucosal block theoy. It was accepted as the physiological mechanism of egulation of ion absoption. Accoding to this hypothesis, ion entes the mucosal cells and conveted completely to feitin ion. This feitin ion is in equilibium with small amounts of 130

13 feous ions in the cells, and the feous ions combined with plasma Fe ++ and get an equilibium state. If ou body is depleted of ion and the plasma ion is found to be loweed, the ion fom mucosa begins to move out into the blood steam. The physiological satuation of the mucosal cells with espect to feous ion is maintained until pat o all of the feitin ion is conveted to feous ion. The depletion of ion leads to a fall in the feous ion below its satuation value in the mucosal cells, the adioactive ion administeed oally begins to be absobed. Ion is found in the hemopotein enzymes, the cytochome C. The ion is concened with oxidative mechanisms of all living cells. Mooe, et al. [269] have pointed clealy to the plasma ion as the majo fom of tanspot ion. Flavopotein enzymes of ion wee discoveed by Mahle and Elowe [270] and ichet and Westefeld [271]. It is vey well established by the eseaches that the ion is intimately involved in oxygen utilization by the tissues as well as in oxygen tanspot as pat of the hemoglobin molecule. The live and spleen contain the highest ion concentation. Kidneys, heat, skeletal muscles, panceas and bain epesent only one tenth of the concentation in live and spleen. The live has a highest stoage capacity of ion in man. Live can stoe 10 g of ion in cetain disease states. Ion occus in blood as hemoglobin in the eythocytes and as tansfein bound in the plasma. The atio is 1000 to 1. A little amount of non-heme ion is also found in the eythocytes of human blood. Hemoglobin is a complex of globin and fou feopotopophyin (heme) moieties. Fishe, et al. [272] have synthesized this complex molecule. Ingam, et. al. [273] have established a thee-dimensional pictue of molecule with its fou attached hemes. The natue of the bond between ion and globin has also studied by Ingam et al. Now ion is stabilized in the feous state completely, which allows it to be evesibly bonded to oxygen. Due to this mechanism, hemoglobin woks as an oxygen caie. The molecula weight of hemoglobin is appoximately 65,000. The aveage ion content is 0.34% of the hemoglobin. The synthesis of heme and its attachment to the globin takes place in the advance stage of ed cell development in the bone maow. The poduction of these two pats occus simultaneously. 131

14 The ion in human seum was studied by Holmbeg and Lauell [274]. The tace element ion may be bounded completely to tansfein. The statement was given by Schade, et al. [275]. The amino-acid-bound faction of ion may have an impotant physiological ole in the biological tanspot of ion acoss cellula membanes. Some faction about 30-40% of the tansfein caies ion. est pat of the tansfein is known as the latent ion-binding capacity. Sleep depivation in human beings may be a facto to decline seum levels of ion. Most of fall in the ion level occus duing the fist 48 hous of sleep depivation. The seum ion levels may etun to the nomal value within a week. It is well documented that feitin and hemosidein ae two nonheme compounds. These occu in the tissues. The live, spleen and bonemaow have a high concentation of ion. Both these compounds ae not chemically simila. Feitin is soluble in wate but hemosidein is insoluble. Thee is 20% of ion found in feitin compound. It is of bown colou. Feitin contains a cental nucleus of ion suounded by a shell of potein. The feitin molecule is defined as a polynuclea ion coated by an assembly of potein chains. The aveage numbe of ion atoms pe molecule of feitin is 3000 o less. Feitin has the stoage capacity of 4500 ion atoms pe molecule. The ion fee apo feitin consists of a shell 130 x m in outside diamete with a cental cavity of 60 x m acoss. Seum feitin is found highe in males in compaison to women. Many eseach scientists have established a coelation between seum feitin, concentation and stoage ion [276, 277]. Hemosidein is an amophous compound. It has 35% of ion only. This type of the stuctue exists in the tissues as a bown, ganula, eadily stainable pigment. The bone maow and muscles contain suitable amount of non-heme ion. The stoage ion concentation of bone maow in nomal man is 100 μg/g. The non-heme ion in the muscle is vey low. The total amount is high due to the lage muscle mass. The total stoage of ion in muscle is equal to that of live. The aveage concentation of ion in human milk is 0-5 μg/ml. The level of ion in colostum is 3-5 times highe than that in milk. Ion occus in milk in combination with potein. An ion-potein compound named feilactin is found in small concentations. This can be isolated fom human milk. The absoption of ion may be affected by the age, ion status, and the state of health. This absoption in man takes place mainly in the duodenum in the fom of feous. 132

