STUDY - Technical - New Dacian's Medicine
Vitamin
Deficiency and Excess (2)
Translation Draft
Let's continue the presentation of vitamins with pyridoxine (vitamin B6)!
From the point of view of biochemistry, the biological activity of the group of B6 vitamins is exercised by pyridoxine, pyridoxine and pyridoxine and by their 5-phosphorylated esters. The form of coenzyme is pyridoxal-5-phosphate, the other components of the group due to their conversion activity into pyridoxal-5-phosphate. Vitamin is present in large and uniform amounts in all foods: meat, muscle, liver, vegetables and unmilled cereals. From the point of view of the mechanism of action pyridoxal phosphate acts as a cofactor of many enzymes involved in the metabolism of amino acids, such as: transaminases, sitetases and hydroxylases.
In humans, vitamin has a special role in the metabolism of tryptophan, glycine, serum, glutamate and sulfide amino acids. Pyridoxal phosphate is also necessary for the synthesis of teta-amino-levulinic acid, a precursor of hem. Much of the body's reserves lie in muscle phosphorylase, where its function is the stabilizer of the enzyme rather than the catalyst. It also plays a little understood role in neuronal excitability, probably due to its participation in transsulphurization reactions or aminobutyric acid (GABA) metabolism. In terms of daily requirement, more than in the case of other vitamins, the requirement of pyridoxine increases under conditions of high protein intake or through hemodialysis and chronic peritoneal dialysis.
Ethanol metabolite, acetaldehyde, partially displaces phosphate from proteins and thus increases its degradation. Pyridoxine deficiencies produce during a week the chemical highlighting of the deficiency, the increase of xanturenic acid and the decrease of pyridoxine in the urine. Electroencephalographic abnormalities occur within 3 weeks and some patients experience grand mal epileptic seizures. Deficiency induced by the administration of the pyridoxin antagonist (deoxypyridoxine) also produces seborrheic dermatitis, cheilitis, glossitis, nausea, vomiting, fatigue and dizziness.
In the case of clinical deficiency, due to its presence in most foods, isolated deficiency of pyridoxine is rare, unless the pyridoxin content of food is destroyed or converted into less available forms, related to proteins, during industrial processing, as is the case in industrial infant milk powder preparations. And yet, apparently paradoxically, pyridoxine deficiency is quite common, due to the antagonistic action of some drugs. Isoniazide, cycloserin, penicillamine and carbonyl compounds form complexes with the aldehyde half of the vitamin and prevent the normal functioning of the coenzyme.
In all situations, abnormal metabolism of tryptophan and seizures can be prevented by additional vitamin. The estimation of vitamin deficiency was made on the basis of the disappearance of clinical signs of deficiency, following the administration of the vitamin, by measuring the excretion of tryptophan metabolites after tryptophan loading tests, measuring the activity of various transmanases in the blood and determining the excretion of pyridoxine, its metabolites or oxalate in the urine. Another indicator is the urinary dosing of tryptophan metabolites (in particular xanturenic acid), following the tryptophan load.
As an alternative, methionine loading and cystation dosing may be used. A true indicator of the level of pyridoxine in vitro may be the determination of erythrocytic glutamico-pyruvice transaminase in the presence and absence of pyridoxal phosphate (even more faithful than the loading test). The right approach is to prevent the onset of the deficit. Supplementation of the diet with 30 mg pyridoxine normalizes the metabolism of tryptophan during pregnancy, in the case of the use of oral contraceptives and in the treatment with isoniazide. Doses of 100 mg/day may be required when taking pinicilamine.
There are diseases susceptible to pyridoxine, a few genetic diseases causing abnormalities in the metabolism of vitamin B6. Such a group of diseases is manifested in children by seizures and brain damage, which can lead to death if high daily doses of pyridoxine are not administered (these children show a decrease in the affinity of pyridoxal phosphate binding by an apoenzyme for glutamic acid decarboxylase). Consequently, the necessary amounts of teta-aminobutyric acid, a physiological inhibitor of neurotransmission, are not formed.
Another group with response to pyridoxine is sideroblastic anaemia due to a mutation in a specific erythrocytic gamma-aminolevinate synthetase (additional administration of pyridoxine produces prompt haematological improvement, but does not correct erythrocytic morphological abnormalities.) The synthesis of cystefrom homocysteine and serein and its split into cysteine and homoserin are catalyzed by two phosphate pyridoxal enzymes. Certain patients with vitamin B6-sensitive cystationinuria or xanturemic aciduria have a mutated apoenzyme that reacts abnormally with pyridoxal phosphate, the defect can be corrected by increased cofactor concentrations.