15 Ion occus in foods in inoganic foms, in combination with potein, in heme compounds as a constituent of hemoglobin and myoglobin, and in othe inoganic complexes. Ion in heme compounds is absobed diectly into the mucosal cells of the intestine without the necessity of elease fom its bound fom. The inoganic foms of ion and the ion potein compounds need to be educed to the feous state and eleased fom conjugation fo effective absoption. Amino acids such as histidine and lysine may help in ion absoption. It has been established that a diect eaction between ion and histidine occus. They fomed a chelate and subsequently absobed. Histidine is a poduct of potein hydolysis in the gastointestinal tact. Amino acid may be involved in the nomal absoption of ion. High intake of zinc, cadmium, coppe and manganese also intefee with ion absoption. Duing pegnancy, the body consumes mg ion in fetus and its adnexa. Although the absoption of ion may be inceased duing pegnancy, in the thid timeste of pegnancy, the hemoglobin levels go down. The only way significant amount of ion ae lost fom the body is by blood loss. In case of women who ae in the menstuation age goup, the loss of ion is likely to be moe than the dietay intake. Loss of ion is a eason of ion deficiency in women due to menstuation. Deficiency of ion may oiginate fom insufficient input, inadequate absoption o too much loss by the bleeding. Inadequate food input is moe usual compaed to what is nomally believed, specially in the aged pesons as a gowing hyochomic micocytic anemia. In nomal situations, the absoption of ion is accuately egulated accoding to the equiements of the body. If a peson consumes alcohol in excess, the absoption of ion becomes excessive. Haemochomotosis is a disease involving the stoage of ion. This may be teated as the inbon defect in the metabolism. The ion deposited in the tissues damages pogessively. The main ogans involved by this mechanism ae the live chihosis, the heat which involved in the cadiac aest and the panceas fo diabetes. Seum ion can be estimated by the dilution of plasma. But the pobability of ion contamination due to the pesence of non-visible hemolysis puts this method as highly 133

16 uneliable. Data indicate that 50% incease can occu fom non-visible hemoglobin and moe than 100% fom seum showing slight haemolysis. In childen anoexia, depessed gowth and deceased esistance to infection but the oal lesions and nail changes ae not so common. Significant fall in the ion content is a phenomenon commonly obseved. In adults and postmenopausal women the pincipal cause is chonic blood loss due to infections, malignancy, bleeding ulces and hookwom infestation. Ion deficiency anemia is much moe common in females compaed to males. It is because women of fetile age ae subject to additional ion losses in menstuation, pegnancy and lactation. Ion is necessay fo ed blood cells fomation and function. The amount of ion needed is highe in women of childbeaing age, which is impotant fo bain function. Magnesium: Magnesium is one of the best plentiful elements on the univese with special efeence to eath. This element is the fouth most abundant cation in the vetebate. Aikawa [278, 279] showed in the studies elated to magnesium and found that magnesium is associated with so many diffeent biological pocesses. Magnesium is pesent in a small concentation in all cells and it is necessay fo cellula metabolism. This tace element is also pesent in bone along with calcium. It shaes so many popeties of calcium so fa as absoption and metabolism and tissue distibution ae concened. This tace element is also implicated to have a ole in cadiovascula disease. Magnesium is essential fo cetain enzymes. It potects mitochondia, which is the stoehouse of enegy fom the dangeous oxidants. Widdson, et al. [280] have studied the magnesium content in human body and found a ange of magnesium, which stated fom 22.7 to 35.0 meq/kg weight of tissues. Magnesium eaches us in many foms. These ae magnesium amino acids chelate, magnesium cabonate, magnesium oxide, magnesium oxide dolomite and magnesium sulfate. Thee is 70% of human body magnesium esides in bones and teeth. This element is essential to the functioning of human body because it tansmits neve impulses, causes of the contaction of muscles and is integal to healthy development of bones and teeth. 134

17 All the chemical eactions in human body equie an enzyme system to help biochemical eaction mechanism. The enzyme system has thee pats. They ae potein molecule, which must be specific, anothe smalle oganic compound called vitamin, such as pyidoxine o vitamin B6 and at the last a chaged mineal, such as zinc, coppe, manganese o magnesium. This element plays an impotant ole of cofacto in moe than 300 enzymatic eactions in the human body. Each mineal when dissolved in fluids has a chaacteistic electical chage, which is called as valance. Mineals with a chage of + called univalent cations, include sodium and potassium. Mineals with a chage of ++ called divalent cations, include coppe, zinc, manganese and magnesium. Potassium and magnesium ae the most abundant cations found within the cells of the body with magnesium. One eadily accessible and easily absobed fom of magnesium is magnesium chloide. It is soluble in wate. This eadily dissociates which can incease the ate of absoption. Magnesium is an impotant mineal that is needed by evey cell in human body. It has been found that half of the magnesium stoes in the body ae deposited in the cells of the body s ogans and tissues and est half of this element is found in ou bones. Magnesium occus hee in combination with phosphous and calcium. It is well established that magnesium occus only in one pecent concentation in the blood. The human body has to wok vey had in ode to keep magnesium levels in the blood fo constant value. The human body contains about 760 mg of magnesium at the bith. It goes upto 5 gm at the age of 4-5 months and it eaches upto 25 g when a body attains an age of adult. About 30 to 40% magnesium is found in muscles and soft tissues and one pecent is found in extacellula fluid, and the emainde is in the skeleton. If we ae going to conside the paticula impotance with espect to the pathological effects of magnesium depletion, we have to take into account the ole of this element in egulating potassium fluxes and its involvement in the metabolism of calcium [ ]. It has been established that magnesium depletion depesses both cellula and extacellula potassium and exacebates the effects of low potassium diets on cellula potassium content. Muscle potassium becomes depleted as magnesium deficiency develops, and tissue epletion of potassium is vitually impossible unless magnesium status is estoed to nomalcy. Low plasma calcium develops fequently as magnesium status declines. About 55 pecent of body magnesium is located within bone, and it foms a suface constituent of the hydoxyapatite (calcium phosphate) mineal component. The magnesium is exchangeable 135

18 with seum and theefoe epesents a modeately accessible magnesium stoe, which can be dawn on in times of deficiency. The popotion of bone magnesium in this exchangeable fom declines significantly with the gowing age. It has been seen that thee is a significant incease in bone mineal density (BMD) of the femu is associated with the incease in eythocyte magnesium. The othe oles of magnesium in skeletal tissues ae not widely known. Magnesium is nothing shot of a miacle tace element. This element has a tendency of healing effect. Due to this popety a wide ange of diseases may educe o disappea completely. This tace metal has an ability to ejuvenate the ageing body. Magnesium is helpful in the development of healthy bain and nevous system. The teeth and bones may get the pope dosage of magnesium. Magnesium helps in the fight of the human body with infection. One of the medical investigatos has cued seveal patients of diphtheia with the dosage of magnesium chloide. The administation of this dosage was fo two days only. Poliomyelitis cases wee also studied and teated with the magnesium. The patients became fit within the couple of days. If the paalysis had aleady pogessed the patients may get ecovey within a month. It has been found that magnesium chloide is effective with asthma, bonchitis, pneumonia and emphysema, phayngitis, tonsillitis, hoaseness, common cold, influenza, whooping cough, measles, ubella, mumps, scalet feve, poisoning, gasto-enteitis, boils, abscesses, whitlow, infected wounds and osteomyelitis. Many eseaches have confimed the healing effect of this salt of magnesium in the diseases such as acute asthma attack, shock, tetanus, hepes zoste, acute and chonic conjunctivitis, optic neuitis, heumatic disease, many allegic diseases, chonic fatigue syndome and shown beneficial effects in human health. It has been found that young women, childen and most of all babies have soft body stuctues and smooth skin with low calcium and high magnesium levels in cells and soft tissues. Thee is a emakable finding in the liteatue available and we may be able to say that as the age gow the old men and postmenopausal women become moe and moe inflexible. The ateies haden to cause atheioscleosis, the skeletal system calcifies to cause igidity with fusion of the spine and joints, kidneys and othe ogans and glands inceasingly calcify and haden with stone fomation, calcification in the eyes causes 136