In contrast to previous cases, the positive response to vitamin B6 in patients with cystery deficiency synthase deficiency patients occurs by increasing the activity of the residual amount of the normal enzyme and less likely by bringing the enzyme levels back to normal.
Let's get to riboflavin now! Riboflavin, in the form of mononucleotide flavin (FMN) and adenin dinucleotide flavon (FAD), participates in numerous redox reactions. In addition, covalentbound flavins are essential components of the structure of some enzymes, with are succinyl dehydrogenase and monoaminoxidase. The vitamin is absorbed intestinally either in free form or in the form of 5' phosphate, pri active transport. The covalent bound shape achieves less than one-tenth of the tissue reserve. The vitamin is excreted in urine predominantly in free form, a small fraction of the daily losses being represented by degradation under the action of the intestinal flora.
Riboflavin deficiency can be produced by ingesting a riboflavin-free diet or by administering antagonists such as galactoflavin. The deficiency is characterized by dry throat, hyperemia and edema of the oral mucous membranes, cheilitis, angular stomatitis, glossitis, seborrheic dermatic and normocytic anemia, normochrome through erythrocytic hypoplasia in the bone marrow. These manifestations are reversible when taking riboflavin. Thyroid hormones and adrenal steroids increase the synthesis of FMN and FAD (phenothiazides and tricyclic antidepressants competitively inhibit the synthesis of flavinic coenzyme, but do not cause deficiency without the help of other factors). The decrease of riboflavin occurs at the same time as the decrease of other hydrosoluble vitamins. The need for riboflavin is increased in patients undergoing chronic hemodialysis or peritoneal dialysis.
The time has come to "analyze" vitamin C and its deficiency represented by scurvy. From a biochemical point of view, most animals synthesize ascorbic acid (vitamin C) from glucose. Humans, other primates and guinea pigs cannot synthesize L-ascorbic acid and require exogenous intake. These species cannot take one of the necessary steps for the synthesis of ascorbic acid in D-glucose, namely the conversion of L-gluconogamalactone to L-ascorbic acid. The presence of a mutation led to the lack of enzyme that catalyzes this reaction (L-guponplacton oxidase), so the need for exogenous vitamin C is the result of an innate error of carbohydrate metabolism.
From the point of view of the mechanism of action, L-ascorbic acid easily undergoes reversible oxidation-reduction reactions. L-ascorbic acid passes in the form of dehydro-L-ascorbic acid (reversible) + 2H+ + 2e. This property is the key to understanding the role of redox agent in biological oxidation. However, ascorbic acid does not act as a conventional cofactor because it can be replaced by other components with similar redox properties. The vitamin reduces the prosthetic groups formed by metal ions in many enzymes and exerts other antioxidant functions by extracting free radicals. The best understood function is that of collagen synthesis (the absence of vitamin C causes alteration of peptidyl hydroxylation of procolagen).
Unhydroxylated collagen cannot form the triple spiral required for a normal tissue structure. In addition, the synthesis of proteoglicans and collagen is reduced in ascorbic acid deficiency, probably due to inhibition of insulin-like growth factor I. Many manifestations in scurvy are the result of this defect in collagen synthesis, including capillary fragility and its hemorrhagic consequences, scarring deficiencies and (partially) bone abnormalities in children. Collagen with high hydroxyproline content is more severely affected, being responsible for early damage to the suction, mean and basal membrane in the blood vessels.
Ascorbic acid prevents the oxidation of tetrahydrofolate, thus protecting the active folic acid reserve, and regulates the distribution and storage of iron, probably by influencing the valence of stored iron and by maintaining the ferritin-hemosiderin ratio within normal limits. Patients with scurvy excrete incomplete oxidized products resulting from tyrosine metabolism, but the significance of this is not known.
Vitamin is found in milk and in some meat strips (kidneys, liver, fish) and is widespread in fruits and vegetables. Some of it is lost after prolonged storage of unprocessed fruits and vegetables (e.g. potatoes), but is stored partially (half or more) in most culinary processes (boiling in water or steam, boiling under pressure, jams and jellies, freezing, dehydration, preserving).