19 cataacts and even the skin hadens, becoming tough and winkled. Now we can say that calcium is in the same scale (league) as oxygen and othe fee adicals, while magnesium woks togethe with hydogen and the antioxidants to keep ou body stuctue soft. Magnesium plays a majo ole in the functioning of the ogans pesent in the human system. It helps in maintaining neve and muscle functions, stengthens the immune system and maintains a steady heat ate. This element also helps in the egulation of suga levels in blood, plays a majo ole in potein synthesis and enegy metabolism and maintains nomal blood pessue. It pevents disode like hypetension, diabetes and cadiovascula disease. About 1% of magnesium is found in the extacellula fluid, inside cells, magnesium may be found bound to phospholipids. It is vey impotant to note that inceasing dietay potein intake may incease magnesium equiements because high potein intake may decline magnesium etention. It is advisable that to completely undestand magnesium function, it is vey impotant to exploe magnesium s elationship with calcium and potassium. Magnesium and potassium also have a close elationship. Magnesium is equied fo the function of sodium and potassium pump. If a magnesium deficiency occus, then pumping of sodium out of the cell and pumping potassium into the cell may be impaied [284]. Cadiac attack comes due to the deficiency of magnesium. Magnesium plays a vey impotant tace element in the cadiac function. The level of magnesium may cause sevee poblems. Many studies [ ] have shown an effect of the level of magnesium egading heat attack. Alcoholism, enal disease, diabetes mellitus may all cause a deficiency of magnesium. Nausea, vomiting, anoexia, muscle weakness, muscle spasms and temos ae the few symptoms and signs elated to deficiency of magnesium. Magnesium has an effect on cental nevous system (CNS). It is used fo a bette sleep. This element may be used to calm iitated and ove excited neves. This is useful with epileptic attacks, convulsions in pegnant women and shakes with temos in alcoholism. If the level of magnesium is vey low, the neves lose contol ove muscle activity, espiation and mental pocesses. Nevous fatigue, ties and twitches, temos, 137

20 iitability, hypesensitivity, muscle spasms, estlessness, anxiety, confusion, disoientation and iegula heatbeat all espond to highe levels of magnesium. Epilepsy is maked by abnomally low magnesium levels in the blood, spinal fluid and bain, causing hypeexcitability in egions of the bain. It has been established that thee is a sudden change in the pogess of impoving o disappeaing of epileptic attack with the administation of pope dosage of magnesium. If the level of magnesium is low, the seveity of epileptic attack goes up. eseach scientist have made the studies on magnesium and found that this element woks best in combination with vitamin B6 and zinc. Magnesium inhibits convulsions by limiting o slowing the spead of the electic dischage fom an isolated goup of bain cells to the est of the bain. Calcium: We know that 99% of the calcium is found in the bones and teeth of a human body. est of the element esides in the soft tissues and blood of the body. Calcium is the most impotant element of the body. Ou body stuctue is made up of calcium and othe mineals. If the calcium is absent, we ae not in a position to make a egula fom o stuctue. We shall lie on the gound and not able to stand. Calcium is the most impotant mineal in the human body. It has been measued and found that the aveage adult body contains in total 1 kg, 99% in the skeleton in the fom of calcium phosphate salt. Extacellula fluid contains 22.5 m mol. We found this element about 9 m mol in the seum. About 500 mmol of calcium is exchanged between extacellula fluid and bone. It is an essential element fo all living things. It can be used fo fetilization of cell and division of cells. This element is used fo homonal activities. Calcium also contols the mechanical stability of the walls and membanes in the cells and stimulates the muscle contactions. It has been epoted in the liteatue that bones ae the best eseve of calcium. Minealization of teeth and bones is the main function of calcium. Mainly 99% of total body calcium is used in the above mentioned pocess. Small amount of the est body calcium is essential fo the function of so many tissues such as clotting of blood, stimulation of secetoy activity in all endocine, exocine, and neuocine cells; and the egulation of contaction and elaxation in cadiac and skeletal muscle. 138