Consequently, the daily requirement can be achieved even through moderate consumption of fruits and vegetables. The use of vitamin C increases in pregnancy and lactation, in thyrotoxicosis, and absorption decreases in diarrhea and achlorhydry. In the case of experimental drealet, the total amount of vitamin C in the body varies between 1,5 and 3g. When a diet deficient in ascorbic acid is established, the reserve decreases at a rate of 4%/ day. The time it takes for a normal person to develop symptoms of hypovitaminosis varies between 1 and 3 months (according to numerous studies), due to the differences that exist in the initial deposits, the turn-over rate, the larger or smaller differences in different diets, individual variations at the cellular or enzymatic level. Manifestations of deficiency correlate better with the total volume of reserves than with the plasma or vascular level.
The first symptom (petesial haemorrhages and bruising) occurs when the reserves are less than 0.5g. If continuous doutation (reserves of 0.1-05 g) appear gum manifestations, hyperkeratosis, congestion of hair follicles, arthralgia, Sjogren's syndrome, brittle and cleft hair, joint effusions. at extreme deplation (reserves less than 0.1g) dyspnoea, edema, oliguria and neuropathies occur. The progression of the disease can then be rapid. Symptoms do not disappear until the reserves are restored, the faster the therapeutic doses are higher. However, low doses of 6.5 mg/ day restore deposits and relieve symptoms.
Clinically, the majority of scurvy cases occur in poor urban areas. The increased incidence exists between 6-12 months in children who receive milk formulas without additional fruit and vegetable juices due to the mother's ignorance or neglect. Another peak of incidence occurs at middle and advanced ages (teethless men who live alone and prepare your food themselves are the most affected). Clinical scurvy is more severe than that produced experimentally, possibly due to the fact that affected individuals have other deficiencies in the diet and due to the special vulnerability of the risk groups (sugars and the elderly).
In adults, scurvy manifestations include hyperkeratosic perifolicular papules in which the hair fragments and grows inwards, perifolicular hemorrhages, purpura that begins in the posterior parts of the lower extremities and which have a tendency to coalescence generating bruising, intramuscular bleeding in the arms and legs, followed by secondary phlebotrombosis, joint hemorrhages, bleeding in the sliver in the bed nail , gum damage (only in people with teeth), which includes inflammation, friability, bleeding, secondary infections, tooth loss, poor scarring, relapse of recently healed wounds, petesial visceral bleeding, mental impairment.
Symptoms similar to Sjogren's syndrome may occur. Finally, jaundice, edema and fever are frequent manifestations, convulsions, hypotension and death can suddenly set in. Painful inflammation and epiphysis separation may occur in infants and children by bleeding in the period of long bones. The sternum can be clogged causing the edges of the ribs to be highlighted (appearance of "scorbutic costal beads"). Purple and skin bruising may occur (if teeth have erupted, gum lesions also occur). Rapid death may occur without treatment, through intracerebral, retrobulbar or subarachnoid haemorrhages.
Normochrome anemia is common and is due to tissue bleeding. It can be macrocytic and/ or megaloblastic (approximately one fifth of patients). Many foods containing vitamin C also have folates, diets that lead to scurvy can also lead to folate deficiency. On the other hand, ascorbic acid deficiency causes increased oxidation of formyl-tetrahydrofolic acid in inactive metabolites and may cause a decrease in folate reserve.
It is not known to what extent the pathogenesis of anaemia is caused by changes in the distribution and storage of iron. Anemia disappears after administration of vitamin C and the establishment of a balanced nutrition. In some hospitals, the platelet concentration of ascorbic acid is used to diagnose scurvy, with pathological values representing less than one-fourth of the usual concentration. Plasma levels correlate less significantly with clinical status. In infants, radiological examination reveals bone changes. Bilirubin is frequently increased. Capillary fragility is abnormal.
Scurvy is potentially fatal (if this diagnosis is suspected, blood will be collected and ascorbic acid therapy will be promptly instituted). The usual dose in adults is 100 mg 3-5 times a day until 4g, then 100 mg/ day orally. Infants and children are given 10-25 mg 3 times a day. Simultaneously will ensure a diet rich in vitamin C. Spontaneous bleeding usually subsides within 24 hours, muscle and bone pain quickly disappears and gums begin to heal after 2-3 days. Even large bruising and hematomas resorb in 10-12 days, although pigmentation of these areas persists for several months. Serum bilirubin returns to normal in 3-5 days, and the anemia is corrected in 2-4 weeks.
Understanding, Love and Gratitude!
Let's continue the presentation of vitamins with pyridoxine (vitamin B6)!
From the point of view of biochemistry, the biological activity of the group of B6 vitamins is exercised by pyridoxine, pyridoxine and pyridoxine and by their 5-phosphorylated esters. The form of coenzyme is pyridoxal-5-phosphate, the other components of the group due to their conversion activity into pyridoxal-5-phosphate. Vitamin is present in large and uniform amounts in all foods: meat, muscle, liver, vegetables and unmilled cereals. From the point of view of the mechanism of action pyridoxal phosphate acts as a cofactor of many enzymes involved in the metabolism of amino acids, such as: transaminases, sitetases and hydroxylases.
In humans, vitamin has a special role in the metabolism of tryptophan, glycine, serum, glutamate and sulfide amino acids. Pyridoxal phosphate is also necessary for the synthesis of teta-amino-levulinic acid, a precursor of hem. Much of the body's reserves lie in muscle phosphorylase, where its function is the stabilizer of the enzyme rather than the catalyst. It also plays a little understood role in neuronal excitability, probably due to its participation in transsulphurization reactions or aminobutyric acid (GABA) metabolism. In terms of daily requirement, more than in the case of other vitamins, the requirement of pyridoxine increases under conditions of high protein intake or through hemodialysis and chronic peritoneal dialysis.
Ethanol metabolite, acetaldehyde, partially displaces phosphate from proteins and thus increases its degradation. Pyridoxine deficiencies produce during a week the chemical highlighting of the deficiency, the increase of xanturenic acid and the decrease of pyridoxine in the urine. Electroencephalographic abnormalities occur within 3 weeks and some patients experience grand mal epileptic seizures. Deficiency induced by the administration of the pyridoxin antagonist (deoxypyridoxine) also produces seborrheic dermatitis, cheilitis, glossitis, nausea, vomiting, fatigue and dizziness.
In the case of clinical deficiency, due to its presence in most foods, isolated deficiency of pyridoxine is rare, unless the pyridoxin content of food is destroyed or converted into less available forms, related to proteins, during industrial processing, as is the case in industrial infant milk powder preparations. And yet, apparently paradoxically, pyridoxine deficiency is quite common, due to the antagonistic action of some drugs. Isoniazide, cycloserin, penicillamine and carbonyl compounds form complexes with the aldehyde half of the vitamin and prevent the normal functioning of the coenzyme.
In all situations, abnormal metabolism of tryptophan and seizures can be prevented by additional vitamin. The estimation of vitamin deficiency was made on the basis of the disappearance of clinical signs of deficiency, following the administration of the vitamin, by measuring the excretion of tryptophan metabolites after tryptophan loading tests, measuring the activity of various transmanases in the blood and determining the excretion of pyridoxine, its metabolites or oxalate in the urine. Another indicator is the urinary dosing of tryptophan metabolites (in particular xanturenic acid), following the tryptophan load.
As an alternative, methionine loading and cystation dosing may be used. A true indicator of the level of pyridoxine in vitro may be the determination of erythrocytic glutamico-pyruvice transaminase in the presence and absence of pyridoxal phosphate (even more faithful than the loading test). The right approach is to prevent the onset of the deficit. Supplementation of the diet with 30 mg pyridoxine normalizes the metabolism of tryptophan during pregnancy, in the case of the use of oral contraceptives and in the treatment with isoniazide. Doses of 100 mg/day may be required when taking pinicilamine.
There are diseases susceptible to pyridoxine, a few genetic diseases causing abnormalities in the metabolism of vitamin B6. Such a group of diseases is manifested in children by seizures and brain damage, which can lead to death if high daily doses of pyridoxine are not administered (these children show a decrease in the affinity of pyridoxal phosphate binding by an apoenzyme for glutamic acid decarboxylase). Consequently, the necessary amounts of teta-aminobutyric acid, a physiological inhibitor of neurotransmission, are not formed.
Another group with response to pyridoxine is sideroblastic anaemia due to a mutation in a specific erythrocytic gamma-aminolevinate synthetase (additional administration of pyridoxine produces prompt haematological improvement, but does not correct erythrocytic morphological abnormalities.) The synthesis of cystefrom homocysteine and serein and its split into cysteine and homoserin are catalyzed by two phosphate pyridoxal enzymes. Certain patients with vitamin B6-sensitive cystationinuria or xanturemic aciduria have a mutated apoenzyme that reacts abnormally with pyridoxal phosphate, the defect can be corrected by increased cofactor concentrations.