21 The skeleton is an impotant and chief esevoi of calcium. It seves both to maintain plasma calcium concentations and to make optimal use of ingested calcium. Calcium seves both functions mainly by adjusting the facto of balance between the bone fomation - tansfe mineal fom blood to bones, and bone esoption tansfe mineal fom bone to blood. Calcium is involved in the function of excitable tissues. Befoe the heat can beat, special cells in a egion of the heat called sinoatial mode (SA node) must spontaneously initiate an electic pulse. Calcium is mainly involved in the initialization the impulse the SA node. This impulse will stimulate the est of the heat to contact. It is also involved in the contaction of heat muscles and muscles of the skeletal. Contaction and expansion of blood vessels is pefomed by the utilization of calcium. Calcium is useful in the secetion of homones and enzymes, as well as communication between the diffeent sections of the CNS. Bones ae always a pat of a continuous pocess of beaking down and econstuction. This mechanism of beaking and building consists mainly of esoption and deposition of calcium into newly fomed bone, with the end esult bone fomation. This pocess o balance of bone absoption and deposition begins to change as the body attains a highe age. At this age beakdowns ae high athe than building of bones. Duing the age of younge side moe gowth of bones stats with a less deteioation. In the case of women afte the menopause the beaking of bones is high and less building of bones. Due to this pocess osteopoosis may develop. It helps in the fomation of weak poous bones which is esponsible fo factue of bones. If we supply a pope dosage of calcium in the human body then osteopoosis disease can be educed and delayed. Calcium shaes left sided cell eceptos and is essential to human health. It pomotes blood clotting by activating the potein fibin along with the help of magnesium to egulate the heat beat, muscle tone, muscle contaction and neve conduction. Paathyoid homone (PHT) which can be seceted by the paathyoid gland and calcitonin seceted by the thyoid gland can maintain seum calcium levels in the ange 8.5 to enal functions etain moe calcium. This element plays an indispensable ole in cell pemeability, fomation of bones and teeth, blood coagulation, tansmission of neve 139

22 impulses, and nomal muscle contaction. Sevee calcium imbalance equies emegency teatment because a deficiency called hypocalcemia can lead to tetany and seizues. If the seum calcium levels go down, it can develop the poblems elated to failue of kidney and neve fibe iitability and epetitive muscle spasms, peioal paestheis, twitching, capopedal spasm, tetany, seizues and cadiac aest. If the levels of calcium in seum ae on the highe side, it causes hypecalcemia. Due to excess of calcium in the human body, it develops the muscle weakness, deceased muscle tone, lethagy, anoexia, constipation, nausea, vomiting, dehydation, polydipsia, and polyuia. If the calcium level goes upto 5.7 meq/l it can wok as a catalyst in the cadiac ahythmias and coma. Depession is mainly associated with hypecalcemia due to hype paathyoidism and hypevitaminosis D. Many patients suffeing fom hypethyoidism eceive diagnosis of psychoneuosis, schizophenia o schizoid pesonality. Iitability, mood swings and paanoid psychosis ae associated with hypocalcemia. Emotional symptoms which occu due to distubances of calcium homeostasis may be elevated with nomalization of calcium metabolism. It has been established that a positive calcium balance may occu in skeleton as a whole fo 10 to 15 yeas afte cessation of linea gowth. In calcium homeostasis, the amount of calcium deposited in bone is the same as the amount eabsobed. This disease develops at the age of 35 yeas. The deposition of calcium inceases and occus in popotion to bone gowth, skeletal tunove, although less apid duing adulthood, in the gowing child. This pocess continues thoughout life upto fouth decade, i.e., 40 yeas. The tunove becomes dominated by bone esoption. It has been epoted in the liteatue [ ] that the ingested calcium mixes with digestive juice calcium in the poximal small intestine fom whee it is absobed by a mechanism. This pocess has an active satuable component and a diffusion component. Calcium is mainly absobed by active tanspot duing the low calcium intake. This active tanspot is called tanscellula tanspot. If the intake of calcium is high, the inceasing 140