In contrast to previous cases, the positive response to vitamin B6 in patients with cystery deficiency synthase deficiency patients occurs by increasing the activity of the residual amount of the normal enzyme and less likely by bringing the enzyme levels back to normal.
Let's get to riboflavin now! Riboflavin, in the form of mononucleotide flavin (FMN) and adenin dinucleotide flavon (FAD), participates in numerous redox reactions. In addition, covalentbound flavins are essential components of the structure of some enzymes, with are succinyl dehydrogenase and monoaminoxidase. The vitamin is absorbed intestinally either in free form or in the form of 5' phosphate, pri active transport. The covalent bound shape achieves less than one-tenth of the tissue reserve. The vitamin is excreted in urine predominantly in free form, a small fraction of the daily losses being represented by degradation under the action of the intestinal flora.
Riboflavin deficiency can be produced by ingesting a riboflavin-free diet or by administering antagonists such as galactoflavin. The deficiency is characterized by dry throat, hyperemia and edema of the oral mucous membranes, cheilitis, angular stomatitis, glossitis, seborrheic dermatic and normocytic anemia, normochrome through erythrocytic hypoplasia in the bone marrow. These manifestations are reversible when taking riboflavin. Thyroid hormones and adrenal steroids increase the synthesis of FMN and FAD (phenothiazides and tricyclic antidepressants competitively inhibit the synthesis of flavinic coenzyme, but do not cause deficiency without the help of other factors). The decrease of riboflavin occurs at the same time as the decrease of other hydrosoluble vitamins. The need for riboflavin is increased in patients undergoing chronic hemodialysis or peritoneal dialysis.
The time has come to "analyze" vitamin C and its deficiency represented by scurvy. From a biochemical point of view, most animals synthesize ascorbic acid (vitamin C) from glucose. Humans, other primates and guinea pigs cannot synthesize L-ascorbic acid and require exogenous intake. These species cannot take one of the necessary steps for the synthesis of ascorbic acid in D-glucose, namely the conversion of L-gluconogamalactone to L-ascorbic acid. The presence of a mutation led to the lack of enzyme that catalyzes this reaction (L-guponplacton oxidase), so the need for exogenous vitamin C is the result of an innate error of carbohydrate metabolism.
From the point of view of the mechanism of action, L-ascorbic acid easily undergoes reversible oxidation-reduction reactions. L-ascorbic acid passes in the form of dehydro-L-ascorbic acid (reversible) + 2H+ + 2e. This property is the key to understanding the role of redox agent in biological oxidation. However, ascorbic acid does not act as a conventional cofactor because it can be replaced by other components with similar redox properties. The vitamin reduces the prosthetic groups formed by metal ions in many enzymes and exerts other antioxidant functions by extracting free radicals. The best understood function is that of collagen synthesis (the absence of vitamin C causes alteration of peptidyl hydroxylation of procolagen).
Unhydroxylated collagen cannot form the triple spiral required for a normal tissue structure. In addition, the synthesis of proteoglicans and collagen is reduced in ascorbic acid deficiency, probably due to inhibition of insulin-like growth factor I. Many manifestations in scurvy are the result of this defect in collagen synthesis, including capillary fragility and its hemorrhagic consequences, scarring deficiencies and (partially) bone abnormalities in children. Collagen with high hydroxyproline content is more severely affected, being responsible for early damage to the suction, mean and basal membrane in the blood vessels.
Ascorbic acid prevents the oxidation of tetrahydrofolate, thus protecting the active folic acid reserve, and regulates the distribution and storage of iron, probably by influencing the valence of stored iron and by maintaining the ferritin-hemosiderin ratio within normal limits. Patients with scurvy excrete incomplete oxidized products resulting from tyrosine metabolism, but the significance of this is not known.
Vitamin is found in milk and in some meat strips (kidneys, liver, fish) and is widespread in fruits and vegetables. Some of it is lost after prolonged storage of unprocessed fruits and vegetables (e.g. potatoes), but is stored partially (half or more) in most culinary processes (boiling in water or steam, boiling under pressure, jams and jellies, freezing, dehydration, preserving).
Consequently, the daily requirement can be achieved even through moderate consumption of fruits and vegetables. The use of vitamin C increases in pregnancy and lactation, in thyrotoxicosis, and absorption decreases in diarrhea and achlorhydry. In the case of experimental drealet, the total amount of vitamin C in the body varies between 1,5 and 3g. When a diet deficient in ascorbic acid is established, the reserve decreases at a rate of 4%/ day. The time it takes for a normal person to develop symptoms of hypovitaminosis varies between 1 and 3 months (according to numerous studies), due to the differences that exist in the initial deposits, the turn-over rate, the larger or smaller differences in different diets, individual variations at the cellular or enzymatic level. Manifestations of deficiency correlate better with the total volume of reserves than with the plasma or vascular level.
The first symptom (petesial haemorrhages and bruising) occurs when the reserves are less than 0.5g. If continuous doutation (reserves of 0.1-05 g) appear gum manifestations, hyperkeratosis, congestion of hair follicles, arthralgia, Sjogren's syndrome, brittle and cleft hair, joint effusions. at extreme deplation (reserves less than 0.1g) dyspnoea, edema, oliguria and neuropathies occur. The progression of the disease can then be rapid. Symptoms do not disappear until the reserves are restored, the faster the therapeutic doses are higher. However, low doses of 6.5 mg/ day restore deposits and relieve symptoms.
Clinically, the majority of scurvy cases occur in poor urban areas. The increased incidence exists between 6-12 months in children who receive milk formulas without additional fruit and vegetable juices due to the mother's ignorance or neglect. Another peak of incidence occurs at middle and advanced ages (teethless men who live alone and prepare your food themselves are the most affected). Clinical scurvy is more severe than that produced experimentally, possibly due to the fact that affected individuals have other deficiencies in the diet and due to the special vulnerability of the risk groups (sugars and the elderly).
In adults, scurvy manifestations include hyperkeratosic perifolicular papules in which the hair fragments and grows inwards, perifolicular hemorrhages, purpura that begins in the posterior parts of the lower extremities and which have a tendency to coalescence generating bruising, intramuscular bleeding in the arms and legs, followed by secondary phlebotrombosis, joint hemorrhages, bleeding in the sliver in the bed nail , gum damage (only in people with teeth), which includes inflammation, friability, bleeding, secondary infections, tooth loss, poor scarring, relapse of recently healed wounds, petesial visceral bleeding, mental impairment.
Symptoms similar to Sjogren's syndrome may occur. Finally, jaundice, edema and fever are frequent manifestations, convulsions, hypotension and death can suddenly set in. Painful inflammation and epiphysis separation may occur in infants and children by bleeding in the period of long bones. The sternum can be clogged causing the edges of the ribs to be highlighted (appearance of "scorbutic costal beads"). Purple and skin bruising may occur (if teeth have erupted, gum lesions also occur). Rapid death may occur without treatment, through intracerebral, retrobulbar or subarachnoid haemorrhages.
Normochrome anemia is common and is due to tissue bleeding. It can be macrocytic and/ or megaloblastic (approximately one fifth of patients). Many foods containing vitamin C also have folates, diets that lead to scurvy can also lead to folate deficiency. On the other hand, ascorbic acid deficiency causes increased oxidation of formyl-tetrahydrofolic acid in inactive metabolites and may cause a decrease in folate reserve.
It is not known to what extent the pathogenesis of anaemia is caused by changes in the distribution and storage of iron. Anemia disappears after administration of vitamin C and the establishment of a balanced nutrition. In some hospitals, the platelet concentration of ascorbic acid is used to diagnose scurvy, with pathological values representing less than one-fourth of the usual concentration. Plasma levels correlate less significantly with clinical status. In infants, radiological examination reveals bone changes. Bilirubin is frequently increased. Capillary fragility is abnormal.
Scurvy is potentially fatal (if this diagnosis is suspected, blood will be collected and ascorbic acid therapy will be promptly instituted). The usual dose in adults is 100 mg 3-5 times a day until 4g, then 100 mg/ day orally. Infants and children are given 10-25 mg 3 times a day. Simultaneously will ensure a diet rich in vitamin C. Spontaneous bleeding usually subsides within 24 hours, muscle and bone pain quickly disappears and gums begin to heal after 2-3 days. Even large bruising and hematomas resorb in 10-12 days, although pigmentation of these areas persists for several months. Serum bilirubin returns to normal in 3-5 days, and the anemia is corrected in 2-4 weeks.
Understanding, Love and Gratitude!
Dorin, Merticaru