23 popotion of calcium many be absobed by paacellula diffusion. The unabsobed component appeas in the faeces togethe with the unabsobed component of digestive juice calcium. This is called as endogeneous faecal calcium. It is concluded that the faeces contain unabsobed dietay calcium and uneabsobed digestive juice calcium. It is vey well known fact that the deficiency of calcium causes osteopoosis. We ae not in a position to say about bone and calcium metabolism duing aging to enable calculation of the calcium necessities of olde men and women. It has been found that calcium absoption deceases with the incease of age in both males and females [ ]. The calcium content of the newbon baby is about 24 g. Maximum pat of this calcium is laid down in the timeste of the pegnancy duing which the fetus etains 240 mg of calcium daily. The calcium content of human milk is 36 mg pe 100 ml [296]. A lactating lady may poduce 750 ml of milk daily. It has been epoted that 280 mg of calcium can be fed to a newbon child. It is vey inteesting esult, which is epoted in the liteatue that the bone is lost duing lactation and estoed afte weaning [297, 298]. This type of loss of calcium may be pevented by the supplementation of calcium [299]. Calcium deficiency is vey seious. eseaches have shown a low bone density. Due to low density, the factue ate is vey high in developing counties. The intake of calcium is also low. ickets has not been epoted in counties. Calcium is a nutient, which plays a ole in neuomuscula function, enzyme mediated mechanism, blood clotting and poviding igidity to the skeleton by vitue of its phosphate salts. Its non-stuctual oles equie the stict maintenance of ionized calcium concentation in tissue fluids at the cost of skeleton. Calcium equiements ae essentially detemined by the elationship between absoptive efficiency and excetoy ate. The excetion may be stated though bowl, kidneys, skin, hai and nails. The ate of calcium absoption fom the gastointestinal tact needs to match the ate of all losses fom the body, if the skeleton is to be maintained at suitable value of calcium with exta input of calcium with wate. It must be stoed in nonoxidizing medium, such as a liquid hydocabon. 141

24 Sodium: Elemental sodium was isolated in 1807 by passing an electic cuent though molten sodium hydoxide. Elemental sodium does not occu natually on eath. The sodium quickly oxidizes in ai and is eactive. The fee metal is used fo chemical synthesis, analysis and heat tansfe applications. Sodium ion is soluble in wate. It is pesent in geat quantities on eath. Sodium ion is also a component of many mineals. Befoe poceeding futhe, we wish to say something egading electolyte because chemically electolyte ae the substances ions in the solution. These ions acquie the capacity to conduct electicity. Human body contains electolytes. The balance of the electolytes is essential fo nomal function of cells and ogans of human beings. Main electolytes, which ae measued in the blood by the doctos, ae sodium, potassium, chloide and bicabonate. Sodium is the positive ion (Na + ), which is called cation. This is found in fluid outside the cells. Sodium is combined with the chloide make a common salt which is vey necessay fo the gowth of human body. Excess of sodium is exceted in the uine. Sodium is vey helpful in egulating the total amount of wate in the body and the tansmission of sodium into and out of the individual cells. It may also play a ole in body functions. Thee ae many pocesses in the human body such as in the bain, nevous system, and muscles. They equie electical signals fo communication. The movement of sodium is vey citical in the geneation of electical signals. Excess and deficit of sodium may lead to malfunction. The exteme value of sodium in the body can be fatal. Sodium is found in both states such as electolyte and mineal. It helps in keeping wate and the electolyte balance of human body. Sodium is vey essential to egulate neves and muscles function. Most of the sodium in the human body is found in blood and lymph fluid. Aldosteone homone contolled patly the levels of sodium in human system. Adenal glands ae esponsible fo the homone. The level of aldosteone in human body tells about the kidneys when to hold the sodium element in the body instead of passing it in uine. Small amounts of sodium may last though the skin duing the pocess of sweating. 142

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